title: Inhibition of complement activation alleviates acute lung injury induced by highly pathogenic avian influenza H5N1 virus infection.

text: The acute lung injury (ALI) that occurs after the highly pathogenic avian influenza H5N1 virus infection is associated with an abnormal host innate immune response. Because the complement system plays a central role in innate immunity and because aberrant complement activation is associated with a variety of autoimmune and inflammatory diseases, we investigated the complement involvement in the pathogenesis of ALI induced by H5N1 virus infection. We showed that ALI in H5N1-infected mice was caused by excessive complement activation, as demonstrated by deposition of C3, C5b-9, and mannose-binding lectin (MBL)-C in lung tissue, and by up-regulation of MBL-associated serine protease-2 and the complement receptors C3aR and C5aR. Treatment of H5N1-infected mice with a C3aR antagonist led to significantly reduced inflammation in lungs, alleviating ALI. Furthermore, complement inhibition with an anti-C5a antibody or complement depletion with cobra venom factor after H5N1 challenge resulted in a similar level of protection to that seen in C3aR antagonist-treated mice. These results indicate that excessive complement activation plays an important role in mediating H5N1-induced ALI and that inhibition of complement may be an effective clinical intervention and adjunctive treatment for H5N1-induced ALI.


title: Investigation of COVID-19-related symptoms based on factor analysis.

text: BACKGROUND The application of factor analysis in the study of the clinical symptoms of coronavirus disease 2019 (COVID-19) was investigated, to provide a reference for basic research on COVID-19 and its prevention and control. METHODS The data of 60 patients with COVID-19 in Jingzhou Hospital of Traditional Chinese Medicine and the Second People's Hospital of Longgang District in Shenzhen were extracted using principal component analysis. Factor analysis was used to investigate the factors related to symptoms of COVID-19. Based on the combination of factors, the clinical types of the factors were defined according to our professional knowledge. Factor loadings were calculated, and pairwise correlation analysis of symptoms was performed. RESULTS Factor analysis showed that the clinical symptoms of COVID-19 cases could be divided into respiratory-digestive, neurological, cough-wheezing, upper respiratory, and digestive symptoms. Pairwise correlation analysis showed that there were a total of eight pairs of symptoms: fever-palpitation, coughexpectoration, expectoration-wheezing, dry mouth-bitter taste in the mouth, poor appetite-fatigue, fatiguedizziness, diarrhea-palpitation, and dizziness-headache. CONCLUSIONS The symptoms and syndromes of COVID-19 are complex. Respiratory symptoms dominate, and digestive symptoms are also present. Factor analysis is suitable for studying the characteristics of the clinical symptoms of COVID-19, providing a new idea for the comprehensive analysis of clinical symptoms.


title: Exercise versus no exercise for the occurrence, severity and duration of acute respiratory infections.

text: BACKGROUND Acute respiratory infections (ARIs) last for less than 30 days and are the most common acute diseases affecting people worldwide. Exercise has been shown to improve health generally and may be effective in reducing the occurrence, severity and duration of acute respiratory infections. OBJECTIVES To evaluate the effectiveness of exercise for altering the occurrence, severity or duration of acute respiratory infections. SEARCH METHODS We searched CENTRAL (2014, Issue 6), MEDLINE (1948 to July week 1, 2014), EMBASE (2010 to July 2014), CINAHL (1981 to July 2014), LILACS (1982 to July 2014), SPORTDiscus (1985 to July 2014), PEDro (searched on 11 July 2014), OTseeker (searched on 11 July 2014), the WHO International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov (searched on 11 July 2014). SELECTION CRITERIA Randomised controlled trials (RCTs) and quasi-RCTs of exercise for ARIs in the general population. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data from the included trials using a standard form. We contacted trial authors to request missing data. One review author entered data and a second review author checked this. There were sufficient differences in the populations trialled and in the nature of the interventions to use the random-effects model (which makes fewer assumptions than the fixed-effect model) in the analysis. MAIN RESULTS We included 11 trials involving 904 adults, published between 1990 and 2014. Eight studies were conducted in the USA, and one each in Canada, Spain and Turkey. Sample sizes ranged from 20 to 154 participants aged between 18 and 85 years old. The proportion of female participants varied between 52% and 100%. The duration of follow-up in the studies varied from seven days to 12 months. The exercise type most prescribed for the intervention was aerobic (walking in 70% of the studies, or bicycle riding or treadmill) at least five times a week. Duration was 30 to 45 minutes at moderate intensity. Participants were supervised in 90% of the studies.For four of the primary outcomes the results did not differ significantly and all were low-quality evidence (number of ARI episodes per person per year, rate ratio 0.91 (95% confidence interval (CI) 0.59 to 1.42); proportion of participants who experienced at least one ARI over the study period, risk ratio 0.76 (95% CI 0.57 to 1.01); severity of ARI symptoms, mean difference (MD) -110 (95% CI -324 to 104); and number of symptom days in the follow-up period, MD -2.1 days (95% CI -4.4 to 0.3)). However, one primary outcome, the number of symptom days per episode of illness, was reduced in those participants who exercised (MD -1.1 day, 95% CI -1.7 to -0.5, moderate-quality evidence).We found no significant differences for the secondary outcomes (laboratory parameters (blood lymphocytes, salivary secretory immunoglobulin and neutrophils); quality of life outcomes; cost-effectiveness and exercise-related injuries).There was good adherence to the intervention with no difference between the exercise and non-exercise groups.We rated the quality of evidence for the primary outcomes as low for most outcomes using the GRADE criteria: allocation concealment was not reported and there was a lack of blinding; in addition, there was imprecision (the CI is very wide because of a small number of participants) and inconsistency, which may be due to differences in study design. AUTHORS' CONCLUSIONS We cannot determine whether exercise is effective at altering the occurrence, severity or duration of acute respiratory infections. One analysis of four trials suggests that the number of days of illness per episode of infection might be reduced by exercise. The small size of the studies, risk of bias and heterogeneous populations trialled all contribute to the uncertainty. Larger studies, with less risk of bias from patient selection, blinding of outcomes assessors, reporting of all outcomes measured and with registration of study protocols, are required to settle the question.


title: Extended Survival and Prognostic Factors for Patients With ALK-Rearranged Non-Small-Cell Lung Cancer and Brain Metastasis.

text: PURPOSE We performed a multi-institutional study to identify prognostic factors and determine outcomes for patients with ALK-rearranged non-small-cell lung cancer (NSCLC) and brain metastasis. PATIENTS AND METHODS A total of 90 patients with brain metastases from ALK-rearranged NSCLC were identified from six institutions; 84 of 90 patients received radiotherapy to the brain (stereotactic radiosurgery [SRS] or whole-brain radiotherapy [WBRT]), and 86 of 90 received tyrosine kinase inhibitor (TKI) therapy. Estimates for overall (OS) and intracranial progression-free survival were determined and clinical prognostic factors were identified by Cox proportional hazards modeling. RESULTS Median OS after development of brain metastases was 49.5 months (95% CI, 29.0 months to not reached), and median intracranial progression-free survival was 11.9 months (95% CI, 10.1 to 18.2 months). Forty-five percent of patients with follow-up had progressive brain metastases at death, and repeated interventions for brain metastases were common. Absence of extracranial metastases, Karnofsky performance score ≥ 90, and no history of TKIs before development of brain metastases were associated with improved survival (P = .003, < .001, and < .001, respectively), whereas a single brain metastasis or initial treatment with SRS versus WBRT were not (P = .633 and .666, respectively). Prognostic factors significant by multivariable analysis were used to describe four patient groups with 2-year OS estimates of 33%, 59%, 76%, and 100%, respectively (P < .001). CONCLUSION Patients with brain metastases from ALK-rearranged NSCLC treated with radiotherapy (SRS and/or WBRT) and TKIs have prolonged survival, suggesting that interventions to control intracranial disease are critical. The refinement of prognosis for this molecular subtype of NSCLC identifies a population of patients likely to benefit from first-line SRS, close CNS observation, and treatment of emergent CNS disease.


title: Conventional laparoscopic adrenalectomy versus laparoscopic adrenalectomy through mono port.

text: A standard procedure for single-port laparoscopic adrenal surgery has not been established. We retrospectively investigated intraoperative and postoperative outcomes after laparoscopic adrenalectomy through mono port (LAMP) and conventional laparoscopic adrenalectomy to assess the feasibility of LAMP. Between March 2008 and December 2009, 22 patients underwent adrenalectomy at the Department of Surgery, Kangbuk Samsung Hospital. Twelve patients underwent conventional laparoscopic adrenalectomy and 10 patients underwent LAMP. The same surgeon performed all the surgeries. The 2 procedures were compared in terms of tumor size, operating time, time to resumption of a soft diet, length of hospital day, and postoperative complications. The 2 groups were similar in terms of tumor size (30.08 vs. 32.50 mm, P=0.796), mean operating time (112.9 vs. 127 min, P=0.316), time to resumption of a soft diet (1.25 vs. 1.30 d, P=0.805), and length of hospital day (4.08 vs. 4.50 d, P=0.447). Despite 1 patient in the LAMP group experiencing ipsilateral pleural effusion as a postoperative complication, this parameter was similar for the 2 groups (P=0.195). Perioperative mortality, blood transfusion, and conversion to open surgery did not occur. Perioperative outcomes for LAMP were similar to those for conventional laparoscopic adrenalectomy. LAMP appears to be a feasible option for adrenalectomy.


title: Clinical course of COVID-19 infection in elderly patient with melanoma on nivolumab.

text: Outbreak of the new type coronavirus infection, known as coronavirus infection 2019 (COVID-19), has begun in December 2019, in Wuhan, China. As of today, 3 April 2020, 972,640 people affected and 50,325 people died from Severe Acute Respiratory Syndrome-Coronavirus 2. There is not any standard treatment for coronavirus infection 2019; however, there are promising data for hydroxychloroquine and some anti-retroviral drugs. Programmed death-1 (PD-1)/programmed death ligand-1 (PDL-1) pathway is an important target for the cancer immunotherapy. However, there is a robust pre-clinical and clinical data regarding inhibitor effect of this pathway on the acute or chronic viral infections. Thus, blockade of this pathway may lead to an anti-viral effect and decrease viral load. Here, we report the clinical course of coronavirus infection 2019 infection of a patient in whom older aged, having multiple co-morbidities, and taking nivolumab for metastatic malignant melanoma. In contrast to her older age, comorbidities, and cancer diagnosis, she was in a good condition, and there was also no pneumonia finding. We think that this good clinical course of coronavirus infection 2019 infection may be related to blockade of PD-1/PDL-1 pathway with nivolumab. It is impossible to say that blockade of PD-1/PDL-1pathway is a treatment option for COVID-19; however, we want to share our experience.


