title: Characterization of HIV-1 subtypes and drug resistance mutations in Henan Province, China (2017–2019)

text: Human immunodeficiency virus type 1 (HIV-1) infection remains a severe public health problem worldwide. In this study, we investigated the distribution of HIV-1 subtypes and the prevalence of drug resistance mutations (DRMs) among patients with HIV-1 infection in Henan Province, China. HIV-1 strains in blood samples taken from inpatients and outpatients visiting the Sixth People’s Hospital of Zhengzhou from August 2017 to July 2019 with a viral load (VL) greater than 1000 copies/ml were subjected to subtype and DRMs analysis. Out of a total of 769 samples, subtype and DRM data were obtained from 657 (85.43%) samples. Phylogenetic analysis based on partial pol gene sequences indicated that the most commonly found genotype was subtype B (45.51%, 299/657), followed by CRF01_AE (28.61%, 188/657), CRF07_BC (15.68%, 103/657), CRF08_BC (0.76%, 5/657), C (0.61%, 4/657), A (0.30%, 2/657), and others (8.52%, 56/657). Circulating recombinant forms (CRFs) were most commonly found in patients who were naïve to antiretroviral treatment (ART) (68.67%, 160/233). The percentage of patients with one or more major drug-resistance mutations was 50.99% (335/657), and it was 6.44% (15/233) in ART-naive patients that were primarily infected with subtype B (17.74%). Resistance mutations were most common at codons 65, 103, 106, 184, and 190 of the reverse transcriptase gene and codon 46 of the protease gene. Our study provides detailed information about the distribution of HIV-1 subtypes and the incidence of drug resistance mutations of different subtypes in ART-experienced and naïve patients. This can guide policymakers in making decisions about treatment strategies against HIV-1.


title: Pressure support ventilation-pro decreases propofol consumption and improves postoperative oxygenation index compared with pressure-controlled ventilation in children undergoing ambulatory surgery: a randomized controlled trial

text: PURPOSE: The PSVPro mode is increasingly being used for surgeries under laryngeal mask airway owing to improved ventilator-patient synchrony and decreased work of breathing. We hypothesized that PSVPro ventilation mode would reduce consumption of anesthetic agents compared with pressure control ventilation (PCV). METHODS: Seventy children between three and eight years of age undergoing elective lower abdominal and urological surgery were randomized into PCV group (n = 35) or PSVPro group (n = 35). General anesthesia was induced with sevoflurane and a Proseal LMA™ was inserted. Anesthesia was maintained with propofol infusion to maintain the entropy values between 40 and 60. In the PCV mode, the inspiratory pressure was adjusted to obtain an expiratory tidal volume of 8 mL·kg(−1) and a respiratory rate of 12–20/min. In the PSVPRO group, the flow trigger was set at 0.4 L·min(−1) and pressure support was adjusted to obtain expiratory tidal volume of 8 mL·kg(−1). Consumption of anesthetic agent was recorded as the primary outcome. Emergence time and discharge time were recorded as secondary outcomes. RESULTS: The PSVPro group showed significant reduction in propofol consumption compared with the PCV group (mean difference, 33.3 µg(−1)·kg(−1)·min(−1); 95% confidence interval [CI], 24.2 to 42.2). There was decrease in the emergence time in the PSVPro group compared with the PCV group (mean difference, 3.5 min; 95% CI, 2.8 to 4.2) and in time to achieve modified Aldrete score > 9 (mean difference, 3.6 min; 95% CI, 1.9 to 5.2). CONCLUSION: The PSVPro mode decreases propofol consumption and emergence time, and improves oxygenation index in children undergoing ambulatory surgery. TRIAL REGISTRATION: Clinical Trial Registry of India (CTRI/2017/12/010942); registered 21 December, 2017.


title: Obesity associated with increased postoperative pulmonary complications and mortality after trauma laparotomy

text: BACKGROUND: Patient-related risk factors for the development of postoperative pulmonary complications (PPCs) include age ≥ 60-years, congestive heart failure, hypoalbuminemia and smoking. The effect of obesity is unclear and has not been shown to independently increase the likelihood of PPCs in trauma patients undergoing trauma laparotomy. We hypothesized the likelihood of mortality and PPCs would increase as body mass index (BMI) increases in trauma patients undergoing trauma laparotomy. METHODS: The Trauma Quality Improvement Program (2010–2016) was queried to identify trauma patients ≥ 18-years-old undergoing trauma laparotomy within 6-h of presentation. A multivariable logistic regression analysis was used to determine the likelihood of PPCs and mortality when stratified by BMI. RESULTS: From 8,330 patients, 2,810 (33.7%) were overweight (25–29.9 kg/m(2)), 1444 (17.3%) obese (30–34.9 kg/m(2)), 580 (7.0%) severely obese (35–39.9 kg/m(2)), and 401 (4.8%) morbidly obese (≥ 40 kg/m(2)). After adjusting for covariates including age, injury severity score, chronic obstructive pulmonary disease, smoking, and rib/lung injury, the likelihood of PPCs increased with increasing BMI: overweight (OR = 1.37, CI 1.07–1.74, p = 0.012), obese (OR = 1.44, CI 1.08–1.92, p = 0.014), severely obese (OR = 2.20, CI 1.55–3.14, p < 0.001), morbidly obese (OR = 2.42, CI 1.67–3.51, p < 0.001), compared to those with normal BMI. In addition, the adjusted likelihood of mortality increased for the morbidly obese (OR = 2.60, CI 1.78–3.80, p < 0.001) compared to those with normal BMI. CONCLUSION: Obese trauma patients undergoing emergent trauma laparotomy have a high likelihood for both PPCs and mortality, with morbidly obese trauma patients having the highest likelihood for both. This suggests obesity should be accounted for in risk prediction models of trauma patients undergoing laparotomy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00068-020-01329-w) contains supplementary material, which is available to authorized users.


title: A Prospective Cohort Study of Factors Associated with Empiric Antibiotic De-escalation in Neonates Suspected with Early Onset Sepsis (EOS)

text: BACKGROUND: Prolonged empiric antibiotic use, resulting from diagnostic uncertainties, in suspected early onset sepsis (EOS) cases constitutes a significant problem. Unnecessary antibiotic use increases the risk of antibiotic resistance. Furthermore, prolonged antibiotic use increases the risk of mortality and morbidity in neonates. Proactive measures including empiric antibiotic de-escalation are crucial to overcome these problems. METHODS: This was a prospective cohort study conducted in the neonatal intensive care units of two public hospitals in Malaysia. Neonates with a gestational age greater than 34 weeks who were started on empiric antibiotics within 72 h of life were screened. The data were then stratified according to de-escalation and non-de-escalation practices, where de-escalation practice was defined as narrowing down or discontinuation of empiric antibiotic within 72 h of treatment. RESULTS: A total of 1045 neonates were screened, and 429 were included. The neonates were then divided based on de-escalation (n = 207) and non-de-escalation (n = 222) practices. Neonates under non-de-escalation practices showed significantly longer durations of antibiotic use compared to those under de-escalation practices (p < 0.05), with no difference in treatment outcomes. Five factors were found to be associated with de-escalation of antibiotics. They are cesarean section delivery, exposure to antenatal steroids, nil history of maternal pyrexia, absence of meconium-stained amniotic fluid, and normal C-reactive protein ≤ 0.5 mg/dL (p < 0.05). CONCLUSIONS: Empiric antibiotic de-escalation appears feasible as a routine form of treatment for EOS in late preterm and term neonates.


Polymorphism analysis and supertype definition of swine leukocyte antigen class I molecules in three-way crossbred (Landrace, Duroc, and Yorkshire) pigs: implications for the vaccine development of African swine fever virus


title: Early oral colostrum administration in preterm infants

text: BACKGROUND: Early administration of colostrum may provide preterm infants with immune components. Previous studies illustrating the effects of oral colostrum (OC) have been confounded by the coincidence of enteral feedings. OBJECTIVE: To quantify OC absorption, as measured by urinary sIgA and lactoferrin, in preterm infants prior to enteral feedings. MATERIALS AND METHODS: Colostrum was obtained from mothers delivering infants ≤32 weeks and ≤1500 g. sIgA and lactoferrin were measured in infant urine, and microflora in saliva and tracheal aspirates were characterized. RESULTS: Urinary sIgA and lactoferrin were significantly greater in infants receiving OC by syringe compared to swab (p < 0.002). Urinary sIgA correlated with the total number of doses in 72 h (R(2) = 43%, p < 0.01). CONCLUSIONS: Administration of OC by syringe and higher cumulative dose are associated with increased absorption of sIgA and lactoferrin, and early dosing may contribute to a more diverse tracheal microbiome.


Antimicrobial de-escalation is part of appropriate antibiotic usage in ICU


title: Nitrosourea, etoposide and cyclophosphamide followed by autologous stem cell transplantation for pediatric lymphoma patients

text: Treatment outcomes in pediatric lymphoma have improved substantially over the past 2 decades; however, the prognosis for patients with high risk or relapsed disease remains poor. We evaluated outcomes of high-dose chemotherapy (HDC) and autologous stem cell transplantation (auto-SCT) in 56 pediatric lymphoma patients. Patients received nitrosourea (51 BCNU; 5 ACNU), etoposide, and cyclophosphamide (BEC; AEC). Median age at HDC/auto-SCT was 12 years (range 2–17 years). Forty-four patients underwent HDC/auto-SCT because they did not achieve complete remission after induction chemotherapy. Eight patients showed relapse and four NK/T-cell lymphoma patients also underwent HDC/auto-SCT. BCNU pneumonitis was diagnosed in nine (16.0%) patients. Eight (14.3%) relapsed after HDC/auto-SCT. Treatment-related mortality occurred in three cases. Five-year event-free survival and overall survival rates were 74.8% [72.7% non-Hodgkin’s lymphoma (NHL); 83.3% Hodgkin’s disease (HD); 72.7%] and 83.6% (81.6% NHL; 91.7% HD), respectively. HDC/auto-SCT with BEC or AEC regimen for pediatric high-risk lymphoma patients showed feasible outcomes. However, treatment modifications are warranted to reduce relapse and toxicity.


