title: Panic prescribing has become omnipresent during the COVID-19 pandemic.

text: Lessons from the Ebola outbreak shows that it is possible to develop rapid and effective clinical research responses without relying on anecdote.


Acute Kidney Injury Related to Sepsis-Reply.


title: Novel human-derived extracellular matrix induces in vitro and in vivo vascularization and inhibits fibrosis.

text: The inability to vascularize engineered organs and revascularize areas of infarction has been a major roadblock to delivering successful regenerative medicine therapies to the clinic. These investigations detail an isolated human extracellular matrix derived from the placenta (hPM) that induces vasculogenesis in vitro and angiogenesis in vivo within bioengineered tissues, with significant immune reductive properties. Compositional analysis showed ECM components (fibrinogen, laminin), angiogenic cytokines (angiogenin, FGF), and immune-related cytokines (annexins, DEFA1) in near physiological ratios. Gene expression profiles of endothelial cells seeded onto the matrix displayed upregulation of angiogenic genes (TGFB1, VEGFA), remodeling genes (MMP9, LAMA5) and vascular development genes (HAND2, LECT1). Angiogenic networks displayed a time dependent stability in comparison to current in vitro approaches that degrade rapidly. In vivo, matrix-dosed bioscaffolds showed enhanced angiogenesis and significantly reduced fibrosis in comparison to current angiogenic biomaterials. Implementation of this human placenta derived extracellular matrix provides an alternative to Matrigel and, due to its human derivation, its development may have significant clinical applications leading to advances in therapeutic angiogenesis techniques and tissue engineering.


title: Interventions to reduce cognitive impairments following critical illness: a topical systematic review.

text: BACKGROUND Critical illness is associated with cognitive impairments. Effective treatment or prevention has not been established. The aim of this review was to create a systematic summary of the current evidence concerning clinical interventions during intensive care admission to reduce cognitive impairments after discharge. METHODS Medline, Embase, Cochrane Central, PsycInfo and Cinahl were searched. Inclusion criteria were studies assessing the effect of interventions during intensive care admission on cognitive function in adult patients. Studies were excluded if they were reviews or reported solely on survivors of cardiac arrest, stroke or traumatic brain injury. RESULTS Of 4877 records were identified. Seven studies fulfilled the eligibility criteria. The interventions described covered strategies for enteral nutrition, fluids, sedation, weaning, mobilization, cognitive activities, statins and sleep quality improvement. Data were synthesized to provide an overview of interventions, quality, follow-up assessments and neuropsychological outcomes. CONCLUSION None of the interventions had significant positive effects on cognitive impairments following critical illness. Quality was negatively affected by study limitations, imprecision and indirectness in evidence. Clinical research on cognition is feasible, but large, well designed trials with a specific aim at reducing cognitive impairments are needed.


title: Immunogenicity and protective efficacy of a replication-defective infectious bronchitis virus vaccine using an adenovirus vector and administered in ovo.

text: In ovo vaccination remains an attractive option for a cost effective, uniform and mass application of vaccines for commercial poultry. However, the vaccines which can be delivered safely by this method are limited and there is no currently licensed embryo-safe vaccine against infectious bronchitis virus (IBV). In this study, a recombinant adenovirus expressing the S1 gene of nephropathogenic IBV (rAd-S1) was constructed and the immune responses and protective efficacy against homologous challenge were evaluated after in ovo vaccination. The results showed that the rAd-S1 led to dramatic augmentation of humoral and cellular responses in birds vaccinated in ovo followed by an intramuscular inoculation. Both IFN-gamma and IL-4 in chicken's lymphocytes were produced by this strategy. Following challenge with IBV, the chickens vaccinated with recombinant adenovirus showed fewer nephropathic lesions and less severe clinical signs as compared to those receiving wild-type adenovirus or PBS. The construction of non-replicating human adenovirus vector encoding S1 gene of IBV and its in ovo delivery demonstrated the potential of an alternative vaccination strategy against IBV.


title: Ischemic outcomes after coronary intervention of calcified vessels in acute coronary syndromes. Pooled analysis from the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) and ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) TRI

text: OBJECTIVES This study sought to determine the frequency and impact of coronary calcification among patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS). BACKGROUND Small studies in patients with stable coronary artery disease have suggested a worse prognosis after PCI of calcified compared with noncalcified lesions. Little is known about the impact of coronary calcification on outcomes after PCI for patients presenting with non-ST-segment elevation and ST-segment elevation ACS. METHODS Data from 6,855 patients presenting with ACS in whom PCI was performed were pooled from 2 large-scale randomized, controlled trials, ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) and HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction). One-year outcomes were analyzed according to the severity of PCI target lesion calcification (none/mild, moderate, or severe) as assessed by an independent angiographic core laboratory. RESULTS Target lesion calcification was severe in 402 patients (5.9%), moderate in 1,788 (26.1%), and none/mild in 4,665 (68.1%). Moderate/severe target lesion calcification was more frequent in older patients, men, hypertensive patients, and those presenting with ST-segment elevation myocardial infarction (STEMI). The unadjusted 1-year rates of death, cardiac death, definite stent thrombosis, and ischemic target lesion revascularization (TLR) and target vessel revascularization were significantly increased in patients with moderate/severe target lesion calcification. By multivariable analysis, the presence of moderate/severe target lesion calcification was an independent predictor of 1-year definite stent thrombosis (hazard ratio [HR]: 1.62; 95% confidence interval [CI]: 1.14 to 2.30; p = 0.007) and ischemic TLR (HR: 1.44; 95% CI: 1.17 to 1.78; p = 0.0007). CONCLUSIONS Moderate/severe lesion calcification was relatively frequent in patients with non-ST-segment elevation ACS and STEMI and was strongly predictive of stent thrombosis and ischemic TLR at 1 year. (Comparison of Angiomax Versus Heparin in Acute Coronary Syndromes [ACS]; NCT00093158; Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966).


title: Outcome of retreatment for recurrent saccular cerebral aneurysms: a propensity score-matched analysis.

text: Although endovascular or surgical treatment has been performed for preventing the rupture of saccular cerebral aneurysms (sCA), in some patients, the aneurysms may recur and require retreatment. We aimed to investigate the clinical and radiological outcomes of treating recurrent sCA. We retrospectively evaluated the data of 52 patients with 60 recurrent sCAs who were retreated and 1534 patients with 1817 sCAs who received initial treatment. The primary outcome was a recurrence of the aneurysm. Secondary outcomes were an additional treatment, rupture after treatment, and a neurological worsening, which was defined as an increase of 1 or more scores using the modified Rankin Scale at 12-month. Safety outcomes included postoperative ischemic and hemorrhagic complications. We compiled the 120 (60 each) propensity score-matched cohort based on a propensity score for the treatment of recurrent sCA. In the propensity score-matched cohort, recurrence after treatment was observed in 25% and 6.7% of cases in the retreatment and initial treatment groups, respectively. The odds ratio of recurrence after treatment was 4.7 (95% CI, 1.4-15; P = 0.011). The secondary and safety outcomes were not significantly different between the two groups. This study showed that the treatment of recurrent sCA was a risk factor for recurrence after treatment but not for additional treatment, rupture after treatment, or neurological worsening. Although decision-making regarding the treatment varies depending on the institutional protocols and personal experience of the physicians, endovascular or surgical retreatment could be performed without hesitation.


Private water operators' contribution to realising the right to water.


title: Validation of a chemiluminescent assay for specific SARS-CoV-2 antibody.

text: Objectives Faced with the COVID-19 pandemic and its impact on the availability and quality of both therapeutic and diagnostic methods, the Belgian authorities have decided to launch a procedure for additional evaluation of the performance of serological tests offered for sale on the national territory. This has been proposed with a double aim: (1) an in-depth verification of the analytical and clinical performances presented by the manufacturer and (2) an economy of scale in terms of centralized validation for all the laboratories using the tests subject to evaluation. Methods A retrospective validation study was conducted including the serum of 125 patients in order to determine the analytical and clinical performances of the LIAISON®SARS-CoV-2 from DiaSorin® detecting anti-SARS-CoV-2 IgG and to compare its clinical performance with the enzyme-linked immunosorbent assay (ELISA) test from Euroimmun®, one of the first commercially available tests allowing the detection of anti-SARS-CoV-2 IgA and IgG. Results The performances of the LIAISON®SARS-CoV-2 satisfied all the acceptance criteria and provided "real world" analytical and clinical performances very close to the ones reported by the manufacturer in its insert kit. Comparison between the LIAISON®SARS-CoV-2 and the ELISA method did not reveal any difference between the two techniques in terms of sensitivities and specificities regarding the determination of the IgG. Conclusions This study reports the validation of the LIAISON®SARS-CoV-2 allowing to detect IgG antibodies specifically directed against SARS-CoV-2. The analytical and clinical performances are excellent, and the automation of the test offers important rates, ideal for absorbing an extension of testing.


title: Identification of phlebovirus and arenavirus RNA sequences that stall and repress the exoribonuclease XRN1.

text: Regulated mRNA decay plays a vital role in determining both the level and quality of cellular gene expression. Viral RNAs must successfully evade this host RNA decay machinery to establish a productive infection. One way for RNA viruses to accomplish this is to target the cellular exoribonuclease XRN1, because this enzyme is accessible in the cytoplasm and plays a major role in mRNA decay. Members of the Flaviviridae use RNA structures in their 5'- or 3'-untranslated regions to stall and repress XRN1, effectively stabilizing viral RNAs while also causing significant dysregulation of host cell mRNA stability. Here, we use a series of biochemical assays to demonstrate that the 3'-terminal portion of the nucleocapsid (N) mRNA of Rift Valley fever virus, a phlebovirus of the Bunyaviridae family, also can effectively stall and repress XRN1. The region responsible for impeding XRN1 includes a G-rich portion that likely forms a G-quadruplex structure. The 3'-terminal portions of ambisense-derived transcripts of multiple arenaviruses also stalled XRN1. Therefore, we conclude that RNAs from two additional families of mammalian RNA viruses stall and repress XRN1. This observation. emphasizes the importance and commonality of this viral strategy to interfere with the 5'-to-3'-exoribonuclease component of the cytoplasmic RNA decay machinery.


title: Split thickness skin grafting in canal wall down tympanomastoidectomy.