Coronavirus Disease 2019 (COVID-19) Pandemic and Lacrimal Practice: Diagnostic and Therapeutic Nasal Endoscopy and Dacryoendoscopy.


Covid-19: Trump halts WHO funding in move labelled "petulant" and "short sighted".


title: Daring discourse: are we ready to recommend neuraxial anesthesia and peripheral nerve blocks during the COVID-19 pandemic? A pro-con.

text: The recent joint statement from the American Society of Regional Anesthesia and Pain Medicine (ASRA) and the European Society of Regional Anesthesia and Pain Therapy (ESRA) recommends neuraxial and peripheral nerve blocks for patients with coronavirus disease 2019 (COVID-2019) illness. The benefits of regional anesthetic and analgesic techniques on patient outcomes and healthcare systems are evident. Regional techniques are now additionally promoted as a mechanism to reduce aerosolizing procedures. However, caring for patients with COVID-19 illness requires rapid redefinition of risks and benefits-both for patients and practitioners. These should be fully considered within the context of available evidence and expert opinion. In this Daring Discourse, we present two opposing perspectives on adopting the ASRA/ESRA recommendation. Areas of controversy in the literature and opportunities for research to address knowledge gaps are highlighted. We hope this will stimulate dialogue and research into the optimal techniques to improve patient outcomes and ensure practitioner safety during the pandemic.


Clozapine and COVID-19: The authors respond.


title: GROWTH, HUSBANDRY, AND DIETS OF FIVE SUCCESSFULLY HAND-REARED ORPHANED GIRAFFE CALVES (GIRAFFA CAMELOPARDALIS ROTHSCHILDI AND GIRAFFA CAMELOPARDALIS RETICULATA).

text: Giraffe in the wild are in ongoing decline because of poaching and habitat loss and fragmentation, and were recently assessed as "vulnerable" on the IUCN (International Union for Conservation of Nature) Red List of Threatened Species. Captive breeding and saving each individual are therefore becoming more important to save this species from extinction. This paper describes the husbandry and diets of successfully hand-reared Rothschild's giraffes (Giraffa camelopardalis rothschildi; n = 3) and reticulated giraffes (Giraffa camelopardalis reticulata; n = 2). All calves were initially fed with bovine colostrum followed by cow's milk (Holstein milk; Holstein milk with 10% of bovine colostrum; Jersey and Guernsey milk). Additionally, lactase enzymes (Lactaidt, Johnson & Johnson Inc., Guelp, Ontario N1K1A5, Canada) and probiotics (Probiost, Vets Plus, Inc., Menomonie, WI 54751, USA) were used. Average growth varied from 764 to 1,239 g/day from birth until 2 mo of age and between 508 and 1,161 g/day from birth until last measurement before weaning. Hand-reared calves gained up to 21 cm in height within the first month and 82-138% of their birth weight during the first 2 mo. The giraffes were weaned at 6 (n = 1), 8 (n = 3), and 11.5 (n = 1) mo and successfully socialized and introduced to other giraffes. The described diets and husbandry proved to be effective in all five calves. Large amounts of cow's milk per feeding (up to 6 L) did not result in gastrointestinal problems.


title: Radiation dose analysis of large and giant internal carotid artery aneurysm treatment with the pipeline embolization device versus traditional coiling techniques.

text: BACKGROUND Flow diversion is an effective and increasingly accepted method for endovascular treatment of cerebral aneurysms. Additionally, the public has heightened concerns regarding radiation exposure from medical procedures. This study analyzes radiation dose and fluoroscopy time during treatment of large and giant proximal internal carotid artery (ICA) aneurysms with the pipeline embolization device (PED) versus traditional coiling techniques. METHODS Radiation dose, fluoroscopy time, and contrast dye administration were retrospectively analyzed in 55 patients undergoing endovascular treatment of aneurysms ≥ 10 mm from petrous to superior hypophyseal ICA segments. Patients were treated by either PED (37 patients) or traditional coiling techniques (18 patients). Aortic arch type and proximal ICA tortuosity were also assessed as markers of access difficulty. RESULTS Average radiation dose with PED treatment was 2840 ± 213 mGy and 4010 ± 708 mGy with traditional coiling techniques (p=0.048; 29% decrease with PED). Mean fluoroscopy time for PED was 56.1 ± 5.0 min and 85.9 ± 11.9 min for coiling cases (p=0.0087; 35% decrease with PED). These benefits existed despite more difficult arch anatomy and a trend towards greater proximal vessel tortuosity in PED cases. Contrast dye amounts were also reduced by 37.5% in PED cases (75 ± 6 mL) versus coiling cases (120 ± 13 mL, p=0.0008). CONCLUSIONS Treatment of large and giant proximal ICA aneurysms using PED requires less radiation, less fluoroscopy time, and less contrast administration than standard coiling techniques. This further demonstrates the benefits of flow diversion for treatment of these aneurysms.


Future-proofing cardiac rehabilitation: Transitioning services to telehealth during COVID-19.


title: Toward a consensus view on the infectious risks associated with land application of sewage sludge.

text: The science linking processed sewage sludge (biosolids) land application with human health has improved in the last ten years. The goal of this review is to develop a consensus view on the human health impacts associated with land-applying biosolids. Pre-existing risk studies are integrated with recent advances in biosolids pathogen exposure science and risk analysis. Other than accidental direct ingestion, the highest public risks of infection from land application are associated with airborne exposure. Multiple, independent risk assessments for enteroviruses similarly estimate the yearly probabilities of infection near 10(-4). However, the inclusion of other emerging pathogens, specifically norovirus, increases this yearly infectious risk by over 2 orders of magnitude. Quantitative microbial risk assessment for biosolids exposure more effectively operates as a tool for analyzing how exposure can be reduced rather than being used to assess "safety". Such analysis demonstrates that the tradition of monitoring pathogen quality by Salmonella spp. and enterovirus content underestimates the infectious risk to the public, and that a rigorous biosolids pathogen treatment process, rather than extending community separation distances, is the most efficient method for reducing pathogen exposure and infectious risk.


title: Detection of hypoventilation by capnography and its association with hypoxia in children undergoing sedation with ketamine.

text: OBJECTIVES Hypopneic hypoventilation, a decrease in tidal volume without a change in respiratory rate, is not easily detected by standard monitoring practices during sedation but can be detected by capnography. Our goal was to determine the frequency of hypopneic hypoventilation and its association with hypoxia in children undergoing sedation with ketamine. METHODS Children who received intravenous ketamine with or without midazolam for sedation in a pediatric emergency department were prospectively enrolled. Heart rate, respiratory rate, pulse oximetry, and end-tidal carbon dioxide (ET(CO2)) levels were recorded every 30 seconds. RESULTS Fifty-eight subjects were included in this study. Fifty percent of subjects had recorded ET(CO2) values less than 30 mm Hg without a rise in respiratory rate. Twenty-eight percent of subjects experienced a decrease in pulse oximetry less than 95%. Patients who experienced a persistent decrease in ET(CO2) at least 30 seconds in length were much more likely to have a persistent decrease in pulse oximetry than those with normal or transient decreases in ET(CO2) (relative risk, 6.6; 95% confidence interval, 1.4-30.5). Decreases in ET(CO2) occurred on an average of 3.7 minutes before decreases in pulse oximetry. CONCLUSIONS Hypopneic hypoventilation as detected by capnography is common in children undergoing sedation with ketamine with or without midazolam. Hypoxia is frequently preceded by low ET(CO2) levels. Further studies are needed to determine if the addition of routine monitoring with capnography can reduce the frequency of hypoxia in children undergoing sedation.


title: Flexor tendon repair: a comparative study between a knotless barbed suture repair and a traditional four-strand monofilament suture repair.

text: We compared the tensile strength of a novel knotless barbed suture method with a traditional four-strand Adelaide technique for flexor tendon repairs. Forty fresh porcine flexor tendons were transected and randomly assigned to one of the repair groups before repair. Biomechanical testing demonstrated that the tensile strengths between both tendon groups were very similar. However, less force was required to create a 2 mm gap in the four-strand repair method compared with the knotless barbed technique. There was a significant reduction in the cross-sectional area in the barbed suture group after repair compared with the Adelaide group. This would create better gliding within the pulley system in vivo and could decrease gapping and tendon rupture.


title: Chemical diversity of biologically active metabolites in the sclerotia of Inonotus obliquus and submerged culture strategies for up-regulating their production.

text: Inonotus obliquus (Fr.) Pilat is a white rot fungus belonging to the family Hymenochaetaceae in the Basidiomycota. In nature, this fungus rarely forms a fruiting body but usually an irregular shape of sclerotial conk called 'Chaga'. Characteristically, I. obliquus produces massive melanins released to the surface of Chaga. As early as in the sixteenth century, Chaga was used as an effective folk medicine in Russia and Northern Europe to treat several human malicious tumors and other diseases in the absence of any unacceptable toxic side effects. Chemical investigations show that I. obliquus produces a diverse range of secondary metabolites including phenolic compounds, melanins, and lanostane-type triterpenoids. Among these are the active components for antioxidant, antitumoral, and antiviral activities and for improving human immunity against infection of pathogenic microbes. Geographically, however, this fungus is restricted to very cold habitats and grows very slowly, suggesting that Chaga is not a reliable source of these bioactive compounds. Attempts for culturing this fungus axenically all resulted in a reduced production of bioactive metabolites. This review examines the current progress in the discovery of chemical diversity of Chaga and their biological activities and the strategies to modulate the expression of desired pathways to diversify and up-regulate the production of bioactive metabolites by the fungus grown in submerged cultures for possible drug discovery.


title: Possible role of carpal hyperextension in superficial digital flexor tendinopathy.

text: REASONS FOR PERFORMING STUDY The specific biomechanical circumstances that induce excessive superficial digital flexor tendon (SDFT) strain in horses are unknown. HYPOTHESIS Carpal joint hyperextension during axial limb loading during the middle of stance disproportionately enhances SDFT strains compared to suspensory ligament (SL) strains. METHODS Superficial digital flexor tendon and SL strains were measured in 7 cadaver limbs during in vitro loading that maintained carpal extension or allowed carpal hyperextension by constraining, or allowing rotation of, the radius during loading conditions that simulated the middle of stance at the walk. The effect of carpal hyperextension on SDFT and SL strains and joint angles was assessed using repeated measures ANOVA. RESULTS Limb loading generally resulted in higher SL strains than SDFT strains for both carpal extension and hyperextension loading conditions. Compared to carpal extension, carpal hyperextension resulted in increased strains in both the SDFT and the SL; however, a greater increase in strain was seen in the SDFT. On average, carpal hyperextension caused approximately 3° greater carpal extension, 1° greater metacarpophalangeal joint hyperextension, 1° greater proximal interphalangeal joint flexion and <1° greater distal interphalangeal joint flexion than did carpal extension. CONCLUSIONS AND CLINICAL RELEVANCE Carpal joint hyperextension is likely to induce disproportionately higher strain in the SDFT than in the SL. Factors that affect carpal stability are likely to affect the risk for superficial digital flexor tendinopathy.


