title: Significance of norovirus in occupational health: a review of published norovirus outbreaks in Central and Northern Europe

text: OBJECTIVES: Globally, norovirus (NoV) is the leading cause of gastroenteritis infection among all ages. The development of prevention strategies in the field of occupational health requires a detailed knowledge about the impact of the disease on employees. This review article aims not only at evaluating the burden of NoV outbreaks on staff but also at discussing implications for future prevention strategies. METHODS: Published NoV outbreaks in Central and Northern Europe were identified via a systematic literature search. Additionally, published NoV outbreaks in Germany were detected via a manual literature search. Key epidemiological data, as the number of symptomatic staff, was then extracted. The proportion of affected employees was calculated for each dataset (single NoV outbreaks or aggregated data of multiple outbreaks). RESULTS: Overall, 116 datasets were extracted from 72 relevant articles. 144,852 persons were affected by NoV gastroenteritis, 25,408 out of them (17.5%) were employees. 23,874 (94.0%) of them fell sick during outbreaks in hospitals and related settings. NoV cases among personnel in food establishments were reported only sporadically (mean ratio: 0.01). CONCLUSIONS: Employees in hospitals and community facilities seem quantitatively to be most vulnerable towards NoV epidemics. Therefore, high quality of prevention measures in these settings, respective compliance with prevention strategies should have the highest priority. The disease can be considered as an occupational disease, even regularly without long-term consequences. Following work safety rules, a vaccination for vulnerable groups should be recommended if the vaccine development turns out to be successful. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00420-020-01543-4) contains supplementary material, which is available to authorized users.


title: Impact of tracheostomy on language and cognitive development in infants with severe bronchopulmonary dysplasia

text: OBJECTIVE: The impact of tracheostomy on language and cognitive development in infants with severe bronchopulmonary dysplasia (BPD) is not known. We hypothesize that tracheostomy has an independent negative impact on language and cognitive development in infants with severe BPD. STUDY DESIGN: This is a retrospective cohort study of de-identified data of infants with severe BPD who received tracheostomy at <2 years of age, compared with infants with severe BPD without tracheostomy. The primary outcomes measured were total language and cognitive scores at 2–3 years of age as determined by Bayley Scales of Infant and Toddler Development, 3rd Edition. RESULTS: A total of 26 patients with tracheostomies and 28 patients without tracheostomies were analyzed. There was no significant difference in total language development or cognitive development between patients with tracheostomies and those without. Insurance status had an effect on language and cognition while controlling for trach status. CONCLUSIONS: Tracheostomy does not independently impact the language and cognitive development of infants with severe BPD.


title: Acquisition of Information About Innovative Practices in Outpatient Mental Health Clinics

text: This study uses qualitative interviews with leaders of 34 mental health clinics in the context of a statewide rollout of clinical and business innovations to explore how clinics first learn about innovations and which external sources of information they access. Clinic leaders reported accessing information about innovations mainly from government agencies, professional associations, peer organizations, and research literature. Leaders mentioned an average of two external sources of information. There was evidence of variation in how leaders accessed information and how information about innovations was communicated within clinics. Findings have implications for improving dissemination of information about innovations in mental health systems.


title: Zielgruppengerechte Krisenintervention – Angehörige und Team

text: Families find themselves in an exceptional situation after the sudden death of someone close. Anxiety, aggression, rage, incomprehension, and distraction are only a few feelings of the concerned people which intensive care staff must take care of. Crisis intervention, developed in the middle of the last century, offers a framework with its concepts for the healthcare staff of how to work with the bereaved people during the first few hours. The BASIS model is a sort of counseling technique that guides nurses and physicians: bonding and urging the acceptance of the facts, providing structure and information, and securing backup support networks. Professionals who offer help need a high level of empathy and compassion for their work. But it is essential to offer help only in situations where advice is possible. Otherwise, physicians and nurses are at high risk to develop compassion fatigue. The right training, advanced education, and supervision are necessary, so that healthcare professionals can support people in crisis.


title: An increasing prevalence of non-GII.4 norovirus genotypes in acute gastroenteritis outbreaks in Huzhou, China, 2014-2018

text: Since 2014, novel non-GII.4 norovirus (NoV) genotypes continue to be reported as the main cause of outbreaks worldwide. In this study, we analyzed the epidemiological and genetic features of NoV outbreaks from July 2014 to June 2018 in Huzhou, China. A total of 450 stool samples collected from 51 AGE outbreaks were tested for NoVs by real-time RT PCR. Partial polymerase and capsid sequences of NoV-positive samples were amplified and sequenced for phylogenetic analysis. NoVs were found to be responsible of 84.3% of AGE outbreaks in Huzhou over the past 5 years. Most NoV outbreaks were reported in the cool months (November-March) and occurred in primary schools and kindergartens. Changes in the diversity of genotypes and the distribution of predominant types were observed in recent years. At least eight genotypes were identified, and 91.9% of the genotyped outbreaks were caused by non-GII.4 strains. The top three circulating genotypes during the study period were GII.2[P16], GII.3[P12], and GII.17[P17]. The predominant NoV genotypes in outbreaks have changed from GII.4 variants to GII.17[P17] in 2014-2015, GII.3[P12] in 2015-2016, and then GII.2[P16] in 2016-2018. Non-GII.4 NoVs play an increasingly important role in outbreaks in Huzhou. Continuous surveillance is needed to monitor the emergence of novel NoV strains and help control NoV outbreaks in the next epidemic season.


title: An audit to analyse the two-week wait pathway at an oral cancer specialist district general hospital

text: Background The incidence of head and neck cancers is increasing, alongside a decrease in associated mortality. Currently, medical and dental practitioners can refer patients to be seen urgently within two weeks. The appropriateness of these referrals has been disputed. In 2020, the Department of Health aims for patients to be given cancer diagnoses within 28 days from referral. Methods A retrospective audit was conducted for all patients referred under the two-week wait pathway in a six-month period. In the first cycle of this audit, one month's worth of urgent referrals were analysed; given the small sample size, very few recommendations could be made. The audit cycle was repeated and it analysed six months' worth of data, which gave a much more representative study. All patients were analysed to see if the 14-day period had been breached. Positive cancer patients were further assessed to see if their diagnosis had been given within 28 days and treatments within 62 days. Results Of the 569 patients seen, there was a positive malignancy diagnostic yield of 7.38%. Nineteen patients breached the 14-day wait. Of the positive patients, 45.2% received their diagnosis more than 28 days from referral, and 22.2% of these patients received treatment after 62 days. Conclusion The department performed well despite the high number of referrals. This audit has touched on some key issues which have been discussed in detail in this article. Furthermore, this audit recommends a concerted effort to improve oral cancer detections skills among GDPs and GMPs. While all referrals may be appropriate from a primary care point of view, this audit makes it apparent that better differentiation is needed between malignant and routinely manageable lesions. All secondary care units alongside general practitioners can learn from the findings of this audit.


title: Outcomes of Severe PARDS on High-Frequency Oscillatory Ventilation – A Single Centre Experience

text: OBJECTIVE: To describe experience with high-frequency oscillatory ventilation (HFOV) in children with acute respiratory distress syndrome (ARDS) transitioned from conventional mechanical ventilation (CMV) due to refractory hypoxemia and to assess factors associated with survival and also compare outcomes of patients who were managed with early HFOV (within 24 h of intubation) vs. late HFOV. METHODS: This retrospective, observational study was conducted in a tertiary care hospital's pediatric intensive care unit. Thirty-four children with pediatric acute respiratory distress syndrome (PARDS) managed with HFOV were included. RESULTS: Of 34 children with PARDS managed with HFOV after failure of conventional ventilation to improve oxygenation, 8 survived. Improvement in the Oxygenation Index (OI) at 48 h of initiation of HFOV along with percent increase in PaO(2)/FiO(2) (P/F ratio) at 24 h of HFOV were predictors of survival. The response to HFOV, based on OI and P/F ratio, between 24 and 48 h of ventilation identified potential survivors. Also, lower positive end-expiratory pressure (PEEP) on CMV and shorter duration of CMV before initiation of HFOV were associated with survival. CONCLUSIONS: Survival in pediatric ARDS patients treated with HFOV could be predicted by using trends of OI – with survivors showing a more rapid decline in OI between 24 and 48 h of initiation compared to non-survivors.


title: Effects of intraoperative positive end-expiratory pressure optimization on respiratory mechanics and the inflammatory response: a randomized controlled trial

text: Applying lung protective mechanical ventilation (LPV) during general anaesthesia even in patients with non-injured lungs is recommended. However, the effects of an individual PEEP-optimisation on respiratory mechanics, oxygenation and their potential correlation with the inflammatory response and postoperative complications have not been evaluated have not been compared to standard LPV in patients undergoing major abdominal surgery. Thirty-nine patients undergoing open radical cystectomy were enrolled in this study. In the study group (SG) optimal PEEP was determined by a decremental titration procedure and defined as the PEEP value resulting the highest static pulmonary compliance. In the control group (CG) PEEP was set to 6 cmH2O. Primary endpoints were intraoperative respiratory mechanics and gas exchange parameters. Secondary outcomes were perioperative procalcitonin kinetics and postoperative pulmonary complications. Optimal PEEP levels (median = 10, range: 8–14 cmH2O), PaO2/FiO2 (451.24 ± 121.78 mmHg vs. 404.15 ± 115.87 mmHg, P = 0.005) and static pulmonary compliance (52.54 ± 13.59 ml cmH2O-1 vs. 45.22 ± 9.13 ml cmH2O-1, P < 0.0001) were significantly higher, while driving pressure (8.26 ± 1.74 cmH2O vs. 9.73 ± 4.02 cmH2O, P < 0.0001) was significantly lower in the SG as compared to the CG. No significant intergroup differences were found in procalcitonin kinetics (P = 0.076). Composite outcome results indicated a non-significant reduction of postoperative complications in the SG. Intraoperative PEEP-optimization resulted in significant improvement in gas exchange and pulmonary mechanics as compared to standard LPV. Whether these have any effect on short and long term outcomes require further investigations. Trial registration: Clinicaltrials.gov, identifier: NCT02931409.