text: OBJECTIVE To characterize the effects of a split thickness skin graft (STSG) on the healing of the mastoid cavity in patients undergoing canal wall down (CWD) procedures. STUDY DESIGN A prospective randomized study. SETTING Tertiary referral center. PATIENTS Twenty-four patients, ages 21 to 82 years, with a diagnosis of cholesteatoma, undergoing CWD tympanomastoidectomy for the first time. INTERVENTION Placement of a STSG to line the mastoid cavity at the time of surgery. MAIN OUTCOME MEASURES The primary outcome was the amount of time required for epithelialization of the mastoid cavity. Secondary outcomes included postoperative complications, specifically, presence of otorrhea, granulation tissue, meatal stenosis, or tympanic membrane perforation. RESULTS Twenty-four patients met inclusion criteria. Thirteen patients were randomized to the study group and 11 patients to the control group. Data were collected at follow-up appointments scheduled at postoperative Weeks 3, 6, 9, and 12, as well as every 6 months thereafter. Average time for successful epithelialization of the cavity in the STSG group was 3.2 weeks. Average time for successful epithelialization of the control group was 6.6 weeks. Using a 1-sided 2 sample t test, this was found to be statistically significant with a p value of 0.000137. There was no significant difference in complications rates between the 2 groups. CONCLUSION Placement of a STSG is a technique available to the otologist to facilitate rapid healing and epithelialization in patients undergoing CWD tympanomastoidectomy.


title: Behaviour change interventions for the management of Raynaud's phenomenon: a systematic review protocol.

text: INTRODUCTION Raynaud's phenomenon (RP) describes excessive peripheral vasospasm to cold exposure and/or emotional stress. RP episodes are associated with digital colour changes, pain and reduced quality of life. Pharmacological interventions are of low to moderate efficacy and often result in adverse effects such as facial flushing and headaches. Recommended lifestyle and behavioural interventions have not been evaluated. The objectives of the proposed systematic review are to assess the comparative safety and efficacy of behaviour change interventions for RP and identify what we can learn to inform future interventions. METHODS AND ANALYSIS Studies eligible for inclusion include randomised controlled trials testing behaviour change interventions with a control comparator. A comprehensive search strategy will include peer review and grey literature up until 30 April 2017. Search databases will include Medline, Embase, PsychINFO and Cochrane. Initial sifting, eligibility, data extraction, risk of bias and quality assessment will be subject to review by two independent reviewers with a third reviewer resolving discrepancies. Risk of bias assessment will be performed using Cochrane risk of a bias assessment tool with quality of evidence assessed using Grading of Recommendations Assessment, Development and Evaluation(GRADE). A meta-analysis will be performed if there are sufficient data. Two subgroup analyses are planned: primary versus secondary RP outcomes; comparison of theoretically informed interventions with pragmatic interventions. ETHICS AND DISSEMINATION This review does not require ethical approval as it will summarise published studies with non-identifiable data. This protocol complies with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines. Findings will be disseminated in peer-reviewed articles and reported according to PRISMA. This review will make a significant contribution to the management of RP where no review of behaviour-change interventions currently exist. The synopsis and protocol for the proposed systematic review is registered in the International Prospective Register of Systematic Reviews (registration number CRD42017049643).


title: Storytelling and Poetry in the time of Coronavirus.

text: The Coronavirus crisis occurs at a time when many clinicians have already experienced burnout. One in three Irish doctors were suffering from burnout in the 2019 National Study of Wellbeing of Hospital Doctors in Ireland; rates are also high in Irish Psychiatry. We present a perspective on the use of Narrative in Medicine, and recognise that storytelling, and the patient history, are very much at the heart of medicine. Clinician storytelling, such as Schwartz Rounds and Balint group work, have very much come to the fore in Irish Psychiatry and in training. Projects such as Mind Reading have explored overlaps between clinicians, humanities experts and experts by experience. We give an overview of some approaches from the movement around narrative in medicine to bolster this. We explore why clinicians write- as ways to support identification, catharsis and a way to process experiences. Clinicians and patients may also use literature and poetry to promote coping. The historic context and practical strategies are highlighted, particularly with reference to Poetry use during the current crisis.


title: Performance of Two Different Pulse Oximeters in Neonatal Transition.

text: OBJECTIVE To evaluate the performance of two different pulse oximeter technologies by comparing the time taken to achieve reliable oxygen saturation readings during neonatal transition. METHODS This cross-sectional study was done to compare the performance of two pulse oximeter technologies - Signal Extraction Technology (SET), and Resistor Calibration (RCAL) technology on 150 inborn, term neonates at birth. Probes of both pulse oximeters were connected to the pre-ductal limb and the time taken to obtain a reliable reading was recorded. Sequential saturation values were recorded every minute till ten minutes of life. Statistical analysis was done with Mann-Whitney U test and intraclass correlation coefficient was calculated. RESULTS Pulse oximeter with SET recorded reliable readings faster than RCAL technology - Median (IQR) 32 (21-60)s vs. 45 (21.75-105)s, p = 0.021. There was a significant difference in the time to record first saturation readings of the two pulse oximeters when used in normal deliveries [RCAL vs. SET-Median (IQR) 50s (25-120.75) vs. 32.5s (21.75-58.25), p = 0.004] but no such difference was observed in Lower Segment Cesarean section (LSCS) [RCAL vs. SET Median (IQR) 35.5s (18.25-70.75) vs. 31s (20-69.75), p = 0.968]. Sequential saturation readings for every minute for the first 10 min of life were higher with SET vs. RCAL technology. The intraclass correlation coefficient between both pulse oximeters, for each minute, was poor (r < 0.80). CONCLUSIONS The SET pulse oximeter picked up first saturation values faster than the RCAL technology pulse oximeters. Studies are needed to evaluate effect of this on decisions made during neonatal resuscitation.


title: Single-cell landscape of bronchoalveolar immune cells in patients with COVID-19.

text: Respiratory immune characteristics associated with Coronavirus Disease 2019 (COVID-19) severity are currently unclear. We characterized bronchoalveolar lavage fluid immune cells from patients with varying severity of COVID-19 and from healthy people by using single-cell RNA sequencing. Proinflammatory monocyte-derived macrophages were abundant in the bronchoalveolar lavage fluid from patients with severe COVID-9. Moderate cases were characterized by the presence of highly clonally expanded CD8+ T cells. This atlas of the bronchoalveolar immune microenvironment suggests potential mechanisms underlying pathogenesis and recovery in COVID-19.


COVID-19 in a patient with systemic sclerosis treated with tocilizumab for SSc-ILD.


title: Feasibility and nutritional impact of laparoscopy-assisted subtotal gastrectomy for early gastric cancer in the upper stomach.

text: BACKGROUND Laparoscopy-assisted total gastrectomy (LATG) is commonly performed for early gastric cancer (EGC) in the upper stomach; however, the incidence of anastomotic complications remains high, and postoperative nutritional status is not satisfactory. This study aimed to evaluate the feasibility and nutritional impact of a novel surgical procedure, laparoscopy-assisted subtotal gastrectomy (LAsTG). METHODS This was a retrospective study of 167 patients with EGC in the upper stomach. Of these, 57 patients underwent LAsTG, while 110 patients underwent LATG. Postoperative change in body weight, and serum concentration of albumin (Alb) and total protein (TP) were compared between the LAsTG and LATG groups. Analysis of covariance (ANCOVA) was used to assess the influence of potential confounding factors. RESULTS Frequency of anastomotic complications was significantly higher in the LATG group (16.3 %) than in the LAsTG group (5.3 %, P = 0.040). Postoperative recovery of body weight at 12 months after surgery was significantly better in the LAsTG group (89.8 ± 1.4 %) than in the LATG group (82.1 ± 1.0 %, P < 0.001). By ANCOVA, adjusted mean differences of Alb and TP at 12 months after surgery between the LAsTG and LATG groups were 0.226 g/dl (95 % CI 0.141-0.312; P < 0.001) and 0.380 g/dl (95 % CI 0.265-0.495; P < 0.001); thus, the surgical procedure was significantly associated with the postoperative Alb and TP levels. CONCLUSIONS LAsTG could be a better choice than LATG for EGC in the upper stomach as a result of improvements in the incidence of anastomotic complications and postoperative nutritional status.


title: Isolation and genetic analysis of a variant porcine epidemic diarrhea virus in China.

text: Porcine epidemic diarrhea virus (PEDV) is having a severe effect on the pig breeding industry in central China. The mucosa and the content of the small intestine from newborn pre-weaned piglets with diarrhea were tested for the presence of PEDV by molecular and morphologic methods, and found to be positive. Negative-staining electron microscopy (EM) revealed the presence of coronavirus- like particles in the samples. The result of molecular detection by nested RT-PCR based on the amplification of the M gene was positive. Using a novel alternative method we successfully propagated the PEDV strain (CH/QX-2) in Vero cells, confirmed by ultrathin sections of the cells and Immunofluorescence assay (IFA). Phylogenetic analysis based on the partial S gene showed that the CH/QX-2 isolate was genetically closer to strains more commonly found in China, but differed genetically from two domestic strains (CH/S, 1986 and LZC, 2007), Korean strains (DR13, 2007), and the vaccine strain (CV777 vs) currently being used in China. CH/QX-2 formed a unique clade in the derived phylogenetic tree indicating that the CH/QX-2 strain currently circulating in central China is a new variant of PEDV. This study extends current knowledge on the diversity and epidemiology of PEDV.


