title: Thrombopoietin mimetics for patients with myelodysplastic syndromes.

text: BACKGROUND Myelodysplastic syndrome (MDS) is one of the most frequent haematologic malignancies of the elderly population and characterised by progenitor cell dysplasia with ineffective haematopoiesis and a high rate of transformation to acute myeloid leukaemia (AML). Thrombocytopenia represents a common problem for patients with MDS. ranging from mild to serious bleeding events and death. To manage thrombocytopenia, the current standard treatment includes platelet transfusion, unfortunately leading to a range of side effects. Thrombopoietin (TPO) mimetics represent an alternative treatment option for MDS patients with thrombocytopenia. However, it remains unclear, whether TPO mimetics influence the increase of blast cells and therefore to premature progression to AML. OBJECTIVES To evaluate the efficacy and safety of thrombopoietin (TPO) mimetics for patients with MDS. SEARCH METHODS We searched for randomised controlled trials in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 2000 to August 2017), trials registries (ISRCTN, EU clinical trials register and clinicaltrials.gov) and conference proceedings. We did not apply any language restrictions. Two review authors independently screened search results, disagreements were solved by discussion. SELECTION CRITERIA We included randomised controlled trials comparing TPO mimetics with placebo, no further treatment or another TPO mimetic in patients with MDS of all risk groups, without gender, age or ethnicity restrictions. Additional chemotherapeutic treatment had to be equal in both arms. DATA COLLECTION AND ANALYSIS Two review authors independently extracted data and assessed the quality of trials, disagreements were resolved by discussion. Risk ratio (RR) was used to analyse mortality during study, transformation to AML, incidence of bleeding events, transfusion requirement, all adverse events, adverse events >= grade 3, serious adverse events and platelet response. Overall survival (OS) and progression-free survival (PFS) have been extracted as hazard ratios, but could not be pooled as results were reported in heterogenous ways. Health-related quality of life and duration of thrombocytopenia would have been analysed as standardised mean differences, but no trial reported these outcomes. MAIN RESULTS We did not identify any trial comparing one TPO mimetic versus another. We analysed six eligible trials involving 746 adult patients. All trials were reported as randomised and double-blind trials including male and female patients. Two trials compared TPO mimetics (romiplostim or eltrombopag) with placebo, one trial evaluated eltrombopag in addition to the hypomethylating agent azacitidine, two trials analysed romiplostim additionally to a hypomethylating agent (azacitidine or decitabine) and one trial evaluated romiplostim in addition to the immunomodulatory drug lenalidomide. There are more data on romiplostim (four included, completed, full-text trials) than on eltrombopag (two trials included: one full-text publication, one abstract publication). Due to small sample sizes and imbalances in baseline characteristics in three trials and premature termination of two studies, we judged the potential risk of bias of all included trials as high.Due to heterogenous reporting, we were not able to pool data for OS. Instead of that, we analysed mortality during study. There is little or no evidence for a difference in mortality during study for thrombopoietin mimetics compared to placebo (RR 0.97, 95% confidence interval (CI) 0.73 to 1.27, N = 6 trials, 746 patients, low-quality evidence). It is unclear whether the use of TPO mimetics induces an acceleration of transformation to AML (RR 1.02, 95% CI 0.59 to 1.77, N = 5 trials, 372 patients, very low-quality evidence).Thrombopoietin mimetics probably improve the incidence of all bleeding events (RR 0.92, 95% CI 0.86 to 0.99, N = 5 trials, 390 patients, moderate-quality evidence). This means that in the study population, 713 out of 1000 in the placebo arm will have a bleeding event, compared to 656 of 1000 (95% CI 613 to 699) in the TPO mimetics arm. There is little or no evidence for a difference that TPO mimetics significantly diminish the rate of transfusion requirement (RR 0.83, 95% CI 0.66 to 1.05, N = 4 trials, 358 patients, low-quality evidence). No studies were found that looked at quality of life or duration of thrombocytopenia.There is no evidence that patients given TPO mimetics suffer more all adverse events (RR 1.01, 95% CI 0.96 to 1.07, N = 5 trials, 390 patients, moderate-quality evidence). There is uncertainty whether the number of serious adverse events decrease under therapy with TPO mimetics (RR 0.89, 95% CI 0.54 to 1.46, N = 4 trials, 356 patients, very low-quality evidence).We identified one ongoing study and one study marked as completed (March 2015), but without publication of results for MDS patients (only results reported for AML and MDS patients together). Both studies evaluate MDS patients receiving eltrombopag in comparison to placebo. AUTHORS' CONCLUSIONS No trial evaluated one TPO mimetic versus another.Six trials including adult patients analysed one TPO mimetic versus placebo, sometimes combined with standard therapy in both arms. Given the uncertainty of the quality of evidence, meta-analyses show that there is little or no evidence for a difference in mortality during study and premature progress to AML. However, these assumptions have to be further explored. Treatment with TPO mimetics resulted in a lower number of MDS patients suffering from bleeding events.There is no evidence for a difference between study groups regarding transfusion requirement. Enlarged sample sizes and a longer follow-up of future trials should improve the estimate of safety and efficacy of TPO mimetics, moreover health-related quality of life should be evaluated. As two ongoing studies currently investigate eltrombopag (one already completed, but without published results), we are awaiting results for this drug.