title: Compassionate Love among Catholic Priests: its Antecedents and its Influence on Affect toward Pastoral Ministry in Indonesia

text: What drives Catholic priests to continue to serve people? That is the main question behind this psychological study. Based on a working model of compassionate love (Underwood 2008), the priestly compassionate love model was tested to determine whether spirituality, social support, priestly commitment, and well-being simultaneously influence compassionate love, which in turn brings out a positive affect in those doing pastoral ministry. The participants were 256 Catholic priests in Indonesia. Using structural equation modeling, the results of the study showed a good fit. Spirituality was the factor that contributed most strongly to compassionate love. Receiving adequate support from multiple sources motivated the priests to love others. Moreover, priestly commitment also influenced the priests to love others compassionately. Although well-being did not significantly influence compassionate love, it still played an important role in the model because it was correlated with all factors. Finally, the results showed that compassionate love powerfully influenced the priests to be enthusiastic and eager in doing pastoral ministry. These findings are discussed theoretically and practically in the context of priestly life and ministry in Indonesia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11089-019-00888-z) contains supplementary material, which is available to authorized users.


title: Satisfaction with Care and Satisfaction with Decision Making are Similar Regardless of Staffing Model in a Neurocritical Care Unit

text: INTRODUCTION: Patient-centered care, particularly shared medical decision making, is difficult to measure in critically ill patients where decisions are often made by a designated surrogate, often receiving information from multiple providers with varying degrees of training. The purpose of this study was to compare short-term satisfaction with care and decision making in patients or surrogates between two neurocritical care units [one staffed by a neurocritical care attending and advanced practice providers (APPs) and one staffed by a neurocritical care attending and resident/fellow trainees] using the Family Satisfaction in the ICU (FS-ICU) survey. METHODS: Over a 6-month period, the FS-ICU was administered on a tablet device to patients or surrogates at least 24 h after admission and stored on REDCap database. RESULTS: One hundred and thirty-four patients or surrogates completed the FS-ICU. The response rates were 59.97% and 46.58% in the APP and trainee units, respectively. There were no differences in patient age, sex, ventilator days or ICU length of stay. Overall, there were no differences in satisfaction with care or perceived shared medical making between the units. Respondents who identified their relationship with the patient as “other” (not a spouse, parent, nor a sibling) were less satisfied with care. Additionally, surrogates who identified as parents of the patient were more satisfied with degree of shared medical decision making. CONCLUSION: This study showed that: (1) collecting FS-ICU in a neurocritical care unit is feasible, (2) overall there is no difference in short-term satisfaction with care or shared decision making between a NICU staffed with trainees compared to one staffed with APPs, and (3) parents of patients have a higher short-term satisfaction with degree of shared medical decision making.


title: Bariatric Surgery Outcomes in Patients with Prior Solid Organ Transplantation: an MBSAQIP Analysis

text: INTRODUCTION: Obesity is a risk factor for poor patient outcomes after organ transplantation (TXP). While metabolic and bariatric surgery (MBS) is safe and effective in treating severe obesity, the role of MBS in transplant patients continues to evolve. METHODS: A retrospective analysis was performed of sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) patients in the 2017 Metabolic and Bariatric Surgery Accreditation Quality and Improvement Project (MBSAQIP) database. Propensity and case-control matching, and multivariable logistic regression were performed for 30-day post-operative outcomes. RESULTS: A total of 336 transplant patients were compared with 157,413 patients without transplant. Propensity and case-control matching reveal no significant differences in mortality (p > 0.2). However, case-control matching revealed longer operative time (104 min versus 76 min, p < 0.001), increased length of stay (2 days versus 1 day, p < 0.05), perioperative transfusions (2% versus 0.22%, p = 0.009), and leak rates (2.2% versus 0.55%, p = 0.02) in the transplant cohort. On multivariable regression analysis, prior transplantation was associated with higher rates of overall (OR 1.6, p = 0.007) and bariatric-related morbidity (OR 1.78, p = 0.004), leak (OR 3.47, p = 0.0027), and surgical site infection (OR 3.32, p = 0.004). Prior transplantation did not predict overall (p = 0.55) nor bariatric-related mortality (p = 0.99). CONCLUSION: MBS in prior solid organ transplantation patients is overall safe, but is associated with increased operative time and length of stay, as well as higher rates of some post-operative morbidity.


title: Molecular Modelling and Insilico Engineering of PapMV-CP Towards Display and Development of Capripox Viral Like Particles Based on Immunogenic P32 Envelop Protein is the Homologous of the Vaccinia-Viral H3L Gene: An Insilico Approach

text: Viral-like particles are assembled from capsid protein structural subunits of different viruses and have ability to establish research in biomedicals, like construction of novel safety vaccines, gene therapy vectors by delivering systems for nucleic acids, small biomolecules and diagnostics. Papaya Mosaic Viral nanoparticals can provide as a vaccine candidate helps to increase the immunity by fusing the epitope based peptide antigen. Capripox viruses are the genus comprises Lymphy skin-disease, Sheep and Goat pox Viruses are notified by The World Animal Health Organization (OIE) based on their economic impotence act as a transboundary animal diseases viruses of sheep, goat, and cattle’s respectively. Plant viral based innovative vaccines have been emerged ineffective vaccine development. This research describes the engineering and development of a new vaccine candidate by display immunogenic peptide using the carrier capsid protein of Papaya Mosaic Virus. The Capripox virus P32 immunogenic protein is homologous of the vaccinia virus H3L gene displayed PapMV CP. The antigenicity of P32 protein epitope lowest score among epitopes C-terminally docked epitopes are EP6 > EP3 > EP8 as well the lowest score among epitopes N-terminally docked epitopes are EP8 > EP3 > EP6 presented on the N-terminus of PMV CP region which are found to be suitable for epitope display. And these modelled immunogenic peptide could be used to develop a viral like particles. Epitope based Antibody developed against immunogenic epitopic regions can contribute to a novel and robust protection from infection. As well might be used for developing cost effective detection kits for Transboundary animal disease viruses.


title: The Golden Hour: a quality improvement initiative for extremely premature infants in the neonatal intensive care unit

text: BACKGROUND: Following delivery, extremely premature infants are vulnerable to rapid development of hypothermia and hypoglycemia. To reduce local rates of these morbidities, a multidisciplinary team developed a protocol standardizing evidence-based care practices during the first hour after birth. METHODS: Using quality improvement methodology, the Golden Hour protocol was implemented for all inborn infants <27 weeks’ gestation. Data were collected (2012–2017) over three phases; pre-protocol (n = 80), Phase I (n = 42), and Phase II (n = 92). RESULTS: There were no significant differences in infant characteristics. Improvements in hypothermia (59% vs 26% vs 38%; p = 0.001), hypoglycemia (18% vs 7% vs 4%; p = 0.012), and minutes to completion of stabilization [median (Q1,Q3) 110 (89,138) vs 111 (94,135) vs 92 (74,129); p = 0.0035] were observed. CONCLUSIONS: Implementation of an evidence-based, Golden Hour protocol is an effective intervention for reducing hypothermia and hypoglycemia in extremely premature infants.


title: Rate and risk factors for rehospitalisation in sepsis survivors: systematic review and meta-analysis

text: PURPOSE: Sepsis survivors have a higher risk of rehospitalisation and of long-term mortality. We assessed the rate, diagnosis, and independent predictors for rehospitalisation in adult sepsis survivors. METHODS: We searched for non-randomized studies and randomized clinical trials in MEDLINE, Cochrane Library, Web of Science, and EMBASE (OVID interface, 1992–October 2019). The search strategy used controlled vocabulary terms and text words for sepsis and hospital readmission, limited to humans, and English language. Two authors independently selected studies and extracted data using predefined criteria and data extraction forms. RESULTS: The literature search identified 12,544 records. Among 56 studies (36 full and 20 conference abstracts) that met our inclusion criteria, all were non-randomised studies. Studies most often report 30-day rehospitalisation rate (mean 21.4%, 95% confidence interval [CI] 17.6–25.4%; N = 36 studies reporting 6,729,617 patients). The mean (95%CI) rehospitalisation rates increased from 9.3% (8.3–10.3%) by 7 days to 39.0% (22.0–59.4%) by 365 days. Infection was the most common rehospitalisation diagnosis. Risk factors that increased the rehospitalisation risk in sepsis survivors were generic characteristics such as older age, male, comorbidities, non-elective admissions, hospitalisation prior to index sepsis admission, and sepsis characteristics such as infection and illness severity, with hospital characteristics showing inconsistent associations. The overall certainty of evidence was moderate for rehospitalisation rates and low for risk factors. CONCLUSIONS: Rehospitalisation events are common in sepsis survivors, with one in five rehospitalisation events occurring within 30 days of hospital discharge following an index sepsis admission. The generic and sepsis-specific characteristics at index sepsis admission are commonly reported risk factors for rehospitalisation. REGISTRATION: PROSPERO CRD 42016039257, registered on 14-06-2016. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05908-3) contains supplementary material, which is available to authorized users.


title: Probiotics in hospitalized adult patients: a systematic review of economic evaluations

text: PURPOSE: Probiotics may prevent healthcare-associated infections, such as ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea, and other adverse outcomes. Despite their potential benefits, there are no summative data examining the cost-effectiveness of probiotics in hospitalized patients. This systematic review summarized studies evaluating the economic impact of using probiotics in hospitalized adult patients. METHODS: We searched MEDLINE, EMBASE, CENTRAL, ACP Journal Club, and other EBM reviews (inception to January 31, 2019) for health economics evaluations examining the use of probiotics in hospitalized adults. Independently and in duplicate, we extracted data study characteristics, risk of bias, effectiveness and total costs (medications, diagnostics/procedures, devices, personnel, hospital) associated with healthcare-associated infections (ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea and antibiotic-associated diarrhea). We used Grading of Recommendations Assessment, Development and Evaluation methods to assess certainty in the overall cost-effectiveness evidence. RESULTS: Of 721 citations identified, we included seven studies. For the clinical outcomes of interest, there was one randomized-controlled trial (RCT)-based health economic evaluation, and six model-based health economic evaluations. Probiotics showed favourable cost-effectiveness in six of seven (86%) economic evaluations. Three of the seven studies were manufacturer-supported, all which suggested cost-effectiveness. Certainty of cost-effectiveness evidence was very low because of risk of bias, imprecision, and inconsistency. CONCLUSION: Probiotics may be an economically attractive intervention for preventing ventilator-associated pneumonia, Clostridioides difficile-associated diarrhea, and antibiotic-associated diarrhea in hospitalized adult patients. Nevertheless, certainty about their cost-effectiveness evidence is very low. Future RCTs examining probiotics should incorporate cost data to inform bedside practice, clinical guidelines, and healthcare policy. Trial registration: PROSPERO CRD42019129929; Registered 25 April, 2019. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12630-019-01525-2) contains supplementary material, which is available to authorized users.