Travel restrictions violate international law.


title: Winning the war against ICU-acquired weakness: new innovations in nutrition and exercise physiology.

text: Over the last 10 years we have significantly reduced hospital mortality from sepsis and critical illness. However, the evidence reveals that over the same period we have tripled the number of patients being sent to rehabilitation settings. Further, given that as many as half of the deaths in the first year following ICU admission occur post ICU discharge, it is unclear how many of these patients ever returned home. For those who do survive, the latest data indicate that 50-70% of ICU "survivors" will suffer cognitive impairment and 60-80% of "survivors" will suffer functional impairment or ICU-acquired weakness (ICU-AW). These observations demand that we as intensive care providers ask the following questions: "Are we creating survivors ... or are we creating victims?" and "Do we accomplish 'Pyrrhic Victories' in the ICU?" Interventions to address ICU-AW must have a renewed focus on optimal nutrition, anabolic/anticatabolic strategies, and in the future employ the personalized muscle and exercise evaluation techniques utilized by elite athletes to optimize performance. Specifically, strategies must include optimal protein delivery (1.2-2.0 g/kg/day), as an athlete would routinely employ. However, as is clear in elite sports performance, optimal nutrition is fundamental but alone is often not enough. We know burn patients can remain catabolic for 2 years post burn; thus, anticatabolic agents (i.e., beta-blockers) and anabolic agents (i.e., oxandrolone) will probably also be essential. In the near future, evaluation techniques such as assessing lean body mass at the bedside using ultrasound to determine nutritional status and ultrasound-measured muscle glycogen as a marker of muscle injury and recovery could be utilized to help find the transition from the acute phase of critical illness to the recovery phase. Finally, exercise physiology testing that evaluates muscle substrate utilization during exercise can be used to diagnose muscle mitochondrial dysfunction and to guide a personalized ideal heart rate, assisting in recovery of muscle mitochondrial function and functional endurance post ICU. In the end, future ICU-AW research must focus on using a combination of modern performance-enhancing nutrition, anticatabolic/anabolic interventions, and muscle/exercise testing so we can begin to create more "survivors" and fewer victims post ICU care.


title: Effect of Tidal Volume and Nebulizer Type and Position on Albuterol Delivery in a Pediatric Model of Mechanical Ventilation.

text: BACKGROUND Optimization of factors affecting aerosol delivery during mechanical ventilation in the pediatric population is important. We hypothesized that increasing the tidal volume (V(T)), using a vibrating mesh nebulizer, and placing the nebulizer at the ventilator would increase lung dose/delivery efficiency. METHODS Continuous-output jet and vibrating mesh nebulizers loaded with albuterol (2.5 mg/3 mL) were compared when placed before the Y-piece and at the ventilator. The model consisted of a ventilator operated in pressure-regulated volume control ventilation mode at a breathing frequency of 20 breaths/min, PEEP of 5 cm H2O, FIO2 of 0.4, inspiratory time of 0.75 s, and bias flow of 0.5 L/min with a humidifier (37 ± 1.5°C) and an adult heated-wired circuit. V(T) values of 100, 150, 200, and 300 mL were studied. The circuit was connected in series to a 5.5-mm inner diameter endotracheal tube with a filter (lung dose) interposed between them. Delivery efficiency was calculated as a percentage of the nominal dose captured on the filter. Albuterol content was analyzed by spectrophotometry (276 nm). RESULTS No differences in lung dose/delivery efficiency were found at different V(T) values for the jet nebulizer (both positions) and the vibrating mesh nebulizer (ventilator). Lung dose/delivery efficiency was higher (P < .02) at a VT of 100 mL compared with the other volumes tested. The vibrating mesh nebulizer had higher lung dose/delivery efficiency compared with the jet nebulizer only when placed before the Y-piece. Moving the nebulizers from before the Y-piece to the ventilator increased lung dose/delivery efficiency for all conditions tested except the vibrating mesh nebulizer at a V(T) of 100 mL (P = .36). CONCLUSIONS Optimization of inhaled drug delivery during pediatric mechanical ventilation should include careful selection of the type of delivery device and its placement in the ventilator circuit. Increasing V(T) during nebulization did not increase lung dose/delivery efficiency.


title: Laparoscopic low ventral rectocolpopexy (LLVR) for rectal and rectogenital prolapse: surgical technique and functional results.

text: BACKGROUND Laparoscopic ventral rectopexy limits the risk of autonomic nerve damage, and the colpopexy allows correction of a concomitant prolapse of the middle compartment. The aim of this study is to describe a modified laparoscopic ventral rectocolpopexy procedure with a low approach to the sacral hollow (laparoscopic low ventral rectocolpopexy: LLVR). We propose this technique to manage combined rectogenital prolapse. METHODS Between November 2006 and June 2009, all patients with symptomatic rectal prolapse associated with genital prolapse and/or enterocele underwent LLVR. Demographics, results of imaging studies, mortality, morbidity, and functional outcome were retrospectively analyzed. RESULTS Thirty patients underwent LLVR: two patients suffered from a full-thickness rectal prolapse while 28 had symptomatic recto-anal intussusception. The mean operating time was 94 ± 39 minutes. Conversion to laparotomy was never needed. Hospital stay ranged between 2 and 14 days (mean of 5 ± 2.5 days). No mortality was recorded and only two complications occurred (6.6%): one trocar site incisional hernia and one vaginal suture erosion in a patient who had concomitant hysterectomy. After a mean follow-up of 13.9 months, constipation was completely resolved or improved in 92.8% patients. Significant reduction in the mean Altomare obstructed defecation score (14.7-5.6; p < 0.05) was recorded. Preoperative incontinence improved after the procedure in all patients affected. No new cases of postoperative constipation or fecal incontinence were registered. Only one case of recurrence in a patient with recto-anal intussusception was recorded (3.4%), after 19 months. CONCLUSIONS Laparoscopic low ventral rectocolpopexy is safe and associated with very low morbidity. In the medium term, it provides good result for prolapse and associated symptoms.


National active surveillance to understand and inform neonatal care in COVID-19.


title: Risk for Death among Children with Pneumonia, Afghanistan.

text: In Afghanistan, childhood deaths from pneumonia are high. Among 639 children at 1 hospital, the case-fatality rate was 12.1%, and 46.8% of pneumococcal serotypes detected were covered by the 13-valent vaccine. Most deaths occurred within 2 days of hospitalization; newborns and malnourished children were at risk. Vaccination could reduce pneumonia and deaths.


title: Impact of real-time ultrasound guidance on complications of percutaneous dilatational tracheostomy: a propensity score analysis.

text: INTRODUCTION Recent studies have demonstrated the feasibility of real-time ultrasound guidance during percutaneous dilatational tracheostomy, including in patients with risk factors such as coagulopathy, cervical spine immobilization and morbid obesity. Use of real-time ultrasound guidance has been shown to improve the technical accuracy of percutaneous dilatational tracheostomy; however, it is unclear if there is an associated reduction in complications. Our objective was to determine whether the peri-procedural use of real-time ultrasound guidance is associated with a reduction in complications of percutaneous dilatational tracheostomy using a propensity score analysis. METHODS This study reviewed all percutaneous dilatational tracheostomies performed in an 8-year period in a neurocritical care unit. Percutaneous dilatational tracheostomies were typically performed by trainees under guidance of the attending intensivist. Bronchoscopic guidance was used for all procedures with addition of real-time ultrasound guidance at the discretion of the attending physician. Real-time ultrasound guidance was used to guide endotracheal tube withdrawal, guide tracheal puncture, identify guidewire entry level and confirm bilateral lung sliding. The primary outcome was a composite of previously defined complications including (among others) bleeding, infection, loss of airway, inability to complete procedure, need for revision, granuloma and early dislodgement. Propensity score analysis was used to ensure that the relationship of not using real-time ultrasound guidance with the probability of an adverse outcome was examined within groups of patients having similar covariate profiles. Covariates included were age, gender, body mass index, diagnosis, Acute Physiology and Chronic Health Evaluation II score, timing of tracheostomy, positive end-expiratory pressure and presence of risk factors including coagulopathy, cervical spine immobilization and prior tracheostomy. RESULTS A total of 200 patients underwent percutaneous dilatational tracheostomy during the specified period, and 107 received real-time ultrasound guidance. Risk factors for percutaneous dilatational tracheostomy were present in 63 (32%). There were nine complications in the group without real-time ultrasound guidance: bleeding (n = 4), need for revision related to inability to ventilate or dislodgement (n = 3) and symptomatic granuloma (n = 2). There was one complication in the real-time ultrasound guidance group (early dislodgement). The odds of having an adverse outcome for patients receiving real-time ultrasound guidance were significantly lower (odds ratio = 0.08; 95% confidence interval, 0.009 to 0.811; P = 0.032) than for those receiving a standard technique while holding the propensity score quartile fixed. CONCLUSIONS The use of real-time ultrasound guidance during percutaneous dilatational tracheostomy was associated with a significant reduction in procedure-related complications.


title: Comparison of laparoendoscopic single-site radical nephrectomy with conventional laparoscopic radical nephrectomy for localized renal-cell carcinoma.

text: PURPOSE To compare the results of laparoendoscopic single-site (LESS) radical nephrectomy with conventional laparoscopic radical nephrectomy for localized renal-cell carcinoma (RCC). PATIENTS AND METHODS This study was designed as a matched case-controlled study from our institute's RCC database. Nineteen consecutive patients who were undergoing LESS radical nephrectomy were compared with 38 patients who were undergoing conventional laparoscopic radical nephrectomy. The matching process accounted for sex, age, operative side, and tumor size. RESULTS No significant differences were observed in mean operative time (190.8 vs 172.4 min, P = 0.249), estimated blood loss (143.2 vs 199.5 mL, P = 0.235), and complication rate (15.8% vs 21.1 %, P = 0.635) between the LESS and conventional laparoscopy groups. Postoperative hospital stay after LESS radical nephrectomy was 2.7 (2-4) days, compared with 3.9 (3-7) days in the conventional laparoscopy group (P < 0.001). Postoperative pain, as measured by visual analog scale at postoperative day 1 (4.7 vs 5.8 points, P = 0.001), 2 (3.4 vs 4.6 points, P < 0.001), and 3 (2.7 vs 4.0 points, P = 0.008) was significantly lower in the LESS group. CONCLUSION LESS radical nephrectomy is a feasible and safe surgical option for localized RCC that demonstrates improved cosmetic outcomes and the additional benefits of decreased postoperative pain and decreased hospital stay.


title: Circles of Life: linking metabolic and epigenetic cycles to immunity.

text: Metabolites are the essential substrates for epigenetic modification enzymes to write or erase the epigenetic blueprint in cells. Thus, the availability of nutrients and activity of metabolic pathways strongly influence the enzymatic function. Recent studies have shed light on the choreography between metabolome and epigenome in the control of immune cell differentiation and function, with a major focus on histone modifications. Yet, despite its importance in gene regulation, DNA methylation and its relationship with metabolism is relatively unclear. In this review, we will describe how the metabolic flux can influence epigenetic networks in innate and adaptive immune cells, with a focus on DNA methylation cycle and the metabolites S-adenosylmethionine (SAM) and α-ketoglutarate (αKG). Future directions will be discussed for this rapidly emerging field.


Does COVID-19 influence sexual behaviours?