title: Predictive impact of early mobilization on rehospitalization for elderly Japanese heart failure patients

text: The aim of this study was to determine whether early mobilization was associated with rehospitalization among elderly heart failure patients. We measured the time from admission to mobilization and other clinical characteristics for 190 heart failure patients (mean age, 80.7 years). The primary outcome was heart failure rehospitalization. Kaplan–Meier survival curves were plotted and the hazard ratios for rehospitalization were determined using Cox proportional hazards regression models. During a median follow-up period of 750 days, 58 patients underwent rehospitalization. The time from admission to mobilization was significantly longer for these patients than for those who were not rehospitalized. Univariate and multivariate Cox proportional hazards analyses showed that the time from admission to mobilization was an independent predictor of rehospitalization, and receiver-operating characteristic analysis determined an optimal cutoff value of 3 days for differentiating the patients more likely to experience a subsequent cardiac event (sensitivity, 76%; specificity, 69%; area under the curve, 0.667). Kaplan–Meier survival curve analysis showed a significantly lower event rate in the ≤ 3-day group (p = 0.001, log-rank test). In conclusion, the time from admission to mobilization may be one of the strongest predictors of rehospitalization in elderly heart failure patients. Early mobilization within 3 days may be an initial target for the acute phase treatment of heart failure.


title: Thoracoscopic repair of esophageal atresia with distal tracheoesophageal fistula: is it a safe procedure in infants weighing less than 2000 g?

text: BACKGROUND: Since Rothenberg first performed thoracoscopic repair for esophageal atresia with distal tracheoesophageal fistula (EA/TEF) successfully in 2000, thoracoscopic repair has achieved status as a routine procedure worldwide. Previously, an international multicenter study reported that this procedure was not inferior to conventional open surgery. However, thoracoscopic surgery is a highly difficult operation for surgeons and anesthesiologists; as a result, the safety and efficacy of the surgery is still under debate. Considering these circumstances, the purpose of this study was to analyze the results of single-center thoracoscopic surgery and to compare the outcomes relative to the patient’s weight at the time of surgery. METHODS: We retrospectively analyzed patients with EA/TEF who underwent thoracoscopic surgery in a single center between October 2008 and February 2017. RESULTS: In total, 41 cases of thoracoscopic repair of EA/TEF were performed. Upon subgrouping by over and under 2000 g of body weight at the time of operation, 34 were found to be over 2000 g and seven were under 2000 g. Intraoperative factors and events were not significantly different between the two groups. Additionally, most of the postoperative outcomes, including the rate of postoperative leakage and strictures, showed no difference. On the other hand, the under 2000 g group had more gastroesophageal reflux requiring fundoplication than did the heavier group (P = 0.04). CONCLUSIONS: The results of this center’s thoracoscopic repair of EA/TEF were not inferior to other centers’ outcomes. Additionally, the intraoperative and postoperative outcomes were similar despite differences in weight at operation. Therefore, thoracoscopic repair might be a feasible surgical option for infants weighing less than 2000 g when performed by a surgeon and anesthesiologist team who are experienced in pediatric thoracoscopic surgery.


title: Collaborative Management Strategies for Drug Shortages in Neurocritical Care

text: Drug shortages have become all too familiar in the health care environment, with over 200 drugs currently on shortage. In the wake of Hurricane Maria in September 2017, hospitals across the USA had to quickly and creatively adjust medication preparation and administration techniques in light of decreased availability of intravenous (IV) bags used for compounding a vast amount of medications. Amino acid preparations, essential for compounding parenteral nutrition, were also directly impacted by the hurricane. Upon realization of the impending drug shortages, hospitals resorted to alternative methods of drug administration, such as IV push routes, formulary substitutions, or alternative drug therapies in hopes of preserving the small supply of IV bags available and prioritizing them for them most critical needs. In some cases, alternative drug therapies were required, which increased the risk of medication errors due to the use of less-familiar treatment options. Clinical pharmacists rounding with medical teams provided essential, patient-specific drug regimen alternatives to help preserve a dwindling supply while ensuring use in the most critical cases. Drug shortages also frequently occur in the setting of manufacturing delays or discontinuation and drug recalls, with potential to negatively impact patient care. The seriousness of the drug shortage crisis reached public attention by December 2017, when political and pharmacy organizations called for response to the national drug shortage crisis. In this article, we review institutional mitigation strategies in response to drug shortages and discuss downstream effects of these shortages, focusing on medications commonly prescribed in neurocritical care patients.


title: MELD–Na Is More Strongly Associated with Risk of Infection and Outcomes Than Other Characteristics of Patients with Cirrhosis

text: BACKGROUND AND AIMS: The nature and outcomes of infection among patients with cirrhosis in safety-net hospitals are not well described. We aimed to characterize the rate of and risk factors for infection, both present on admission and nosocomial, in this unique population. We hypothesized that infections would be associated with adverse outcomes such as short-term mortality. METHODS: We used descriptive statistics to characterize infections within a retrospective cohort characterized previously. We used multivariable logistic regression models to assess potential risk factors for infection and associations with key outcomes such as short-term mortality and length of stay. RESULTS: The study cohort of 1112 patients included 33% women with a mean age of 56 ± 10 years. Infections were common (20%), with respiratory and urinary tract infections the most frequent. We did not observe a difference in the incidence of infection on admission based on patient demographic factors such as race/ethnicity or estimated household income. Infections on admission were associated with greater short-term mortality (12% vs 4% in-hospital and 14% vs 7% 30-day), longer length of stay (6 vs 3 days), intensive care unit admission (28% vs 18%), and acute-on-chronic liver failure (10% vs 2%) (p < 0.01 for all). Nosocomial infections were relatively uncommon (4%), but more frequent among patients admitted to the intensive care unit. Antibiotic resistance was common (38%), but not associated with negative outcomes. CONCLUSION: We did not identify demographic risk factors for infection, but did confirm its morbid effect among patients with cirrhosis in safety-net hospitals. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10620-020-06164-y) contains supplementary material, which is available to authorized users.


title: Urgent intubation without neuromuscular blocking agents and the risk of tracheostomy

text: Neuromuscular blocking agents play a significant role in improving the success rate for urgent intubation, although there is limited evidence about the effect on subsequent outcomes, such as the incidence of tracheostomy. In this retrospective cohort study, we aimed to examine the association between avoidance of neuromuscular blocking agents for urgent tracheal intubation and incidence of tracheostomy among patients in the intensive care unit (ICU). The setting of this study was an eight-bed ICU at a tertiary-care hospital in Okayama, Japan. We included patients who underwent urgent tracheal intubation at the emergency department or the ICU and were admitted to the ICU between April 2013 and November 2017. We extracted data on methods and medications of intubation, predictors for difficult intubation, Cormack–Lehane grade, patient demographics, primary diagnoses, reintubation. We estimated odds ratios and their 95% confidence intervals for elective tracheostomy during the ICU stay using logistic regression models. Of 411 patients, 46 patients underwent intubation without neuromuscular blocking agents and 61 patients underwent tracheostomy. After adjusting for potential confounders, patients who avoided neuromuscular blocking agents had more than double the odds of tracheostomy (odds ratio 2.59, 95% confidence interval 1.06–6.34, p value = 0.04). When stratifying the subjects by risk status for tracheostomy, the association was more pronounced in high-risk group, while we observed less significant association in the low-risk group. Avoidance of neuromuscular blocking agents for urgent intubation increases the risk of tracheostomy among emergency patients, especially those who have a higher risk for tracheostomy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11739-019-02214-0) contains supplementary material, which is available to authorized users.


title: Comparison of the use of AnaConDa® versus AnaConDa-S® during the post-operative period of cardiac surgery under standard conditions of practice

text: Changes have been made to the AnaConDa device (Sedana Medical, Stockholm, Sweden), decreasing its size to reduce dead space and carbon dioxide (CO(2)) retention. However, this also involves a decrease in the surface area of the activated carbon filter. The CO(2) elimination and sevoflurane (SEV) reflection of the old device (ACD-100) were thus compared with the new version (ACD-50) in patients sedated after coronary artery bypass graft surgery. After ERC approval and written informed consent, 23 patients were sedated with SEV, using first the ACD-100 and then the ACD-50 for 60 min each. With each device, patients were ventilated with tidal volumes (TV) of 5 ml/kg of ideal body weight for the first 30 min, and with 7 ml/kg for the next 30 min. Ventilation parameters, arterial blood gases, Bispectral-Index™ (BIS, Aspect Medical Systems Inc., Newton, MA, USA), SEV concentrations exhaled by the patient (SEV-exhaled) and from the expiratory hose (SEV-lost) were recorded every 30 min. A SEV reflection index was calculated: SRI [%] = 100 × (1 − (SEV-lost/SEV-exhaled)). Data were compared using ANOVA with repeated measurements and Student’s T-tests for pairs. Respiratory rates, tidal and minute volumes were not significantly different between the two devices. End tidal and arterial CO(2) partial pressures were significantly higher with the ACD-100 as compared with the ACD-50. SEV infusion rate remained constant. SEV reflection was higher (SRI: ACD-100 vs. ACD-50, TV 5 ml/kg: 95.29 ± 6.45 vs. 85.54 ± 11.15, p = 0.001; 7 ml/kg: 93.42 ± 6.55 vs. 88.77 ± 12.26, p = 0.003). BIS was significantly lower when using the higher TV (60.91 ± 9.99 vs. 66.57 ± 8.22, p = 0.012), although this difference was not clinically relevant. During postoperative sedation, the use of ACD-50 significantly reduced CO(2) retention. SEV reflection was slightly reduced. However, patients remained sufficiently sedated without increasing SEV infusion.


title: Cardiorespiratory behavior of preterm infants receiving continuous positive airway pressure and high flow nasal cannula post extubation: randomized crossover study

text: BACKGROUND: Nasal continuous positive airway pressure (NCPAP) and high flow nasal cannula (HFNC) are modes of non-invasive respiratory support commonly used after extubation in extremely preterm infants. However, the cardiorespiratory physiology of these infants on each mode is unknown. METHODS: Prospective, randomized crossover study in infants with birth weight ≤1250 g undergoing their first extubation attempt. NCPAP and HFNC were applied randomly for 45 min each, while ribcage and abdominal movements, electrocardiogram, oxygen saturation, and fraction of inspired oxygen (FiO(2)) were recorded. Respiratory signals were analyzed using an automated method, and differences between NCPAP and HFNC features and changes in FiO(2) were analyzed. RESULTS: A total of 30 infants with median [interquartile range] gestational age of 27 weeks [25.7, 27.9] and birth weight of 930 g [780, 1090] were studied. Infants were extubated at 5 days [2, 13] of life with 973 g [880, 1170] and three failed (10%). No differences in cardiorespiratory behavior were noted, except for longer respiratory pauses (9.2 s [5.0, 11.5] vs. 7.3 s [4.6, 9.3]; p = 0.04) and higher FiO(2) levels (p = 0.02) during HFNC compared to NCPAP. CONCLUSIONS: In extremely preterm infants studied shortly after extubation, the use of HFNC was associated with longer respiratory pauses and higher FiO(2) requirements.