What I Learned From SARS in 2003 That Will Help Me Cope With COVID-19 in 2020.


title: Indications and guidelines for pectus excavatum repair.

text: PURPOSE OF REVIEW The introduction of the Nuss procedure in 1997 for treatment of pectus excavatum, in conjunction with the ever-expanding body of medical information available on the internet, significantly raised the level of awareness for this deformity as both an anatomic and a functional problem. The subsequent increase in referrals for pectus excavatum repair provided large patient series for clinical analyses to better define underlying physiologic impairments and stimulated surgeons to develop technical improvements to enhance the safety and effectiveness of pectus excavatum repair. RECENT FINDINGS Clinical assessment, diagnostic imaging, and cardiorespiratory testing of patients with pectus excavatum have helped to characterize physiologic impairments associated with severe pectus excavatum and to define inclusion criteria for surgical repair. Appropriate timing of repair is important to minimize complications, especially recurrence. Evidence of improved cardiorespiratory function after pectus excavatum repair has been presented. As a result of numerous technical improvements, safe and effective operative correction of pectus excavatum has been reported for both the Nuss procedure and open repair. SUMMARY The findings presented in this review provide objective evidence of the cardiorespiratory impairment associated with severe pectus excavatum. Clinical identification of affected patients should prompt timely work-up and referral for pectus excavatum repair if inclusion criteria are met. Regular follow-up through pubertal growth is recommended.


Gastric tube insertion under visual control with the use of the Pentax-AWS®.


ASGE position statement on endoscopic bariatric therapies in clinical practice.


title: Analysis of saccular aneurysms in the Barrow Ruptured Aneurysm Trial.