title: Outcomes in conventional laparoscopic versus robotic-assisted primary bariatric surgery: a retrospective, case–controlled study of the MBSAQIP database

text: INTRODUCTION: Robotic-assisted bariatric surgery is increasingly performed. There remains controversy about the overall benefit of robotic-assisted (RBS) compared to conventional laparoscopic (LBS) bariatric surgery. In this study, we used a large national risk-stratified bariatric clinical database to compare outcomes between robotic and laparoscopic gastric bypass (RNYGB) and sleeve gastrectomy (SG). METHODS: A retrospective analysis of the 2015 and 2016 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) Participant Use Data File (PUF) was performed. Primary robotic and laparoscopic RYNGB and SG were analyzed. Descriptive analysis was performed of the unmatched cohorts, followed by 1:3 case-controlled matching. Cases and controls were matched by patient demographics and pre-operative comorbidities, and peri-operative outcomes compared. RESULTS: 77,991 Roux-en-Y gastric bypass (RnYGB) (7.5% robotic-assisted) and 189,503 SG (6.8% robotic-assisted) cases were identified. Operative length was significantly higher in both the robotic-assisted RnYGB and SG cohorts (p < 0.0001). Outcomes were similar between the robotic-assisted and laparoscopic RnYGB cohorts, except a lower mortality rate (p = 0.05), transfusion requirement (p = 0.005), aggregate bleeding (p = 0.04), and surgical site infections (SSI) (p = 0.006) in the robotic-assisted cohort. Outcomes were also similar between robotic-assisted and laparoscopic SG, except for a longer length of stay (p < 0.0001) and higher rates of conversion (p < 0.0001), 30-day intervention (p = 0.01), operative drain present (p < 0.0001), sepsis (p = 0.01), and organ space SSI (p = 0.0002) in the robotic cohort. Bleeding was lower in the robotic SG cohort and mortality was similar. CONCLUSION: Both robotic-assisted and laparoscopic RnYGB and SG are overall very safe. Robotic-assisted gastric bypass is associated with a lower mortality and morbidity; however, a clear benefit for robotic-assisted SG compared to laparoscopic SG was not seen. Given the longer operative and hospital duration, robotic SG is not cost-effective. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00464-019-06915-7) contains supplementary material, which is available to authorized users.


The zero-VAP sophistry and controversies surrounding prevention of ventilator-associated pneumonia


Fast tracking after repair of congenital heart defects (CHD) is a process involving the reduction of perioperative period by timely admission, early extubation after surgery, short intensive care unit (ICU) stay, early mobilisation, and faster hospital discharge. It requires a coordinated multidisciplinary team involvement. In the last 2 decades, many centres have adopted the fast tracking strategy in paediatric cardiac population, safely and successfully extubating patients in the OR with reported benefits in terms of reduced morbidity and ICU/hospital stay. In this manuscript, we will review the literature available on early extubation after repair of CHD and share our experience with this approach.


title: Patients who develop post-operative atrial fibrillation have reduced survival after off-pump coronary artery bypass grafting

text: OBJECTIVE: Post-operative atrial fibrillation (POAF) increases hospital stay, resource utilization, morbidity, and mortality. However, there is paucity of data about its effect in Indian patients undergoing off-pump coronary artery bypass grafting (CABG). METHODS: Seven hundred forty-eight patients underwent off-pump CABG from January 2015 to December 2016 (24 months). One hundred twenty-seven patients (16.7%) developed POAF. In an effort to mitigate the effects of wider risk factors on perioperative outcomes, a separate sub-analysis of patients based on risks quantified by EuroSCORE II (<> 3) was also performed. RESULTS: Age > 60 years and development of sepsis were the independent predictors for the development of POAF. Thirty-day/mortality rate was higher in the POAF group (7.1% vs. 1.4%; p value < 0.001). POAF was associated with increased ICU and hospital stay and increased incidence of stroke and renal dysfunction. The survival was significantly lower in the POAF group compared with the normal sinus rhythm (NSR) (3-year survival in POAF was 81.3% vs. 94.4% in the NSR group; Hazard ratio (HR) 3.867 (1.989–7.516)). Intra-aortic balloon pump (IABP) usage, age ≥ 60 years and sepsis were independent predictors for the development of POAF in low-risk patients. For the NSR group, 1-year survival was 98% and 3-year survival was 95.7%. For the POAF group, 1-year survival was 94.4% and 3-year survival was 84.0% (HR. 3.794 (1.897–7.591)). CONCLUSION: The incidence of POAF was lower than reported in the wider global literature. Increasing age and development of post-operative sepsis were strong independent predictors of POAF. POAF increases the morbidity; length of hospital stay and these patients show decreased survival after off-pump CABG.


title: Comparison of extubation success using noninvasive positive pressure ventilation (NIPPV) versus noninvasive neurally adjusted ventilatory assist (NI-NAVA)

text: OBJECTIVE: Compare rates of initial extubation success in preterm infants extubated to NIPPV or NI-NAVA. STUDY DESIGN: In this pilot study, we randomized 30 mechanically ventilated preterm infants at the time of initial elective extubation to NI-NAVA or NIPPV in a 1:1 assignment. Primary study outcome was initial extubation success. RESULTS: Rates of continuous extubation for 120 h were 92% in the NI-NAVA group and 69% in the NIPPV group (12/13 vs. 9/13, respectively, p = 0.14). Infants extubated to NI-NAVA remained extubated longer (median 18 vs. 4 days, p = 0.02) and experienced lower peak inspiratory pressures (PIP) than infants managed with NIPPV throughout the first 3 days after extubation. Survival analysis through 14 days post extubation showed a sustained difference in the primary study outcome until 12 days post extubation. CONCLUSIONS: Our study is the first to suggest that a strategy of extubating preterm infants to NI-NAVA may be more successful.


title: Ultrasonographic evaluation of lung and heart in predicting successful weaning in mechanically ventilated neurosurgical patients

text: In critically ill neurosurgical patients, delayed and premature extubation increases the risk of morbidity and mortality. Assessment of critically ill patients before and during spontaneous breathing trial (SBT) is crucial in predicting weaning failure. We explored the trend of changes with integrated lung and cardiac ultrasonography in predicting success of weaning in neurosurgical patients. Lung ultrasound and cardiac ultrasound was performed before and after 30 min and 120 min of SBT. Lung ultrasound score (LUS, range 0–36) was calculated using a predefined method of assessment of six chest regions on either side. The left ventricular function was evaluated by measuring fractional area change. The maximum velocities of mitral inflow E and A waves (E/A), deceleration time of E wave (DTE) and tissue doppler based E′ wave at lateral annulus to calculate E/E′, were measured to assess left ventricular filling pressure. Twenty seven patients underwent SBT, among these 22 had success and five had failure of SBT. The SBT failure group had higher baseline LUS and progressively higher LUS during SBT compared to the success group, suggesting significant lung de-recruitment. There was significant increase in the LV filling pressure (increase E/A and E/E′, decrease in DTE) after 30 and 120 min of SBT in failure group compared to the success group. Point of care lung and cardiac ultrasonography may be useful in detecting cardiopulmonary changes induced by SBT. Higher lung aeration loss and LV filling pressure were observed with SBT failure group.


title: Conceptualizing LGBT Stigma and Associated HIV Vulnerabilities Among LGBT Persons in Lesotho

text: Social marginalization harms lesbian, gay, bisexual, and transgender (LGBT) persons’ wellbeing in Lesotho. Socio-cultural mechanisms linking LGBT stigma, depression, substance use, and HIV among LGBT persons in Lesotho are understudied. We explore associations between LGBT stigma, mental health stressors, and HIV vulnerabilities among LGBT persons in Lesotho. We conducted in-depth, semi-structured interviews with 46 LGBT persons and six key informants (e.g. healthcare providers). Participants described depression, substance use, and HIV as mutually reinforcing and situated in larger social contexts of stigma. Alcohol use was a stigma coping strategy and a way to build LGBT connections. At the same time, alcohol use elevated HIV vulnerabilities by lowering condom use uptake. Pervasive stigma reinforced barriers to healthcare engagement. Community-led support and services were leveraged to navigate stigma, reduce HIV vulnerabilities, and ultimately improve health. Findings emphasize the key role contexts play in shaping sexual and mental health among LGBT persons in Lesotho.


title: Multidomain Interventions to Prevent Cognitive Impairment, Alzheimer’s Disease, and Dementia: From FINGER to World-Wide FINGERS

text: Alzheimer’s disease (AD) and dementia are a global public health priority, and prevention has been highlighted as a pivotal component in managing the dementia epidemic. Modifiable risk factors of dementia and AD include lifestyle-related factors, vascular and metabolic disorders, and psychosocial factors. Randomized controlled clinical trials (RCTs) are needed to clarify whether modifying such factors can prevent or postpone cognitive impairment and dementia in older adults. Given the complex, multifactorial, and heterogeneous nature of late-onset AD and dementia, interventions targeting several risk factors and mechanisms simultaneously may be required for optimal preventive effects. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is the first large, long-term RCT to demonstrate that a multidomain lifestyle-based intervention ameliorating vascular and lifestyle-related risk factors can preserve cognitive functioning and reduce the risk of cognitive decline among older adults at increased risk of dementia. To investigate the multidomain intervention in other populations and diverse cultural and geographical settings, the World-Wide FINGERS (WW-FINGERS) network was recently launched (https://alz.org/wwfingers). Within this network, new FINGER-type trials with shared core methodology, but local culture and context-specific adaptations, will be conducted in several countries. The WW-FINGERS initiative facilitates international collaborations, provides a platform for testing multidomain strategies to prevent cognitive impairment and dementia, and aims at generating high-quality scientific evidence to support public health and clinical decision-making. Furthermore, the WW-FINGERS network can support the implementation of preventive strategies and translation of research findings into practice.