title: ECLS-associated infections in adults: what we know and what we don’t yet know

text: Extracorporeal life support (ECLS) is increasingly used in the management of patients with severe cardiopulmonary disease. Infections are frequently the etiologies underlying the respiratory, and occasionally cardiac, failure that necessitates ECLS. Just as importantly, infections are among the most commonly reported adverse events during ECLS. Infections in this setting may be the sequelae of prolonged critical illness or of underlying immune dysregulation; they may be hospital-acquired infections, and they may or may not be attributable to the presence of ECLS itself, the latter being an aspect that can be difficult to determine. Current registry data and evidence from the literature offer some insights, but also leave open many questions regarding the nature and significance of infections reported both before and during ECLS, including the question of any causal link between ECLS and the development of infections. An ongoing lack of consistency in the identification, diagnosis, management, and prevention of infections during ECLS is limiting our ability to interpret literature data and thus highlighting the need for more rigorous investigation and standardization of definitions. This review aims to characterize the current understanding of infections associated with the use of ECLS, taking into account data from the updated Extracorporeal Life Support Organization Registry, which provides important context for understanding the epidemiology and outcomes of these patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05847-z) contains supplementary material, which is available to authorized users.


title: Does additional coronary artery bypass grafting to aortic valve replacement in elderly patients affect the early and long-term outcome?

text: Early and long-term outcomes in elderly patients who underwent isolated aortic valve replacement (iAVR) are well defined. Conflicting data exist in elderly patients who underwent AVR plus coronary artery bypass grafting (CABG). We sought to evaluate the early and long-term outcomes of combined AVR + CABG in patients older than 75 years of age. From June 1999 to June 2018, 402 patients ≥ 75 years who underwent iAVR (n = 200; 49.7%) or combined AVR plus CABG (n = 202; 50.3%) were retrospectively analysed. AVR + CABG patients were older than iAVR patients (78.5 ± 2.5 vs 77.6 ± 2.8 years; p < 0.0001), with greater co-morbidities and more urgent/emergency surgery. 30-day mortality was 6.5% in the AVR + CABG and 4.5% in the iAVR group (p = 0.38). Multivariate analysis identified EuroSCORE II [odd ratio (OR) 1.13] postoperative stroke (OR 12.53), postoperative low cardiac output syndrome (OR 8.72) and postoperative mechanical ventilation > 48 h (OR 8.92) as independent predictors of 30-day mortality; preoperative cerebrovascular events (OR 3.43), creatinine (OR 7.27) and extracorporeal circulation time (OR 1.01) were independent predictors of in-hospital major adverse cardiovascular and cerebral events (MACCE). Treatment was not an independent predictor of 30-day mortality and in-hospital MACCE. Survival at 1, 5 and 10 years was 94.7 ± 1.6%, 72.6 ± 3.6% and 31.7 ± 4.8% for iAVR patients and 89.1 ± 2.3%, 73.9 ± 3.5% and 37.2 ± 4.8% for AVR + CABG subjects (p = 0.99). Using adjusted Cox regression model, creatinine [hazard ration (HR) 1.50; p = 0.018], COPD (HR 1.97; p = 0.003) and NYHA class (HR 1.39; p < 0.0001) were independent predictors of late mortality; the combined AVR + CABG was not associated with increased risk of late mortality (HR 0.83; p = 0.30). In patients aged ≥ 75 years, combined AVR + CABG was not associated with increased 30-day mortality, in-hospital MACCE and long-term mortality. Surgical revascularization can be safely undertaken at the time of AVR in elderly patients.


Spinal-cardiac crosstalk


title: Systematic evidence-based review: outcomes from exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability

text: PURPOSE: Exome and genome sequencing (ES/GS) are performed frequently in patients with congenital anomalies, developmental delay, or intellectual disability (CA/DD/ID), but the impact of results from ES/GS on clinical management and patient outcomes is not well characterized. A systematic evidence review (SER) can support future evidence-based guideline development for use of ES/GS in this patient population. METHODS: We undertook an SER to identify primary literature from January 2007 to March 2019 describing health, clinical, reproductive, and psychosocial outcomes resulting from ES/GS in patients with CA/DD/ID. A narrative synthesis of results was performed. RESULTS: We retrieved 2654 publications for full-text review from 7178 articles. Only 167 articles met our inclusion criteria, and these were primarily case reports or small case series of fewer than 20 patients. The most frequently reported outcomes from ES/GS were changes to clinical management or reproductive decision-making. Two studies reported on the reduction of mortality or morbidity or impact on quality of life following ES/GS. CONCLUSION: There is evidence that ES/GS for patients with CA/DD/ID informs clinical and reproductive decision-making, which could lead to improved outcomes for patients and their family members. Further research is needed to generate evidence regarding health outcomes to inform robust guidelines regarding ES/GS in the care of patients with CA/DD/ID.


title: Racial Disparity in 30-Day Outcomes of Metabolic and Bariatric Surgery

text: BACKGROUND: There is evidence of racial disparity in the long-term weight loss outcomes of bariatric surgery. However, there has been a more limited evaluation of the impact of race on immediate perioperative outcomes. The aim of this study was to compare 30-day postoperative outcomes among different races. STUDY DESIGN: The 2016 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database was queried to identify patients aged ≥ 18 and body mass index ≥ 35 who underwent primary laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) with known information on race. We then evaluated the effect of five different races on four different 30-day outcomes. RESULTS: Of the total 106,932 patients (79.5% White, 19.3% African American (AA), 0.5% Asian, 0.4% American Indian or Alaska Native, 0.3% Native Hawaiian or other Pacific Islander), 30-day rates of postoperative complication, readmission, re-intervention, and reoperation were 6, 3.8, 1.3, and 1.2%, respectively. After controlling for other covariates in multivariate logistic regression and selecting White as reference, AA was the only race associated with a higher risk of postoperative complications (odds ratio [OR] 1.13; confidence interval [CI] 1.06–1.2) and readmissions (OR 1.47; CI 1.3–1.6). AA and American Indian or Alaska Native were also associated with higher re-interventions (OR 1.31; CI 1.15–1.51 and OR 2.11; CI 1.03–4.34). Furthermore, AA was associated with lower 30-day reoperations (OR 0.83; CI 0.7–0.9). CONCLUSION: This study found significant racial differences in short-term outcomes following bariatric surgery. Factors underlying these disparities are unclear and warrant further investigation.


title: Sepsis-Induced Cardiomyopathy: a Comprehensive Review

text: PURPOSE OF REVIEW: To briefly review epidemiology and pathophysiology of SICM and provide a more extensive review of the data on diagnostic and management strategies. RECENT FINDINGS: SICM is likely underdiagnosed and that has mortality implications. Current evidence supports speckle tracking echocardiography to identify decreased contractility irrespective of left ventricular ejection fraction for the diagnosis of SICM. There continues to be a dearth of large clinical trials evaluating the treatment of SICM and current consensus focuses on supportive measures such as vasopressors and inotropes. SUMMARY: Sepsis is a significant cause of mortality, and sepsis-induced cardiomyopathy has both prognostic and management implications for these patients. Individualized work-up and management of these patients is crucial to improving outcomes.


title: Inter-country variability over time in the mortality of mechanically ventilated patients

text: PURPOSE: Variations in clinical characteristics and management and in the mortality of mechanically ventilated patients have not been sufficiently evaluated. We hypothesized that mortality shows a variability associated with country after adjustment for clinical characteristics and management. METHODS: Analysis of four studies carried out at 6-year intervals over an 18-year period. The studies included 26,024 patients (5183 in 1998, 4968 in 2004, 8108 in 2010, and 7765 in 2016) admitted to 1253 units from 38 countries. The primary outcome was 28-day mortality. We performed analyses using multilevel logistic modeling with mixed-random effects, including country as a random variable. To evaluate the effect of management strategies on mortality, a mediation analysis was performed. RESULTS: Adjusted 28-day mortality decreased significantly over time (first study as reference): 2004: odds ratio 0.82 (95% confidence interval [CI] 0.72–0.93); 2010: 0.63 (95% CI 0.53–0.75); 2016: 0.49 (95% CI 0.39–0.61). A protective ventilatory strategy and the use of continuous sedation mediated a moderate fraction of the effect of time on mortality in patients with moderate hypoxemia and without hypoxemia, respectively. Logistic multilevel modeling showed a significant effect of country on mortality: median odds ratio (MOR) in 1998: 2.02 (95% CI 1.57–2.48); in 2004: 1.76 (95% CI 1.47–2.06); in 2010: 1.55 (95% CI 1.37–1.74), and in 2016: 1.39 (95% CI 1.25–1.54). CONCLUSIONS: These findings suggest that country could contribute, independently of confounder variables, to outcome. The magnitude of the effect of country decreased over time. Clinical trials registered with http://www.clinicaltrials.gov (NCT02731898). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-019-05867-9) contains supplementary material, which is available to authorized users.


title: The effect of patent ductus arteriosus on coronary artery blood flow in premature infants: a prospective observational pilot study

text: OBJECTIVE: To compare coronary flows between premature infants with and without hemodynamically significant patent ductus arteriosus (hsPDA) and to determine if coronary flow is influenced by medical PDA treatment. DESIGN: Prospective, observational pilot study. Forty-three infants <32 weeks gestation underwent echocardiography when routinely indicated. Study group included infants with hsPDA requiring treatment. Comparison groups included infants with nonsignificant PDA and infants without PDA. RESULTS: The study group (n = 13), compared with the comparison groups with nonsignificant PDA (n = 12) and without PDA (n = 18) had higher troponin levels (p = 0.003 and 0.004, respectively). In infants with hsPDA compared with infants with no PDA there was a significant increase in myocardial oxygen demand and decrease in left main coronary artery flow, with nonsignificant increase in cardiac output. CONCLUSIONS: Decrease in coronary artery flows and higher troponin values may suggest a “steal effect,” not allowing to meet the elevated myocardial oxygen demand in infants with hsPDA.