title: Quality indicators for hip fracture care, a systematic review.

text: Quality indicators are used to measure quality of care and enable benchmarking. An overview of all existing hip fracture quality indicators is lacking. The primary aim was to identify quality indicators for hip fracture care reported in literature, hip fracture audits, and guidelines. The secondary aim was to compose a set of methodologically sound quality indicators for the evaluation of hip fracture care in clinical practice. A literature search according to the PRISMA guidelines and an internet search were performed to identify hip fracture quality indicators. The indicators were subdivided into process, structure, and outcome indicators. The methodological quality of the indicators was judged using the Appraisal of Indicators through Research and Evaluation (AIRE) instrument. For structure and process indicators, the construct validity was assessed. Sixteen publications, nine audits and five guidelines were included. In total, 97 unique quality indicators were found: 9 structure, 63 process, and 25 outcome indicators. Since detailed methodological information about the indicators was lacking, the AIRE instrument could not be applied. Seven indicators correlated with an outcome measure. A set of nine quality indicators was extracted from the literature, audits, and guidelines. Many quality indicators are described and used. Not all of them correlate with outcomes of care and have been assessed methodologically. As methodological evidence is lacking, we recommend the extracted set of nine indicators to be used as the starting point for further clinical research. Future research should focus on assessing the clinimetric properties of the existing quality indicators.


title: Caries Progression Rates Revisited: A Systematic Review.

text: Caries progression seems to follow universal, predictable rates, depending largely on the caries severity in populations: the higher the caries severity, the higher the progression rates. Quantification of these rates would allow prediction of future caries increments. Our aim was to describe caries progression rates in the primary and permanent dentition in Western populations (not in lesions) of children and adolescents. Therefore, we systematically searched MEDLINE-PubMed, Embase, CINAHL, and the Cochrane library for studies reporting caries progression data. Eligibility criteria were reporting empirical data from at least 2 full-mouth dental caries examinations in a closed cohort during a follow-up of at least 3 y, a first examination after 1974, a second examination before the age of 22 y, caries assessed as dentine caries (d3/D3), and caries reported in dmfs/DMFS (decayed, missing, and filled surfaces), dmft/DMFT (decayed, missing, and filled teeth), or caries-free participants. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we described the results for the primary and permanent dentition in a systematic review, performed a meta-analysis for the caries incidence rate in the permanent dentition, and conducted multivariate, hierarchical meta-regression analyses for the caries incidence rate and the increments in DMFS and DMFT. Of the 6,343 unique studies retrieved, 43 studies (56,376 participants) were included for systematic review and 32 for meta-analyses (39,429 participants). The annual decline in caries-free children in the permanent dentition ranged from 0.8% to 10.2%. The annual increment ranged from 0.07 to 1.77 in DMFS and from 0.06 to 0.73 in DMFT. The pooled caries incidence rate was 0.11 (0.09-0.13) per person-year at risk. Meta-regression analyses showed that the methods of individual studies influenced pooled caries incidence rates and increments in DMFS and DMFT. This should be taken into account in planning and evaluation of oral health care services. However, the caries incidence rate is promising for prediction of future caries increments in populations.


title: Evaluation and quantification of geographical differences in wound complication rates following the extended lateral approach in displaced intra-articular calcaneal fractures - A systematic review of the literature.

text: INTRODUCTION Calcaneal fracture surgery is often performed via the extended lateral approach (ELA). Large differences are reported in literature on wound complication rates. Aim was to perform a systematic review on reported postoperative wound complication (POWC) and postoperative wound infection (POWI) rates following the ELA and evaluate and quantify geographical differences. METHODS A literature search was conducted in the MEDLINE and EMBASE databases and Cochrane Library. Studies before 2000, with <10 patients, biomechanical studies and reviews were excluded. No restrictions regarding language were applied. RESULTS 3068 articles were identified of which 123 were included, with 8584 calcaneal fractures in 28 different countries. The average total number of POWC was 14.3%, with 3.8% of superficial and 2.2% of deep infections. The highest POWI rate was found in Europe (12.1%) and the lowest in North America (2.8%). A significant difference in incidence of deep POWI between continents was detected (median 0-3.8%). No differences were found in incidence of POWC and POWI between retro- and prospective studies (respectively p=0.970, p=0.748) or studies with <10 or ≥10 operations per year (respectively p=0.326, p=0.378). However, lower rates of POWI were found in studies with a follow up of >3months (p=0.01). CONCLUSION Large differences were detected in incidence of POWC and POWI following calcaneal fracture surgery with the ELA between countries and continents. We did not find a lower POWC or POWI rate in retrospective studies compared to prospective studies, larger studies or in studies in which more patients were treated annually. However, the rate of POWI was significantly lower in studies with a follow up of >3months. We advise the use of a reliable postoperative complication registration system and uniformity in the use of standardized definitions of wound complications for calcaneal fracture surgery.


title: What every orthopaedic surgeon should know about COVID-19: A review of the current literature.

text: The coronavirus (COVID-19) pandemic has severely affected the medical community and stopped the world in its tracks. This review aims to provide the basic information necessary for us, orthopaedic surgeons to prepare ourselves to face this pandemic together. Herein, we cover the background of COVID-19, presentation, investigations, transmission, infection control and touch upon emerging treatments. It is of paramount importance that we should stay vigilant for our patients, our families and ourselves. Adequate infection control measures are necessary during day-to-day clinical work.


title: Fetal exposure to maternal type 1 diabetes is associated with renal dysfunction at adult age.

text: OBJECTIVE In animal studies, hyperglycemia during fetal development reduces nephron numbers. We tested whether this observation translates into renal dysfunction in humans by studying renal functional reserve in adult offspring exposed in utero to maternal type 1 diabetes. RESEARCH DESIGN AND METHODS We compared 19 nondiabetic offspring of type 1 diabetic mothers with 18 offspring of type 1 diabetic fathers (control subjects). Glomerular filtration rate ((51)Cr-EDTA clearance), effective renal plasma flow ((123)I-hippurate clearance), mean arterial pressure, and renal vascular resistances were measured at baseline and during amino acid infusion, which mobilizes renal functional reserve. RESULTS Offspring of type 1 diabetic mothers were similar to control subjects for age (median 27, range 18-41, years), sex, BMI (23.1 ± 3.7 kg/m(2)), and birth weight (3,288 ± 550 vs. 3,440 ± 489 g). During amino acid infusion, glomerular filtration rate and effective renal plasma flow increased less in offspring of type 1 diabetic mothers than in control subjects: from 103 ± 14 to 111 ± 17 ml/min (8 ± 13%) vs. from 108 ± 17 to 128 ± 23 ml/min (19 ± 7%, P = 0.009) and from 509 ± 58 to 536 ± 80 ml/min (5 ± 9%) vs. from 536 ± 114 to 620 ± 140 ml/min (16 ± 11%, P = 0.0035). Mean arterial pressure and renal vascular resistances declined less than in control subjects: 2 ± 5 vs. -2 ± 3% (P = 0.019) and 3 ± 9 vs. -14 ± 8% (P = 0.001). CONCLUSIONS Reduced functional reserve may reflect a reduced number of nephrons undergoing individual hyperfiltration. If so, offspring of type 1 diabetic mothers may be predisposed to glomerular and vascular diseases.


The perfect storm: a foreign body and splenic infarct mimicking a sleeve gastrectomy leak.


title: Monitoring fluid responsiveness.

text: Functional hemodynamic parameters, such as stroke volume variation (SVV) and pulse pressure variation (PPV), are useful hemodynamic monitoring tools for the assessment of fluid responsiveness. These parameters are based on heart-lung interaction during positive mechanical pressure ventilation: Cyclic changes of intrathoracic pressure result in a reduced venous return and a decreased cardiac stroke volume after inspiration followed by a restoration of preload and stroke volume after expiration. Hemodynamic monitoring systems based on pulse wave analysis allow an automatic assessment of SVV and--at least for some of the devices--of PPV. Moreover, PPV is being integrated in the standard monitoring in the operating room and the intensive care unit, and the noninvasive plethysmographic assessment of fluid responsiveness has been recently introduced. These developments will result in a broader application of functional hemodynamic parameters in the near future. In contrast to traditional preload parameters (i.e. central venous pressure), SVV and PPV allow the prediction of fluid responsiveness and thus the determination of the actual position on an individual Frank-Starling curve or--in other words--the assessment of an individual preload reserve. Different studies in the last decade were able to prove the validity of this concept. However, to use these functional hemodynamic parameters in daily clinical practice, some limitations have to be considered. Arrhythmia and right heart failure, but also spontaneous breathing of a patient, or small tidal volumes may preclude reliable assessment. Based on these aspects, an ideal area of application of these parameters may be the use during perioperative hemodynamic optimization to improve patient outcome. However, only few studies on goal-directed therapy guided by these parameters have been published so far.


title: Absence of Severe Acute Respiratory Syndrome-Coronavirus-2 RNA in Human Corneal Tissues.

text: PURPOSE To examine corneal tissue for SARS-CoV-2 positivity with regard to implications for tissue procurement, processing, corneal transplantation and ocular surgery on healthy patients. We performed quantitative (q)RT-PCR-testing for SARS-CoV-2 RNA on corneal stroma and endothelium, bulbar conjunctiva, conjunctival fluid swabs, anterior chamber fluid and corneal epithelium of COVID-19 postmortem donors. METHODS Included in this study were 10 bulbi of 5 COVID-19 patients who passed away due to respiratory insufficiency. Informed consent and Institutional Review Board approval was obtained prior to this study (241/2020BO2). SARS-CoV-2 was detected via a pharyngeal swab and broncho-alveolar lavage. Tissue procurement and tissue preparation were performed with personal protective equipment (PPE) and the necessary protective measures. qRT-PCR-testing was performed for each of the above mentioned tissues and intraocular fluids. RESULTS The qRT-PCRs yielded no viral RNA in the following ocular tissues and intraocular fluid: Corneal stroma and endothelium, bulbar-limbal conjunctiva, conjunctival fluid swabs, anterior chamber fluid and corneal epithelium. CONCLUSION In this study no SARS-CoV-2-RNA was detected in conjunctiva, anterior chamber fluid and corneal tissues (endothelium, stroma and epithelium) of COVID-19 donors. This implicates that the risk for SARS-CoV-2 infection via corneal or conjunctival tissue is very low. However, further studies on a higher number of COVID-19 patients are necessary to confirm these results. This might be of high importance for donor tissue procurement, processing and corneal transplantation.