title: The Obesity Paradox in the Trauma Patient: Normal May not Be Better

text: OBJECTIVE: The obesity paradox is the association of increased survival for overweight and obese patients compared to normal and underweight patients, despite an increased risk of morbidity. The obesity paradox has been demonstrated in many disease states but has yet to be studied in trauma. The objective of this study is to elucidate the presence of the obesity paradox in trauma patients by evaluating the association between BMI and outcomes. METHODS: Using the 2014–2015 National Trauma Database (NTDB), adults were categorized by WHO BMI category. Logistic regression was used to assess the odds of mortality associated with each category, adjusting for statistically significant covariables. Length of stay (LOS), ICU LOS and ventilator days were also analyzed, adjusting for statistically significant covariables. RESULTS: A total of 415,807 patients were identified. Underweight patients had increased odds of mortality (OR 1.378, p < 0.001 95% CI 1.252–1.514), while being overweight had a protective effect (OR 0.916, p = 0.002 95% CI 0.867–0.968). Class I obesity was not associated with increased mortality compared to normal weight (OR 1.013, p = 0.707 95% CI 0.946–1.085). Class II and Class III obesity were associated with increased mortality risk (Class II OR 1.178, p = 0.001 95% CI 1.069–1.299; Class III OR 1.515, p < 0.001 95% CI 1.368–1.677). Hospital and ICU LOS increased with each successive increase in BMI category above normal weight. Obesity was associated with increased ventilator days; Class I obese patients had a 22% increase in ventilator days (IRR 1.217 95% CI 1.171–1.263), and Class III obese patients had a 54% increase (IRR 1.536 95% CI 1.450–1.627). CONCLUSION: The obesity paradox exists in trauma patients. Further investigation is needed to elucidate what specific phenotypic aspects confer this benefit and how these can enhance patient care. LEVEL OF EVIDENCE: Level III, prognostic study


title: Wide variation in caffeine discontinuation timing in premature infants

text: OBJECTIVE: To assess site variability and concomitant respiratory support related to the timing of caffeine discontinuation, and compare clinical characteristics of infants who discontinued caffeine before vs. within the last week of hospitalization. STUDY DESIGN: Cohort study of 81,110 infants <35 weeks gestational age and <1500 g birth weight discharged from 304 neonatal intensive care units from 2001–2016. RESULTS: The mean postmenstrual age at caffeine discontinuation ranged from 32 to 37 weeks among sites. Respiratory support at the time of discontinuation was common, but variable, with 0–57% of infants receiving positive airway pressure at caffeine discontinuation by site. Infants who discontinued caffeine within the last week of hospitalization had longer total duration of caffeine, but were discharged from the hospital at an earlier postmenstrual age. CONCLUSION: There was substantial variability among sites in the timing of caffeine discontinuation before discharge and respiratory support at the time of caffeine discontinuation.


title: Novel vaccine technologies for the 21st century

text: Novel approaches to vaccine development include structure-based immunogen design, gene-based vaccine platforms and formulation of recombinant antigens with potent adjuvants. These technologies are producing encouraging results in the development of vaccines for globally important diseases such as tuberculosis, influenza and respiratory syncytial virus. Here we highlight the most important developments in these areas over the past 18 months.


Diffuse varicella zoster virus reactivation in critically ill immunocompromised patient


title: Comparison of ATG-thymoglobulin with ATG-Fresenius for Epstein-Barr virus infections and graft-versus-host-disease in patients with hematological malignances after haploidentical hematopoietic stem cell transplantation: a single-center experience

text: Two anti-thymocyte globulin (ATG) forms are used in graft-versus-host disease (GVHD) prophylaxis during haploidentical hematopoietic stem cell transplantations (haplo-HSCTs): ATG-thymoglobulin (ATG-T) and ATG-fresenious (ATG-F). However, comparable dosages for haplo-HSCT remain unclear. We compared and evaluated the effects of ATG-T (7.5 mg/kg) or ATG-F (20 mg/kg) dosages in a relatively homogenous population in haplotype HSCT settings. Patients administered ATG-T 7.5 mg/kg (n = 81) or ATG-F 20 mg/kg (n = 35) as part of GVHD prophylaxis during haplo-HSCT were enrolled. Incidence and severity of GVHD, Epstein–Barr virus (EBV) infection, and immune cell recovery were compared using the Mann-Whitney U rank test and chi-square test. Cumulative incidences of GVHD, EBV infection and its subgroups, and relapse mortality were computed; overall survival (OS) was analyzed using the Kaplan-Meier method, with the log-rank test used for univariate comparison. Risk factors for OS were analyzed by the Cox proportional hazards model. Incidence and cumulative incidence of all grades of acute GVHD and subgroups were comparable in both groups (all p > 0.05); however, cumulative incidence of any grade and limited chronic GVHD was significantly higher in the ATG-T group (p = 0.002, p = 0.007, respectively). Cumulative incidences of EBV infections, EBV-DNAemia, and EBV-related diseases were similar; relapse mortality and OS rates were comparable between both groups (all p > 0.05). ATG-T dosage (7.5 mg/kg) appeared comparable to ATG-F dosage (20 mg/kg) for haplo-HSCT. Currently approved ATG-T and ATG-F doses appear efficient to balance the risk–benefit ratio of GVHD, OS, relapse mortality, and EBV infection in haplo-HSCT.


title: Vaccination during pregnancy: current and possible future recommendations

text: Immunizing pregnant women to protect the mother, fetus and infant from infection has increasingly been used over the last decade. Protection against infectious diseases in neonates is mainly provided by maternal antibodies transferred from mother to infant during pregnancy through transplacental transport or after delivery via breastfeeding. Both the transplacental- and breast milk–derived maternal antibodies function as the primary source of protection against infectious diseases in neonates during the first vulnerable weeks of life. During recent infectious disease outbreaks (influenza, pertussis, Zika…) and for other infectious diseases (CMV, GBS…), pregnant women are increasingly identified as an important target for vaccination. For some of these diseases, vaccines are already on the market, and recommended during pregnancy. For others, vaccines are currently under development; furthermore, some are even specifically designed to be administered during pregnancy. Conclusion: This review article provides an overview on the rationale and main mechanism of the maternal vaccination strategy and gives a summary about the current and possible future recommendations for maternal vaccination.


title: Influence of a temporary stabilization device on respiratory status in patients with severe trauma with a femoral shaft fracture treated by damage control strategy

text: BACKGROUND: There are few studies on the safety and respiratory consequences of the use of a skeletal traction (ST) device in the management of femoral shaft fractures with damage control orthopaedics (DCO) strategy, particularly in cases of prolonged use. The aim of this study was to assess the influence of ST compared with an external fixator (EF) on respiratory complications and mechanical ventilation requirements in patients with severe trauma with a femoral shaft fracture managed by DCO strategy. METHODS: We retrospectively reviewed all patients with severe trauma patients with a unilateral femoral shaft fracture admitted to our institution from 2010 to 2015. Patients who did not undergo definitive osteosynthesis during the first 24 h were included and divided into two groups: DCO-ST group and DCO-EF group. In addition to trauma severity, global management of respiratory complications, the incidence of acute respiratory distress syndrome (ARDS) and mechanical ventilation requirements and outcome were compared. RESULTS: Fifty-five patients were managed with DCO strategy (mean Injury Severity Score, 28.4); there were 31 in the DCO-ST group and 24 in the DCO-EF group. No significant difference in terms of the main characteristics, initial severity and associated injuries was observed between the two groups. In contrast, ARDS was found more frequently in the DCO-ST group (81% versus 54%; P = 0.035). Number of ventilation days also tended to be higher in the DCO-ST group (9 days [IQR 3–15 days] versus 7 [IQR 2–16 days]; P = 0.24). No difference was found for mortality and hospitalization duration between the DCO-ST and DCO-EF groups. CONCLUSION: The prolonged use of an ST device in the present cohort was associated with a higher incidence of impaired respiratory function. Therefore, our findings suggest that EF is preferable to ST in the DCO setting for femoral shaft fracture, especially in trauma patients at high risk of developing delayed respiratory failure.


Treatment of An Acute Severe Cadmium Poisoning Patient Combined with Multiple Organ Dysfunction Syndromes by Integrated Chinese and Western Medicines: A Case Report


title: Clinical relevance and impact of Corynebacterium isolation in lower respiratory tract of critically ill patients requiring mechanical ventilation

text: PURPOSE: Corynebacterium spp. (C. spp.) is commonly considered as a contaminant in respiratory specimens. No study has ever focused on its clinical relevance in the lower respiratory tract of patients admitted to the intensive care unit (ICU) and requiring mechanical ventilation. The aims were to describe the characteristics of ICU patients with a C. spp. positive deep respiratory specimen, to investigate the impact of C. spp. on the occurrence of pneumonia, and to evaluate the outcomes of these pneumonia. METHODS: We retrospectively included all adult patients admitted to ICU in a 1000-bed University Hospital (2007–2017) who had a C. spp. positive lower respiratory tract specimen at a significant quantitative level. We used clinical, radiological, and microbiological criteria to classify the likelihood of such pneumonia. RESULTS: Among the 31 patients included, acute respiratory failure and postoperative care after major surgery were the main reasons of admission. SAPS II was 47 [34–60]. C. spp. pneumonia was considered as probable, possible and unlikely in 10, 14, and 7 patients, respectively. Fifty-two and 94% of C. spp. strains were sensitive to amoxicillin, and vancomycin/linezolid, respectively. Seventeen patients had a complete course of antibiotic against C. spp. The overall ICU mortality was 58%. CONCLUSION: Corynebacterium spp seems to be responsible for authentic pneumonia in mechanically ventilated patients. It should be considered as clinically relevant when predominantly present in respiratory specimen from patients suspected with pneumonia in ICU, and empirically treated.


title: Intracranial pressure monitors associated with increased venous thromboembolism in severe traumatic brain injury

text: BACKGROUND: Utilization of intracranial pressure monitors (ICPMs) has not been consistently shown to improve mortality in patients with severe traumatic brain injury (TBI). A single-center analysis concluded that venous thromboembolism (VTE) chemoprophylaxis (CP) posed no significant bleeding risk in patients following ICPM implementation; however, there is still debate about the optimal use and timing of CP in patients with ICPMs for fear of worsening intracranial hemorrhage. We hypothesized that ICPM use is associated with increased time to VTE CP and thus increased VTE in patients with severe TBI. METHODS: A retrospective analysis of the Trauma Quality Improvement Program (2010–2016) was performed to compare severe TBI patients with and without ICPMs. A multivariable logistic regression analysis was completed. RESULTS: From 35,673 patients with severe TBI, 12,487 (35%) had an ICPM. Those with ICPMs had a higher rate of VTE CP (64.3% vs. 49.4%, p < 0.001) but a longer median time to CP initiation (5 vs. 4 days, p < 0.001) as well as a longer hospital length of stay (LOS) (18 vs. 9 days, p < 0.001) compared to those without ICPMs. After adjusting for covariates, ICPM use was found to be associated with a higher risk of VTE (9.2% vs 4.3%, OR = 1.75, CI = 1.42–2.15, p < 0.001). CONCLUSIONS: Compared to patients without ICPMs, those with ICPMs had a longer delay to initiation of CP leading to an increase in VTE. In addition, there was a nearly two-fold higher associated risk for VTE in patients with ICPMs even when controlling for known VTE risk factors. Improved adherence to initiation of CP in the setting of ICPMs may help decrease the associated risk of VTE with ICPMs.