title: Effect of early cognitive interventions on delirium in critically ill patients: a systematic review

text: PURPOSE: A systematic review of the literature was conducted to determine the effects of early cognitive interventions on delirium outcomes in critically ill patients. SOURCE: Search strategies were developed for MEDLINE, EMBASE, Joanna Briggs Institute, Cochrane, Scopus, and CINAHL databases. Eligible studies described the application of early cognitive interventions for delirium prevention or treatment within any intensive care setting. Study designs included randomized-controlled trials, quasi-experimental trials, and pre/post interventional trials. Two reviewers independently extracted data and assessed risk of bias using Cochrane methodology. PRINCIPAL FINDINGS: Four hundred and four citations were found. Seven full-text articles were included in the final review. Six of the included studies had an overall serious, high, or critical risk of bias. After application of cognitive intervention protocols, a significant reduction in delirium incidence, duration, occurrence, and development was found in four studies. Feasibility of cognitive interventions was measured in three studies. Cognitive stimulation techniques were described in the majority of studies. CONCLUSION: The study of early cognitive interventions in critically ill patients was identified in a small number of studies with limited sample sizes. An overall high risk of bias and variability within protocols limit the utility of the findings for widespread practice implications. This review may help to promote future large, multi-centre trials studying the addition of cognitive interventions to current delirium prevention practices. The need for robust data is essential to support the implementation of early cognitive interventions protocols.


title: Treatment of ventilator-associated pneumonia (VAP) caused by Acinetobacter: results of prospective and multicenter ID-IRI study

text: Ventilator-associated pneumonia (VAP) due to Acinetobacter spp. is one of the most common infections in the intensive care unit. Hence, we performed this prospective-observational multicenter study, and described the course and outcome of the disease. This study was performed in 24 centers between January 06, 2014, and December 02, 2016. The patients were evaluated at time of pneumonia diagnosis, when culture results were available, and at 72 h, at the 7th day, and finally at the 28th day of follow-up. Patients with coexistent infections were excluded and only those with a first VAP episode were enrolled. Logistic regression analysis was performed. A total of 177 patients were included; empiric antimicrobial therapy was appropriate (when the patient received at least one antibiotic that the infecting strain was ultimately shown to be susceptible) in only 69 (39%) patients. During the 28-day period, antibiotics were modified for side effects in 27 (15.2%) patients and renal dose adjustment was made in 38 (21.5%). Ultimately, 89 (50.3%) patients died. Predictors of mortality were creatinine level (OR, 1.84 (95% CI 1.279–2.657); p = 0.001), fever (OR, 0.663 (95% CI 0.454–0.967); p = 0.033), malignancy (OR, 7.095 (95% CI 2.142–23.500); p = 0.001), congestive heart failure (OR, 2.341 (95% CI 1.046–5.239); p = 0.038), appropriate empiric antimicrobial treatment (OR, 0.445 (95% CI 0.216–0.914); p = 0.027), and surgery in the last month (OR, 0.137 (95% CI 0.037–0.499); p = 0.003). Appropriate empiric antimicrobial treatment in VAP due to Acinetobacter spp. was associated with survival while renal injury and comorbid conditions increased mortality. Hence, early diagnosis and appropriate antibiotic therapy remain crucial to improve outcomes.


title: Utility of echocardiography in predicting mortality in infants with severe bronchopulmonary dysplasia

text: OBJECTIVE: To determine the relationship between interventricular septal position (SP) and right ventricular systolic pressure (RVSP) and mortality in infants with severe BPD (sBPD). STUDY DESIGN: Infants with sBPD in the Children’s Hospitals Neonatal Database who had echocardiograms 34–44 weeks’ postmenstrual age (PMA) were included. SP and RVSP were categorized normal, abnormal (flattened/bowed SP or RVSP > 40 mmHg) or missing. RESULTS: Of 1157 infants, 115 infants (10%) died. Abnormal SP or RVSP increased mortality (SP 19% vs. 8% normal/missing, RVSP 20% vs. 9% normal/missing, both p < 0.01) in unadjusted and multivariable models, adjusted for significant covariates (SP OR 1.9, 95% CI 1.2–3.0; RVSP OR 2.2, 95% CI 1.1–4.7). Abnormal parameters had high specificity (SP 82%; RVSP 94%), and negative predictive value (SP 94%, NPV 91%) for mortality. CONCLUSIONS: Abnormal SP or RVSP is independently associated with mortality in sBPD infants. Negative predictive values distinguish infants most likely to survive.


title: Peptide Phage Display: Molecular Principles and Biomedical Applications

text: Phage display (PD) is a technology based on the presentation of functional exogenous peptides on the capsid surface of bacteriophages. PD is performed by introducing a DNA sequence of interest at a specific position within a functional viral gene. In addition, peptide phage libraries are powerful tools for expressing a wide range of random peptides and for specific peptide screening. Specifically, PD applications include the analysis of binding and interactions between proteins, the identification of bioactive peptides that bind to receptors, the identification of disease-associated antigens, and the identification of cell-specific peptides. Since its emergence, PD technology has revolutionized several fields in the biological sciences, such as oncology, cell biology, and pharmacology, the innumerable applications for which will be described throughout this review.


Correction to: Ventilator-associated pneumonia caused by multidrug-resistant Gram-negative bacteria: understanding nebulization of aminoglycosides and colistin


title: Respiratory outcomes of late preterm infants of mothers with early and late onset preeclampsia

text: OBJECTIVE: To study the effect of early and late onset preeclampsia (EOPE, LOPE, respectively) on outcomes of late preterm infants. STUDY DESIGN: Cohort study of late preterm infants admitted to a tertiary care NICU from January 2014–July 2015. Outcomes of late preterm infants of EOPE mothers were compared with the next late preterm infant of a LOPE mother and the next two late preterm infants of normotensive non-PE mothers. Primary outcome comprised use of continuous positive airway pressure, mechanical ventilation and/or surfactant in the 24 h after birth. RESULTS: Compared to normotensives (n = 131), adjusted odds ratio (AORs) of the primary outcome was higher in the EOPE (n = 64) and LOPE (n = 65) groups but reached statistical significance only in the EOPE group, AORs 12.9, 95% CI 3.5–37 and 2.7, 95% CI 0.95–8.1, respectively. CONCLUSIONS: Compared to late preterm infants of normotensive and LOPE mothers, infants of mothers with EOPE have significantly higher respiratory morbidity.


title: Do not drink and lyse: alcohol intoxication increases fibrinolysis shutdown in injured patients

text: INTRODUCTION: High alcohol consumption has been associated with decreased fibrinolysis and enhanced thrombosis risk in cardiovascular disease. In trauma, alcohol has been associated with poor clot formation; however, its effect on fibrinolysis has not been fully investigated. We assessed the association of blood alcohol levels and fibrinolysis in trauma activation patients. METHODS: We queried our prospective registry of trauma activations from 2014 to 2016. Associations between viscoelastic measurements [rapid thrombelastography (rTEG)] and blood alcohol level (BAL) were determined and adjusted for confounders by a multinomial logistic regression. Lysis phenotypes were defined by the % lysis in 30 min (LY30) as follows: hyperfibrinolysis ≥ 3%, physiologic 0.9–2.9%, and fibrinolysis shutdown < 0.9%. RESULTS: Overall, 191 (43.8%) had BAL measured. There were 65 (34%) patients that had no detectable BAL, 32 (16.8%) had BAL of 10–150 mg/dL, and 94 (49.2%) patients had BAL > 150 mg/dL. BAL had a moderate, but significant inverse correlation with LY30 (Rho = − 0.315, p < 0.001), while there were no significant correlations between BAL and other TEG values. The distribution of fibrinolysis phenotypes varied significantly by BAL levels (p < 0.009, with high BAL having more shutdown and less hyperfibrinolysis than the other two BAL level groups. Multinomial logistic regression showed that after adjustment for confounders, BAL levels > 150 mg/dL were independently associated with a threefold increase in the odds of shutdown compared to undetectable BAL (OR 3.37, 95% CI 1.04–8.05, p = 0.006). High BAL was also significantly associated with higher odds of shutdown compared to low BAL (OR 2.63, 95% CI 1.15–6.06). Compared to physiologic fibrinolysis, fibrinolysis shutdown was associated with increased mortality (OR 2.87, 95% CI 1.41–5.83) and VFD < 28 (OR 2.54, 95% CI 1.47–4.39). CONCLUSION: In the injured patient, high blood alcohol levels are associated with increased incidence of fibrinolysis shutdown. This finding has implications for postinjury hemostatic resuscitation as these patients may be harmed by anti-fibrinolytics. Further research is needed to assess whether the association with fibrinolysis is modified by the chronicity and type of alcohol consumed and whether anti-fibrinolytic therapy in intoxicated patients produces adverse effects.


title: A Rare Cause of Hypophosphatemia: Raine Syndrome Changing Clinical Features with Age

text: Raine Syndrome (RS) is caused by biallelic loss-of-function mutations in FAM20C gene and characterized by hypophosphatemia, typical facial and skeletal features. Subperiosteal bone formation and generalized osteosclerosis are the most common radiological findings. Here we present a new case with RS. A 9-month-old male patient on a home-type ventilator was referred for hypophosphatemia. He was born with a weight of 3800 g to non-consanguineous parents. Prenatal ultrasound had demonstrated nasal bone agenesis. A large anterior fontanel, frontal bossing, exophthalmos, hypoplastic nose, high arched palate, low set ears, triangular mouth, and corneal opacification were detected on physical examination. Serial skeletal X-rays revealed diffuse osteosclerosis at birth which was gradually decreased by the age of 5 months with subperiosteal undermineralized bone formation and medullary space of long bone could be distinguishable with bone-within-a-bone appearance. At 9 months of age, hand X-ray revealed cupping of the ulna with loose radial bone margin with minimal fraying and osteopenia. Cranial computed tomography scan showed bilateral periventricular calcification and hydrocephalus in progress. The clinical, laboratory, and radiological examinations were consistent with RS. Molecular analyses revealed a compound heterozygous mutation in FAM20C gene (a known pathogenic mutation, c.1645C > T, p.Arg549Trp; and a novel c.863 + 5 G > C variant). The patient died due to respiratory failure at 17 months of age. This case allowed us to demonstrate natural progression of skeletal features in RS. Furthermore, we have described a novel FAM20C variant causing RS. Previous literature on RS is also reviewed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00223-020-00694-3) contains supplementary material, which is available to authorized users.