title: Development and evaluation of a real-time RT-PCR assay for the detection of Ebola virus (Zaire) during an Ebola outbreak in Guinea in 2014-2015.

text: In early February 2014, an outbreak of the Ebola virus disease caused by Zaire ebolavirus (EBOV) occurred in Guinea; cases were also recorded in other West African countries with a combined population of approximately 25 million. A rapid, sensitive and inexpensive method for detecting EBOV is needed to effectively control such outbreak. Here, we report a real-time reverse-transcription PCR assay for Z. ebolavirus detection used by the Specialized Anti-epidemic Team of the Russian Federation during the Ebola virus disease prevention mission in the Republic of Guinea. The analytical sensitivity of the assay is 5 × 10(2) viral particles per ml, and high specificity is demonstrated using representative sampling of viral, bacterial and human nucleic acids. This assay can be applied successfully for detecting the West African strains of Z. ebolavirus as well as on strains isolated in the Democratic Republic of the Congo in 2014.


title: The S Gene Is Necessary but Not Sufficient for the Virulence of Porcine Epidemic Diarrhea Virus Novel Variant Strain BJ2011C.

text: The recently emerged highly virulent variants of porcine epidemic diarrhea virus (PEDV) have caused colossal economic losses to the worldwide swine industry. In this study, we investigated the viral virulence determinants by constructing a series of chimeric mutants between the highly virulent strain BJ2011C and the avirulent strain CHM2013. When tested in the 2-day-old piglet model, wild-type (WT) BJ2011C caused severe diarrhea and death of the piglets within 72 h. In contrast, its chimeric derivative carrying the S gene from CHM2013 (BJ2011C-SCHM) was avirulent to the piglets. Moreover, reciprocal substitution of the BJ2011C S gene (CHM2013-SBJ) did not enable CHM2013 to gain any virulence. However, when the whole structural protein-coding region of BJ2011C (CHM2013-SPBJ) was swapped, CHM2013 started to gain the ability to efficiently colonize the intestinal tract and caused diarrhea in piglets. A further gain of virulence required additional acquisition of the 3' untranslated region (UTR) of BJ2011C, and the resultant virus (CHM2013-SP + 3UTRBJ) caused more severe diarrhea and death of piglets. Together, our findings suggest that the virulence of PEDV epidemic strains is a multigenic event and that the S gene is only one of the necessary determinants.IMPORTANCE The recently emerged highly virulent PEDV variants are the major cause of the global porcine epidemic diarrhea (PED) pandemic. The S gene of the variants undergoes remarkable variations and has been thought to be the virulence determinant for the enhanced pathogenesis. Our studies here showed that the S gene is only part of the story and that full virulence requires cooperation from other genes. Our findings provide insight into the pathogenic mechanism of the highly virulent PEDV variants and have implications for future vaccine development.


title: The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome.

text: BACKGROUND Few observations exist with respect to the pro-coagulant profile of patients with COVID-19 acute respiratory distress syndrome (ARDS). Reports of thromboembolic complications are scarce but suggestive for a clinical relevance of the problem. OBJECTIVES Prospective observational study aimed to characterize the coagulation profile of COVID-19 ARDS patients with standard and viscoelastic coagulation tests, and to evaluate their changes after establishment of an aggressive thromboprophylaxis. METHODS Sixteen patients with COVID-19 ARDS received a complete coagulation profile at the admission in the intensive care unit. Ten patients were followed in the subsequent 7 days, after increasing the dose of low molecular weight heparin, antithrombin levels correction, and clopidogrel in selected cases. RESULTS At baseline, the patients showed a pro-coagulant profile characterized by an increased clot strength (CS, median 55 hPa, 95% interquartile range 35-63), platelet contribution to CS (PCS, 43 hPa, interquartile range 24-45), fibrinogen contribution to CS (FCS, 12 hPa, interquartile range 6-13.5 elevated D-dimer levels (5.5 μg/mL, interquartile range 2.5-6.5), hyperfibrinogenemia (794 mg/dL, interquartile range 583-933). Fibrinogen levels were associated (R2 =0.506, P=0.003) with interleukin-6 values. After increasing the thromboprophylaxis, there was a significant (P=0.001) time-related decrease of fibrinogen levels, D-dimers (P=0.017), CS (P=0.013), PCS (P=0.035) and FCS (P=0.038). CONCLUSION The pro-coagulant pattern of these patients may justify the clinical reports of thromboembolic complications (pulmonary embolism) during the course of the disease. Further studies are needed to assess the best prophylaxis and treatment of this condition.


title: Coagulation pattern in critical liver dysfunction.

text: PURPOSE OF REVIEW This article reviews the current literature dealing with pathophysiology, diagnostics, bleeding management, and thromboprophylaxis in patients with acute and chronic liver dysfunction. RECENT FINDINGS Routine coagulation tests such as prothrombin time and International Normalized Ratio (INR) are not able to define whether a patient with critical liver dysfunction is hypocoagulable or hypercoagulable and are not able to predict the risk of bleeding in patients with liver dysfunction. Therefore, prophylactic transfusion of fresh frozen plasma and platelets in order to correct laboratory values is not appropriate. Notably, patients with liver dysfunction and increased INR are not 'autoanticoagulated'. In contrast, thrombin generation assays in the presence and absence of thrombomodulin or Protac, a snake venom that activates protein C in a manner similar to thrombomodulin, as well as viscoelastic tests (thrombelastography/thromboelastometry) indicate that patients with liver dysfunction are rather hypercoagulable with the inherent risk of thrombosis. SUMMARY Coagulopathy in patients with critical liver dysfunction is complex and can quickly decompensate to bleeding as well as to thrombosis. Both are associated with worse outcome. Hemostatic interventions should only be performed in case of clinically relevant bleeding and thromboprophylaxis should strongly be considered.


title: Laparoendoscopic single-site Heller myotomy with anterior fundoplication for achalasia.

text: BACKGROUND Laparoendoscopic single-site (LESS) surgery is beginning to include advanced laparoscopic operations such as Heller myotomy with anterior fundoplication. However, the efficacy of LESS Heller myotomy has not been established. This study aimed to evaluate the authors' initial experience with LESS Heller myotomy for achalasia. METHODS Transumbilical LESS Heller myotomy with concomitant anterior fundoplication for achalasia was undertaken for 66 patients after October 2007. Outcomes including operative time, complications, and length of hospital stay were recorded and compared with those for an earlier contiguous group of 66 consecutive patients undergoing conventional multi-incision laparoscopic Heller myotomy with anterior fundoplication. Symptoms before and after myotomy were scored by the patients using a Likert scale ranging from 0 (never/not severe) to 10 (always/very severe). Data were analyzed using the Mann-Whitney U test, the Wilcoxon matched-pairs test, and Fisher's exact test where appropriate. RESULTS Patients undergoing LESS Heller myotomy were similar to those undergoing conventional laparoscopic Heller myotomy in gender, age, body mass index (BMI), blood loss, and length of hospital stay. However, the patients undergoing LESS Heller myotomies had operations of significantly longer duration (median, 117 vs. 93 min with the conventional laparoscopic approach) (p<0.003). For 11 patients (16%) undergoing LESS Heller myotomy, additional ports/incisions were required. No patients were converted to "open" operations, and no patients had procedure-specific complications. Symptom reduction was dramatic and satisfying after both LESS and conventional laparoscopic myotomy with fundoplication. The symptom reduction was similar with the two procedures. The LESS approach left no apparent umbilical scar. CONCLUSION Heller myotomy with anterior fundoplication effectively treats achalasia. The findings showed LESS Heller myotomy with anterior fundoplication to be feasible, safe, and efficacious. Although the LESS approach increases operative time, it does not increase procedure-related morbidity or hospital length of stay and avoids apparent umbilical scarring. Laparoendoscopic single-site surgery represents a paradigm shift to more minimally invasive surgery and is applicable to advanced laparoscopic operations such as Heller myotomy and anterior fundoplication.


WHO: the world's most powerful international organisation?


Alternative strategies for CT unit management during the COVID-19 pandemic: a single center experience.


title: Centhaquin improves survival in a swine model of hemorrhagic shock.

text: BACKGROUND Hemorrhage is a frequent event in hospital and prehospital settings. The aim of the present study was to investigate whether centhaquin improves 24-h survival and reduces the total volume of required fluids in an established model of swine hemorrhagic shock. MATERIAL AND METHODS Twenty-five pigs were instrumented and subjected to hemorrhagic shock. The animals were randomly allocated in two experimental groups, the control (vehicle) (n = 10) and the centhaquin groups (0.015 mg/kg, n = 10); all animals received lactated Ringer solution in the resuscitation phase until their mean arterial pressure reached 90% of the baseline. A sham group (n = 5) was added a posteriori to mimic the hemodynamic profile of the centhaquin group. RESULTS A statistically significant difference was observed in the time required for the three groups to reach their target mean aortic pressure, 36.88 ± 3.26 min for the control group versus 9.40 ± 1.01 min for the sham group and 7.10 ± 0.97 min for the centhaquin group (P < 0.001). The total amount of fluids in the control and the sham groups was significantly higher when compared with that of the centhaquin-treated animals (P < 0.001). All 10 animals in the centhaquin group survived for 24 h, whereas only three animals survived in the control group and one animal in the sham group (P = 0.002). CONCLUSIONS Centhaquin 0.015 mg/kg administered in the fluid resuscitation phase resulted in lower volume of fluids and better survival compared with control and sham-operated animals.


title: Efficacy and safety of ambroxol lozenges in the treatment of acute uncomplicated sore throat. EBM-based clinical documentation.

text: Sore throat is the hallmark of acute pharyngitis. Although usually caused by viral infections, it is frequently treated with antibiotics. Such inappropriate use of antibiotics might best be challenged by offering efficacious and safe symptomatic pain relief instead. However, there is need for robust evidence to support such alternatives. Presently, the evidence from randomised, placebo-controlled, double-blind clinical trials (RCT) with the local anaesthetic ambroxol (CAS 23828-92-4) in the treatment of sore throat is being reviewed. This relates to five RCT in 1,772 patients; 1,713 were evaluable with regard to efficacy. Treatment with ambroxol lozenges was statistically significantly superior to placebo in reducing sore throat pain intensity with a high level of consistency of the estimated effect across the different studies. The effect had an early onset and lasted up to at least 3 h after a single first lozenge. The pain relief was associated with a statistically superior regression of pharyngeal redness and inflammation; with ambroxol, the overall efficacy was more frequently rated as at least "good". Treatment with the ambroxol lozenges was well tolerated. There was heterogeneity in reporting adverse events: in one later study with less severe baseline pain intensity there was more frequent reporting of hypoaesthesia of the oral cavity and tongue as an untoward phenomenon. In patients with more severe baseline pain this reflection of the medication's pharmacological action was only rarely reported as untoward. It is concluded that lozenges containing 20 mg ambroxol are a safe and efficacious treatment for acute uncomplicated sore throat of recent onset in adult patients.