text: OBJECTIVE The Barrow Ruptured Aneurysm Trial (BRAT) is a prospective, randomized trial in which treatment with clipping was compared to treatment with coil embolization. Patients were randomized to treatment on presentation with any nontraumatic subarachnoid hemorrhage (SAH). Because all other randomized trials comparing these 2 types of treatments have been limited to saccular aneurysms, the authors analyzed the current BRAT data for this subgroup of lesions. METHODS The primary BRAT analysis included all sources of SAH: nonaneurysmal lesions; saccular, blister, fusiform, and dissecting aneurysms; and SAHs from an aneurysm associated with either an arteriovenous malformation or a fistula. In this post hoc review, the outcomes for the subgroup of patients with saccular aneurysms were further analyzed by type of treatment. The extent of aneurysm obliteration was adjudicated by an independent neuroradiologist not involved in treatment. RESULTS Of the 471 patients enrolled in the BRAT, 362 (77%) had an SAH from a saccular aneurysm. Patients with saccular aneurysms were assigned equally to the clipping and the coiling cohorts (181 each). In each cohort, 3 patients died before treatment and 178 were treated. Of the 178 clip-assigned patients with saccular aneurysms, 1 (1%) was crossed over to coiling, and 64 (36%) of the 178 coil-assigned patients were crossed over to clipping. There was no statistically significant difference in poor outcome (modified Rankin Scale score > 2) between these 2 treatment arms at any recorded time point during 6 years of follow-up. After the initial hospitalization, 1 of 241 (0.4%) clipped saccular aneurysms and 21 of 115 (18%) coiled saccular aneurysms required retreatment (p < 0.001). At the 6-year follow-up, 95% (95/100) of the clipped aneurysms were completely obliterated, compared with 40% (16/40) of the coiled aneurysms (p < 0.001). There was no difference in morbidity between the 2 treatment groups (p = 0.10). CONCLUSIONS In the subgroup of patients with saccular aneurysms enrolled in the BRAT, there was no significant difference between modified Rankin Scale outcomes at any follow-up time in patients with saccular aneurysms assigned to clipping compared with those assigned to coiling (intent-to-treat analysis). At the 6-year follow-up evaluation, rates of retreatment and complete aneurysm obliteration significantly favored patients who underwent clipping compared with those who underwent coiling. Clinical trial registration no.: NCT01593267 (clinicaltrials.gov).


title: Construct validity of the PERF-FIT, a test of motor skill-related fitness for children in low resource areas.

text: BACKGROUND Given the relationship between physical fitness and motor performance a test battery was developed that measures both components combined. AIM Following the development of the Performance and Fitness (PERF-FIT) battery, this study investigated the construct validity with the ultimate aim of identifying attributes that discriminate between different levels of motor abilities and anaerobic or musculoskeletal fitness. METHODS In this cross-sectional study, 34 children with developmental coordination disorder (DCD) and 34 matched typically developing children participated (7-10 years). The PERF-FIT was used to examine known group validity. The PERF-FIT items were also compared to test items of well-known standardized tests to examine concurrent validity. RESULTS Concurrent validity was found to be of the expected low to moderate magnitude. Children with DCD were consistently found to have lower levels of motor skill-related fitness compared to typically developing children. CONCLUSION AND IMPLICATIONS The PERF-FIT seems to be a valid test to measure movement skills, musculoskeletal fitness and agility in children between the ages of 7 and 10 years in low resourced communities. The test seems to discriminate between gross motor skills, and agility and power in children with and without DCD.


title: The Ongoing Challenge of Acute Mesenteric Ischemia.

text: Background The lethality of acute mesenteric ischemia (AMI) remains quite high with 50-70%. The main reasons for that are the fact that AMI is rarely taken into consideration by the differential diagnosis of acute abdomen, the time-consuming diagnostic process, and the lack of a standardized therapeutic concept. The present interdisciplinary review aims to increase awareness among physicians and to help improve clinical outcomes. Methods This clinical therapeutic review is based on author expertise as well as a selective literature survey in PubMed based on the term 'mesenteric ischemia', combined with the terms 'arterial', 'clinical presentation', 'diagnosis', 'therapy', 'surgery', and 'interventional radiology'. Based on these search results as well as on the guidelines of the German Society of Vascular Surgery, the American College of Cardiology, and the American Heart Association, we present an interdisciplinary treatment concept. Results AMI is a vascular emergency that can be successfully treated only within the first hours after the onset of symptoms. Computed tomography angiography is the diagnostic method of choice. Intensive care unit treatment can prevent the occurrence of multiple organ failure. Treatment primarily consists of the revascularization of the mesenteric arteries. Endovascular techniques should be given priority, whereas signs of peritonitis or a central arterial occlusion with high thrombus load primarily require a surgical approach in order to save time and increase patient safety. Additional bowel resections can play a significant role in the treatment of intestinal sepsis. Conclusion Prompt and goal-oriented diagnosis and consistent treatment of AMI within 4-6 h from the onset of symptoms can be decisive for the reduction of AMI-associated lethality. In order for this to happen, a standardized concept of emergency treatment needs to be implemented.