United States strains to act as cases set record.


title: Effects of oncological care pathways in primary and secondary care on patient, professional, and health systems outcomes: protocol for a systematic review and meta-analysis.

text: BACKGROUND The high impact of a cancer diagnosis on patients and their families and the increasing costs of cancer treatment call for optimal and efficient oncological care. To improve the quality of care and to minimize healthcare costs and its economic burden, many healthcare organizations introduce care pathways to improve efficiency across the continuum of cancer care. However, there is limited research on the effects of cancer care pathways in different settings. METHODS The aim of this systematic review and meta-analysis described in this protocol is to synthesize existing literature on the effects of oncological care pathways. We will conduct a systematic search strategy to identify all relevant literature in several biomedical databases, including Cochrane library, MEDLINE, Embase, and CINAHL. We will follow the methodology of Cochrane Effective Practice and Organisation of Care (EPOC), and we will include randomized trials, non-randomized trials, controlled before-after studies, and interrupted time series studies. In addition, we will include full economic evaluations (cost-effectiveness analyses, cost-utility analyses, and cost-benefit analyses), cost analyses, and comparative resource utilization studies, if available. Two reviewers will independently screen all studies and evaluate those included for risk of bias. From these studies, we will extract data regarding patient, professional, and health systems outcomes. Our systematic review will follow the PRISMA set of items for reporting in systematic reviews and meta-analyses. DISCUSSION Following the protocol outlined in this article, we aim to identify, assess, and synthesize all available evidence in order to provide an evidence base on the effects of oncological care pathways as reported in the literature. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42017057592 .


title: Use of soft tissue matrices as an adjunct to achilles repair and reconstruction.

text: The Achilles tendon is the thickest and strongest tendon in the human body. In spite of this, it is also one of the most frequently ruptured tendons. This article reviews the history of and debate about the appropriate course of treatment. A case study of an Achilles repair illustrates that the use soft tissue matrices is a successful adjunct to both the primary repair and gastrocnemius recession, with full return to activity and no inflammatory response at long-term follow up. The authors anticipate that the use of soft tissue matrices for the repair of tendon and soft tissue defects will expand over time as this material has distinct advantages over synthetics and highly crosslinked biologic materials.


title: COVID-19, Australia: Epidemiology Report 15 (Reporting week to 23:59 AEST 10 May 2020).

text: Confirmed cases in Australia notified up to 10 May 2020: notifications = 6,971; deaths = 98. The incidence of new cases of COVID-19 has reduced dramatically since a peak in mid-March. The reduction in international travel, social distancing measures and public health action have likely been effective in slowing the spread of the disease, in the Australian community. Cases of COVID-19 continue to be notified by jurisdictions, albeit at a slowed rate. Testing rates over the past week have increased markedly, with a very low proportion of people testing positive. These low rates of detection are indicative of low levels of COVID-19 transmission. It is important that testing rates and community adherence to public health measures remain high to support the continued suppression of the virus, particularly in vulnerable high-risk groups and settings. In the past reporting week new cases in Australia are mostly considered to be locally acquired, consistent with the drop in international travel. Most locally-acquired cases can be linked back to a known case or cluster. Although the proportion of locally-acquired cases has increased, the overall rate of cases, regardless of place of acquisition, continues to decrease. The crude case fatality rate in Australia remains low (1.4%), compared with the WHO reported global rate (6.9%). The low case fatality rate is likely reflective of high case detection and high quality of health care services in Australia. Deaths from COVID-19 in Australia have occurred predominantly among the elderly and those with comorbidities, with no deaths occurring in those under 40 years. The highest rate of COVID-19 continues to be among people aged 60-79 years, with a third of these cases associated with several outbreaks linked to cruise ships. The lowest rate of disease is in young children, a pattern reflected in international reports. Internationally, cases continue to increase, with some areas such as Brazil and India showing a dramatic rise in reported cases. Although some low-income countries have currently reported few cases, it is possible that this is due to limited diagnostic and public health capacity, and may not be reflective of disease occurrence.


title: Predicting fluid responsiveness with stroke volume variation despite multiple extrasystoles.

text: OBJECTIVE To investigate the ability of a new stroke volume variation algorithm to predict fluid responsiveness during general anesthesia and mechanical ventilation in animals with multiple extrasystoles. DESIGN Prospective laboratory animal experiment. SETTING Investigational laboratory. SUBJECTS Eight instrumented pigs. INTERVENTIONS Eight anesthetized and mechanically ventilated pigs were monitored with an arterial line and a pulmonary artery catheter. Multiple extrasystoles were induced by right ventricular pacing (25% of heart beats). Arterial pressure waveforms were recorded and stroke volume variation was computed from the new and from the standard algorithm. The new stroke volume variation algorithm is designed to restore the respiratory component of the arterial pressure waveform despite multiple ectopic heart beats. Cardiac output was measured before and after 56 fluid boluses (7 mL/kg of 6% hydroxy ethyl starch) performed at different volemic states. MEASUREMENTS AND MAIN RESULTS A positive response to fluid boluses (>15% increase in cardiac output) was observed in 21 of 56 boluses. The new stroke volume variation was higher in responders than in nonresponders (19% ± 5% vs. 12% ± 3%, p < .05), whereas the standard stroke volume variation was similar in the two groups (29% ± 8% vs. 26% ± 11%, p = .4). Receiver operating characteristic curve analysis showed that the new stroke volume variation was an accurate predictor of fluid responsiveness (sensitivity = 86%, specificity = 85%, best cutoff value = 14%, area under the curve = 0.892 ±, whereas the standard stroke volume variation was not (area under the curve = 0.596 ± 0.077). CONCLUSIONS In contrast to the standard stroke volume variation, the new stroke volume variation algorithm was able to predict fluid responsiveness in animals with multiple ventricular extrasystoles.


title: Temporary stent scaffolding during aneurysm coiling.

text: We report a case of temporary Solitaire FR stent (Covidien, Mansfield, MA, USA) scaffolding to reduce coil herniation during embolization of a large neck anterior communicating artery aneurysm. In contrast to classic stent-assisted coiling, the fully retrievable stent is recaptured prior to detachment of the last coil. The presented technical nuance hence does not require institution of prolonged antiplatelet coverage. But the door is left open for coil-repositioning in case of coil basket instability. Permanent stent redeployment remains a fall-back option if critical hardware conflict occurs. In comparison to classic balloon remodeling, the presented method may offer easier distal access, particularly in tortuous arterial anatomy. Temporary occlusion of the parent artery, side branches, and perforators is also avoided. Given its specific potential advantages, temporary stent scaffolding using the fully retrievable Solitaire FR device may find its niche as a bailout option, primarily in a very specific subset of distally located wide neck aneurysms.


Perioperative fluid therapy.


title: Internalized HIV Stigma and Pain among Women with HIV in the United States: The Mediating Role of Depressive Symptoms.

text: Pain is common in women with HIV, though little research has focused on psychosocial experiences contributing to pain in this population. In the present study we examined whether internalized HIV stigma predicts pain, and whether depressive symptoms mediate this relationship among women with HIV. Data were drawn from the Women's Interagency HIV Study (WIHS), for 1,364 women with HIV who completed three study visits between 2015 and 2016. We used a sequential longitudinal design to assess the relationship between internalized HIV stigma at time 1 on pain at time 3 through depressive symptoms at time 2. Analyses revealed internalized HIV stigma was prospectively associated with greater pain, B = 5.30, 95% CI [2.84, 7.60]. The indirect effect through depressive symptoms supported mediation, B = 3.68, 95% CI [2.69, 4.79]. Depression is a modifiable risk factor that can be addressed to improve pain prevention and intervention for women with HIV.


Maxillofacial Trauma Management During COVID-19: Multidisciplinary Recommendations.


title: Use of fibrin-based sealants and gelatin-matrix hemostats in laparoscopic liver surgery.

text: BACKGROUND During surgery, liver tissue is particularly prone to bleeding which can be difficult to control, especially in patients with liver disease-associated coagulopathy. Topical sealants and hemostats can enhance clot formation and wound healing, and can be useful for controlling or preventing troublesome bleeding during surgical interventions where conventional methods of hemostasis are inadequate. METHODS An extensive customized literature search was conducted using medical reference databases to identify publications related to the use of potential agents in laparoscopic liver surgery. Citations from these articles were also used. Details of the authors' own experience in this area is also included. RESULTS Routine use of fibrin-based sealants in open liver surgery now seems to be widespread. Data from several large prospective randomized controlled clinical trials have indicated that application of fibrin-based sealants to the cut liver surface during hepatectomy does provide some benefit in terms of a shorter time to hemostasis and a reduction in postoperative drainage fluid, even when compared with argon beam coagulation. Another trial found no additional benefit of fibrin sealants when applied after coagulation of the cut liver surface. A prospective, uncontrolled study found that application of the flowable gelatin matrix-based hemostat Floseal provided rapid effective control of mild-to-severe bleeding during surgical removal of primary or metastatic liver tumors, even in those with cirrhosis. Some of these topical hemostatic agents are already being used on a routine basis by many surgeons performing laparoscopic liver surgery. Although there are no randomized clinical trials, there are several anecdotal or case reports of their effective use during laparoscopic liver surgery. CONCLUSIONS On the basis of current evidence of using hemostats and sealants in open liver surgery, there is potential of developing these strategies in laparoscopic liver surgery.


How imaging should properly be used in COVID-19 outbreak: an Italian experience.