title: Triple and quadruple cervical artery dissections: a systematic review of individual patient data.

text: BACKGROUND AND PURPOSE Simultaneous dissection of three or four cervical arteries rarely occurs. As a result, limited information is available on clinical characteristics, underlying causes, treatment, and outcome of these patients. METHODS We performed a systematic review of individual patient data on triple and quadruple cervical artery dissection (CeAD). We included all cases for whom, at minimum, data on age, sex and affected cervical arteries were available. RESULTS Out of 1396 publications identified in the initial search, 52 were included, with data available on 96 patients. Mean age was 42 years and 66% were women. 63% had triple CeAD. The most common manifestations were headache (69%), neck pain (44%), motor deficit (36%), and Horner syndrome (34%). 57% had an ischemic stroke, in the majority of these patients the stroke was confined to the vascular territory of a single artery. 83% were managed medically (antiplatelets or anticoagulants) and 11% underwent endovascular treatment. An underlying disease or triggering event was identified in 71%, most commonly trauma (35%, cervical manipulative therapy in 13%), infection (18%), fibromuscular dysplasia (16%), and hereditary connective tissue disorder (8%). In-hospital mortality was 1%. 80% of patients had a good functional outcome (mRS 0-1) at follow-up. Two recurrences (3%) were reported. CONCLUSIONS Triple or quadruple CeAD mostly affected young women, and underlying disease or triggering event could be identified in more than two-thirds of patients. Less than two-thirds of triple or quadruple CeAD patients suffered ischemic stroke. Most patients were managed medically and the majority had a favorable outcome.


Foot Manifestations in a COVID-19 Positive Patient: A Case Study.


title: RNA Viruses: A Case Study of the Biology of Emerging Infectious Diseases.

text: There are 180 currently recognized species of RNA virus that can infect humans, and on average, 2 new species are added every year. RNA viruses are routinely exchanged between humans and other hosts (particularly other mammals and sometimes birds) over both epidemiological and evolutionary time: 89% of human-infective species are considered zoonotic and many of the remainder have zoonotic origins. Some viruses that have crossed the species barrier into humans have persisted and become human-adapted viruses, as exemplified by the emergence of HIV-1. Most, however, have remained as zoonoses, and a substantial number have apparently disappeared again. We still know relatively little about what determines whether a virus is able to infect, transmit from, and cause disease in humans, but there is evidence that factors such as host range, cell receptor usage, tissue tropisms, and transmission route all play a role. Although systematic surveillance for potential new human viruses in nonhuman hosts would be enormously challenging, we can reasonably aspire to much better knowledge of the diversity of mammalian and avian RNA viruses than exists at present.


title: Involvement of CD16 in antibody-dependent enhancement of porcine reproductive and respiratory syndrome virus infection.

text: The immunological effect of porcine reproductive and respiratory syndrome disease virus (PRRSV) vaccines is thought to be influenced by a variety of host factors, in which antibody-dependent enhancement (ADE) of infection is one crucial factor. Here, we assessed the mechanism of ADE of PRRSV infection. First, we found that subneutralizing serum could induce ADE of PRRSV infection in porcine alveolar macrophages (PAMs). Quantitative PCR, Western blotting and flow cytometry revealed that CD16 is the most abundant Fcγ receptor (FcγR) expressed on the surface of PAMs; thus, the role of CD16 in ADE of PRRSV infection was examined in PAMs. By using functional blocking antibodies, we demonstrated that CD16 is involved in enhanced virus production in PRRSV-antibody immune complex-infected PAMs. Because PAMs co-express different FcγR isoforms, we evaluated the effects of CD16 in FcγR-non-bearing cells by transfection. Using these engineered cells, we found that CD16 could specifically bind to the PRRSV-antibody immune complex and subsequently mediate internalization of the virus, resulting in the generation of progeny virus. We also showed that efficient expression of CD16 required association of the FcR γ-chain. Together, our findings provide significant new insights into PRRSV infection, which can be enhanced by CD16-mediated PRRSV-antibody immune complexes. This CD16-mediated ADE may induce a shift in PRRSV tropism towards CD16-expressing cells, distributing virus to more organs during virus infection.


title: Embolization of pulmonary sequestration with Onyx: an unusual application.

text: We report a baby with intralobar pulmonary sequestration who was successfully treated with a new embolization agent, Onyx. A 1.5-month-old female infant was admitted to our hospital with sweating and fatigue. Telecardiography showed cardiomegaly, dextrocardia, and increased pulmonary vascular markings. In thoracic computerized tomography, pulmonary sequestration, right pulmonary hypoplasia, and large collateral arteries were seen. The collateral arteries were originating from the celiac trunk and aorta. Echocardiography revealed enlargement of the left atrium and ventricle and left ventricle systolic dysfunction. Angiography revealed a large feeding artery and three branches originating from the aorta and another feeding artery originating from the celiac trunk. We performed embolization of the feeding arteries and their branches, with coils and Onyx. The procedure was performed without complications, and all feeding arteries were completely occluded. The infant started to gain weight. One year later, the infant's body weight had increased and she had no respiratory problems or signs of congestive heart failure. In this case report, we suggest that embolization with Onyx is a reliable alternative method to surgery for infants with pulmonary sequestration. With future studies, pulmonary sequestration embolization with Onyx may become an acceptable and easy treatment option in pediatric patients.


title: Evaluation of a type 1 diabetes serum cohort by SELDI-TOF MS protein profiling.

text: Proteomics analysis of serum from patients with type 1 diabetes (T1D) may lead to novel biomarkers for prediction of disease and for patient monitoring. However, the serum proteome is highly sensitive to sample processing and before proteomics biomarker research serum cohorts should preferably be examined for potential bias between sample groups. SELDI-TOF MS protein profiling was used for preliminary evaluation of a biological-bank with 766 serum samples from 270 patients with T1D, collected at 18 different paediatric centers representing 15 countries in Europe and Japan over 2 years (2000-2002). Samples collected 1 (n = 270), 6 (n = 248), and 12 (n = 248) months after T1D diagnosis were grouped across centers and compared. The serum protein profiles varied with collection site and day of analysis; however, markers of sample processing were not systematically different between samples collected at different times after diagnosis. Three members of the apolipoprotein family increased with time in patient serum collected 1, 6, and 12 months after diagnosis (ANOVA, p<0.001). These results support the use of this serum cohort for further proteomic studies and illustrate the potential of high-throughput MALDI/SELDI-TOF MS protein profiling for evaluation of serum cohorts before proteomics biomarker research.


title: Comparative dendritic cell biology of veterinary mammals.

text: Dendritic cells (DC) have a main function in innate immunity in that they sense infections and environmental antigens at the skin and mucosal surfaces and thereby critically influence decisions about immune activation or tolerance. As professional antigen-presenting cells, they are essential for induction of adaptive immune responses. Consequently, knowledge on this cell type is required to understand the immune systems of veterinary mammals, including cattle, sheep, pigs, dogs, cats, and horses. Recent ontogenic studies define bona fide DC as an independent lineage of hematopoietic cells originating from a common precursor. Distinct transcription factors control the development into the two subsets of classical DC and plasmacytoid DC. These DC subsets express a distinguishable transcriptome, which differs from that of monocyte-derived DC. Using a comparative approach based on phenotype and function, this review attempts to classify DC of veterinary mammals and to describe important knowledge gaps.


Opioid Use Disorder Treatment and Potential Interactions With Novel COVID-19 Medications: A Clinical Perspective.


title: Effect of fesoterodine 4 mg on bladder diary and patient-reported outcomes during the first week of treatment in subjects with overactive bladder.

text: OBJECTIVE To assess the onset of efficacy of fesoterodine 4 mg versus placebo in subjects with overactive bladder (OAB) symptoms. RESEARCH DESIGN AND METHODS Subjects who reported OAB symptoms for ≥ 3 months and recorded ≥ 8 micturitions and ≥ 1 urgency urinary incontinence (UUI) episode per 24 hours in 3-day baseline diaries were randomized to fesoterodine 4 mg, tolterodine extended release (ER) 4 mg, or placebo. This is an analysis of first week data from a 12-week, double-blind trial. ClinicalTrials.gov unique ID: NCT00444925. MAIN OUTCOME MEASURES Baseline to week 1 changes in 3-day bladder diary variables, Patient Perception of Bladder Condition (PPBC), and Urgency Perception Scale (UPS) scores reported by subjects receiving fesoterodine 4 mg or placebo. RESULTS By week 1, fesoterodine 4 mg (n = 679) was associated with significantly greater improvements compared with placebo (n = 334) in micturitions, urgency, severe urgency and UUI episodes, frequency-urgency sum, and MVV per 24 hours and 3-day diary-dry rate (all p < 0.05), but not nocturnal micturitions per 24 hours (p = 0.273). These differences were significant as early as day 5 of treatment (i.e., day 1 of the 3-day diary) for all diary endpoints except nocturnal micturitions and MVV. Changes in PPBC scores were significantly more favorable with fesoterodine 4 mg versus placebo (p = 0.0143); changes in UPS scores were not significantly different (p = 0.077). CONCLUSION The results provide evidence that patients receiving fesoterodine 4 mg for their OAB symptoms may expect to experience a response as early as 1 week after initiating treatment. One limitation is that, although 65% of subjects had received treatment with antimuscarinics before the study, whether subjects were dissatisfied with previous treatment and reasons for dissatisfaction were not collected. This might affect the magnitude of outcome improvements. Also, it is not known whether the UPS is sensitive enough to detect treatment differences as early as week 1.


title: Case of pneumatosis intestinalis and hepatic portal venous gas following a laparoscopic right hemicolectomy.

text: Hepatic portal venous gas (HPVG) in most cases signifies either mechanical migration of air into the portal system due to bowel ischaemia (pneumatosis intestinalis) or portal sepsis due to gas-forming organisms. Successful management of portal sepsis involves early identification of the condition, intensive resuscitation, broad-spectrum antibiotics and a laparotomy for possible bowel ischaemia. In this report, we discuss the case of a patient with pneumatosis intestinalis and HPVG after an elective laparoscopic right hemicolectomy. After an initial slow recovery, on postoperative day seven, the patient had profuse diarrhoea and confusion, and was hyponatraemic. A CT scan revealed pneumatosis intestinalis and HPVG. A laparotomy showed no obvious cause for HPVG and there was no ischaemic bowel. She was managed with intensive care, hyperbaric oxygen therapy, broad-spectrum antibiotics and total-parenteral nutrition. She has made a good recovery. This case highlights the presenting features, differential diagnoses, and management of pneumatosis intestinalis and HPVG.


title: Understanding COVID-19: Digit ratio (2D:4D) and sex differences in national case fatality rates

text: Abstract Background The reported national case fatality rates (CFRs) for coronavirus disease 2019 (COVID-19) shows a sex bias with males > females. The relative lengths of the index (2D) and ring (4D) fingers (digit ratio; 2D:4D) is a sexually dimorphic (males < females) proxy of fetal sex steroids (low 2D:4D indicates high prenatal testosterone/low prenatal estrogen). Aim To examine sex-specific relationships of 2D:4D per nation with national values of COVID-19 CFRs. Study design: COVID-19 CFRs and the percent of male deaths were related to mean national (self-reported) 2D:4D by sex and hand from a large online survey (the BBC Internet Study). Subjects 103,482 men and 83,366 women. Outcome measures Relationships of mean national 2D:4D with CFRs from 41 countries and with national male death rates from 16 countries. Results Male right and left hand 2D:4D showed positive relationships with CFR. These relationships remained significant after removing the influence of female 2D:4D. A positive association of male right and left 2D:4D was detected with the percentage of male deaths. Conclusions At the national level, high mean 2D:4D (indicating low prenatal testosterone/high prenatal estrogen) is associated with high CFRs and percent male mortality. At the individual level, high 2D:4D may be a risk factor for severity of COVID-19 in males. We speculate that male 2D:4D is a negative correlate for expression of the SARS-CoV2 receptor (ACE2).