Stroke patients with suspected atrial fibrillation should be started on anticoagulation pending the results of long-term cardiac monitoring.


title: Professionalism under fire: Conflict, war and epidemics.

text: Today's medical students (tomorrow's doctors) will be entering a world of conflict, war and regular outbreaks of infectious diseases. Despite numerous international declarations and treaties protecting human rights, the last few decades has been fraught with reports of "lapses" in medical professionalism involving torture and force-feeding of detainees (e.g. captured during the War on Terror) and health care professionals refusing to treat infected patients (e.g. HIV and Ebola). This paper provides some historical background to the changing status of a physician's duty to treat and how medical practitioners came to be involved in the inhumane treatment of detainees during the War on Terror, culminating in reports of "lapses" in professionalism. The Theory of Planned Behavior, which takes into account the individual, the environment and the social context, is used to explain the factors that might influence an individual's behavior in challenging situations. The paper concludes with some recommendations for medical and health professions education. The recommendations include selecting students who, as a minimum, can provide evidence of "basic" professionalism, engaging them in exploring the history of the medical profession, exposing them to contexts of uncertainty and moral dilemmas and challenging them to reflect on their responses.


Isolation precautions for visitors.


title: Blocking type I interferon (IFN) signaling impairs antigen responsiveness of circulating lymphocytes and alters their homing to lymphoid organs: protective role of type I IFN.

text: BACKGROUND We recently demonstrated that type I Interferon (IFN) rescues in vitro, human B-lymphocytes from apoptosis via PI3Kδ/Akt, Rho-A, NFκB and Bcl-2/BclXL. In the present study we extended our work to clarify, in vivo, the role of type I IFN signalling on the circulating and lymphoid organs homing lymphocytes. METHODOLOGY Two groups of mice 13 in each were set: type I IFN signalling blocked mice injected with anti-IFNAR1 antagonist antibody (10 mg/kg body weight) once/day for up to 20 days, and control group were injected with vehicle alone. RESULTS Flow cytometry analysis to monitor the blood lymphocyte phenotype and proliferation have shown a significant decrease in CD45R/B220(+) [corrected] B cells, CD4(+) and CD8(+) T cells in treated animals. Furthermore, the proliferative capacities of these lymphocyte subsets were significantly decreased in treated animals compared to those of control mice. Marked reduction in the plasma levels of IL-2 and IL-7 (cytokines important for the development of T and B cells) but not of IL-6 or IL-10 was observed in treated mice and this may a cause for emergence decrease in B and T cell numbers. Immunohistochemical studies have further shown a marked reduction in the numbers of CD20(+) B cells in spleen and Peyer's patches and CD3(+) T cells in thymus of treated animals. Moreover, electron microscopy examinations have revealed a loss of lymphocytes with characteristic features of apoptosis. CONCLUSION Our data confirmed that the in vivo inhibition of type I IFN signaling induce decrease in the numbers and defective functions of circulating and lymphoid organs homing lymphocytes providing a strong evidence for the protective effects of type 1 IFNs (IFN-α/β) on B and T lymphocytes.


COVID-19 current controversies.


title: Clinical tools for cardiorespiratory assessment and rehabilitation: A primary care perspective.

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people worldwide. It mainly affects the respiratory system, seen as pneumonia or acute respiratory distress syndrome. Cardiovascular manifestations have been observed in some patients. Hence, cardiorespiratory assessment is an important component of diagnosis, management and follow-up of this disease. Primary care is the first point of contact with the healthcare system for most patients. Therefore, methods for assessment and rehabilitation should be feasible in a primary care setting. This commentary aims to provide a primary care perspective on existing clinical tools for cardiorespiratory assessment and rehabilitation.