title: Coupling the Macroscale to the Microscale in a Spatiotemporal Context to Examine Effects of Spatial Diffusion on Disease Transmission

text: There are many challenges to coupling the macroscale to the microscale in temporal or spatial contexts. In order to examine effects of an individual movement and spatial control measures on a disease outbreak, we developed a multiscale model and extended the semi-stochastic simulation method by linking individual movements to pathogen’s diffusion, linking the slow dynamics for disease transmission at the population level to the fast dynamics for pathogen shedding/excretion at the individual level. Numerical simulations indicate that during a disease outbreak individuals with the same infection status show the property of clustering and, in particular, individuals’ rapid movements lead to an increase in the average reproduction number [Formula: see text] , the final size and the peak value of the outbreak. It is interesting that a high level of aggregation the individuals’ movement results in low new infections and a small final size of the infected population. Further, we obtained that either high diffusion rate of the pathogen or frequent environmental clearance lead to a decline in the total number of infected individuals, indicating the need for control measures such as improving air circulation or environmental hygiene. We found that the level of spatial heterogeneity when implementing control greatly affects the control efficacy, and in particular, an uniform isolation strategy leads to low a final size and small peak, compared with local measures, indicating that a large-scale isolation strategy with frequent clearance of the environment is beneficial for disease control.


title: Effects of oropharyngeal administration of colostrum on the incidence of necrotizing enterocolitis, late-onset sepsis, and death in preterm infants: a meta-analysis of RCTs

text: Necrotizing enterocolitis (NEC) and late-onset sepsis (LOS) are two major contributors to death among preterm infants. Oropharyngeal administration of colostrum (OAC) has been proved as an easy, safe, and economically viable technique to help preterm neonates to build up their immunity. In this review, we assessed the effects of OAC on preterm infants. Several mainstream databases were searched including PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and a website of clinical trials. Randomized controlled trials (RCTs) comparing OAC vs. placebo or no intervention in preterm infants (gestation age <34 weeks or birth weight <1500 g) were eligible. Overall, nine RCTs (n = 689) were included in the review. Meta-analysis showed no statistical significance in terms of the incidence of NEC (RR = 0.59, 95% CI = 0.33–1.06, p = 0.08), LOS (RR = 0.78, 95% CI = 0.60–1.03, p = 0.08) and mortality rate (RR = 0.63, 95% CI = 0.38–1.05, p = 0.07). No significant difference was found in the subgroup analysis, apart from the group of the undeveloped region in NEC and mortality. In addition, time was significantly reduced in terms of achieving full enteral feeding (MD = −3.60, 95% CI = −6.55–0.64, p = 0.02) and hospital stay (MD = −10.38, 95% CI = −18.47–2.29, p = 0.01). The results show that OAC does not reduce the incidences of NEC, LOS, and death in preterm infants, but there is a trend toward a positive effect. It is therefore recommended as routine care for preterm infants in the NICU.


title: Ionizing Radiation Exposure in NICU

text: The authors prospectively studied ionizing radiation exposure in consecutive 107 very low birth weight (VLBW) neonates, admitted to their Level III neonatal intensive care unit (NICU). Number of X-rays, their indications and calculated dose of radiation were documented. Their mean birth weight (+SD) and gestational age (+SD) were 1077 (±219.8) g and 29.7 (+2.57) wk respectively. Extremely low birth weight (ELBW) neonates underwent significantly higher radiographs when compared with VLBW neonates; 7.5(5–13.25) vs. 2(1–6); p < 0.0001. ELBW neonates received 3 times higher dose of radiation, when compared with VLBW neonates; 139.4 μsv (81.6–256.15) vs. 46.6 μsv (14.4–115.7); p < 0.0001. Seven percent of ELBW neonates received >1msv radiation. Lifetime risk associated with high radiation exposure during neonatal period is unknown. Every effort should be taken to reduce number of radiographs. Imaging modalities without radiation exposure such as, point of care ultrasound should be used wherever possible.


title: The Role of Networks in Racial Disparities in HIV Incidence Among Men Who Have Sex with Men in the United States

text: Network factors have been proposed as potential drivers of racial disparities in HIV among Black and Latino men who have sex with men (MSM). This review aimed to synthesize the extant literature on networks and racial disparities in HIV among MSM and identify potential directions for future research. We searched databases for peer-reviewed articles published between January 1, 2008 and July 1, 2018. Articles were included if the sample was comprised primarily of racial/ethnic minority MSM and measured one or more network characteristics. (n = 25). HIV prevalence in networks, social support, and structural barriers were linked to disparities in HIV for Black MSM. Future research should focus on intervention development around social support and other strategies for risk reduction within networks. Given the contribution of structural factors to racial/ethnic HIV disparities, network-level interventions should be paired with policies that improve access to housing, jobs, and education for MSM.


title: Characterization of the highly immunogenic VP2 protrusion domain as a diagnostic antigen for members of Birnaviridae family

text: Birnaviridae is a family of viruses (birnaviruses) which consists of four genera, members of which cause diseases in fish, birds, mollusks, and insects. The genome of birnaviruses encodes the highly immunogenic VP2 capsid protein. In order to demonstrate that the VP2 protein can be exploited as a diagnostic antigen for birnaviruses, we developed a lateral flow assay based on the surface-exposed VP2 protrusion domain of a representative birnavirus, infectious bursal disease virus (IBDV) of serotype 1 which causes the highly devastating infectious bursal disease in chickens. The biophysical characterization of the purified domain reveals that the domain predominantly consists of β-sheets, exists in a trimeric form, and remains folded at high temperatures, making it suitable for diagnostic purposes. Owing to its highly immunogenic nature and excellent biophysical properties, we employed the VP2 protrusion domain in a gold nanoparticle-based lateral flow assay for rapid detection of anti-IBDV antibodies in serum samples of infected chickens. Our results indicate that the domain binds anti-IBDV antibodies with high specificity during laboratory testing and on-site testing. The lateral flow assay reported here yields comparable results in a qualitative manner as obtained through a commercial enzyme-linked immunosorbent assay (ELISA). As VP2 is a common capsid protein of birnaviruses, the lateral flow assay can be generalized for other birnaviruses, and members of Tetraviridae and Nodaviridae families which contain homologous VP2 capsid proteins. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00253-020-10458-6) contains supplementary material, which is available to authorized users.


title: Whole-Transcriptome Analysis of Dermal Fibroblasts, Derived from Three Pairs of Monozygotic Twins, Discordant for Parkinson’s Disease

text: Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. In most cases, the development of the disease is sporadic and is not associated with any currently known mutations associated with PD. It is believed that changes associated with the epigenetic regulation of gene expression may play an important role in the pathogenesis of this disease. The study of individuals with an almost identical genetic background, such as monozygotic twins, is one of the best approaches to the analysis of such changes. A whole-transcriptome analysis of dermal fibroblasts obtained from three pairs of monozygotic twins discordant for PD was carried out in this work. Twenty-nine differentially expressed genes were identified in the three pairs of twins. These genes were included in seven processes within two clusters, according to the results of an enrichment analysis. The cluster with the greatest statistical significance included processes associated with the regulation of the differentiation of fat cells, the action potential, and the regulation of glutamatergic synaptic transmission. The most significant genes, which occupied a central position in this cluster, were PTGS2, SCN9A, and GRIK2. These genes can be considered as potential candidate genes for PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12031-019-01452-3) contains supplementary material, which is available to authorized users.


title: Current understanding of the therapeutic benefits of mesenchymal stem cells in acute respiratory distress syndrome

text: The acute respiratory distress syndrome (ARDS) is a multifaceted lung disorder in which no specific therapeutic intervention is able to effectively improve clinical outcomes. Despite an improved understanding of molecular mechanisms and advances in supportive care strategies, ARDS remains associated with high mortality, and survivors usually face long-term morbidity. In recent years, preclinical studies have provided mounting evidence of the potential of mesenchymal stem cell (MSC)-based therapies in lung diseases and critical illnesses. In several models of ARDS, MSCs have been demonstrated to induce anti-inflammatory and anti-apoptotic effects, improve epithelial and endothelial cell recovery, and enhance microbial and alveolar fluid clearance, thus resulting in improved lung and distal organ function and survival. Early-stage clinical trials have also demonstrated the safety of MSC administration in patients with ARDS, but further, large-scale investigations are required to assess the safety and efficacy profile of these therapies. In this review, we summarize the main mechanisms whereby MSCs have been shown to exert therapeutic effects in experimental ARDS. We also highlight questions that need to be further elucidated and barriers that must be overcome in order to efficiently translate MSC research into clinical practice.


title: Impact of Sleep Deprivation in the Neurological Intensive Care Unit: A Narrative Review

text: Sleep is fundamental for everyday functioning, yet it is often negatively impacted in critically ill patients by the intensive care setting. With a focus on the neurological intensive care unit (NeuroICU), this narrative review summarizes methods of measuring sleep and addresses common causes of sleep disturbance in the hospital including environmental, pharmacological, and patient-related factors. The effects of sleep deprivation on the cardiovascular, pulmonary, immune, endocrine, and neuropsychological systems are discussed, with a focus on short-term deprivation in critically ill populations. Where evidence is lacking in the literature, long-term sleep deprivation studies and the effects of sleep deprivation in healthy individuals are also referenced. Lastly, strategies for the promotion of sleep in the NeuroICU are presented.


title: Neurological Manifestations of Influenza A (H1N1): Clinical Features, Intensive Care Needs, and Outcome

text: OBJECTIVES: To describe neurological manifestations in children with Influenza A (H1N1). METHODS: This retrospective study was conducted in the Pediatric intensive care unit (PICU) and Pediatric Neurology unit of a tertiary care teaching hospital in North India involving children with PCR confirmed Influenza A (H1N1) with neurological manifestations during 2019 outbreak. RESULTS: Six children (5 females, 1 male) were enrolled. All presented with neurological symptoms (seizures and altered sensorium) accompanied with fever and respiratory symptoms with duration of illness of 2–7 d. The admission Glasgow Coma Scale ranged from 4 to 12. Only 2 cases showed cerebrospinal fluid pleocytosis. Neuroimaging was suggestive of diffuse cerebral edema, acute necrotizing encephalopathy of childhood, and acute disseminated encephalomyelitis. All were treated with Oseltamivir. Four cases had clinical features of raised intracranial pressure (ICP) and were managed in PICU, 3 of them needed mechanical ventilation, 3 needed vasoactive drugs, 3 received 3% saline infusion, 1 underwent invasive ICP monitoring, and 3 (cases 4, 5 and 6) received intravenous methylprednisolone (30 mg/kg) for 5 d. Total duration of hospital stay was 10–30 d. Case 2 expired due to refractory raised ICP. Among survivors, 3 children had residual neurological deficits and the remaining 2 had achieved premorbid condition. CONCLUSIONS: Influenza A (H1N1) can present with isolated or predominant neurological manifestations which can contribute to poor outcome. The authors suggest to rule out H1N1 in any child who presents with unexplained neurological manifestations during seasonal outbreaks of H1N1.