title: Cumulative Antenatal Risk and Kindergarten Readiness in Preterm-Born Preschoolers

text: A suboptimal intrauterine environment is thought to increase the probability of deviation from the typical neurodevelopmental trajectory, potentially contributing to the etiology of learning disorders. Yet the cumulative influence of individual antenatal risk factors on emergent learning skills has not been sufficiently examined. We sought to determine whether antenatal complications, in aggregate, are a source of variability in preschoolers’ kindergarten readiness, and whether specific classes of antenatal risk play a prominent role. We recruited 160 preschoolers (85 girls; ages 3–4 years), born ≤33(6)/(7) weeks’ gestation, and reviewed their hospitalization records. Kindergarten readiness skills were assessed with standardized intellectual, oral-language, prewriting, and prenumeracy tasks. Cumulative antenatal risk was operationalized as the sum of complications identified out of nine common risks. These were also grouped into four classes in follow-up analyses: complications associated with intra-amniotic infection, placental insufficiency, endocrine dysfunction, and uteroplacental bleeding. Linear mixed model analyses, adjusting for sociodemographic and medical background characteristics (socioeconomic status, sex, gestational age, and sum of perinatal complications) revealed an inverse relationship between the sum of antenatal complications and performance in three domains: intelligence, language, and prenumeracy (p = 0.003, 0.002, 0.005, respectively). Each of the four classes of antenatal risk accounted for little variance, yet together they explained 10.5%, 9.8%, and 8.4% of the variance in the cognitive, literacy, and numeracy readiness domains, respectively. We conclude that an increase in the co-occurrence of antenatal complications is moderately linked to poorer kindergarten readiness skills even after statistical adjustment for perinatal risk. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10802-019-00577-8) contains supplementary material, which is available to authorized users.


title: Global Regulatory Landscape for Aggregate Safety Assessments: Recent Developments and Future Directions

text: Notwithstanding successful harmonization efforts, the global regulatory framework governing product safety is complex and continually evolving, as evidenced by additional regional guidance and regulations. In this regulatory review, we provide an overview from both global and regional perspectives. A historical perspective, with a focus on recent developments, enables identification of important long–term trends, such as a shift from single–case medical review of serious adverse events to an interdisciplinary evaluation of aggregate data for the purpose of judging product causality and informing benefit–risk assessments. We will show how these trends lead to opportunities for closer interdisciplinary collaboration, for bridging the gap between preand postmarketing surveillance, and for a more proactive determination of patient populations with a positive benefit–risk profile for product use. We will conclude by pointing to ongoing and future work that seeks to provide specific solutions for ongoing aggregate safety evaluation.


title: Adaptive immunity: an emerging player in the progression of NAFLD

text: In the past decade, nonalcoholic fatty liver disease (NAFLD) has become a leading cause of chronic liver disease and cirrhosis, as well as an important risk factor for hepatocellular carcinoma (HCC). NAFLD encompasses a spectrum of liver lesions, including simple steatosis, steatohepatitis and fibrosis. Although steatosis is often harmless, the lobular inflammation that characterizes nonalcoholic steatohepatitis (NASH) is considered a driving force in the progression of NAFLD. The current view is that innate immune mechanisms represent a key element in supporting hepatic inflammation in NASH. However, increasing evidence points to the role of adaptive immunity as an additional factor promoting liver inflammation. This Review discusses data regarding the role of B cells and T cells in sustaining the progression of NASH to fibrosis and HCC, along with the findings that antigens originating from oxidative stress act as a trigger for immune responses. We also highlight the mechanisms affecting liver immune tolerance in the setting of steatohepatitis that favour lymphocyte activation. Finally, we analyse emerging evidence concerning the possible application of immune modulating treatments in NASH therapy.


title: Immunotherapies for Aging-Related Neurodegenerative Diseases—Emerging Perspectives and New Targets

text: Neurological disorders such as Alzheimer’s disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD), and vascular dementia (VCID) have no disease-modifying treatments to date and now constitute a dementia crisis that affects 5 million in the USA and over 50 million worldwide. The most common pathological hallmark of these age-related neurodegenerative diseases is the accumulation of specific proteins, including amyloid beta (Aβ), tau, α-synuclein (α-syn), TAR DNA-binding protein 43 (TDP43), and repeat-associated non-ATG (RAN) peptides, in the intra- and extracellular spaces of selected brain regions. Whereas it remains controversial whether these accumulations are pathogenic or merely a byproduct of disease, the majority of therapeutic research has focused on clearing protein aggregates. Immunotherapies have garnered particular attention for their ability to target specific protein strains and conformations as well as promote clearance. Immunotherapies can also be neuroprotective: by neutralizing extracellular protein aggregates, they reduce spread, synaptic damage, and neuroinflammation. This review will briefly examine the current state of research in immunotherapies against the 3 most commonly targeted proteins for age-related neurodegenerative disease: Aβ, tau, and α-syn. The discussion will then turn to combinatorial strategies that enhance the effects of immunotherapy against aggregating protein, followed by new potential targets of immunotherapy such as aging-related processes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13311-020-00853-2) contains supplementary material, which is available to authorized users.


title: Selenium and selenoproteins: it’s role in regulation of inflammation

text: ABSTRACT: Selenium is an essential immunonutrient which holds the human’s metabolic activity with its chemical bonds. The organic forms of selenium naturally present in human body are selenocysteine and selenoproteins. These forms have a unique way of synthesis and translational coding. Selenoproteins act as antioxidant warriors for thyroid regulation, male-fertility enhancement, and anti-inflammatory actions. They also participate indirectly in the mechanism of wound healing as oxidative stress reducers. Glutathione peroxidase (GPX) is the major selenoprotein present in the human body, which assists in the control of excessive production of free radical at the site of inflammation. Other than GPX, other selenoproteins include selenoprotein-S that regulates the inflammatory cytokines and selenoprotein-P that serves as an inducer of homeostasis. Previously, reports were mainly focused on the cellular and molecular mechanism of wound healing with reference to various animal models and cell lines. In this review, the role of selenium and its possible routes in translational decoding of selenocysteine, synthesis of selenoproteins, systemic action of selenoproteins and their indirect assimilation in the process of wound healing are explained in detail. Some of the selenium containing compounds which can acts as cancer preventive and therapeutics are also discussed. These compounds directly or indirectly exhibit antioxidant properties which can sustain the intracellular redox status and these activities protect the healthy cells from reactive oxygen species induced oxidative damage. Although the review covers the importance of selenium/selenoproteins in wound healing process, still some unresolved mystery persists which may be resolved in near future. GRAPHIC ABSTRACT: [Image: see text]


title: A study of comorbidities in myasthenia gravis

text: Management of myasthenia gravis (MG) in the presence of comorbidities may be difficult. We report the effect of comorbidities in the outcome of MG. The patients with MG during 1991–2016 were included and evaluated including their demographic variables, clinical findings, Myasthenia Gravis Foundation of America (MGFA) score. The patients were categorized into early onset (≤ 40 years) and late onset (> 40 years) MG. The comorbidities (autoimmune and miscellaneous) and iatrogenic complications were compared between early and late onset, and in good and poor outcome groups. Out of 81 patients with MG, 48 patients had early and 33 late onset. In 71 (88%) patients, comorbidities were present and were autoimmune in 8 (10%) and miscellaneous in all the patients (88%). Iatrogenic complications were present in 54 (67%) patients. Thymectomy was done in 19 patients; 16 had thymoma and 3 thymic hyperplasia. Myasthenic crisis occurred in 28 patients; 5 (18%) had autoimmune and all had miscellaneous comorbidities. The patients with poor outcome had ≥ 2 comorbidities, myasthenic crisis, leukocytosis, elevated serum bilirubin and creatinine, and increased number of hospital admissions (P < 0.05). Myasthenia gravis is associated with comorbidities in majority of patients especially in late onset group, and more than two comorbidities are related to poor outcome.


title: Frailty Predicts Morbidity and Mortality After Laparoscopic Cholecystectomy for Acute Cholecystitis: An ACS-NSQIP Cohort Analysis

text: BACKGROUND: Current guidelines recommend laparoscopic cholecystectomy be offered for patients with acute cholecystitis except those deemed as high risk. Few studies have examined the impact of frailty on outcomes for patients undergoing laparoscopic cholecystectomy. Therefore, the aim of this study was to determine the association of frailty with postoperative morbidity and mortality in patients undergoing laparoscopic cholecystectomy for acute cholecystitis. METHODS: Patients undergoing laparoscopic cholecystectomy for acute cholecystectomy were identified from 2005 to 2010 in the American College of Surgeons National Surgical Quality Improvement Project (NSQIP). The Modified Frailty Index (mFI) was used a surrogate for frailty, and patients were stratified as non-frail (mFI 0), low frailty (mFI 1–2), intermediate frailty (mFI 3–4) and high frailty (mFI ≥ 5). Univariable and multivariable analyses were performed. Receiver operator curves (ROC) and an area under the curve (AUC) were generated to determine accuracy of mFI in predicting postoperative morbidity and mortality. RESULTS: Of the 6898 patients undergoing laparoscopic cholecystectomy, 3245 (47%) patients were non-frail. There were 2913 (42%) patients with low-frailty, 649 (9%) patients with intermediate frailty, and 91 (2%) with high frailty. Clavien IV complications were higher for intermediate frail patients (OR 1.81, 95% CI 1.00–3.28, p = 0.050) and high-frail patients (OR 4.59, 95% CI 1.98–10.7, p < 0.001). Additionally, mortality was higher for patients with intermediate frailty (OR 4.69, 95% CI 1.37–16.0, p = 0.014) and high frailty (OR 12.2, 95% CI 2.67–55.5, p = 0.001). The mFI had excellent accuracy for mortality (AUC = 0.83) and Clavien IV complications (AUC = 0.73). CONCLUSION: Frailty is associated with postoperative morbidity and mortality in patients undergoing laparoscopic cholecystectomy for acute cholecystitis.