Fauci's straight talk.


title: Informal carers' experience of assistive technology use in dementia care at home: a systematic review.

text: BACKGROUND Dementia is a health and care priority globally. Caring for persons with dementia is a challenge and can lead to negative psychological, physiological and financial consequences for informal carers. Advances in technology have the potential to assist persons with dementia and their carers, through assistive technology devices such as electronic medication dispensers, robotic devices trackers and motion detectors. However, little is known about carers' experience and the impact of these technologies on them. This review aims to investigate the outcomes and experience of carers of persons with dementia, who live at home and use assistive technology. METHODS A systematic search in seven databases and manual searches were carried out using pre-defined inclusion and exclusion criteria to identify studies on carers of persons with dementia involving the use of assistive technology. The search identified 56 publications with quantitative, qualitative and mixed-method designs. RESULTS The studies reported positive and negative findings and focused on a wide variety of assistive technology devices. There were large differences in the uses of assistive technology, outcome measures used and the quality of studies. Knowledge and acceptance, competence to use and ethical issues when using assistive technology were themes that emerged from the studies. Carers generally appreciated using assistive technology and their experience of use varied. CONCLUSIONS The intention of this systematic review is to list and classify the various types of assistive technology used by carers of persons with dementia and explores the positive and negative aspects, knowledge, acceptance and ethical issues in the use of assistive technology by carers of persons with dementia. We recommend the use of a standard and person-centred system of classifying and naming assistive technology devices and systems and for future research efforts in assistive technology to incorporate a family/carer centred model. SYSTEMATIC REVIEW REGISTRATION PROSPERO - CRD42017082268 .


title: Vaginal cuff dehiscence: risk factors and associated morbidities.

text: BACKGROUND AND OBJECTIVES To evaluate whether the route and surgical technique by which hysterectomy is performed influence the incidence of vaginal cuff dehiscence. METHODS We performed a retrospective analysis of total hysterectomy cases performed at Brigham and Woman's Hospital or Faulkner Hospital during 2009 through 2011. RESULTS During the study period, 2382 total hysterectomies were performed; 23 of these (0.96%) were diagnosed with cuff dehiscence, and 4 women had recurrent dehiscence. Both laparoscopic (odds ratio, 23.4; P = .007) and robotic (odds ratio, 73; P = .0006) hysterectomies were associated with increased odds of cuff dehiscence in a multivariate regression analysis. The type of energy used during colpotomy, mode of closure (hand sewn, laparoscopic suturing, or suturing assisted by a device), and suture material did not differ significantly between groups; however, continuous suturing of the cuff was a protective factor (odds ratio, 0.24; P = .03). Women with dehiscence had more extensive procedures, as well as an increased incidence of additional major postoperative complications (17.4% vs 3%, P = .004). CONCLUSION The rate of cuff dehiscence in our cohort correlates with the current literature. This study suggests that the risk of dehiscence is influenced mainly by the scope and complexity of the surgical procedure. It seems that different colpotomy techniques do not influence the rate of cuff dehiscence; however, continuous suturing of the cuff may be superior to interrupted suturing.


title: Long-term outcomes of percutaneous paravalvular regurgitation closure after transcatheter aortic valve replacement: a multicenter experience.