Changes to legal forensic inspections in Sicily during Covid-19.


title: Clinical nursing care guidance for management of patient with COVID-19.

text: COVID-19 is a highly contagious disease, which has human-to-human transmission through droplet and contact. It is commonly manifested as fever, dry cough, myalgia, and dyspnoea; the severity of this disease may range from mild, severe to a critical-illness. Currently, there is no definitive treatment or vaccine for COVID-19. The only proven form of management is isolation and supportive care. Therefore, nurses have a pivotal role to play in its management. This evidence-based comprehensive literature review provides the role of nurses in the management of patients with COVID-19, which starts from the initial assessment and triaging, sample collection, care of patients with mild-to-moderate symptoms, care of the critically-ill patient, and care of the dead body.


title: Body image concerns in patients with an implantable cardioverter defibrillator: A scoping review.

text: BACKGROUND Patients with an implantable cardioverter defibrillator (ICD) retain a scar and a bump at the site of implant. This may lead to body image concerns (BICs) that influence patients' quality of life. Few studies have examined the prevalence and impact of BICs postimplant, prompting us to conduct a scoping review of the field. METHODS We searched the Medline, Embase, PsycINFO, and Cinahl databases in August 2016 and repeated in May 2017. Included were studies reporting on patients ≥ 18 years, an ICD implant (transvenous, subcutaneous, or ICD with cardiac resynchronization therapy [CRT-D]), reporting on BICs, and published in peer-reviewed English-language journals. We excluded nonsystematic reviews, opinion pieces/letters, case studies, conference abstracts, PhD dissertations, protocol papers, studies of ICD shock treatment of atrial fibrillation, and of abdominally or submammary implanted ICDs. RESULTS A total of 40 articles were included: 16 qualitative and 24 quantitative. None of the included studies had BICs as their primary endpoint. Results showed that BICs are present in various degrees in the ICD population and can be attributed to the visibility of the ICD (the scar and bump). Women and younger patients had greater problems with BICs, although men also had concerns. Two items of the "Florida Patient Acceptance Survey" were the most frequently used to assess BICs. CONCLUSION BICs were present among ICD patients, but the degree of impact on their lives varied. There is a need for developing a BICs questionnaire to examine the prevalence of BICs and the potential impact on patients' lives in longitudinal studies.


title: Using Remote Medical Care Services to prevent the spread of the novel coronavirus.

text: UNSTRUCTURED This manuscript is in the category of Letters to editor, and there is no abstract.


title: Video: laparoscopic right hepatectomy and partial resection of the diaphragm for liver metastases.

text: BACKGROUND Indications for minimally invasive major hepatectomies have been increasing as experience with these techniques grows. Invasion into the diaphragm is considered a contraindication to the laparoscopic approach. At their institution, the authors have begun approaching all tumors laparoscopically. This report presents the techniques necessary to perform right hepatectomy, partial diaphragm resection, and repair using totally laparoscopic techniques. METHODS Five trocars are placed in a semilunar fashion approximately one handbreadth apart along a line one handbreadth below the right subcostal margin. The hepatic inflow is taken extraparenchymally before transection of the hepatic parenchyma in an anterior-to-posterior fashion. The hepatic inflow then is transected, and the involved portion of diaphragm is transected with ultrasonic shears. Next, the diaphragm is repaired primarily and buttressed with an absorbable material to decrease the incidence of recurrent diaphragmatic hernia. RESULTS Laparoscopic treatment was attempted for ten patients and successfully completed for nine of these patients (90%). All 10 patients had secondary liver tumors. Three patients required concomitant partial diaphragm resection. The median estimated blood loss (EBL) was 500 ml (range, 300-3,000 ml). All margins were negative, and the average hospital stay was 8 days (range, 5-17 days). Two patients (20%) experienced complications, which consisted of biliary leaks, which were treated with percutaneous drainage. One of these patients underwent conversion to an open procedure due to an inferior vena cava injury. No mortality occurred at 30 or 90 days of follow-up evaluation. CONCLUSION The minimally invasive approach to secondary tumors requiring right hepatectomy is feasible and safe even when there is diaphragmatic involvement. Larger series with long-term follow-up evaluation are needed to determine whether these short-term results translate into durable benefits.


title: Caribbean nurse migration-a scoping review.

text: BACKGROUND The migration of Caribbean nurses, particularly to developed countries such as Canada, the United States, and the United Kingdom, remains a matter of concern for most countries of the region. With nursing vacancy rates averaging 40%, individual countries and the region collectively are challenged to address this issue through the development and implementation of sustainable, feasible strategies. The aim of this scoping review is to examine the amount, type, sources, distribution, and focus of the conceptual and empirical literature on the migration of Caribbean nurses, and to identify gaps in the literature. METHODS Identified records were selected and reviewed using Arksey and O'Malley's scoping framework. A comprehensive search was conducted of eight electronic databases and the Google search engine. Findings were summarized numerically and thematically, with themes emerging through an iterative, inductive process. RESULTS Much of the literature included in our study (N = 6, 33%) originated in the United States. Publications steadily increased between 2003 and 2016, and half of them (N = 9) were journal articles. Many (N = 6, 33%) of the records used quantitative methods. The themes identified were as follows: (1) migration patterns and trends; (2) post-migration experiences; (3) past and present, policies, programs, and practices; and (4) consequences of migration to donor countries. More than half (N = 11, 56%) of the literature addressed nurse migration policies, programs, or practices, either solely or in part. Several gaps were identified including the need for evaluation of the effectiveness of current nurse migration management strategies and to study policies, trends, and impacts in understudied Caribbean countries. CONCLUSION This review demonstrates the need for future research in key areas such as the impact of nurse migration on health systems and population health. The literature tends to focus on Caribbean countries with higher levels of nurse migration. However, data regarding this phenomenon in other Caribbean countries is needed for a more comprehensive understanding of the plight of the Caribbean region and would answer the call from the International Organization for Migration to study policies, trends, and impacts in understudied Caribbean countries.


title: Mechanistic basis for the effects of process parameters on quality attributes in high shear wet granulation.

text: Three model compounds were used to study the effect of process parameters on in-process critical material attributes and a final product critical quality attribute. The effect of four process parameters was evaluated using design of experiment approach. Batches were characterized for particle size distribution, density (porosity), flow, compaction, and dissolution rate. The mechanisms of the effect of process parameters on primary granule properties (size and density) were proposed. Water amount showed significant effect on granule size and density. The effect of impeller speed was dependent on the granule mechanical properties and efficiency of liquid distribution in the granulator. Blend density was found to increase rapidly during wet massing. Liquid addition rate was the least consequential factor and showed minimal impact on granule density and growth. Correlations of primary properties with granulation bulk powder properties (compaction and flow) and tablet dissolution were also identified. The effects of the process parameters on the bulk powder properties and tablet dissolution were consistent with their proposed link to primary granule properties. Understanding the impact of primary granule properties on bulk powder properties and final product critical quality attributes provides the basis for modulating granulation parameters in order to optimize product performance.


Randomized controlled trial of vertebroplasty versus kyphoplasty in the treatment of vertebral compression fractures.


title: Fresh frozen cadaver workshops for advanced vascular surgical training.

text: BACKGROUND Reduction in working hours, streamlined training schemes and increasing use of endovascular techniques has meant a reduction in operative experience for newer vascular surgical trainees, especially those exposures which are not routinely performed such as thoracoabdominal, thoracotomy and retroperitoneal aortic, for example. METHODS This paper describes an Advanced Anatomy of Exposure course which was designed and convened at the Clinical Training & Evaluation Centre in Western Australia and uses fresh frozen cadavers. Feedback was obtained from the participants who attended over three courses by questionnaire. RESULTS Feedback was strongly positive for the course meeting both its learning outcomes and personal learning objectives, and in addition, making a significant contribution to specialty skills. Most participants thought the fresh frozen cadaveric model significantly improved the learning objectives for training. CONCLUSIONS The fresh frozen cadaver is an excellent teaching model highly representative of the living open surgical scenario where advanced trainees and newly qualified consultants can improve their operative confidence and consequently patient safety in vascular surgery. An efficient fresh frozen cadaver teaching programme can benefit many health professionals simultaneously maximizing the use of donated human tissue.


title: Be aware of misdiagnosis---A 21-Year-Old Primipara with Suspected COVID-19.

text: A 21-year-old woman (primipara) at 33w+6 d gestation was admitted to the Third Affiliated Hospital of Guangzhou Medical University on February 3, 2020. None of her prenatal screening results were abnormal. She complained of cold symptoms on January 29, 2020. Upon onset a fever of 39°C on January 31, she went to a local clinic, where her blood pressure was 170/110 mmHg. Her white blood cell count was 10.92×109 /L, total lymphocyte count was 0.85×10 9 /L, hemoglobin was 9.8 g/dl, and platelet count was 56×1010 /L and acetaminophen was given.


title: Cold spring prolongs Nematodirus infective period in Northern Ireland.

text: Nematodirosis in lambs Jejunal haemorrhagic syndrome in a heifer Epitheliogenesis imperfecta in a bovine fetus Plant poisoning in cattle and sheep Abomasal emptying defect in a ewe Cholangiocellular carcinoma in a duck These are among matters discussed in the Northern Ireland animal disease surveillance quarterly report for April to June 2013.