A Vesicular Stomatitis Virus-Based Vaccine Carrying Zika Virus Capsid Protein Protects Mice from Viral Infection.


title: Comprehensive process model of clinical information interaction in primary care: results of a "best-fit" framework synthesis.

text: Objective To describe a new, comprehensive process model of clinical information interaction in primary care (Clinical Information Interaction Model, or CIIM) based on a systematic synthesis of published research. Materials and Methods We used the "best fit" framework synthesis approach. Searches were performed in PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Library and Information Science Abstracts, Library, Information Science and Technology Abstracts, and Engineering Village. Two authors reviewed articles according to inclusion and exclusion criteria. Data abstraction and content analysis of 443 published papers were used to create a model in which every element was supported by empirical research. Results The CIIM documents how primary care clinicians interact with information as they make point-of-care clinical decisions. The model highlights 3 major process components: (1) context, (2) activity (usual and contingent), and (3) influence. Usual activities include information processing, source-user interaction, information evaluation, selection of information, information use, clinical reasoning, and clinical decisions. Clinician characteristics, patient behaviors, and other professionals influence the process. Discussion The CIIM depicts the complete process of information interaction, enabling a grasp of relationships previously difficult to discern. The CIIM suggests potentially helpful functionality for clinical decision support systems (CDSSs) to support primary care, including a greater focus on information processing and use. The CIIM also documents the role of influence in clinical information interaction; influencers may affect the success of CDSS implementations. Conclusion The CIIM offers a new framework for achieving CDSS workflow integration and new directions for CDSS design that can support the work of diverse primary care clinicians.


title: The ox-foot-model for investigating endoluminal thermal treatment modalities of varicosis vein diseases.

text: The introduction of technical surgical innovations in clinical medicine is preceded by preclinical evaluation of prototypes. Surgical aspects such as energy dependent tissue response and tissue sealing to reduce bleeding are usually investigated in animal experiments. Extra-corporal organ models can provide the required experimental information without harming animals and thus reduce or even replace in vivo experiments. Here we describe the ex vivo ox-foot-model, which can be used for surgical investigations and for training purposes. In the ox-foot-model the vein remains in its anatomical bed under reproducible experimental conditions, i.e., blood perfusion, blood pressure, and temperature. Innovative endoluminal surgical procedures using laser light and radio frequency for varicosis treatment were tested. Treatment parameters were investigated systematically in a large number of samples. A standardized preclinical testing procedure could be established and optimized on the basis of acute macroscopic and histological findings. Further, optical coherence tomography could be evaluated as a time-saving diagnostic tool. The ox-foot-model is suitable for training surgical techniques relevant for the treatment of varicosis veins. It is a cost-effective alternative to conventional in vivo experiments, providing standardized experimental conditions and reproducible experimental results while respecting the Principles of Humane Experimental Techniques: Reduction, Refinement, and Replacement of animal experiments.


title: [Nutritional management of the critically ill inpatient with COVID-19. A narrative review].

text: The current COVID-19 pandemic mainly affects older people, those with obesity or other coexisting chronic diseases such as type-2 diabetes and high blood pressure. It has been observed that about 20 % of patients will require hospitalization, and some of them will need the support of invasive mechanical ventilation in intensive care units. Nutritional status appears to be a relevant factor influencing the clinical outcome of critically ill patients with COVID-19. Several international guidelines have provided recommendations to ensure energy and protein intake in people with COVID-19, with safety measures to reduce the risk of infection in healthcare personnel. The purpose of this review is to analyze the main recommendations related to adequate nutritional management for critically ill patients with COVID-19 in order to improve their prognosis and clinical outcomes.


title: Cranial base repair with combined vascularized nasal septal flap and autologous tissue graft following expanded endonasal endoscopic neurosurgery.

text: BACKGROUND The expanded endonasal endoscopic approach provides excellent visualization and access to midline skull base lesions, albeit with a relatively high risk of postoperative cerebrospinal fluid (CSF) leakage. We present our experience with the expanded endonasal endoscopic approach to the skull base in an institution where, previously, a traditional transsphenoidal approach with a surgical microscope had been used. PATIENTS We performed a retrospective review to identify patients who underwent expanded endonasal endoscopic surgery and analyzed demographic, pathological, and operative data with particular attention to repair of the skull base defects in 55 procedures performed on 49 patients. We compared the outcomes of 10 primary operations in which we repaired skull base defects using only autologous or allogeneic tissue grafts and 39 primary operations in which we used a vascularized mucoperichondrial nasal septal flap with or without a layered autologous tissue graft. RESULTS Primary expanded endonasal endoscopic procedures were performed in 49 patients with sellar pathology (33 pituitary adenomas, 4 Rathke's cleft cysts, 1 pituicytoma, 1 pituitary metastasis) and non-sellar pathology (3 meningiomas, 3 clival chordomas, 1 clival mucocele, 1 craniopharyngioma, and 2 esthesioneuroblastomas). Postoperative CSF leakage occurred following 5 of the 49 primary operations (10.2%). This occurred in 2 of 10 primary operations (20.0%) in which the skull base defect was repaired using only autologous and/or allogeneic tissue grafts, necessitating a total of 3 operative CSF leak repairs in those 2 patients. The remaining 3 postoperative CSF leaks occurred in the 39 primary operations (7.7%) in which skull base repair was performed using a mucoperichondrial nasal septal flap, necessitating operative repair in 2 of those patients. CONCLUSION The repair of skull base defects created during expanded endonasal endoscopic surgery is improved by use of a mucoperichondrial nasal septal flap combined with a layered autologous tissue graft. When CSF leakage occurs despite nasal septal flap closure, the site of the leakage may be easier to localize and repair.


title: Detection of a spontaneous pulse in photoplethysmograms during automated cardiopulmonary resuscitation in a porcine model.

text: INTRODUCTION Reliable, non-invasive detection of return of spontaneous circulation (ROSC) with minimal interruptions to chest compressions would be valuable for high-quality cardiopulmonary resuscitation (CPR). We investigated the potential of photoplethysmography (PPG) to detect the presence of a spontaneous pulse during automated CPR in an animal study. METHODS Twelve anesthetized pigs were instrumented to monitor circulatory and respiratory parameters. Here we present the simultaneously recorded PPG and arterial blood pressure (ABP) signals. Ventricular fibrillation was induced, followed by 20 min of automated CPR and subsequent defibrillation. After defibrillation, pediatric-guidelines-style life support was given in cycles of 2 min. PPG and ABP waveforms were recorded during all stages of the protocol. Raw PPG waveforms were acquired with a custom-built photoplethysmograph controlling a commercial reflectance pulse oximetry probe attached to the nose. ABP was measured in the aorta. RESULTS In nine animals ROSC was achieved. Throughout the protocol, PPG and ABP frequency content showed strong resemblance. We demonstrate that (1) the PPG waveform allows for the detection of a spontaneous pulse during ventilation pauses, and that (2) frequency analysis of the PPG waveform allows for the detection of a spontaneous pulse and the determination of the pulse rate, even during ongoing chest compressions, if the pulse and compression rates are sufficiently distinct. CONCLUSIONS These results demonstrate the potential of PPG as a non-invasive means to detect pulse presence or absence, as well as pulse rate during CPR.


title: Structural basis for ligand and substrate recognition by torovirus hemagglutinin esterases.

text: Hemagglutinin esterases (HEs), closely related envelope glycoproteins in influenza C and corona- and toroviruses, mediate reversible attachment to O-acetylated sialic acids (Sias). They do so by acting both as lectins and as receptor-destroying enzymes, functions exerted by separate protein domains. HE divergence was accompanied by changes in quaternary structure and in receptor and substrate specificity. The selective forces underlying HE diversity and the molecular basis for Sia specificity are poorly understood. Here we present crystal structures of porcine and bovine torovirus HEs in complex with receptor analogs. Torovirus HEs form homodimers with sialate-O-acetylesterase domains almost identical to corresponding domains in orthomyxo- and coronavirus HEs, but with unique lectin sites. Structure-guided biochemical analysis of the esterase domains revealed that a functionally, but not structurally conserved arginine-Sia carboxylate interaction is critical for the binding and positioning of glycosidically bound Sias in the catalytic pocket. Although essential for efficient de-O-acetylation of Sias, this interaction is not required for catalysis nor does it affect substrate specificity. In fact, the distinct preference of the porcine torovirus enzyme for 9-mono- over 7,9-di-O-acetylated Sias can be explained from a single-residue difference with HEs of more promiscuous specificity. Apparently, esterase and lectin pockets coevolved; also the porcine torovirus HE receptor-binding site seems to have been designed to use 9-mono- and exclude di-O-acetylated Sias, possibly as an adaptation to replication in swine. Our findings shed light on HE evolution and provide fundamental insight into mechanisms of substrate binding, substrate recognition, and receptor selection in this important class of virion proteins.


title: Laparo-endoscopic single-site (LESS) cholecystectomy with epidural vs. general anesthesia.

text: BACKGROUND Laparo-endoscopic single-site (LESS) surgery involves a single umbilical incision, lending itself to epidural anesthesia. This prospective, randomized study was undertaken to evaluate epidural anesthesia for patients undergoing LESS cholecystectomy, to assess the feasibility, and to analyze all intraoperative and postoperative complications. The secondary objectives were to determine differences in postoperative pain and time until PACU discharge-to-home readiness between patients. METHODS With institutional review board approval, 20 patients with chronic cholecystitis, cholelithiasis, and/or biliary dyskinesia were randomized to receive spinal epidural anesthesia (n = 10) or general anesthesia (n = 10). Postoperative pain at rest was recorded in the PACU every 10 min, and at rest and walking at discharge using the visual analog scale (VAS). Operative time and time until PACU discharge-to-home readiness were recorded. Results are expressed as mean ± SD. RESULTS Patient age, American Society of Anesthesiologists class, and body mass index were similar. There were no additional ports/incisions, conversions to "open" operations, or conversions to general anesthesia. There were no differences in operative duration. Time until postanesthesia care unit discharge-to-home ready was not significantly different. The most common postoperative adverse event was urinary retention (1 epidural and 3 general anesthesia patients). Resting postoperative VAS pain score at discharge was 4.7 ± 2.5 vs. 2.2 ± 1.6 (p = 0.02, general versus epidural anesthesia respectively); the stressed VAS pain score at discharge was 6.1 ± 2.3 vs. 3.1 ± 2.8 (p = 0.02, general versus epidural anesthesia respectively). CONCLUSIONS LESS cholecystectomy with epidural anesthesia was completed with no operative or anesthetic conversions, and less postoperative pain at discharge. Epidural anesthesia appears to be a preferable alternative to general anesthesia for patients undergoing LESS cholecystectomy.


title: Are routine intensive care admissions needed after endovascular treatment of unruptured aneurysms?

text: SUMMARY Routine intensive care unit monitoring is common after elective embolization of unruptured intracranial aneurysms. In this series of 200 consecutive endovascular procedures for unruptured intracranial aneurysms, 65% of patients were triaged to routine (non-intensive care unit) floor care based on intraoperative findings, aneurysm morphology, and absence of major co-morbidities. Only 1 patient (0.5%) required subsequent transfer to the intensive care unit for management of a perioperative complication. The authors conclude that patients without major co-morbidities, intraoperative complications, or complex aneurysm morphology can be safely observed in a regular ward rather than being admitted to the intensive care unit.


title: Management of renal arteriovenous malformations: A pictorial review.