text: OBJECTIVES This study sought to evaluate acute and long-term outcomes of percutaneous paravalvular regurgitation (PVR) closure after transcatheter aortic valve replacement (TAVR). BACKGROUND Severe symptomatic PVR is a predictor of all-cause mortality after TAVR. The current use of devices for transcatheter closure of PVR has been adapted from other indications without known long-term outcomes. METHODS The study population consisted of a series of cases pooled together from an international multicenter experience. Patients underwent transcatheter implantation of a closure device for the treatment of clinically relevant PVR after TAVR with balloon-expandable or self-expandable prostheses. Procedural success was defined by successful deployment of a device with immediate reduction of PVR to a final grade ≤2 as assessed by echocardiography. RESULTS Twenty-seven procedures were performed in 24 patients with clinically relevant PVR after the index TAVR procedure (54.2% Edwards Sapien [Edwards Lifesciences, Irvine, California], 45.8% CoreValve [Medtronic, Minneapolis, Minnesota]). The study population included 75% men with a mean age of 80.6 ± 7.1 years and mean Society of Thoracic Surgeon score of 6.6%. The most frequently used device was Amplatzer Vascular Plug (St. Jude Medical, St. Paul, Minnesota) in 80% of the cases. Overall, 88.9% (24 of 27) of the procedures were technically successful and the results assessed by echocardiography were durable. However, cumulative survival rates at 1, 6, and 12 months were 83.3%, 66.7%, and 61.5%. Most of the deaths (8 of 11) were due to noncardiac causes. CONCLUSIONS Transcatheter closure of PVR after TAVR can be performed with a high procedural success rate; however, the long-term mortality remains high mainly due to noncardiac causes.


title: The workday of hospital surgeons: what they do, what makes them satisfied, and the role of core tasks and administrative tasks; a diary study.

text: BACKGROUND Many surgeons report passion for their work, but not all tasks are likely to be satisfying. Little is known about how hospital surgeons spend their days, how they like specific tasks, and the role of core tasks (i.e. surgery-related tasks) versus tasks that may keep them from core tasks (e.g., administrative work). This study aimed at a more detailed picture of hospital surgeons' daily work - how much time they spend with different tasks, how they like them, and associations with satisfaction. METHODS Hospital surgeons (N = 105) responded to a general survey, and 81 of these provided up to five daily questionnaires concerning daily activities and their attractiveness, as well as their job satisfaction. The data were analyzed using t-tests, analysis of variance, as well as analysis of covariance and repeated measures analysis of variance for comparing means across tasks. RESULTS Among 14 tasks, surgery-related tasks took 21.2%, patient-related tasks 21.7% of the surgeons' time; 10.4% entailed meetings and communicating about patients, and 18.6% documentation and administration. The remaining time was spent with teaching, research, leadership and management, and not task-related activities (e.g. walking between rooms). Surgery was rated as most (4.25; SD = .66), administration as least attractive (2.63; SD = .78). A higher percentage of administration predicted lower perceived legitimacy; perceived legitimacy of administrative work predicted job satisfaction (r = .47). Residents were least satisfied; there were few gender differences. CONCLUSIONS Surgeons seem to thrive on their core tasks, most notably surgery. By contrast, administrative duties are likely perceived as keeping them from their core medical tasks. Increasing the percentage of medical tasks proper, notably surgery, and reducing administrative duties may contribute to hospital surgeons' job satisfaction.


title: Long term experience using the ADAPT technique for the treatment of acute ischemic stroke.

text: INTRODUCTION The direct aspiration first pass technique (ADAPT) has been introduced as a simple and fast method for achieving good angiographic and clinical outcomes using large bore aspiration catheters for the treatment of acute ischemic stroke (AIS). We present a single center's long term experience with ADAPT. METHODS Retrospective analysis of a database was gathered on patients undergoing stroke thrombectomy with ADAPT at a stroke center. Speciﬁc parameters captured included age, gender, National Institutes of Health Stroke Scale (NIHSS) score at presentation, time to presentation from last normal, and modiﬁed Rankin Scale (mRS) score at the 90 day follow-up. Radiological and angiographic imaging was reviewed to document the location of the vascular occlusion, Thrombolysis in Cerebral Infarction (TICI) ﬂow postprocedure, and procedural complications. RESULTS 191 consecutive patients who suffered an AIS treated with ADAPT were reviewed; 91 were women, and mean age was 67 years. Patients presented with a mean NIHSS score of 15.4, and 71 patients received intravenous tissue plasminogen activator. The average time from onset to puncture was 7.8 h. The average time for recanalization was 37.3 min. TICI 2B or better recanalization was achieved in 180 (94.2%) patients. 98 (54.1%) patients had an mRS of 0-2 at 90 days. Direct aspiration alone was performed in 145 cases, and 43 cases required the additional use of a stent retriever. There was no significant difference in presenting NIHSS score, average time to presentation, average mRS at 90 days, or 90 day mortality between the two groups. Time to recanalization was 29.6 min for direct aspiration compared with 61.4 min in cases that required adjunct devices (p=0.00000201). 79 (57.7%) patients who underwent direct aspiration only achieved a good outcome at 90 days (mRS 0-2) compared with 19 (43.2%) who underwent adjunct therapies (p=0.12). CONCLUSIONS ADAPT is an effective method to achieve good clinical and angiographic outcomes, and serves as a useful firstline method for revascularization.