Regarding: Lui RN, Wong SH, Sánchez-Luna SA, et al. Overview of guidance for endoscopy during the coronavirus disease 2019 pandemic. J Gastroenterol Hepatol. 2020;35(5):749-759. doi:10.1111/jgh.15053.


title: Differences in Characteristics and Outcomes Between Asian and Non-Asian Patients in the TIAregistry.org.

text: BACKGROUND AND PURPOSE This study provides the contemporary causes and prognosis of transient ischemic attack (TIA) and minor stroke in Asians and the direct comparisons with non-Asians. METHODS The TIAregistry.org enrolled 4789 patients (1149 Asians and 3640 non-Asians) with a TIA or minor ischemic stroke within 7 days of onset. Every participating facility had systems dedicated to urgent intervention of TIA/stroke patients by specialists. The primary outcome was a composite of cardiovascular death, nonfatal stroke, and nonfatal acute coronary syndrome. RESULTS Approximately 80% of patients were evaluated within 24 hours of symptom onset. At 1 year, there were no differences in the rates of composite cardiovascular events (6.8% versus 6.0%; P=0.38) and stroke (6.0% versus 4.8%; P=0.11) between Asians and non-Asians. Asians had a lower risk of cerebrovascular disease (stroke or TIA) than non-Asians (adjusted hazard ratio, 0.79; 95% confidence interval, 0.63-0.98; P=0.03); the difference was primarily driven by a lower rate of TIA in Asians (4.2% versus 8.3%; P<0.001). Moderately severe bleeding was more frequent in Asians (0.8% versus 0.3%; P=0.02). In multivariable analysis, multiple acute infarcts (P=0.005) and alcohol consumption (P=0.02) were independent predictors of stroke recurrence in Asians, whereas intracranial stenosis (P<0.001), ABCD2 score (P<0.001), atrial fibrillation (P=0.008), extracranial stenosis (P=0.03), and previous stroke or TIA (P=0.03) were independent predictors in non-Asians. CONCLUSIONS The short-term stroke risk after a TIA or minor stroke was lower than expected when urgent evidence-based care was delivered, irrespective of race/ethnicity or region. However, the predictors of stroke were different for Asians and non-Asians.


title: Video-assisted thoracoscopic surgery in swine: an animal model for thoracoscopic lobectomy training.

text: OBJECTIVES Minimally invasive thoracic procedures have been increasingly used; however, only a small number of lobectomies are performed by videothoracoscopy, showing the need for training on this technique. The objective of this study is to demonstrate the technique of lobectomy using videothoracoscopy in swine, highlighting the steps to be taken during its use in surgical experimentation. METHODS During the advanced course on video-assisted and thoracoscopic procedures carried out at IRCAD Latin America, Barretos, Brazil, 40 swine were used for the hands-on course on video-assisted upper left lobectomy. Monopulmonary ventilation was performed by blocking the left main bronchus. Surgical procedures were performed using three ports and the anterior dissection technique (fissureless approach). The pulmonary hilar structures were dissected using conventional open surgery and video-assisted surgical tools. The first structure treated in the approach of the hilar structures was the upper lobe vein, followed by the bronchus and the branches of the pulmonary artery. RESULTS The mean time required to anaesthetize the animals was 3 h. Intraoperative hypoventilation was observed in 26 animals (65%) and 4 (10%) of them had a poor outcome and died in the last third part of the surgery. Eight (20%) animals had bradycardia, and six responded to the use of atropine. In two (5%), it was not possible to revert the bradycardia and the animals died at the end of the procedures. The surgical procedures had a mean duration of 3 h and the total time of anaesthesia was about 6 h. DISCUSSION Swine have been frequently used for hands-on training in surgery but there are no reports in the literature describing the anatomical, anaesthetic and technical peculiarities that must be observed during videothoracoscopic lobectomy training in swine. Video-assisted thoracoscopic surgery lobectomy using swine is an adequate method to train thoracic surgeons. For surgeons to make the best use of minimally invasive technique training, it is essential that issues related to the anatomy, anaesthesia, monopulmonary ventilation and surgical technique described in this study are taken into account.


title: Characterization of a novel betacoronavirus related to middle East respiratory syndrome coronavirus in European hedgehogs.

text: Bats are known to host viruses closely related to important human coronaviruses (HCoVs), such as HCoV-229E, severe-acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome CoV (MERS-CoV). As RNA viruses may coevolve with their hosts, we sought to investigate the closest sister taxon to bats, the Eulipotyphla, and screened European hedgehogs (Erinaceus europaeus) from Germany for CoV by nested reverse transcriptase PCR. A novel betacoronavirus species in a phylogenetic sister relationship to MERS-CoV and clade c bat CoVs was detected and characterized on the whole-genome level. A total of 58.9% of hedgehog fecal specimens were positive for the novel CoV (EriCoV) at 7.9 log10 mean RNA copies per ml. EriCoV RNA concentrations were higher in the intestine than in other solid organs, blood, or urine. Detailed analyses of the full hedgehog intestine showed the highest EriCoV concentrations in lower gastrointestinal tract specimens, compatible with viral replication in the lower intestine and fecal-oral transmission. Thirteen of 27 (48.2%) hedgehog sera contained non-neutralizing antibodies against MERS-CoV. The animal origins of this betacoronavirus clade that includes MERS-CoV may thus include both bat and nonbat hosts.


title: Landmark papers in cerebrovascular neurosurgery 2015.

text: The management of cerebrovascular disease has advanced considerably in 2015. Five randomized control trials have firmly established the role of endovascular thrombectomy for ischemic strokes due to large vessel occlusion. The randomized trial of intraarterial treatment for acute ischemic stroke (MR CLEAN) (Berkhemer et al. NEJM 2015;372:11-20) was the first of a series on the topic. There was a total of 5 randomized controlled trials published showing benefit in terms of functional outcomes at 90days for mechanical thrombectomy including the Endovascular Therapy for Ischemic stroke with perfusion-imaging selection (EXTEND IA) (Campbell et al. NEJM 2015;372:1009-18), the Randomized assessment of rapid endovascular treatment of ischemic stroke (ESCAPE) (Goyal et al. NEJM 2015;372:1019-30) trials, the stent-retriever thrombectomy after IV t-PA is t-PA alone in stroke (SWIFT-PRIME) (Saver et al. NEJM 2015;372:2285-95), and the thrombectomy within 8h after symptom onset in Ischemic stroke (REVASCAT) trial (Jovin et al. NEJM 2015; 372:2296-306). Six-year results from randomized controlled Barrow Ruptured Aneurysm Trial (BRAT) found no significant difference in functional outcomes in patients ruptured aneurysms treated surgically clippings versus endovascular treatment (Spetzler et al. JNS 2015;123:609-17. The 10-year results of the International Subarachnoid Aneurysm trial (ISAT) reported similar mortality rates and good functional outcomes between clipped and coiled patients (Molyneux et al. Lancet 2015;385:691-7). We also discuss the impact of genome wide sequencing studies in familial aneurysms, the largest publication on stent assisted coiling and flow diverter for aneurysms and noteworthy papers relevant to Moyamoya and cavernous malformations (Yang et al. Neurosurgery 2015;77:241-7).


Management of an incidental finding of right internal jugular vein agenesis.


All India Ophthalmological Society: Stance on COVID-19 pandemic.


title: Dynamic intermittent strain can rapidly impair ventral hernia repair.

text: Ventral hernia repair fails frequently despite advanced mesh inserting surgery. A model for dynamic intermittent straining (DIS) of ventral hernia repairs was developed. The influence of phospholipids, position, overlap, fixation and tissue quality of various meshes on the durability of hernia repair was studied. DIS comprises the repetition of submaximal impacts delivered via a hydraulically driven plastic containment. Pig tissues simulate a ventral hernia with a standardized 5cm defect. Commercially available meshes strengthened with tacks, glue and sutures were used to bridge this defect in an underlay (IPOM) or sublay (retromuscular) position starting with a 5cm overlap in all directions. We tested 35 different ways of ventral hernia repair with up to 425 submaximal intermittent dynamic impacts until mesh dislocation occurred 10 times or a maximum of 4000 impacts each were withstood. The likelihood of a failing repair was related to the mesh, the lubricants, the position, the overlap, the fixation and the tissue quality. Most meshes dislocated easily and required fixation. One of the meshes tested was stable without fixation with a 5cm overlap and failed after reducing the overlap. Phospholipids exerted a strong influence on the biomaterial tested. The sublay position was about 10% more durable in comparison to the IPOM position. DIS revealed distinct degrees of stability with primarily stable, intermediate and primarily unstable repairs. Based on the DIS results available, the currently used ventral hernia repair options can be classified. In the future, DIS investigations can improve the durability of hernia repair.


Palliative Care for Patients With Cancer in the COVID-19 Era.


Covid-19: Concerns rise as cases expand rapidly in South America.


title: Hepatitis C RNA assay differences in results: Potential implications for shortened therapy and determination of Sustained Virologic Response.

text: Approval of Ledipasvir/Sofosbuvir for the treatment of chronic hepatitis C (HCV) includes the truncation of therapy from 12 to 8 weeks in treatment naïve, non-cirrhotic patients with baseline HCV RNA levels <6 million IU/mL (6.8 log10 IU/mL). The aim of this study was to evaluate this clinical cutoff with a different widely used commercially available HCV RNA test. Results from samples tested prospectively with Roche High Pure TaqMan HCV 2.0 test (HPS) were compared to those tested retrospectively with the Abbott RealTime HCV RNA test (ART). Using 6 million IU/mL as the cut-off, pre-treatment results were concordant in 70.4% of cases. When results with the same test measured at screening and baseline, clinical decisions could be impacted in 14.4% and 6.2% of cases for HPS and ART respectively. Using only HCV RNA cutoff of 6 million IU/mL, 29.55% of subjects would receive a different and potentially incorrect treatment duration based solely on HCV RNA test method used. A further 6-14% of subjects would have treatment decision change based on the day the sample was taken.


title: RNA interference against animal viruses: how morbilliviruses generate extended diversity to escape small interfering RNA control.

text: Viruses are serious threats to human and animal health. Vaccines can prevent viral diseases, but few antiviral treatments are available to control evolving infections. Among new antiviral therapies, RNA interference (RNAi) has been the focus of intensive research. However, along with the development of efficient RNAi-based therapeutics comes the risk of emergence of resistant viruses. In this study, we challenged the in vitro propensity of a morbillivirus (peste des petits ruminants virus), a stable RNA virus, to escape the inhibition conferred by single or multiple small interfering RNAs (siRNAs) against conserved regions of the N gene. Except with the combination of three different siRNAs, the virus systematically escaped RNAi after 3 to 20 consecutive passages. The genetic modifications involved consisted of single or multiple point nucleotide mutations and a deletion of a stretch of six nucleotides, illustrating that this virus has an unusual genomic malleability.


title: The Preventive Effect of Endovascular Treatment for Recurrent Hemorrhage in Patients with Spinal Cord Arteriovenous Malformations.