title: Semi-quantitative cultures of throat and rectal swabs are efficient tests to predict ESBL-Enterobacterales ventilator-associated pneumonia in mechanically ventilated ESBL carriers

text: PURPOSE: In ICU patients with carriage of extended spectrum beta-lactamase producing Enterobacterales (ESBL-E) and suspected Gram-negative bacilli ventilator-associated pneumonia (GNB-VAP), the quantification of the rectal and throat ESBL-E carriage might predict the ESBL-E involvement in GNB-VAP. Our aim was to evaluate whether a semi-quantitative assessment of rectal/throat ESBL-E carriage can predict ESBL-E-associated VAP in medical ICU patients. METHODS: From May 2014 to May 2017, all ESBL-E carriers had a semi-quantitative assessment of ESBL-E density in swabs cultures. For those who developed GNB-VAP (diagnosed using bronchoalveolar lavage or plugged telescopic catheter with significant quantitative culture), the last positive swab collected at least 48 h before GNB-VAP onset was selected. Clinical data were extracted from a prospectively collected database. RESULTS: Among 365 ESBL-E carriers, 82 developed 107 episodes of GNB-VAP (ESBL-E VAP, n = 50; and non-ESBL-E GNB-VAP, n = 57) after 13 days of mechanical ventilation in median. Antimicrobials use before VAP onset was similar between groups. The last swabs were collected 5 days in median before VAP onset. ESBL-E. coli carriers developed ESBL-E VAP less frequently (n = 13, 34%) than others (n = 32, 67.3%, p < .01). Throat swab positivity (39 (78%) vs. 12 (23%), p < .01) was more frequent for ESBL-E VAP. ESBL-E VAP was associated with significantly higher ESBL-E density in rectal swabs. In multivariate models, non-E. coli ESBL-E carriage and rectal ESBL-E carriage density, or throat carriage, remained associated with ESBL-E VAP. CONCLUSION: In carriers of ESBL-E other than E. coli, ESBL-E throat carriage or a high-density ESBL-E rectal carriage are risk factors of ESBL-E VAP in case of GNB-VAP. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00134-020-06029-y) contains supplementary material, which is available to authorized users.


title: Prolonged Outbreak of Candida krusei Candidemia in Paediatric Ward of Tertiary Care Hospital

text: BACKGROUND: A sudden rise of Candida krusei candidemia cases was noticed in our hospital within 1 year with maximum cases from paediatric unit. The present study reports the results of epidemiological investigation of possible outbreak of candidemia by C. krusei in paediatric unit at our tertiary care centre. METHODS: Clinical characteristics and risk factors associated with C. krusei candidemia were evaluated. Yeast identification and antifungal susceptibility testing was performed according to standard protocol. To find the potential source of C. krusei in hospital environment and hand colonization, swabs were collected from different fomites (n = 40) and hand washings from 24 health care workers (HCW), respectively. Infection control and prevention practices were intensified following the recognition of outbreak. Genetic typing was done by fluorescent amplified fragment length polymorphism (FAFLP) technique. Case–control comparison was performed with C. tropicalis and C. pelliculosa cases. RESULTS: Candida krusei fungaemia significantly affected paediatric group (82/186, 44%) as compared to adults (14/130, 10.8%; p < 0.001). Among paediatric group, maximum isolation was reported from neonatal unit of paediatric emergency (NUPE). C. krusei was isolated from hands of one HCW and washbasin in NUPE. FAFLP revealed clonality between blood and environmental isolates indicating cross-transmission of C. krusei. Gastrointestinal disease (p = 0.018), previous antibiotics (p = 0.021) especially to carbapenems (p = 0.039), was significant among C. krusei candidemia cases compared to C. pelliculosa cases. CONCLUSION: We report the largest outbreak of C. krusei candidemia in paediatric unit within 1 year with isolation of related strains from environment and hands of HCW. Routine screening of hand hygiene practices revealed non-compliance to standard practices leading to the increase in C. krusei candidemia cases.


title: Recombination Between High-Risk Human Papillomaviruses and Non-Human Primate Papillomaviruses: Evidence of Ancient Host Switching Among Alphapapillomaviruses

text: We use all the currently known 405 Papillomavirus (PV) sequences, 343 curated PV sequences from both humans and animals from the PAVE data base, to analyse the recombination dynamics of these viruses at the whole genome levels. After showing some evidence of human and non-human primate PV recombination, we report a comprehensive recombination analysis of all currently known 82 Alphapapillomaviruses (Alpha-PVs). We carried out an exploratory study and found novel recombination events between High-Risk HPV Types and Macaca fascicularis PV1 (MfPV1), Macaca Fuscata PV2 (MfuPV2) and Pan Paniscus PV1 (PpPV1) Papillomaviruses. This is the first evidence of interactions between PVs from different hosts and hence postulates the likelihood of ancient host switching among Alpha-PVs. Notwithstanding these results should be interpreted with caution because the major and minor parents indicated by RDP4 program are simply the sequences in the alignment that most closely resemble the actual parents. We found statistically significant differences between the phylogenies of the PV sequences with recombination regions and PV sequences without recombination regions using the Shimodaira–Hasegawa phylogenetic incongruence testing. We show that not more than 76MYA Alpha-PVs were in the same biological niche, a pre-requisite for recombination, and as the hosts evolved and diversified, the viruses adapted to specific host niches which eventually led to coevolution with specific hosts before speciation of primate species. Thus providing evidence that in ancient times no earlier than the Cretaceous period of the Mesozoic age, Alpha-PVs recombined and switched hosts, but whether this host switching is occurring currently is unknown. However, a clearer picture of the PVs evolutionary landscape can only be achieved with the incremental discovery of PV sequences, especially from the animal kingdom. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00239-020-09946-0) contains supplementary material, which is available to authorized users.


title: Junctional and somatic hypermutation-induced CX(4)C motif is critical for the recognition of a highly conserved epitope on HCV E2 by a human broadly neutralizing antibody

text: Induction of broadly neutralizing monoclonal antibodies (bNAbs) that bind to the viral envelope glycoproteins is a major goal of hepatitis C virus (HCV) vaccine research. The study of bNAbs arising in natural infection is essential in this endeavor. We generated a human antibody, 8D6, recognizing the E2 protein of HCV isolated from a chronic hepatitis C patient. This antibody shows broadly neutralizing activity, which covers a pan-genotypic panel of cell culture-derived HCV virions (HCVcc). Functional and epitope analyses demonstrated that 8D6 can block the interaction between E2 and CD81 by targeting a highly conserved epitope on E2. We describe how the 8D6 lineage evolved via somatic hypermutation to achieve broad neutralization. We found that the V(D)J recombination-generated junctional and somatic hypermutation-induced disulfide bridge (C-C) motif in the CDRH3 is critical for the broad neutralization and binding activity of 8D6. This motif is conserved among a series of broadly neutralizing HCV antibodies, indicating a common binding model. Next, the 8D6 inferred germline (iGL) was reconstructed and tested for its binding affinity and neutralization activity. Interestingly, 8D6 iGL-mediated relatively strong inhibition of the 1b genotype PR79L9 strain, suggesting that PR79L9 may serve as a potential natural viral strain that provides E2 sequences that induce bNAbs. Overall, our detailed epitope mapping and genetic studies of the HCV E2-specific mAb 8D6 have allowed for further refinement of antigenic sites on E2 and reveal a new mechanism to generate a functional CDRH3, while its iGL can serve as a probe to identify potential HCV vaccine strains.


title: Developing metrics for nursing quality of care for low- and middle-income countries: a scoping review linked to stakeholder engagement

text: BACKGROUND: The use of appropriate and relevant nurse-sensitive indicators provides an opportunity to demonstrate the unique contributions of nurses to patient outcomes. The aim of this work was to develop relevant metrics to assess the quality of nursing care in low- and middle-income countries (LMICs) where they are scarce. MAIN BODY: We conducted a scoping review using EMBASE, CINAHL and MEDLINE databases of studies published in English focused on quality nursing care and with identified measurement methods. Indicators identified were reviewed by a diverse panel of nursing stakeholders in Kenya to develop a contextually appropriate set of nurse-sensitive indicators for Kenyan hospitals specific to the five major inpatient disciplines. We extracted data on study characteristics, nursing indicators reported, location and the tools used. A total of 23 articles quantifying the quality of nursing care services met the inclusion criteria. All studies identified were from high-income countries. Pooled together, 159 indicators were reported in the reviewed studies with 25 identified as the most commonly reported. Through the stakeholder consultative process, 52 nurse-sensitive indicators were recommended for Kenyan hospitals. CONCLUSIONS: Although nurse-sensitive indicators are increasingly used in high-income countries to improve quality of care, there is a wide heterogeneity in the way indicators are defined and interpreted. Whilst some indicators were regarded as useful by a Kenyan expert panel, contextual differences prompted them to recommend additional new indicators to improve the evaluations of nursing care provision in Kenyan hospitals and potentially similar LMIC settings. Taken forward through implementation, refinement and adaptation, the proposed indicators could be more standardised and may provide a common base to establish national or regional professional learning networks with the common goal of achieving high-quality care through quality improvement and learning.


title: Proteomic analysis revealed T cell hyporesponsiveness induced by Haemonchus contortus excretory and secretory proteins

text: Haemonchus contortus has evolved highly integrated and sophisticated mechanisms to promote coexistence with hosts. The excretory-secretory (ES) products generated by this parasite contribute to the regulation of the host immune response to facilitate immune evasion and induce chronicity, but the proteins responsible for this process and the exact cellular mechanisms have yet to be defined. In this study, we identified 114 H. contortus ES proteins (HcESPs) interacting with host T cells and 15 T cell binding receptors via co-immunoprecipitation and shotgun liquid chromatography-tandem mass spectrometry analysis. Based on bioinformatics analysis, we demonstrated that HcESPs could inhibit T cell viability, induce cell apoptosis, suppress T cell proliferation and cause cell cycle arrest. Furthermore, the stimulation of HcESPs exerted critical control effects on T cell cytokine production profiles, predominantly promoting the secretion of interleukin (IL)-10, IL-17A and transforming growth factor-β1 and inhibiting IL-2, IL-4 and interferon-γ production. Collectively, these findings may provide insights into the interaction between ES proteins and key host effector cells, enhancing our understanding of the molecular mechanism underlying parasite immune evasion and providing new clues for novel vaccine development.