title: Broad and differential animal ACE2 receptor usage by SARS-CoV-2.

text: The COVID-19 pandemic has caused an unprecedented global public health and economy crisis. The origin and emergence of its causal agent, SARS-CoV-2, in the human population remains mysterious, although bat and pangolin were proposed to be the natural reservoirs. Strikingly, comparing to the SARS-CoV-2-like CoVs identified in bats and pangolins, SARS-CoV-2 harbors a polybasic furin cleavage site in its spike (S) glycoprotein. SARS-CoV-2 uses human ACE2 as its receptor to infect cells. Receptor recognition by the S protein is the major determinant of host range, tissue tropism, and pathogenesis of coronaviruses. In an effort to search for the potential intermediate or amplifying animal hosts of SARS-CoV-2, we examined receptor activity of ACE2 from 14 mammal species and found that ACE2 from multiple species can support the infectious entry of lentiviral particles pseudotyped with the wild-type or furin cleavage site deficient S protein of SARS-CoV-2. ACE2 of human/rhesus monkey and rat/mouse exhibited the highest and lowest receptor activity, respectively. Among the remaining species, ACE2 from rabbit and pangolin strongly bound to the S1 subunit of SARS-CoV-2 S protein and efficiently supported the pseudotyped virus infection. These findings have important implications for understanding potential natural reservoirs, zoonotic transmission, human-to-animal transmission, and use of animal models.IMPORTANCE SARS-CoV-2 uses human ACE2 as primary receptor for host cell entry. Viral entry mediated by the interaction of ACE2 with spike protein largely determines host range and is the major constraint to interspecies transmission. We examined the receptor activity of 14 ACE2 orthologues and found that wild type and mutant SARS-CoV-2 lacking the furin cleavage site in S protein could utilize ACE2 from a broad range of animal species to enter host cells. These results have important implications in the natural hosts, interspecies transmission, animal models and molecular basis of receptor binding for SARS-CoV-2.


title: Development of molecular and histological methods to evaluate stress oxidative biomarkers in sea bass (Dicentrarchus labrax).

text: In aquaculture, fish species may experience stressful episodes caused by poor farming conditions. The exponential increase of global aquaculture has raised the number of research studies aimed at demonstrating the sensitivity of aquatic animals in confined environments. The development of a real-time PCR and immunohistochemistry methods were investigated to evaluate the presence, localization, and quantity of biomarkers of oxidative stress in European sea bass (Dicentrarchus labrax). In particular, stress tests such as manipulation and temperature changes were conducted through molecular methods to identify the expression level of heat shock protein 70 (HSP70) in stressed animals compared with a control group. The immunohistochemical technique was also applied to locate and study the trends-levels of nitrotyrosine (NT), heat shock protein 70 (HSP70), malondialdehyde (MDA), and 4-hydroxy-2-nonenal (HNE) in different tissues from stressed animals and control group. The presence of the rodlet cell (RCs) was evaluated by histology in both a control and stressed group. Our results show that the real-time PCR method developed is specific for the evaluated target gene and that manipulation and temperature increase are strong stressors for animals. Relative quantification data revealed a gene expression increase of HSP70 in the stressed group of animals compared to the control group. The antibodies used for the immunohistochemical staining were efficient, and it was possible to appreciate the increase of immunoprecipitates in European sea bass either manipulated or stressed by temperature increase. The present study can be a starting point to allow the quantification of HSP70 and the identification of other stress biomarkers in D. labrax.