text: BACKGROUND AND PURPOSE Spinal cord AVMs represent rare and insufficiently studied pathologic entities. Embolization is thought to play an important role in the management of spinal cord AVMs. Factors for recurrent hemorrhage and the impact of endovascular treatment on prevention of recurrent hemorrhage remain to be confirmed. We aimed to assess recurrent hemorrhagic incidence of spinal cord AVMs and its prevention by endovascular treatment. MATERIALS AND METHODS We reviewed 80 patients with spinal cord AVMs by spinal cord angiography who had hemorrhage before the first endovascular treatment at New York University Medical Center, Beth Israel Medical Center, or Roosevelt Hospital in New York. We compared the baseline and radiologic characteristics of patients with and without recurrent hemorrhage by the log-rank test and the Cox proportional hazards model. RESULTS We observed recurrent hemorrhage in 35 (44%) patients (1/41 patients with endovascular treatment and 34/39 patients without endovascular treatment). The median length of total follow-up was 659 days (interquartile range, 129-2640 days), and the median length from first-to-recurrent hemorrhage was 369 days (interquartile range, 30-1596 days). The log-rank test revealed that endovascular treatment and venous thrombosis reduced recurrent hemorrhage, and associated aneurysm was related to recurrent hemorrhage. Even in multivariate analysis, the endovascular treatment reduced (hazard ratio, 0.027; P < .0001) and associated aneurysm increased (hazard ratio, 3.4; P = .044) the risk of recurrent hemorrhage. CONCLUSIONS Endovascular embolization is the first choice of treatment for spinal cord AVMs and is effective in preventing recurrent hemorrhage.


Abortion in the context of COVID-19: a human rights imperative.


title: The C-type lectin receptor CLEC4M binds, internalizes, and clears von Willebrand factor and contributes to the variation in plasma von Willebrand factor levels.

text: Genetic variation in or near the C-type lectin domain family 4 member M (CLEC4M) has been associated with plasma levels of von Willebrand factor (VWF) in healthy individuals. CLEC4M is a lectin receptor with a polymorphic extracellular neck region possessing a variable number of tandem repeats (VNTR). A total of 491 participants (318 patients with type 1 von Willebrand disease [VWD] and 173 unaffected family members) were genotyped for the CLEC4M VNTR polymorphism. Family-based association analysis on kindreds with type 1 VWD demonstrated an excess transmission of VNTR 6 to unaffected individuals (P = .0096) and an association of this allele with increased VWF:RCo (P = .029). CLEC4M-Fc bound to VWF. Immunofluorescence and enzyme-linked immunosorbent assay demonstrated that HEK 293 cells transfected with CLEC4M bound and internalized VWF. Cells expressing 4 or 9 copies of the CLEC4M neck region VNTR showed reduced interaction with VWF relative to CLEC4M with 7 VNTR (CLEC4M 4%-60% reduction, P < .001; CLEC4M 9%-45% reduction, P = .006). Mice expressing CLEC4M after hydrodynamic liver transfer have a 46% decrease in plasma levels of VWF (P = .0094). CLEC4M binds to and internalizes VWF, and polymorphisms in the CLEC4M gene contribute to variable plasma levels of VWF.


title: Associations between multimorbidity, all-cause mortality and glycaemia in people with type 2 diabetes: A systematic review.

text: INTRODUCTION Type 2 diabetes (T2D) is a major health priority worldwide and the majority of people with diabetes live with multimorbidity (MM) (the co-occurrence of ≥2 chronic conditions). The aim of this systematic review was to explore the association between MM and all-cause mortality and glycaemic outcomes in people with T2D. METHODS The search strategy centred on: T2D, MM, comorbidity, mortality and glycaemia. Databases searched: MEDLINE, EMBASE, CINAHL Complete, The Cochrane Library, and SCOPUS. Restrictions included: English language, quantitative empirical studies. Two reviewers independently carried out: abstract and full text screening, data extraction, and quality appraisal. Disagreements adjudicated by a third reviewer. RESULTS Of the 4882 papers identified; 41 met inclusion criteria. The outcome was all-cause mortality in 16 studies, glycaemia in 24 studies and both outcomes in one study. There were 28 longitudinal cohort studies and 13 cross-sectional studies, with the number of participants ranging from 96-892,223. Included studies were conducted in high or upper-middle-income countries. Fifteen of 17 studies showed a statistically significant association between increasing MM and higher mortality. Ten of 14 studies showed no significant associations between MM and HbA1c. Four of 14 studies found higher levels of MM associated with higher HbA1c. Increasing MM was significantly associated with hypoglycaemia in 9/10 studies. There was no significant association between MM and fasting glucose (one study). No studies explored effects on glycaemic variability. CONCLUSIONS This review demonstrates that MM in T2D is associated with higher mortality and hypoglycaemia, whilst evidence regarding the association with other measures of glycaemic control is mixed. The current single disease focused approach to management of T2D seems inappropriate. Our findings highlight the need for clinical guidelines to support a holistic approach to the complex care needs of those with T2D and MM, accounting for the various conditions that people with T2D may be living with. SYSTEMATIC REVIEW REGISTRATION International Prospective Register of Systematic Reviews CRD42017079500.


title: Woven Endobridge (WEB) Device for endovascular treatment of ruptured intracranial wide-neck aneurysms: a single-center experience.

text: INTRODUCTION Endovascular treatment of ruptured wide-neck bifurcation aneurysms presents a challenge. While still under evaluation, the Woven Endobridge (WEB) aneurysm embolization system has so far shown promising results in the treatment of complex bifurcation aneurysms. We aimed to evaluate the feasibility and short-term follow-up of endovascular treatment of ruptured wide-neck aneurysm with the WEB device. METHODS Six patients referred to our institution for acute symptomatic subarachnoid hemorrhage (SAH) and treated with the WEB device were enrolled in this study. Clinical presentations, technical details, intraoperative and postoperative complications, and outcomes were recorded. Immediate and 3-month angiographic results were also evaluated. RESULTS Three middle cerebral artery (MCA) and three anterior communicating artery aneurysms were treated between 1 and 14 days after rupturing. Average dome width was 5.8 mm (range 5-7), average neck size was 4.5 mm (range 4-5), and average dome-to-neck ratio was 1.3 (range 1-1.7). The WEB system was the exclusive treatment and was successfully deployed in all cases. Per procedural thromboembolic events occurred in two cases and were treated with intra-arterial administration of antiplatelet agents without any clinical consequences. The modified Rankin Scale (mRS) score at discharge was 0 for all patients. The 3-month angiographic follow-up showed adequate occlusion in four of our six patients (67 %). CONCLUSION From this preliminary study, the high feasibility rate and lack of need for systematic antiplatelet agents favor the WEB device providing a solution for endovascular treatment of ruptured wide-neck bifurcation aneurysms during the acute phase. However, further studies are needed to evaluate the complication rate and long-term efficiency.


title: Outcomes in patients with acute ischemic stroke from proximal intracranial vessel occlusion and NIHSS score below 8.

text: OBJECTIVE Acute ischemic stroke due to proximal intracranial vessel occlusion is associated with poor prognosis and neurologic outcomes. Outcomes specifically in patients with stroke due to these occlusions and lower National Institutes of Health Stroke Scale (NIHSS) scores (0-7 range) have not been described previously. METHODS We retrospectively reviewed discharge outcomes (reported in our 'Get With the Guidelines-Stroke' database) in patients with an admission NIHSS score of 0-7 due to proximal intracranial large vessel occlusion (based on CT angiography results) who were excluded from receiving intravenous (IV) thrombolysis with recombinant tissue plasminogen activator and endovascular intra-arterial (IA) stroke interventions. RESULTS Among the 204 patients included in our analysis, younger age and lower admission NIHSS score (0-4 range) were strong predictors of good outcome (defined as ability to ambulate independently) at discharge whereas female sex was a predictor of poor outcome. There was no significant difference between cerebrovascular risk factors, specific sites of occlusion, or presenting symptoms and outcomes at discharge. There was great variability in functional outcomes at discharge and discharge disposition (home versus acute or subacute facility or nursing home versus death/hospice) with a trend toward worse outcomes in patients with higher (5-7 range) NIHSS scores on admission. CONCLUSIONS Patients with acute stroke due to large vessel occlusion and low admission NIHSS scores (0-7 range) may have poor functional outcomes at discharge. These patients, if not eligible for IV thrombolysis, might benefit from IA revascularization therapies.


title: Race/Ethnicity, Underlying Medical Conditions, Homelessness, and Hospitalization Status of Adult Patients with COVID-19 at an Urban Safety-Net Medical Center - Boston, Massachusetts, 2020.

text: As of July 5, 2020, approximately 2.8 million coronavirus disease 2019 (COVID-19) cases and 130,000 COVID-19-associated deaths had been reported in the United States (1). Populations historically affected by health disparities, including certain racial and ethnic minority populations, have been disproportionally affected by and hospitalized with COVID-19 (2-4). Data also suggest a higher prevalence of infection with SARS-CoV-2, the virus that causes COVID-19, among persons experiencing homelessness (5). Safety-net hospitals,† such as Boston Medical Center (BMC), which provide health care to persons regardless of their insurance status or ability to pay, treat higher proportions of these populations and might experience challenges during the COVID-19 pandemic. This report describes the characteristics and clinical outcomes of adult patients with laboratory-confirmed COVID-19 treated at BMC during March 1-May 18, 2020. During this time, 2,729 patients with SARS-CoV-2 infection were treated at BMC and categorized into one of the following mutually exclusive clinical severity designations: exclusive outpatient management (1,543; 56.5%), non-intensive care unit (ICU) hospitalization (900; 33.0%), ICU hospitalization without invasive mechanical ventilation (69; 2.5%), ICU hospitalization with mechanical ventilation (119; 4.4%), and death (98; 3.6%). The cohort comprised 44.6% non-Hispanic black (black) patients and 30.1% Hispanic or Latino (Hispanic) patients. Persons experiencing homelessness accounted for 16.4% of patients. Most patients who died were aged ≥60 years (81.6%). Clinical severity differed by age, race/ethnicity, underlying medical conditions, and homelessness. A higher proportion of Hispanic patients were hospitalized (46.5%) than were black (39.5%) or non-Hispanic white (white) (34.4%) patients, a finding most pronounced among those aged <60 years. A higher proportion of non-ICU inpatients were experiencing homelessness (24.3%), compared with homeless patients who were admitted to the ICU without mechanical ventilation (15.9%), with mechanical ventilation (15.1%), or who died (15.3%). Patient characteristics associated with illness and clinical severity, such as age, race/ethnicity, homelessness, and underlying medical conditions can inform tailored strategies that might improve outcomes and mitigate strain on the health care system from COVID-19.