title: Healthcare needs of vulnerable patient groups: available data and existing gaps in Germany with respect to long-term mechanical ventilation

text: AIM: Long-term invasively ventilated patients exhibit exceptional and resource-intensive healthcare needs. However, major knowledge gaps in Germany complicate appropriate approaches to best address these demands. This paper evaluates available information on the patient group and their healthcare needs from German data sources and derives implications for healthcare planning and regulation by national/federal self-governing bodies, political decision-makers, and specialized providers. METHODS: Based on the concept of needs, we addressed the normative dimension typically characterized by epidemiological data. Based on existing German health system data resources, an explorative approach was utilized to identify and characterize available databases providing information on the patient group and/or their healthcare. RESULTS: To date, no available database provides information on the healthcare needs of this patient group. As of the reporting year 2017, the diagnosis-related groups (DRG) statistics will provide hospital-specific data on home invasive ventilation interventions, but the data do not provide information on long-term care. Claims data may be a promising source for cross-sectoral evaluation of healthcare needs but feature methodological challenges. These results call for efforts to address limited data eligibility, adopt a broader understanding of healthcare needs, and identify actions needed to evidence informed and needs-oriented healthcare. CONCLUSION: Future approaches on needs-oriented specialized healthcare should close the existing knowledge gap based on reliable data. In addition to normative information, they should consider subjective dimensions on a life course perspective and quantitative and qualitative service performance characteristics across multiple sectors and professions.


title: Immunophenotypic analysis of cerebrospinal fluid reveals concurrent development of ATL in the CNS of a HAM/TSP patient

text: Both adult T-cell leukemia/lymphoma (ATL) and human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) can be induced by HTLV-1, but concurrent development has been rarely reported. We present the case of a 55-year-old female who developed cranial nerve symptoms after a 20-year history of HAM/TSP. Although multiple white matter lesions were observed on brain magnetic resonance imaging, no abnormalities were seen on a systemic computed tomography scan. Quantitative flow-cytometric analysis of cell populations in the cerebrospinal fluid (CSF) revealed that most of the infiltrating cells were not inflammatory cells, but HTLV-1-infected CD4(+) CADM-1(+) T-cells completely lacking CD7 expression. As stepwise downregulation of CD7 is correlated with disease progression from HTLV-1 carrier to aggressive ATL, the CSF cells were classified as aggressive ATL; these cells exhibited a more progressed phenotype than those in peripheral blood (PB). HAM/TSP disease activity was estimated to be low. From these and other examinations, we made a diagnosis of acute-type ATL, which unusually developed in the central nervous system at initial onset prior to systemic progression. In ATL cases with a challenging diagnosis, immunophenotypic characterization of CSF and PB is valuable for differential diagnosis and understanding disease status.


title: CD8(+) T cells in HIV control, cure and prevention

text: HIV infection can be effectively treated by lifelong administration of combination antiretroviral therapy, but an effective vaccine will likely be required to end the HIV epidemic. Although the majority of current vaccine strategies focus on the induction of neutralizing antibodies, there is substantial evidence that cellular immunity mediated by CD8(+) T cells can sustain long-term disease-free and transmission-free HIV control and may be harnessed to induce both therapeutic and preventive antiviral effects. In this Review, we discuss the increasing evidence derived from individuals who spontaneously control infection without antiretroviral therapy as well as preclinical immunization studies that provide a clear rationale for renewed efforts to develop a CD8(+) T cell-based HIV vaccine in conjunction with B cell vaccine efforts. Further, we outline the remaining challenges in translating these findings into viable HIV prevention, treatment and cure strategies.


Society of Surgical Oncology SSO 2020 – International Conference on Surgical Cancer Care


A Change of Course: The Case for a Neurorecovery Clinic


title: An extensive field study reveals the circulation of new genetic variants of subtype 1a of bovine viral diarrhea virus in Uruguay

text: Bovine viral diarrhea virus (BVDV) is a major pathogen worldwide, causing significant economic losses to the livestock sector. In Uruguay, BVDV seroprevalence at the farm level is >80%. In this work, 2546 serum, blood or tissue samples collected from animals suspected of being affected by BVD between 2015 and 2017 were analyzed by reverse transcription PCR and sequencing. Analysis of the BVDV genomic regions 5’UTR/N(pro), N(pro) and E2 revealed that BVDV-1a, 1i and 2b circulate in the country, with BVDV-1a being the most prevalent subtype. Population dynamics studies revealed that BVDV-1a has been circulating in our herds since ~1990. This subtype began to spread and evolve, accumulating point mutations at a rate of 3.48 × 10(−3) substitutions/site/year, acquiring specific genetic characteristics that gave rise to two local genetic lineages of BVDV-1a. These lineages are divergent from those circulating worldwide, as well as the vaccine strain currently used in Uruguay. The most notable differences between field and vaccine strains were found in the E2 glycoprotein, suggesting that the amino acid substitutions could result in failure of cross-protection/neutralization after vaccination. This is the first study that compares Uruguayan BVDV field and vaccine strains with other BVDV strains from throughout the world. The results obtained in this study will be very useful for developing a suitable immunization program for BVDV in Uruguay by identifying local field strains as candidates for vaccine development. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-019-04446-z) contains supplementary material, which is available to authorized users.


title: Colletotrichum species causing cassava (Manihot esculenta Crantz) anthracnose in different eco-zones within the Recôncavo Region of Bahia, Brazil

text: A survey to investigate the occurrence of cassava anthracnose disease (CAD) and distribution of Colletotrichum spp. in cassava plantations in different eco-zones of the Reconcavo Region in Bahia, Brazil, investigated during the rainy season of 2014. A total of 50 cassava fields distributed among 18 municipalities were visited and intensity of anthracnose evaluated. The highest disease incidence (DI) (83.3%) was in samples collected in São Félix, and the lowest (34.4%), in Varzedo. Municipalities that presented the highest values for DI were located within the ‘Af’ Köppen–Geiger eco-zone, also presenting the highest values for the estimated McKinney disease index. Based on previous studies of multilocus phylogeny, seven different species of Colletotrichum were identified (Colletotrichum fructicola, Colletotrichum tropicale, Colletotrichum gloeosporioides s.s, Colletotrichum theobromicola, Colletotrichum siamense, Colletotrichum brevisporum and Colletotrichum plurivorum) and a new approach based on ERIC-PCR was used aiming to group the 82 isolates according to these findings. The highest percentage of genetic variance (> 78%) was among isolates within fields. Based on the survey and genetic analysis, C. fructicola is probably the main causal agent of cassava anthracnose in the Recôncavo Region, since this species was present with highest incidence in all eco-zones, 47.61, 42.86 and 57.14% for Af (tropical rainforest climate), As (tropical dry savanna climate) and Aw (tropical wet savanna climate), respectively. This study is the first report of C. fructicola lineages as the most likely pathogen causing anthracnose disease of cassava in Brazil, and these findings may be used to guide the selection of resistant varieties.


title: Bacterial etiology of community-acquired pneumonia in immunocompetent hospitalized patients and appropriateness of empirical treatment recommendations: an international point-prevalence study

text: An accurate knowledge of the epidemiology of community-acquired pneumonia (CAP) is key for selecting appropriate antimicrobial treatments. Very few etiological studies assessed the appropriateness of empiric guideline recommendations at a multinational level. This study aims at the following: (i) describing the bacterial etiologic distribution of CAP and (ii) assessing the appropriateness of the empirical treatment recommendations by clinical practice guidelines (CPGs) for CAP in light of the bacterial pathogens diagnosed as causative agents of CAP. Secondary analysis of the GLIMP, a point-prevalence international study which enrolled adults hospitalized with CAP in 2015. The analysis was limited to immunocompetent patients tested for bacterial CAP agents within 24 h of admission. The CAP CPGs evaluated included the following: the 2007 and 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA), the European Respiratory Society (ERS), and selected country-specific CPGs. Among 2564 patients enrolled, 35.3% had an identifiable pathogen. Streptococcus pneumoniae (8.2%) was the most frequently identified pathogen, followed by Pseudomonas aeruginosa (4.1%) and Klebsiella pneumoniae (3.4%). CPGs appropriately recommend covering more than 90% of all the potential pathogens causing CAP, with the exception of patients enrolled from Germany, Pakistan, and Croatia. The 2019 ATS/IDSA CPGs appropriately recommend covering 93.6% of the cases compared with 90.3% of the ERS CPGs (p < 0.01). S. pneumoniae remains the most common pathogen in patients hospitalized with CAP. Multinational CPG recommendations for patients with CAP seem to appropriately cover the most common pathogens and should be strongly encouraged for the management of CAP patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10096-020-03870-3) contains supplementary material, which is available to authorized users.


title: High-resolution melting curve analysis: a novel method for identification of Mycoplasma species isolated from clinical cases of bovine and porcine respiratory disease

text: Mycoplasma species cause wide ranges of infectious diseases in human and animals. The aim of the present study was to evaluate a real-time polymerase chain reaction (RT-PCR) followed by a high-resolution melting curve assay (HRM) for rapid differentiation of Mycoplasma species isolated from clinical cases of bovine and porcine respiratory disease. Lung samples from suspected cases to respiratory infections from cows and pigs were cultured on specific media, and the extracted DNA were tested by conventional polymerase chain reaction (PCR) assays for Mycoplasma. A set of universal primers specific for the 16S ribosomal RNA gene was designed and used for RT-PCR and HRM. The HRM analysis was able to differentiate between five different species of Mycoplasmas, namely, M. hyopneumoniae, M. bovis, M. hyorhinis, M. hyosynoviae and other uncultured Mycoplasma. All results were confirmed based on 16S rRNA gene sequencing. This rapid and reliable assay was as a simple alternative to PCR and sequencing, differentiating bovine and porcine mycoplasmas in species level.


title: Bioinformatics design and experimental validation of influenza A virus multi-epitopes that induce neutralizing antibodies

text: Pandemics caused by influenza A virus (IAV) are responsible for the deaths of millions of humans around the world. One of these pandemics occurred in Mexico in 2009. Despite the impact of IAV on human health, there is no effective vaccine. Gene mutations and translocation of genome segments of different IAV subtypes infecting a single host cell make the development of a universal vaccine difficult. The design of immunogenic peptides using bioinformatics tools could be an interesting strategy to increase the success of vaccines. In this work, we used the predicted amino acid sequences of the neuraminidase (NA) and hemagglutinin (HA) proteins of different IAV subtypes to perform multiple alignments, epitope predictions, molecular dynamics simulations, and experimental validation. Peptide selection was based on the following criteria: promiscuity, protein surface exposure, and the degree of conservation among different medically relevant IAV strains. These peptides were tested using immunological assays to test their ability to induce production of antibodies against IAV. We immunized rabbits and mice and measured the levels of IgG and IgA antibodies in serum samples and nasal washes. Rabbit antibodies against the peptides P11 and P14 (both of which are hybrids of NA and HA) recognized HA from both group 1 (H1, H2, and H5) and group 2 (H3 and H7) IAV and also recognized the purified NA protein from the viral stock (influenza A Puerto Rico/916/34). IgG antibodies from rabbits immunized with P11 and P14 were capable of recognizing viral particles and inhibited virus hemagglutination. Additionally, intranasal immunization of mice with P11 and P14 induced specific IgG and IgA antibodies in serum and nasal mucosa, respectively. Interestingly, the IgG antibodies were found to have neutralizing capability. In conclusion, the peptides designed through in silico studies were validated in experimental assays. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00705-020-04537-2) contains supplementary material, which is available to authorized users.