text: BACKGROUND Arteriovenous malformations (AVMs) are communications between an artery and a vein outside the capillary level. This pathologic communication may be either a fistula, a simple communication between a single artery and a dilated vein, or a more complex communication, a nidus of tortuous channels between one or more arteries/arterioles and one or more draining veins. The latter type of lesion is most frequently seen in the extremities; in the kidney they tend to appear more rarely. The most common clinical presentation of renal arteriovenous malformations (RAVMs) is haematuria. Percutaneous treatment with selective endovascular techniques offers a minimally invasive, nephron-sparing option in comparison to the more invasive surgical approaches. The purpose of this pictorial review is to highlight the general lines of management and to show the range of imaging findings of the percutaneous treatment of RAVMs. METHODS The imaging characteristics of a selection of cases of percutaneously managed congenital RAVMs are presented and the most common lines of approach are discussed. CONCLUSION The imaging spectrum of diagnosis and percutaneous treatment of RAVMs is presented in order to aid interpretation and endovascular management. TEACHING POINTS • Renal arteriovenous malformations are very rare lesions. • Clinical expression is usually haematuria. • Diagnosis is made with CT or MRI but the gold standard is digital subtraction angiography. • Catheter-directed treatment with the use of coils or liquid embolics is minimally invasive, safe and effective.


title: Role of the Insect Supervectors Bemisia tabaci and Frankliniella occidentalis in the Emergence and Global Spread of Plant Viruses.

text: Emergence of insect-transmitted plant viruses over the past 10-20 years has been disproportionately driven by two so-called supervectors: the whitefly, Bemisia tabaci, and the Western flower thrips, Frankliniella occidentalis. High rates of reproduction and dispersal, extreme polyphagy, and development of insecticide resistance, together with human activities, have made these insects global pests. These supervectors transmit a diversity of plant viruses by different mechanisms and mediate virus emergence through local evolution, host shifts, mixed infections, and global spread. Associated virus evolution involves reassortment, recombination, and component capture. Emergence of B. tabaci-transmitted geminiviruses (begomoviruses), ipomoviruses, and torradoviruses has led to global disease outbreaks as well as multiple paradigm shifts. Similarly, F. occidentalis has mediated tospovirus host shifts and global dissemination and the emergence of pollen-transmitted ilarviruses. The plant virus-supervector interaction offers exciting opportunities for basic research and global implementation of generalized disease management strategies to reduce economic and environmental impacts.


title: Successful radiofrequency ablation strategies for benign thyroid nodules.

text: PURPOSE This study aimed to evaluate the effectiveness of ultrasound (US)-guided radiofrequency ablation (RFA) treatment of benign thyroid nodules in consecutive large number series. To find out whether there is any difference according to the nature of the nodules, nodules were subdivided into two groups of predominantly solid vs. predominantly cystic lesions. METHODS We retrospectively analyzed clinical data of thyroid nodules receiving percutaneous RFA treatment in our institution. We subdivided data into two groups according to the nodule's sonographic characteristics. We defined therapeutic success as a volume reduction rate >50% at 6 months post-RFA. The second ablation was performed in case where <50% VRR was achieved at 6 months. The primary endpoint was to identify factors prognosticating response to RFA treatment. RESULTS A total of 1000 patients with 1619 thyroid nodules received US-guided RFA treatment. A volume reduction of >50% (therapeutic success) after the first ablation was 78.9% vs. 78.2% (p = 0.439) and 91.4% vs. 93.4% (p = 0.148) after the final ablation for predominantly cystic vs. predominantly solid lesions, respectively, with comparable post-interventional morbidity. RFA sessions were more frequent in the solid group than in the cystic group. Small volume of thyroid nodule (<4 mL) was the only factor significantly associated with therapeutic success in the multivariate analysis (OR 1.848; 95% CI 1.537-2.789, p = 0.030). CONCLUSION RFA was effective in reducing the volume of benign thyroid nodules volume with non-inferior result in PS group comparing to PC group and can be considered a principal treatment method for treating benign thyroid nodules, including cystic nodules.


title: A Systematic Review of Community Health Center Based Interventions for People with Diabetes.

text: Community health centers (CHCs) focus on serving socioeconomically disadvantaged populations with heightened chronic disease burden, making CHCs an ideal setting for implementing diabetes care programs that target vulnerable populations. We aimed to synthesize evidence concerning the effects of CHC interventions in people with diabetes. To do this, four electronic databases were searched, including PubMed, EMBASE, CINAHL, and Scopus, and hand searches of reference collections were undertaken to identify intervention trials published in English. We screened 892 unique titles and abstracts. Two reviewers then independently evaluated 221 full-text articles. We discovered 29 articles met our eligibility criteria for inclusion. We found 27 unique studies with two companion articles. Seventeen studies were randomized controlled trials and the majority had a higher proportion of female and racial/ethnic minorities in the study sample. CHC interventions often involved either one-on-one or group education sessions supplemented by a phone follow-up that were delivered by health providers, nutritionists, or community health workers. CHC interventions using education sessions combined with follow up via phone generally resulted in significant improvements in hemoglobin A1C, while sole telephone-based education studies showed no significant improvements. CHC interventions had no significant effects on physical activity in all six studies that examined the outcome. Overall, we found that CHC interventions were in general effective in improving glucose control when using face-to-face interactions in low-income, underserved, and racial and ethnic minority patients with diabetes. Evidence was limited, however, in regards to other outcomes which suggests the need for continued evaluations of CHC intervention models.


title: Receptor variation and susceptibility to Middle East respiratory syndrome coronavirus infection.

text: UNLABELLED The Middle East respiratory syndrome coronavirus (MERS-CoV) recently spread from an animal reservoir to infect humans, causing sporadic severe and frequently fatal respiratory disease. Appropriate public health and control measures will require discovery of the zoonotic MERS coronavirus reservoirs. The relevant animal hosts are liable to be those that offer optimal MERS virus cell entry. Cell entry begins with virus spike (S) protein binding to DPP4 receptors. We constructed chimeric DPP4 receptors that have the virus-binding domains of indigenous Middle Eastern animals and assessed the activities of these receptors in supporting S protein binding and virus entry. Human, camel, and horse receptors were potent and nearly equally effective MERS virus receptors, while goat and bat receptors were considerably less effective. These patterns reflected S protein affinities for the receptors. However, even the low-affinity receptors could hypersensitize cells to infection when an S-cleaving protease(s) was present, indicating that affinity thresholds for virus entry must be considered in the context of host-cell proteolytic environments. These findings suggest that virus receptors and S protein-cleaving proteases combine in a variety of animals to offer efficient virus entry and that several Middle Eastern animals are potential reservoirs for transmitting MERS-CoV to humans. IMPORTANCE MERS is a frequently fatal disease that is caused by a zoonotic CoV. The animals transmitting MERS-CoV to humans are not yet known. Infection by MERS-CoV requires receptors and proteases on host cells. We compared the receptors of humans and Middle Eastern animals and found that human, camel, and horse receptors sensitized cells to MERS-CoV infection more robustly than goat and bat receptors. Infection susceptibility correlated with affinities of the receptors for viral spike proteins. We also found that the presence of a cell surface lung protease greatly increases susceptibility to MERS-CoV, particularly in conjunction with low-affinity receptors. This cataloguing of human and animal host cell factors allows one to make inferences on the distribution of MERS-CoV in nature.


title: Pittsburgh outcomes after stroke thrombectomy score predicts outcomes after endovascular therapy for anterior circulation large vessel occlusions.

text: BACKGROUND AND PURPOSE Prognostication tools that predict good outcome in patients with anterior circulation large vessel occlusions after endovascular therapy are lacking. We aim to develop a tool that incorporates clinical and imaging data to predict outcomes after endovascular therapy. METHODS In a derivation cohort of anterior circulation large vessel occlusion stroke patients treated with endovascular therapy within 8 hours from time last seen well (n=247), we performed logistic regression to identify independent predictors of good outcome (90-day modified Rankin Scale, 0-2). Factors were weighted based on β-coefficients to derive the Pittsburgh Outcomes After Stroke Thrombectomy (POST) score. POST was validated in an institutional endovascular database (University of Pittsburgh Medical Center, n=393) and the Diffusion-Weighted Imaging Evaluation for Understanding Stroke Evolution Study-2 (DEFUSE-2) data set (n=105), as well as in patients treated beyond 8 hours (n=194) and in octogenarians (n=111). RESULTS In the derivation cohort, independent predictors (P<0.1) of good outcome included 24- to 72-hour final infarct volume (in cm(3), P<0.001), age (years, P<0.001), and parenchymal hematoma types 1 and 2 (H, P=0.01). POST was calculated as age+0.5×final infarct volume+15×H. Patients with POST score <60 had a 91% chance of good outcome compared with 4% with POST score ≥120. POST accurately predicted good outcomes in the derivation (area under the curve [AUC]=0.85) and validation cohorts (University of Pittsburgh Medical Center, AUC=0.81; DEFUSE-2, AUC=0.86), as well as in patients treated beyond 8 hours (AUC, 0.85) and octogenarians (AUC=0.76). POST had better predictive accuracy for good and poor outcome than the ischemic stroke predictive risk score (iSCORE). CONCLUSIONS POST score is a validated predictor of outcome in patients with anterior circulation large vessel occlusions after endovascular therapy.


title: The transition from laparoscopic to retroperitoneoscopic live donor nephrectomy: a matched pair pilot study.

text: BACKGROUND Retroperitoneoscopic live donor nephrectomy (RetroNeph) offers an intrinsic advantage over conventional transperitoneal laparoscopic nephrectomy (LapNeph) because of the potentially lower risk for early and late intraperitoneal donor complications. RetroNeph, however, is infrequently performed and has not been systematically and directly compared with LapNeph in nonselected donors. METHODS In November 2007, after 10 years of programmatic experience with transperitoneal LapNeph, we implemented RetroNeph at once for all live donor nephrectomies. Donor selection criteria, laparoscopic port positions, and hand-assistance mode were identical for RetroNeph and preceding LapNeph donors. We compared outcomes of retroperitoneoscopically completed cases with those of previous transperitoneal LapNeph cases that were pair matched for donor sex, body mass index, and donor kidney laterality. RESULTS Of the first 52 donor nephrectomies (48 left, 4 right) consecutively started with the intent to perform a RetroNeph November 2007 to April 2009, 45 (87%) were completed retroperitoneoscopically, and seven (13%) were switched intraoperatively to transperitoneal LapNeph. We observed no conversions to open nephrectomy, donor blood transfusions, readmissions, or reoperations. Matched-pair analysis of the 45 RetroNeph versus 45 LapNeph cases showed no significant differences for warm ischemia time and other donor outcomes, delayed graft function rates, recipient creatinine at 1 week, and 1-year graft survival. CONCLUSIONS Implementation of a RetroNeph program had no adverse impact on donor morbidity and quality of early graft function. Our pilot experience suggests that the RetroNeph learning curve is short. Given the potential advantages of an extraperitoneal approach for the donor, RetroNeph is an attractive alternative to LapNeph, particularly for surgeons with previous LapNeph experience.