title: Clinical application and evaluation of metagenomic next-generation sequencing in suspected adult central nervous system infection

text: BACKGROUND: Accurate etiology diagnosis is crucial for central nervous system infections (CNS infections). The diagnostic value of metagenomic next-generation sequencing (mNGS), an emerging powerful platform, remains to be studied in CNS infections. METHODS: We conducted a single-center prospective cohort study to compare mNGS with conventional methods including culture, smear and etc. 248 suspected CNS infectious patients were enrolled and clinical data were recorded. RESULTS: mNGS reported a 90.00% (9/10) sensitivity in culture-positive patients without empirical treatment and 66.67% (6/9) in empirically-treated patients. Detected an extra of 48 bacteria and fungi in culture-negative patients, mNGS provided a higher detection rate compared to culture in patients with (34.45% vs. 7.56%, McNemar test, p < 0.0083) or without empirical therapy (50.00% vs. 25.00%, McNemar test, p > 0.0083). Compared to conventional methods, positive percent agreement and negative percent agreement was 75.00% and 69.11% separately. mNGS detection rate was significantly higher in patients with cerebrospinal fluid (CSF) WBC > 300 * 10(6)/L, CSF protein > 500 mg/L or glucose ratio ≤ 0.3. mNGS sequencing read is correlated with CSF WBC, glucose ratio levels and clinical disease progression. CONCLUSION: mNGS showed a satisfying diagnostic performance in CNS infections and had an overall superior detection rate to culture. mNGS may held diagnostic advantages especially in empirically treated patients. CSF laboratory results were statistically relevant to mNGS detection rate, and mNGS could dynamically monitor disease progression.


title: Improving transitions in care for children with complex and medically fragile needs: a mixed methods study

text: BACKGROUND: Children with medical complexity are a small yet resource intensive population in the Canadian health care system. The process for discharging these children from hospital to home is not yet optimal. The overall goal of this project was to develop recommendations to be included in a provincial strategy to support transitions in care for children with complex and medically fragile needs. METHODS: A wide assortment of stakeholders participated in this mixed method, multiphase project. During Phase 1, data was gathered from a range of sources to document families’ experiences transitioning from an inpatient hospital stay back to their home communities. In Phase 2, pediatricians, nurses, and health administrators participated in key stakeholder interviews to identify barriers and facilitators to a successful transition in care for children and families with complex care needs. A multi-sector consensus meeting was held during Phase 3 to discuss study findings and refine key recommendations for inclusion in a provincial strategy. RESULTS: Six case studies were developed involving children and families discharged home with a variety of complex care needs. Children ranged in age from 15 days to 9 years old. Nine telephone interviews were conducted in Phase 2 with pediatricians, nurses, and administrators from across the province. A variety of inter-institutional communication challenges were described as a major barrier to the transition process. A consistent message across all interviews was the need for improved coordination to facilitate transitions in care. The consensus meeting to review study findings included physicians, nurses, paramedics, senior administrators, and policy analysts from different health and government sectors and resulted in six recommendations for inclusion in a provincial strategy. CONCLUSIONS: This project identified policy and practice gaps that currently exist related to transitions in care for children with complex and medically fragile needs and their families. Our collaborative patient-centred approach to understanding how children and families currently navigate transitions in care provided a foundation for developing recommendations for a provincial wide strategy.


title: Chlamydia psittaci Triggers the Invasion of H9N2 Avian Influenza Virus by Impairing the Functions of Chicken Macrophages

text: SIMPLE SUMMARY: Chlamydia psittaci, an obligate, intracellular, Gram-negative bacterium and economically relevant pathogen in poultry and pet bird, could cause psittacosis/ornithosis, and is also a human pathogen causing atypical pneumonia after zoonotic transmission. H9N2 influenza virus, a low pathogenic avian influenza viruses’ subtype, has become endemic in different types of domestic poultry in lots of countries, resulting in great economic loss due to reduced egg production or high mortality associated with coinfection with other pathogens. These two pathogens are easily mixed with other pathogens to aggravate the disease, and often cause mixed infection in clinics. Co-infection of C. psittaci with H9N2 commonly induces severe pneumonia and high mortality in specific pathogen-free (SPF) chickens. According to previous studies, we postulated that C. psittaci infection may beneficial for the replication of H9N2 in HD11. Consequently, in this study, we clarify the pathogenic mechanism of coinfection with C. psittaci and H9N2 in the chicken macrophage cell line HD11, which is the first study of the coinfection of C. psittaci and H9N2 in vitro. ABSTRACT: In a pilot study, simultaneous infection with Chlamydia psittaci (C. psittaci) and H9N2 virus induced 20% mortality and severe avian airsacculitis, shedding light on animal models of poultry respiratory diseases. However, the pathogenesis is still unclear. In the current study, we hypothesized that C. psittaci infection execrates macrophage function and facilitates H9N2 infection. To explore the potential mechanism, we studied the effect of C. psittaci and H9N2 on the functions of HD11 cells in vitro by simultaneous infection of C. psittaci and H9N2. At the same time, we used infection with C. psittaci or H9N2 alone as the control groups. The results showed that coinfection with C. psittaci and H9N2 could significantly aggravate the mortality of HD11 cells compared to C. psittaci or H9N2 infection alone. In addition, coinfection with C. psittaci and H9N2 did not induce high C. psittaci loads compared to C. psittaci infection alone at 12- and 24-hours post-inoculation (hpi), but coinfection with C. psittaci and H9N2 could increase the loads of H9N2 compared to H9N2 alone in HD11 cells at 12 hpi. More importantly, inducible nitric oxide synthase (iNOS) expression levels, enzyme activity, nitric oxide (NO) production, and phagocytosis were reduced significantly in the group with C. psittaci and H9N2 coinfection compared to those of H9N2 or C. psittaci alone at 24 hpi. Finally, C. psittaci infection induced robust expressions of type Th2 cytokines interleukin (IL)-4 and IL-10, while interferon gamma (IFN-γ) and tumor necrosis factor-α (TNF-α) displayed a significant decrease compared to H9N2 infection alone at 24 hpi. All the above data indicate that C. psittaci infection can facilitate H9N2 invasion and to aggravate severe avian airsacculitis by impairing macrophage functions.


title: Residual Neuromuscular Blockade and Postoperative Pulmonary Complications: What Does the Recent Evidence Demonstrate?

text: PURPOSE OF REVIEW: The purpose of this review is to assess how residual neuromuscular block impacts postoperative pulmonary complications and whether we can modify the risk by improving certain aspects in daily clinical care. RECENT FINDINGS: Postoperative respiratory impairment may be due to various causes, such as age, surgery type, comorbidity, smoking, preoperative anemia, and general anesthesia. However, increasing evidence suggests that residual neuromuscular block is an important risk factor for postoperative pulmonary complications and may affect the outcome. Conflicting data from some recent reports show that the use of quantitative neuromuscular monitoring alone does not preclude residual neuromuscular block and that improvements in the interpretation of neuromuscular monitoring may be required. Pulmonary complications seem to be reduced for train-of-four ratios > 0.95 before tracheal extubation compared with > 0.9. SUMMARY: This review stresses the need for appropriate management of neuromuscular block in the prevention of postoperative pulmonary complications but acknowledges that the causes are multifactorial.


title: Critical Issues in Leadership Development for Peer Support Specialists

text: This paper is a qualitative analysis of perspectives on leadership development among working peer support specialists and highlights the challenges, needs and efficacy these individuals experience in their work settings. Six participants engaged in a 2 h semi-structured focus group. Participants were guided through a series of nine questions regarding their transition to leadership, professional communication and relationships. Seven themes emerged: managing dual relationships; having difficult conversations; push and pull of leadership; taking responsibility for others; taking responsibility for self-care; addressing stigma in the workplace, and, spirituality/a calling to help. These professionals integrate their personal experiences of recovery into their direct care and leadership approaches in the workplace. This blending of recovery concepts and supervision approaches reflect some of the powerful elements that peer recovery specialists are uniquely qualified to lead in the healthcare workforce. These findings provide important implications for leadership development among this growing segment of the healthcare workforce.


title: Hypersensitivity Reactions to Biologicals: from Bench to Bedside

text: PURPOSE OF REVIEW: Biologic agents are new treatment options for chronic inflammatory diseases and cancers. As a result of their unique mechanism of action, they are more effective and less toxic treatment option and their clinical usage is increasing. While they are more commonly used, various adverse effects have been observed including life-threatening ones, including anaphylaxis. The aim of this review is to distinguish the anaphylaxis from other hypersensitivity reactions (HSR) and provide a management algorithm for the anaphylactic reactions induced by biological agents. RECENT FINDINGS: Many case reports and series have been published regarding anaphylaxis and other hypersensitivity reactions (concerning cytokine release syndrome, acute infusion–related reactions) due to biologic agents. Although acute treatment of HSR varies according to the clinical presentation, desensitization with the drug is the major management option for subsequent administrations in the case of anaphylactic reactions. SUMMARY: Anaphylaxis and other immediate onset hypersensitivity reactions are occasionally difficult to differentiate from each other, and mixed-type reactions may be observed. Immediate management of anaphylaxis includes discontinuation of infusion, immediate administration of adrenaline, antihistamines, corticosteroids, and other treatment options depending on the symptoms. After 30–120 min of the reaction, a blood sample for serum tryptase levels should be obtained and after 4–6 weeks skin testing with the culprit drug should be performed for decision of long-term management via either graded challenge or desensitization.


title: Occupational traumatic injuries rarely affect genitourinary organs: a retrospective, comparative study

text: PURPOSE: To determine the mechanisms of injury associated with occupational injuries (OI) to genitourinary (GU) organs and compare GU OIs with GU non-OIs. METHODS: A single institution, retrospective study was conducted at a level 1 trauma center between 2010 and 2016 of all patients with GU injuries. OI was defined as any traumatic event that occurred in the workplace requiring hospital admission. Types of occupations were recorded in addition to the location of injury, mechanisms of injury, concomitant injuries, operative interventions, total cost, and mortality. GU OI patients were then compared to GU non-OI patients. RESULTS: 623 patients suffered a GU injury, of which 39 (6.3%) had a GU OI. Fall (43%) was the most common mechanism of injury; followed by motor vehicle collision/motorcycle crash (31%), crush injury (18%), and pedestrian struck (8%). The adrenal gland (38%) and kidney (38%) were the most commonly injured organs. There was no difference in mortality (13% GU OI vs. 15% GU non-OI, p = 0.70) or total direct cost ($21,192 ± 28,543 GU OI vs. $28,215 ± 32,332 GU non-OI, p = 0.45). Total costs were decreased with mortality from a GU injury (odds ratio (OR) 0.3, CI 0.26–0.59; p = < 0.001) and increased with higher injury severity scores (OR 1.1, CI 1.09–1.2; p = < 0.0001). Total costs were not affected by OI status. CONCLUSIONS: Occupational GU trauma presents with similar patterns of injury, hospital course, and direct cost as GU trauma that occurs in non-occupational settings.