title: Preoperative Assessment and Management of Patients with Pain and Anxiety Disorders

text: PURPOSE OF REVIEW: This review summarizes selected recent evidence on issues important for preoperative pain evaluation. RECENT FINDINGS: Opioids, though a mainstay of postoperative pain management, are associated with both short and increasingly recognized long-term risks, including persistent opioid use. Risk factors for high levels of acute postoperative pain as well as chronic postsurgical pain may overlap, including psychological factors such as depression, anxiety, and catastrophizing. Tools to predict those at risk for poor postoperative pain outcomes are being studied. SUMMARY: Preoperative pain and psychological factors can affect postoperative pain outcomes. More work is needed in the future to develop practical interventions in the preoperative period to address these factors.


title: Novel targets and strategies to combat borreliosis

text: Lyme borreliosis is a bacterial infection that can be spread to humans by infected ticks and may severely affect many organs and tissues. Nearly four decades have elapsed since the discovery of the disease agent called Borrelia burgdorferi. Although there is a plethora of knowledge on the infectious agent and thousands of scientific publications, an effective way on how to combat and prevent Lyme borreliosis has not been found yet. There is no vaccine for humans available, and only one active vaccine program in clinical development is currently running. A spirited search for possible disease interventions is of high public interest as surveillance data indicates that the number of cases of Lyme borreliosis is steadily increasing in Europe and North America. This review provides a condensed digest of the history of vaccine development up to new promising vaccine candidates and strategies that are targeted against Lyme borreliosis, including elements of the tick vector, the reservoir hosts, and the Borrelia pathogen itself.


title: Development of Population and Bayesian Models for Applied Use in Patients Receiving Cefepime

text: BACKGROUND AND OBJECTIVE: Understanding pharmacokinetic disposition of cefepime, a β-lactam antibiotic, is crucial for developing regimens to achieve optimal exposure and improved clinical outcomes. This study sought to develop and evaluate a unified population pharmacokinetic model in both pediatric and adult patients receiving cefepime treatment. METHODS: Multiple physiologically relevant models were fit to pediatric and adult subject data. To evaluate the final model performance, a withheld group of 12 pediatric patients and two separate adult populations were assessed. RESULTS: Seventy subjects with a total of 604 cefepime concentrations were included in this study. All adults (n = 34) on average weighed 82.7 kg and displayed a mean creatinine clearance of 106.7 mL/min. All pediatric subjects (n = 36) had mean weight and creatinine clearance of 16.0 kg and 195.6 mL/min, respectively. A covariate-adjusted two-compartment model described the observed concentrations well (population model R(2), 87.0%; Bayesian model R(2), 96.5%). In the evaluation subsets, the model performed similarly well (population R(2), 84.0%; Bayesian R(2), 90.2%). CONCLUSION: The identified model serves well for population dosing and as a Bayesian prior for precision dosing. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40262-020-00873-3) contains supplementary material, which is available to authorized users.


title: A Comprehensive Review of Cutaneous Leishmaniasis in Sri Lanka and Identification of Existing Knowledge Gaps

text: PURPOSE: Sri Lanka is endemic to cutaneous leishmaniasis and reported as the latest focus of leishmaniasis in the Asian subcontinent. Annually, the number of leishmaniasis cases is increasing; therefore, more efficient diagnostic tools, treatment methods and effective prevention measures are indispensable. For this reason, many studies were conducted regarding leishmaniasis infections in Sri Lanka; however, some areas need more attention. Thus, in this review, we comprehensively discussed the studies on leishmaniasis carried out in Sri Lanka. METHODS: Published articles on leishmaniasis in Sri Lanka were searched on PubMed, Google Scholar and ResearchGate databases. Inclusion criteria for the articles were based on keyword searches including ‘Leishmaniasis in Sri Lanka’, ‘Leishmaniasis vector in Sri Lanka’, ‘Sandfly species in Sri Lanka’, ‘Leishmaniasis epidemiology in Sri Lanka’ which are publicly accessible as of 15th July 2019. RESULTS: In this study, we evaluated and summarized the leishmaniasis reports in Sri Lanka and mainly focused on clinical presentation of leishmaniasis infection, genetic characteristics of Leishmania donovani Sri Lankan strain, geographical distribution and associated environmental factors, immunological aspects of the infection, vector, reservoir host, risk factors, diagnosis and treatment, and prevention and control. Furthermore, we identified the areas where further research is needed to fill the essential knowledge gaps. CONCLUSIONS: Leishmaniasis has become a critically important parasitic infection in Sri Lanka, whereas the significant clinical form is cutaneous leishmaniasis. Prevalence of the leishmaniasis infections is reported from all the districts of the country. Therefore, more studies are essential to be carried out to fill the existing knowledge gaps emphasized in this review.


title: Validity and reliability of pocket-sized ultrasound devices in measurement of optic nerve sheath diameter in ICU patients

text: The measurement of the optic nerve sheath diameter (ONSD) by ultrasonography (USG) is particularly important for intracranial pressure (ICP) monitoring when invasive measurements are not possible or are contraindicated. Standard USG (SUDs) devices can be bulky and may break down the workflow. The validity and reliability of pocket-sized USG devices (PSUDs) compared to SUDs for ONSD measurement has not been investigated, yet. We compared the reliability and validity of PSUDs with SUDs for ONSD measurement. 35 patients were included in the study. ONSD measurements with PSUDs and SUDs were performed by two clinicians as three different measurements in both sagittal and transverse axis of the eye. There was agreement between mean transverse ONSD (mtONSD), mean sagittal ONSD (msONSD), and mean ONSD(mONSD) values measured with each device according to Bland–Altman test (p = 0.166, p = 0.135, p = 0.066, respectively) with no proportional bias (p = 0.544, p = 0.868, p = 0.929, respectively). Intraclass correlation coefficients (ICC) were found to be greater than 0.7 for mtONSD, msONSD, and mONSD values measured by SUD (ICC = 0.790, ICC = 0.817, and ICC = 0.844, respectively). Similarly, for mtONSD, msONSD, and mONSD values measured by PSUD, ICC were found greater than 0.7 (ICC = 0.763, ICC = 0.814, and ICC = 0.843, respectively). There was no statistically significant difference between mtONSD and msONSD (p = 0.441 for SUD and p = 0.893 for PSUD). There was a good correlation between mtONSD and msONSD (r = 0.767 for SUD and r = 0.816 for PSUD). The total variance between three different measurements in the transverse and sagittal axis was ± 0.6 mm. PSUDs can be used with similar validity and reliability as SUDs for ONSD measurement.


title: Green synthesis of zinc oxide nanoparticles from the leaf, stem and in vitro grown callus of Mussaenda frondosa L.: characterization and their applications

text: Biosynthesis of zinc oxide nanoparticles (ZnO-NPs) was achieved by utilizing the reducing and capping potential of leaf, stem and callus aqueous extracts of Mussaenda frondosa.The bioreduced ZnO-NPs were characterized using powder X-ray diffraction (XRD), ultraviolet–visible spectroscopy (UV–Vis spectroscopy), scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), fourier transform infrared spectroscopy (FTIR) and dynamic light scattering (DLS) techniques. UV–visible spectra of ZnO-NPs showed a strong absorption peak at 370, 376 and 373 nm corresponding to the band gap energy of 3.33, 3.27 and 3.30 eV for ZnO-NPs obtained from leaf (L-ZnO-NP), stem (S-ZnO-NP) and callus (C-ZnO-NP) aqueous extracts, respectively. XRD analysis confirmed the formation of hexagonal wurtzite structures having an average grain size between 5 and 20 nm in diameter. FTIR spectra revealed the presence of stretching vibrations of –O–H, C–H, C–N, C = O groups involved in reduction and stabilization of nanoparticles. SEM images recognize the presence of spongy, spherical, porous agglomerated nanoparticles. DLS analysis and zeta potential values validated the stability of ZnO-NPs. The present investigation puts light on the photocatalytic activity and biological (antioxidant, anti-inflammatory, antidiabetic, antimicrobial, anticancerous) applications of ZnO-NPs. The current study is an attempt to describe an effective, simple and eco-friendly method of ZnO-NP synthesis and to evaluate its potential for various industrial and medical applications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13204-020-01382-2) contains supplementary material, which is available to authorized users.


title: New markers for sepsis caused by Pseudomonas aeruginosa during burn infection

text: INTRODUCTION: Sepsis is a leading cause of mortality in burn patients. One of the major causes of sepsis in burn patients is Pseudomonas aeruginosa. We hypothesized that during dissemination from infected burn wounds and subsequent sepsis, P. aeruginosa affects the metabolome of the blood resulting in changes to specific metabolites that would serve as biomarkers for early diagnosis of sepsis caused by P. aeruginosa. OBJECTIVES: To identify specific biomarkers in the blood after sepsis caused by P. aeruginosa infection of burns. METHODS: Gas chromatography with time-of-flight mass spectrometry was used to compare the serum metabolome of mice that were thermally injured and infected with P. aeruginosa (B–I) to that of mice that were neither injured nor infected, mice that were injured but not infected, and mice that were infected but not injured. RESULTS: Serum levels of 19 metabolites were significantly increased in the B–I group compared to controls while levels of eight metabolites were significantly decreased. Thymidine, thymine, uridine, and uracil (related to pyrimidine metabolism), malate and succinate (a possible sign of imbalance in the tricarboxylic acid cycle), 5-oxoproline (related to glutamine and glutathione metabolism), and trans-4-hydroxyproline (a major component of the protein collagen) were increased. Products of amino acid metabolism were significantly decreased in the B–I group, including methionine, tyrosine, indole-3-acetate, and indole-3-propionate. CONCLUSION: In all, 26 metabolites were identified, including a unique combination of five metabolites (trans-4-hydroxyproline, 5-oxoproline, glycerol-3-galactoside, indole-3-acetate, and indole-3-propionate) that could serve as a set of biomarkers for early diagnosis of sepsis caused by P. aeruginosa in burn patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11306-020-01658-2) contains supplementary material, which is available to authorized users.