title: Real-time estimation of lesion depth and control of radiofrequency ablation within ex vivo animal tissues using a neural network.

text: BACKGROUND Radiofrequency ablation (RFA), a method of inducing thermal ablation (cell death), is often used to destroy tumours or potentially cancerous tissue. Current techniques for RFA estimation (electrical impedance tomography, Nakagami ultrasound, etc.) require long compute times (≥ 2 s) and measurement devices other than the RFA device. This study aims to determine if a neural network (NN) can estimate ablation lesion depth for control of bipolar RFA using complex electrical impedance - since tissue electrical conductivity varies as a function of tissue temperature - in real time using only the RFA therapy device's electrodes. METHODS Three-dimensional, cubic models comprised of beef liver, pork loin or pork belly represented target tissue. Temperature and complex electrical impedance from 72 data generation ablations in pork loin and belly were used for training the NN (403 s on Xeon processor). NN inputs were inquiry depth, starting complex impedance and current complex impedance. Training-validation-test splits were 70%-0%-30% and 80%-10%-10% (overfit test). Once the NN-estimated lesion depth for a margin reached the target lesion depth, RFA was stopped for that margin of tissue. RESULTS The NN trained to 93% accuracy and an NN-integrated control ablated tissue to within 1.0 mm of the target lesion depth on average. Full 15-mm depth maps were calculated in 0.2 s on a single-core ARMv7 processor. CONCLUSIONS The results show that a NN could make lesion depth estimations in real-time using less in situ devices than current techniques. With the NN-based technique, physicians could deliver quicker and more precise ablation therapy.


How Slovakia Is Handling the Outbreak?


title: Microglia development and function.

text: Proper development and function of the mammalian central nervous system (CNS) depend critically on the activity of parenchymal sentinels referred to as microglia. Although microglia were first described as ramified brain-resident phagocytes, research conducted over the past century has expanded considerably upon this narrow view and ascribed many functions to these dynamic CNS inhabitants. Microglia are now considered among the most versatile cells in the body, possessing the capacity to morphologically and functionally adapt to their ever-changing surroundings. Even in a resting state, the processes of microglia are highly dynamic and perpetually scan the CNS. Microglia are in fact vital participants in CNS homeostasis, and dysregulation of these sentinels can give rise to neurological disease. In this review, we discuss the exciting developments in our understanding of microglial biology, from their developmental origin to their participation in CNS homeostasis and pathophysiological states such as neuropsychiatric disorders, neurodegeneration, sterile injury responses, and infectious diseases. We also delve into the world of microglial dynamics recently uncovered using real-time imaging techniques.


Laparo-endoscopic single site paraaortic lymphadenectomy facilitated by a new articulating vessel sealing device.


title: Single-center, single-blinded, randomized study of self-gripping versus sutured mesh in open inguinal hernia repair.

text: BACKGROUND The primary aim of the present study was to evaluate whether usage of self-gripping mesh in open inguinal hernia repair, compared with standard Lichtenstein repair with sutured mesh, could result in a decreased rate of chronic pain at 6-mo follow-up. The secondary outcome was to evaluate foreign body feeling and the quality of life after inguinal hernia repair. METHODS The patients were randomized into two study groups as follows: the OLP group received Optilene LP mesh and the PPG group received self-gripping Parietex ProGrip mesh. Pain scores were measured on a visual analog scale. Foreign body feeling was registered as a yes or no question. Quality of life was evaluated using the Medical Outcome Study Short-Form 36 questionnaire. RESULTS A total of 75 patients in the OLP group and 70 patients in the PPG group were included in the analysis. According to the primary end point, 45.3% and 31.4% of the patients in the OLP group and PPG group experienced pain during different activities at 6-mo follow-up, respectively (P = 0.092). Per secondary end point, 22.7% in the OLP group and 40% in the PPG group reported foreign body feeling at the operation site at 6-mo follow-up (P = 0.031, risk ratio 0.57, 95% confidence interval 0.29-1.07). There were no significant differences in any domain of quality of life according to the Short-Form 36 questionnaire between the two study groups at 6-mo follow-up, except for the social functioning domain (P = 0.035). In the OLP group, the quality of life scores improved significantly after operation in all domains except for general health and mental health. In the PPG group, the quality of life scores improved significantly after operation in the domains of bodily pain, physical functioning, and physical role. CONCLUSIONS Self-gripping mesh compared with standard Lichtenstein operation has no advantages in reducing chronic pain 6-mo after surgery. The rate of foreign body feeling was higher in the self-gripping mesh group. Scores of bodily pain, physical functioning, and physical role improved significantly in both study groups after hernia surgery.


title: Laparoscopic inguinal hernia repair in men with lightweight meshes may significantly impair sperm motility: a randomized controlled trial.

text: OBJECTIVE To compare quality of life and fertility aspects after laparoscopic inguinal hernia repair in men using a heavyweight or lightweight mesh. SUMMARY BACKGROUND DATA The use of lightweight meshes in laparoscopic inguinal hernia repair could have beneficial effects on quality of life and preservation of the spermatic structures due to a decreased foreign-body reaction. METHODS A total of 59 male patients planned for primary, unilateral or bilateral inguinal hernia repair were randomized between a standard polypropylene (Marlex) or lightweight mesh (Vypro II, TiMesh). Main outcome measures were fertility aspects, assessed preoperatively and at 1-year follow-up by semen analysis and scrotal ultrasonography. Secondary outcomes were quality of life (SF-36 and McGill Pain Questionnaire) and recurrence up to 1 year postoperatively. RESULTS Patients operated on with a VyproII or TiMesh mesh exhibited a decreased sperm motility (vs. preoperatively) compared with Marlex patients, respectively -9.5% and -5.5% versus +2% (P = 0.013). When the results after uni- and bilateral hernia repair were analyzed separately, this difference only remained significant in the bilateral hernia subgroup: -10% for VyproII and -17% for TiMesh versus +1% for Marlex (P = 0.037). Other fertility parameters (sperm concentration, morphology, and alpha-glucosidase level) were unchanged. There were no differences at any study point between the 3 groups regarding quality of life. Only for resumption of sport activities was a small advantage noted for VyproII versus Marlex patients (P = 0.045). After 1 year, no recurrences were observed; 3 patients (6%) complained of chronic disabling pain. CONCLUSIONS Our data suggest that the use of lightweight meshes for laparoscopic inguinal hernia repair in male patients negatively influences sperm motility, without any benefit on quality of life. These alterations might be important in a subgroup of young male patients operated on laparoscopically for a bilateral hernia. This study was registered in the clinicaltrials.gov database (ID number NCT00925067).


title: Fast and furious: a retrospective study of catheter-associated bloodstream infections with internal jugular nontunneled hemodialysis catheters at a tropical center.

text: Background Nontunneled hemodialysis catheters (NTHCs) remain the preferred vascular access at hemodialysis (HD) initiation in developing countries. We studied the incidence, risk factors and microbiological spectrum of jugular NTHC-associated bloodstream infections (CABSIs) at a tertiary care center in South Asia. Methods In this retrospective cohort study, all adult (≥18 years) incident patients who underwent jugular NTHC insertion for HD between January 2016 and June 2017, had no prior history of temporary vascular access insertion and were followed up for ≥14 days were included. Results A total of 897 patients underwent NTHC insertion during the study period and 169 patients fulfilled the inclusion criteria and contributed 7079 patient days of follow-up. CABSI incidence was 7.34 episodes per 1000 catheter days and median infection-free survival and time to CABSI were 96 and 24.5 days, respectively. In multivariate Cox regression analysis, immunosuppressive medication {hazard ratio [HR] 2.87 [95% confidence interval (CI) 1.09-7.55]; P = 0.033} and intravenous cefazolin use [HR 0.51 (95% CI 0.28-0.94); P = 0.031] was independently associated with CABSI. The cumulative hazard of CABSI was 8.3, 13.3, 17.6 and 20.9% at Weeks 1, 2, 3 and 4, respectively. Gram-negative organisms were the most common etiological agents (54.7%) and 40.3% of CABSIs were caused by drug-resistant organisms. Gram-negative and Gram-positive CABSIs were associated with neutrophil left shift and higher procalcitonin compared with coagulase-negative staphylococcal CABSIs. Conclusion In South Asia, NTHC-associated CABSIs occur early and are predominantly Gram negative. We hypothesize that poor hygiene practices may play a role in this phenomenon.


In Briefs.


title: Homelessness and the response to emerging infectious disease outbreaks: lessons from SARS.

text: During the 2003 severe acute respiratory syndrome (SARS) outbreak in Toronto, the potential introduction of SARS into the homeless population was a serious concern. Although no homeless individual in Toronto contracted SARS, the outbreak highlighted the need to develop an outbreak preparedness plan that accounts for unique issues related to homeless people. We conducted key informant interviews with homeless service providers and public health officials (n = 17) and identified challenges specific to the homeless population in the areas of communication, infection control, isolation and quarantine, and resource allocation. Planning for future outbreaks should take into account the need to (1) develop systems that enable rapid two-way communication between public health officials and homeless service providers, (2) ensure that homeless service providers have access to infection control supplies and staff training, (3) prepare for possible homeless shelter closures due to staff shortages or high attack rates among clients, and (4) plan for where and how clinically ill homeless individuals will be isolated and treated. The Toronto SARS experience provided insights that are relevant to response planning for future outbreaks in cities with substantial numbers of homeless individuals.


Personal protective equipment in eye examination after the coronavirus pandemic: everything like before?


title: Potent neutralization of MERS-CoV by human neutralizing monoclonal antibodies to the viral spike glycoprotein.

text: The recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no prophylactic and therapeutic agents specifically against MERS-CoV are currently available. Entry of MERS-CoV into target cells depends on binding of the receptor binding domain (RBD) of the viral envelope spike glycoprotein to the cellular receptor dipeptidyl peptidase 4 (DPP4). We report the isolation and characterization of two potent human RBD-specific neutralizing monoclonal antibodies (MERS-4 and MERS-27) derived from single-chain variable region fragments of a nonimmune human antibody library. MERS-4 and MERS-27 inhibited infection of both pseudotyped and live MERS-CoV with IC50 (half-maximal inhibitory concentration) at nanomolar concentrations. MERS-4 also showed inhibitory activity against syncytia formation mediated by interaction between MERS-CoV spike glycoprotein and DPP4. Combination of MERS-4 and MERS-27 demonstrated a synergistic effect in neutralization against pseudotyped MERS-CoV. Biochemical analysis indicated that MERS-4 and MERS-27 blocked RBD interaction with DPP4 on the cell surface. MERS-4, in particular, bound soluble RBD with an about 45-fold higher affinity than DPP4. Mutagenesis analysis suggested that MERS-4 and MERS-27 recognized distinct regions in RBD. These results suggest that MERS-4 and MERS-27 are RBD-specific potent inhibitors and could serve as promising candidates for prophylactic and therapeutic interventions against MERS-CoV infection.