title: Development of a Hospital Medical Surge Preparedness Index using a national hospital survey

text: To generate a Hospital Medical Surge Preparedness Index that can be used to evaluate hospitals across the United States in regard to their capacity to handle patient surges during mass casualty events. Data from the American Hospital Association’s annual survey, conducted from 2005 to 2014. Our sample comprised 6239 hospitals across all 50 states, with an annual average of 5769 admissions. An extensive review of the American Hospital Association survey was conducted and relevant variables applicable to hospital inpatient services were extracted. Subject matter experts then categorized these items according to the following subdomains of the “Science of Surge” construct: staff, supplies, space, and system. The variables within these categories were then analyzed through exploratory and confirmatory factor analyses, concluding with the evaluation of internal reliability. Based on the combined results, we generated individual (by hospital) scores for each of the four metrics and an overall score. The exploratory factor analysis indicated a clustering of variables consistent with the “Science of Surge” subdomains, and this finding was in agreement with the statistics generated through the confirmatory factor analysis. We also found high internal reliability coefficients, with Cronbach’s alpha values for all constructs exceeding 0.9. A novel Hospital Medical Surge Preparedness Index linked to hospital metrics has been developed to assess a health care facility’s capacity to manage patients from mass casualty events. This index could be used by hospitals and emergency management planners to assess a facility’s readiness to provide care during disasters.


title: Nonoperative treatment of traumatic spinal injuries in Tanzania: who is not undergoing surgery and why?

text: STUDY DESIGN: Retrospective, cohort study of a prospectively collected database. OBJECTIVES: In a cohort of patients with traumatic spine injury (TSI) in Tanzania who did not undergo surgery, we sought to: (1) describe this nonoperative population, (2) compare outcomes to operative patients, and (3) determine predictors of nonoperative treatment. SETTING: Tertiary referral hospital. METHODS: All patients admitted for TSI over a 33-month period were reviewed. Variables included demographics, fracture morphology, neurologic exam, indication for surgery, length of hospitalization, and mortality. Regression analyses were used to report outcomes and predictors of nonoperative treatment. RESULTS: 270 patients met inclusion criteria, of which 145 were managed nonoperatively. Demographics between groups were similar. The nonoperative group was young (mean = 35.5 years) and primarily male (n = 125, 86%). Nonoperative patients had 7.39 times the odds of death (p = 0.003). Patients with AO type A0/1/2/3 fractures (p < 0.001), ASIA E exams (p = 0.016), cervical spine injuries (p = 0.005), and central cord syndrome (p = 0.016) were more commonly managed nonoperatively. One hundred and twenty-four patients (86%) had indications for but did not undergo surgery. After multivariate analysis, the only predictor of nonoperative management was sustaining a cervical injury (p < 0.001). CONCLUSIONS: Eighty-six percent of nonoperative TSI patients had an indication for surgery. Nonoperative management was associated with an increased risk of mortality. Cervical injury was the single independent risk factor for not undergoing surgery. The principle reason for nonoperative management was cost of implants. While a causal relationship between nonoperative management and inferior outcomes cannot be made, efforts should be made to provide surgery when indicated, regardless of a patient’s ability to pay.


title: Diagnosis and Management of Tuberculous Pericarditis: What Is New?

text: PURPOSE OF REVIEW: This review provides an update on the immunopathogenesis of tuberculous pericarditis (TBP), investigations to confirm tuberculous etiology, the limitations of anti-tuberculous therapy (ATT), and recent efficacy trials. RECENT FINDINGS: A profibrotic immune response characterizes TBP, with low levels of AcSDKP, high levels of γ-interferon and IL-10 in the pericardium, and high levels of TGF-β and IL-10 in the blood. These findings may have implications for future therapeutic targets. Despite advances in nucleic acid amplification approaches, these tests remain disappointing for TBP. Trials of corticosteroids and colchicine have had mixed results, with no impact on mortality, evidence of a reduction in rates of constrictive pericarditis and potential harm in those with advanced HIV. Small studies suggest that ATT penetrates the pericardium poorly. Given that there is a close association between high bacillary burden and mortality, a rethink about the optimal drug doses and duration may be required. SUMMARY: The high mortality and morbidity from TBP despite use of anti-tuberculous drugs call for researches targeting host-directed immunological determinants of treatment outcome. There is also a need for the identification of steps in clinical management where interventions are needed to improve outcomes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11886-020-1254-1) contains supplementary material, which is available to authorized users.


title: Transthyretin at Admission and Over Time as a Marker for Clinical Outcomes in Critically Ill Trauma Patients: A Prospective Single-Center Study

text: BACKGROUND: Transthyretin (TTR) has been described as a predictor for outcomes in medical and surgical patients. However, the association of TTR on admission and over time on outcomes has not yet been prospectively assessed in trauma patients. METHODS: This is a prospective observational study including trauma patients admitted to the intensive care unit (ICU) of a large Level I trauma center 05/2014–05/2015. TTR levels at ICU admission and all subsequent values over time were recorded. Patients were observed for 28 days or until hospital discharge. The association of outcomes and TTR levels at admission and over time was assessed using multivariable regression and generalized estimating equation (GEE) analysis, respectively. RESULTS: A total of 237 patients with TTR obtained at admission were included, 69 of whom had repeated TTR measurements. Median age was 40.0 years and median ISS 16.0; 83.1% were male. Below-normal TTR levels at admission (41.8%) were independently associated with higher in-hospital mortality (p = 0.042), more infectious complications (p = 0.032), longer total hospital length of stay (LOS) (p = 0.013), and ICU LOS (p = 0.041). Higher TTR levels over time were independently associated with lower in-hospital mortality (p = 0.015), fewer infections complications (p = 0.028), shorter total hospital and ICU LOS (both p < 0.001), and fewer ventilator days (0.004). CONCLUSIONS: In critically ill trauma patients, below-normal TTR levels at admission were independently associated with worse outcomes and higher TTR levels over time with better outcomes, including lower in-hospital mortality, less infectious complications, shorter total hospital and ICU LOS, and fewer ventilator days. Based on these results, TTR may be considered as a prognostic marker in this patient population.


title: Guidelines to the Practice of Anesthesia – Revised Edition 2020

text: The Guidelines to the Practice of Anesthesia Revised Edition 2020 (the Guidelines) were prepared by the Canadian Anesthesiologists’ Society (CAS), which reserves the right to determine their publication and distribution. The Guidelines are subject to revision and updated versions are published annually. The Guidelines to the Practice of Anesthesia Revised Edition 2020 supersedes all previously published versions of this document. Although the CAS encourages Canadian anesthesiologists to adhere to its practice guidelines to ensure high-quality patient care, the CAS cannot guarantee any specific patient outcome. Anesthesiologists should exercise their own professional judgement in determining the proper course of action for any patient’s circumstances. The CAS assumes no responsibility or liability for any error or omission arising from the use of any information contained in its Guidelines to the Practice of Anesthesia. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12630-019-01507-4) contains supplementary material, which is available to authorized users.


title: Continuous feeding versus intermittent bolus feeding for premature infants with low birth weight: a meta-analysis of randomized controlled trials

text: BACKGROUND/OBJECTIVES: Clinical risks and advantages of both continuous feeding and intermittent feeding for preterm infants have been presented in previous studies. To determine the most appropriate feeding method for low-birth-weight infants, a meta-analysis was conducted. SUBJECTS/METHODS: Articles related to this topic were searched in PubMed, EMBASE, and Cochrane Library electronic database from the onset to May 2019. Heterogeneity analysis was performed with Chi-square and I(2) test. Pooled analysis was based on fixed effects model, if heterogeneity between the eligible studies was negligible (I(2) < 50%, P > 0.05). In contrast, a random effects model was carried out. The quality of including studies were evaluated by Cochrane assessment tool. RESULTS: A total of 1030 articles identified. Altogether, eight articles including 707 infants were included in final analysis based on eligibility criteria. In continuous feeding infants, time to achieving full feeds was longer (weight mean difference 0.98 (95% CI 0.26–1.71, P = 0.008) days) compared with intermittent feeding infants. Pooled analysis indicated there were no significant difference in other variables such as feeding intolerance, duration of hospitalization, days to regain birth weight, days to first successful oral feeding, duration of parenteral feeding, weight growth, length increment, head circumference growth, proven necrotizing enterocolitis, and probable necrotizing enterocolitis. In subgroup analysis for birth weight (<1000 g and >1000 g), we did not identify significant difference in time to full feeds, time to regain birth weight, and duration of hospitalization. CONCLUSIONS: Intermittent feeding may be more beneficial for low-birth weight infants, However, well-designed studies and evidenced-based clinical practice are required to determine the most appropriate feeding method for premature infants with low birth weight.


title: Who’s Your Enemy?: Incorporating Stories of Trauma into a Medical Humanities Course

text: This article discusses the theoretical and practical experiment of creating, promoting and co-teaching a medical humanities course: Medicine, War and the Arts at a School of Medicine in the United States from the viewpoint of the students who took the class. Specifically, it analyses how three themes emerged in students’ responses to the oral, literary and visual stories of war and trauma in the course and how they revealed the subjective and ambivalent nature of all medical encounters with patients. The conclusion is that actively encouraging students to view the role of the physician through the lens of historical and contemporary trauma enables them to contemplate the difficult question, “Who’s Your Enemy?” when caring for the sick and themselves.


title: Noninvasive ventilation for pediatric interfacility transports: a retrospective study

text: BACKGROUND: To characterize pediatric patients supported with continuous positive airway pressure and bilevel positive airway pressure (CPAP/BiPAP) or high-flow nasal cannula (HFNC) during interfacility transport (IFT). METHODS: A retrospective study with a provincial pediatric transport team from a tertiary hospital pediatric intensive care unit. Pediatric patients aged 28 days to < 17 years, who required IFT between January 2017 and December 2018, were identified through a transport registry and were included in the study. RESULTS: A total of 118 (26.7%) patients received CPAP/BIPAP or HFNC support for IFT. The most common respiratory diagnosis was bronchiolitis (46%). These patients were placed on respiratory support, 31.4 minutes after the transport team’s arrival. None required intubation during their IFT, despite mean transport times of 163 minutes. CONCLUSIONS: This study may provide important information for programs with large catchment areas, in which large distances and transport times should not be barriers to NIV implementation.