title: The performance of biological and tertiary wastewater treatment procedures for rotaviruses A removal

text: Enteric viruses, generally found in sewage, are recognized as the main cause of waterborne and foodborne public health outbreaks. Among leading enteric viruses, the Rotavirus A (RVA) detection in wastewater appeared to be a novel approach to monitor the emergence of these viruses in some countries where the viral gastroenteritis surveillance is almost absent such as in Tunisia. The RVA detection and quantification in an industrial sewage purification plant of Charguia I (Tunis, Tunisia) were achieved to evaluate the performance of activated sludge procedures coupled to a macrofiltration monolamp ultraviolet irradiation type C (UV-C(254)) disinfection reactor. This UV-C(254) system was preceded by a fiberglass cartridge filter system with an average porosity of 45 μm to clarify the water and thus increase its UV transmittance. A total of 140 composite sewage samples was collected from this line of treatment and analyzed for RVA detection. The detection and the viral load quantification of RVA were performed using real-time reverse transcription polymerase chain reaction (RT-PCR). The virological results showed in general that RVA were detected at high frequency of 98% (137/140). In fact, the RVA detection rates at the exit of the two studied wastewater treatment were about 100% at the exit of the activated sludge procedure. It means that all wastewater sampled at this last step of treatment was positive for RVA detection. On the other hand, 92.5% of the wastewater samples taken at the exit of the monolamp UV-C(254) reactor were positive for the RVA. However, the RVA quantification results expressed as viral load showed a significant reduction in the means of RVA viral loads at the exit of the biological activated sludge procedure and the tertiary UV-C(254) treatment, showing in general an improved treated wastewater virological quality. Therefore, the RVA load removal rates recorded at the two successive stages of treatment, the activated sludge and the UV-C(254) treatment, were around 85% and 73%, respectively, as compared to the one with 100% registered for the raw wastewater. In addition, good physical-chemical and bacteriological qualities of the treated sewage were found at the exit of the two considered wastewater treatment procedures. The present investigation represents the first Tunisian environmental report showing the good effectiveness and performance of the biological and the tertiary treatments for RVA removal. Therefore, an improved and an optimized tertiary disinfection treatment was needed since it could be a good means for getting better viral water quality and for minimizing the transmission and dissemination of human infectious viral diseases.


title: Enhanced oral hygiene interventions as a risk mitigation strategy for the prevention of non-ventilator-associated pneumonia: a systematic review and meta-analysis

text: Background Healthcare-acquired pneumonias are a significant risk for nursing home and hospital patients. While oral care interventions (OCIs) have been found to be effective in reducing the risk of ventilator-associated pneumonia (VAP), their utility in mitigating non-ventilator-associated pneumonias (NVAP) remains unknown. We performed a structured meta-analysis of randomised and non-randomised clinical trials of enhanced oral hygiene procedures on NVAP. Methods We searched PubMed and Embase to include clinical trials (randomised and non-randomised), and observational (retrospective and prospective) and quasi-experimental studies examining the effect of any method of OCI on incidence of NVAP. Results After quality assessment and consensus agreement between authors, we synthesised six randomised clinical trials (3,891 patients), two non-randomised trials (2,993 patients), and separately assessed a retrospective trial (143 patients) and a quasi-experimental study (83 patients). Most studies, performed in nursing homes, did not show a significant association between OCI and NVAP prevention (RR random 0.89, 95% CI 0.64-1.25, p value 0.50). Likewise, the non-randomised trials failed to show an association between NVAP risk and OCI (RR random 1.42, 95% CI, 0.70-2.88, p value 0.32). However, in the subgroup analysis comparing dental professional involvement in care vs usual care, reduced NVAP risk was demonstrated (RR random 0.65, 95% CI 0.43-0.98, p value 0.03). Conclusions Study results suggest that professional dental care may confer some benefit among NVAP patients. The lack of consistent OCI protocols, data in hospitalised patients and robust randomised clinical trials do not allow definitive conclusions about the contribution of OCI in mitigating NVAP risk. Zusatzmaterial online: Zu diesem Beitrag sind unter 10.1038/s41415-020-1452-7 für autorisierte Leser zusätzliche Dateien abrufbar.


title: Macrophage-like THP-1 cells show effective uptake of silica nanoparticles carrying inactivated diphtheria toxoid for vaccination

text: Nanoparticles may be used in vaccinology as an antigen delivery and/or an immunostimulant to enhance immunity. Porous silica has been identified as an effective adjuvant for more than a decade, and we have therefore investigated the take up rate by an immortalized macrophage-like cell line of a number of mesoporous silica nanoparticles (MSNPs) with differing diameter and pore size. The MSNPs were synthesized using a sol-gel reaction and post-synthesis removal of the template. The MSNPs showed a clear distribution in take up rate peaking at 217 nm, whereas a comparison with solid spherical nanoparticles showed a similar distribution peaking at 377 nm. The MSNPs were investigated before and after loading with antigen. Diphtheria toxoid was used as a proof-of-concept antigen and showed a peak macrophage internalization of 53.42% for loaded LP3 particles which had a diameter of 217.75 ± 5.44 nm and large 16.5 nm pores. Optimal MSNP sizes appeared to be in the 200–400 nm range, and larger pores showed better antigen loading. The mesoporous silica particles were shown to be generally biocompatible, and cell viability was not altered by the loading of particles with or without antigen. [Figure: see text]


title: Bubble bilevel ventilation facilitates gas exchange in anesthetized rabbits

text: BACKGROUND: Bubble continuous positive airway pressure is an established therapy for infants in respiratory distress. In resource-limited settings, few treatment options exist for infants requiring further respiratory support. A bubble bilevel device has been developed to provide nonelectric, time-cycled, pressure-limited respiratory support. We compared the efficacy of bubble bilevel ventilation with conventional mechanical ventilation in sedated rabbits. METHODS: Six adult rabbits under inhaled isoflurane general anesthesia were ventilated by alternating intervals of conventional and bubble bilevel ventilation for three 10−15-min periods. During each period, interval arterial blood gas (ABG) measurements were obtained after at least 10 min on the respective mode of ventilation. RESULTS: The bubble bilevel system was able to deliver the following pressures: 20/7, 15/5, 12/5, 8/5 cm H(2)O. The estimated differences in arterial blood gas values on bubble bilevel vs. ventilator were as follows (normalized values): pH 7.41 vs. 7.40, pCO(2) 37.7 vs. 40, pO(2) 97.6 vs. 80. In addition, the bubble bilevel ventilation delivered consistent pressure waveforms without interruption for over 60 min on two rabbits. CONCLUSION: This study demonstrates promising in vivo results on the efficacy of a novel bubble bilevel device, which may prove useful for infants in respiratory distress. IMPACT: Given the lack of personnel, funds or infrastructure to provide neonatal mechanical ventilation in resource-limited settings, additional low-cost, low-tech treatments are necessary to save infant lives. Bubble bilevel ventilation reliably delivers two levels of airway pressure to anesthetized rabbits resulting in normalization of blood gases comparable to those achieved on a traditional ventilator. If proven effective, simple technologies like this device have the potential to significantly impact neonatal mortality due to respiratory distress globally.


title: Streptovertimycins A–H, new fasamycin-type antibiotics produced by a soil-derived Streptomyces morookaense strain

text: Eight new fasamycin-type polyketides, streptovertimycins A–H (1−8), were isolated from soil-derived Streptomyces morookaense SC1169 cultivated on wheat grains. Their structures were established by extensive spectroscopic analysis and theoretical computations of ECD spectra. Compounds 1−8 have a fasamycin-type pentacyclic structure featuring a 15-O-methyl group. They exhibited potent activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE) with MIC values in the range of 0.63–5.0 μg/ml. The activity profile provided new insights into the structure–activity relationships of fasamycin-type antibiotics.


title: Selecting the dosage of ceftazidime–avibactam in the perfect storm of nosocomial pneumonia

text: PURPOSE: Ceftazidime–avibactam is a novel β-lactam/β-lactamase inhibitor combination recently approved in Europe and the USA for the treatment of adults with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP), among other indications. In the phase III REPROVE trial (NCT01808092), ceftazidime–avibactam demonstrated non-inferiority to meropenem for the treatment of patients with nosocomial pneumonia (NP), including VAP. As ceftazidime–avibactam was not studied in patients with NP prior to REPROVE, selecting an appropriate dosage regimen in the “perfect storm” of NP required careful consideration of potential determinants and confounders of response specific to the NP patient population. METHODS: This review describes the series of preclinical studies and pharmacokinetic/pharmacodynamic (PK/PD) analyses that supported ceftazidime–avibactam dosage selection for patients with NP/VAP (2000/500 mg by 2-h intravenous infusion every 8 h, adjusted for renal function). In parallel, important considerations for antibiotic dosage selection in patients with NP are highlighted, including adequate drug penetration into the lungs, the suitability of murine-derived plasma PK/PD targets, evaluation of MIC distributions against clinical bacterial isolates from patients with NP, and consideration of PK in patients with NP, who are often critically ill. These analyses also supported the European approval of ceftazidime–avibactam for adults with HAP, including VAP, before the completion of REPROVE. CONCLUSIONS: This work serves as a successful practical example of dosage design for a new antibacterial drug therapy in the indication of NP, including VAP, where previous drug therapies have failed, possibly as a result of evaluation of too few variables, thereby limiting the accuracy of pharmacodynamic predictions. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00228-019-02804-z) contains supplementary material, which is available to authorized users.


title: Peculiarities of biofilm formation by Paracoccus denitrificans

text: Most bacteria form biofilms, which are thick multicellular communities covered in extracellular matrix. Biofilms can become thick enough to be even observed by the naked eye, and biofilm formation is a tightly regulated process. Paracoccus denitrificans is a non-motile, Gram-negative bacterium that forms a very thin, unique biofilm. A key factor in the biofilm formed by this bacterium is a large surface protein named biofilm-associated protein A (BapA), which was recently reported to be regulated by cyclic diguanosine monophosphate (cyclic-di-GMP or c-di-GMP). Cyclic-di-GMP is a major second messenger involved in biofilm formation in many bacteria. Though cyclic-di-GMP is generally reported as a positive regulatory factor in biofilm formation, it represses biofilm formation in P. denitrificans. Furthermore, quorum sensing (QS) represses biofilm formation in this bacterium, which is also reported as a positive regulator of biofilm formation in most bacteria. The QS signal used in P. denitrificans is hydrophobic and is delivered through membrane vesicles. Studies on QS show that P. denitrificans can potentially form a thick biofilm but maintains a thin biofilm under normal growth conditions. In this review, we discuss the peculiarities of biofilm formation by P. denitrificans with the aim of deepening the overall understanding of bacterial biofilm formation and functions.