Rare & Special Cases.


title: Dissecting the human immunologic memory for pathogens.

text: Studies on immunologic memory in animal models and especially in the human system are instrumental to identify mechanisms and correlates of protection necessary for vaccine development. In this article, we provide an overview of the cellular basis of immunologic memory. We also describe experimental approaches based on high throughput cell cultures, which we have developed to interrogate human memory T cells, B cells, and plasma cells. We discuss how these approaches can provide new tools and information for vaccine design, in a process that we define as 'analytic vaccinology'.


title: Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy: American Society of Clinical Oncology and Infectious Diseases Society of America Clinical Practice Guideline Update.

text: Purpose To provide an updated joint ASCO/Infectious Diseases Society of American (IDSA) guideline on outpatient management of fever and neutropenia in patients with cancer. Methods ASCO and IDSA convened an Update Expert Panel and conducted a systematic review of relevant studies. The guideline recommendations were based on the review of evidence by the Expert Panel. Results Six new or updated meta-analyses and six new primary studies were added to the updated systematic review. Recommendation Clinical judgment is recommended when determining which patients are candidates for outpatient management, using clinical criteria or a validated tool such as the Multinational Association of Support Care in Cancer risk index. In addition, psychosocial and logistic considerations are outlined within the guideline. The panel continued to endorse consensus recommendations from the previous version of this guideline that patients with febrile neutropenia receive initial doses of empirical antibacterial therapy within 1 hour of triage and be monitored for ≥ 4 hours before discharge. An oral fluoroquinolone plus amoxicillin/clavulanate (or clindamycin, if penicillin allergic) is recommended as empirical outpatient therapy, unless fluoroquinolone prophylaxis was used before fever developed. Patients who do not defervesce after 2 to 3 days of an initial, empirical, broad-spectrum antibiotic regimen should be re-evaluated and considered as candidates for inpatient treatment. Additional information is available at www.asco.org/supportive-care-guidelines and www.asco.org/guidelineswiki .


title: Patent Foramen Ovale Closure or Anticoagulation vs. Antiplatelets after Stroke.

text: BACKGROUND Trials of patent foramen ovale (PFO) closure to prevent recurrent stroke have been inconclusive. We investigated whether patients with cryptogenic stroke and echocardiographic features representing risk of stroke would benefit from PFO closure or anticoagulation, as compared with antiplatelet therapy. METHODS In a multicenter, randomized, open-label trial, we assigned, in a 1:1:1 ratio, patients 16 to 60 years of age who had had a recent stroke attributed to PFO, with an associated atrial septal aneurysm or large interatrial shunt, to transcatheter PFO closure plus long-term antiplatelet therapy (PFO closure group), antiplatelet therapy alone (antiplatelet-only group), or oral anticoagulation (anticoagulation group) (randomization group 1). Patients with contraindications to anticoagulants or to PFO closure were randomly assigned to the alternative noncontraindicated treatment or to antiplatelet therapy (randomization groups 2 and 3). The primary outcome was occurrence of stroke. The comparison of PFO closure plus antiplatelet therapy with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 2, and the comparison of oral anticoagulation with antiplatelet therapy alone was performed with combined data from randomization groups 1 and 3. RESULTS A total of 663 patients underwent randomization and were followed for a mean (±SD) of 5.3±2.0 years. In the analysis of randomization groups 1 and 2, no stroke occurred among the 238 patients in the PFO closure group, whereas stroke occurred in 14 of the 235 patients in the antiplatelet-only group (hazard ratio, 0.03; 95% confidence interval, 0 to 0.26; P<0.001). Procedural complications from PFO closure occurred in 14 patients (5.9%). The rate of atrial fibrillation was higher in the PFO closure group than in the antiplatelet-only group (4.6% vs. 0.9%, P=0.02). The number of serious adverse events did not differ significantly between the treatment groups (P=0.56). In the analysis of randomization groups 1 and 3, stroke occurred in 3 of 187 patients assigned to oral anticoagulants and in 7 of 174 patients assigned to antiplatelet therapy alone. CONCLUSIONS Among patients who had had a recent cryptogenic stroke attributed to PFO with an associated atrial septal aneurysm or large interatrial shunt, the rate of stroke recurrence was lower among those assigned to PFO closure combined with antiplatelet therapy than among those assigned to antiplatelet therapy alone. PFO closure was associated with an increased risk of atrial fibrillation. (Funded by the French Ministry of Health; CLOSE ClinicalTrials.gov number, NCT00562289 .).


title: The minipterional craniotomy for anterior circulation aneurysms: initial experience with 72 patients.

text: BACKGROUND The pterional craniotomy is well established for microsurgical clipping of most anterior circulation aneurysms. The incision and temporalis muscle dissection impacts postoperative recovery and cosmetic outcomes. The minipterional (MPT) craniotomy offers similar microsurgical corridors, with a substantially shorter incision, less muscle dissection, and a smaller craniotomy flap. OBJECTIVE To report our experience with the MPT craniotomy in select unruptured anterior circulation aneurysms. METHODS From January 2009 to July 2013, 82 unruptured aneurysms were treated in 72 patients, with 74 MPT craniotomies. Seven patients had multiple aneurysms treated with a single MPT craniotomy. The average patient age was 56 years (range: 24-87). Aneurysms were located along the middle cerebral artery (n = 36), posterior communicating (n = 22), paraophthalmic (n = 22), choroidal (n = 1), and dorsal ICA segments (n = 1). The MPT craniotomy utilized an incision just posterior to the hairline and a single myocutaneous flap. RESULTS The average aneurysm size was 5.45 mm (range: 1-14). There were no instances of compromised operative corridors requiring craniotomy extension. Three significant early postoperative complications included epidural and subdural hematomas requiring evacuation, and a middle cerebral artery infarction. Average length of hospitalization was 3.96 days (range: 2-20). Two patients required reoperation for wound infections. Average follow-up was 421 days (range: 5-1618). Minimal to no temporalis muscle wasting was noted in 96% of patients. CONCLUSION The MPT craniotomy is a worthwhile alternative to the standard pterional craniotomy. There were no instances of suboptimal operative corridors and clip applications when the MPT craniotomy was utilized in the treatment of unruptured middle cerebral artery and supraclinoid internal carotid artery aneurysms proximal to the terminal internal carotid artery bifurcation.


title: Meropenem for management of valproic acid overdose: a case report.

text: Objectives Valproic acid (VPA) is an anticonvulsant used in several clinical scenarios. VPA has been increasingly associated with intentional or unintentional overdose. In patients presenting with severe VPA overdose, supportive care and airway protection are cornerstones of treatment, while levocarnitine is suggested in patients with hyperammonemia and hemodialysis is recommended in patients with VPA serum concentrations (SC) >1,300 mg/L and presence of cerebral edema or shock. Meropenem is a carbapenem antibiotic with a broad spectrum of activity. The pharmacological interaction between VPA and meropenem is characterized by a rapid decrease in VPA concentrations, which contraindicates concurrent use. Case presentation The following case report describes the use of meropenem to enhance the clearance of VPA in the case of severe VPA overdose. A patient with altered mental status was transported to the emergency department (ED) after VPA overdose. Meropenem was prescribed for significant elevated VPA SC. An important decline in SC was observed with short-term meropenem dosing, and an improvement in mental status occurred shortly after administration. Conclusions Carbapenem therapy has the potential to be used as last line strategy in the management of severe VPA overdose in patients where SC represent a significant risk of toxicity and clinical symptoms suggest difficulty managing the patient.


title: Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins.

text: The ongoing outbreak of viral pneumonia in China and beyond is associated with a novel coronavirus, SARS-CoV-21. This outbreak has been tentatively associated with a seafood market in Wuhan, China, where the sale of wild animals may be the source of zoonotic infection2. Although bats are likely reservoir hosts for SARS-CoV-2, the identity of any intermediate host that might have facilitated transfer to humans is unknown. Here, we report the identification of SARS-CoV-2-related coronaviruses in Malayan pangolins (Manis javanica) seized in anti-smuggling operations in southern China. Metagenomic sequencing identified pangolin-associated coronaviruses that belong to two sub-lineages of SARS-CoV-2-related coronaviruses, including one that exhibits strong similarity to SARS-CoV-2 in the receptor-binding domain. The discovery of multiple lineages of pangolin coronavirus and their similarity to SARS-CoV-2 suggests that pangolins should be considered as possible hosts in the emergence of novel coronaviruses and should be removed from wet markets to prevent zoonotic transmission.


Postinfectious brainstem encephalitis associated with SARS-CoV-2.


title: Low-voltage coagulation, polyglycolic acid sheets, and fibrin glue to control air leaks in lung surgery.

text: OBJECTIVE We evaluated the efficacy of low-voltage coagulation (LVC) with polyglycolic acid (PGA) sheets (Neoveil, GUNZE Ltd., Japan) and fibrin glue to control intraoperative alveolar air leaks after lung surgery. METHODS We included 176 patients with non-small cell lung cancer who underwent thoracoscopic lobectomies. When alveolar air leak was confirmed after lung resection, we applied LVC system to the pleural defect followed by layers of PGA sheets and fibrin glue (n = 40). We then analyzed postoperative air leaks (rate of occurrence and duration time). RESULTS 73% of patients (29/40 cases) experienced no postoperative air leaks. Although 11 patients experienced air leaks after surgery, there were no prolonged air leaks (>7 days) (resolution time, 3.5 ± 1.4 days; range, 2-6 days). Two patients required drainage for late-onset air leaks, but their conditions improved without further treatment. There were no further adverse events. CONCLUSIONS The use of LVC with PGA sheets and fibrin glue following pulmonary resection efficiently prevented both intraoperative air leaks and prolonged air leaks after lung surgery.