title: SERUM BIOCHEMISTRY VALUES AND SELECT SEROLOGIC SCREENING OF BROWN HYENAS ( PARAHYAENA BRUNNEA) FROM THE NAMIB DESERT, NAMIBIA.

text: Blood from 30 free-ranging brown hyenas ( Parahyaena brunnea) was collected for biochemical analysis and select serologic screening in Namibia from 1997 to 2010. Age was found to have an influence on several biochemical parameters that may be related to growth, a developing immune system, and differences in diet. Seasonal differences in diet of coastal brown hyenas also had an overall significant effect on lipemia values, and differences in stress due to varying capture methods could be associated with an increase in glucose and creatinine kinase. Comparisons among hyena species from published data were inconclusive, as some samples may have been derived from captive populations and individuals. Sera were tested for antibodies against 18 pathogens. Antibodies were not detected for most pathogens, but the proportion of sera containing antibodies against canine adenovirus-1 (CAV-1) and canine adenovirus-2 (CAV-2) was 65% and 84%, respectively. There was no effect of sex, age, year of sampling, or contact with domestic dogs, indicating that CAV-1 or CAV-2 may be enzootic. The prevalence of antibodies to canine distemper virus (CDV) was 43%, and older brown hyenas were 6.9 times more likely to have been exposed to CDV, adjusting for year of sampling and degree of estimated contact with domestic dogs, suggesting epizootic outbreaks. This study is the first to present biochemical reference intervals for wild brown hyenas and provides an indication of disease exposure in this species.


title: Pharmacokinetics of N-acetylcysteine after oral and intravenous administration to healthy cats.

text: OBJECTIVE To describe the pharmacokinetics of N-acetylcysteine (NAC) in healthy cats after oral and IV administration. ANIMALS 6 healthy cats. PROCEDURES In a crossover study, cats received NAC (100 mg/kg) via IV and oral routes of administration; there was a 4-week washout period between treatments. Plasma samples were obtained at 0, 5, 15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 36, and 48 hours after administration, and NAC concentrations were quantified by use of a validated high-performance liquid chromatography-mass spectrometry protocol. Data were analyzed via compartmental and noncompartmental pharmacokinetic analysis. RESULTS Pharmacokinetics for both routes of administration were best described by a 2-compartment model. Mean ± SD elimination half-life was 0.78 ± 0.16 hours and 1.34 ± 0.24 hours for the IV and oral routes of administration, respectively. Mean bioavailability of NAC after oral administration was 19.3 ± 4.4%. CONCLUSIONS AND CLINICAL RELEVANCE The pharmacokinetics of NAC for this small population of healthy cats differed from values reported for humans. Assuming there would be similar pharmacokinetics in diseased cats, dose extrapolations from human medicine may result in underdosing of NAC in cats with acute disease. Despite the low bioavailability, plasma concentrations of NAC after oral administration at 100 mg/kg may be effective in the treatment of chronic diseases.


title: Prevalence and prognosis of acutely ill patients with organ failure at arrival to hospital: protocol for a systematic review.

text: BACKGROUND Acutely ill patients are a heterogeneous group, and some of these suffer from organ failure. As the prognosis of organ failure improves with early treatment, it is important to identify these patients as early as possible. Most studies on organ failure have been performed in intensive care settings, or on selected groups of patients, where a high prevalence and mortality have been reported. Before patients arrive to the intensive care unit, or the general ward, most of them have passed through the emergency department (ED), where diagnosis and treatment has been initiated. The prevalence and prognosis of acutely ill patients, with organ failure, at arrival have been studied in some selected groups, but methods and results differ. This systematic review aims to identify, summarize, and analyze studies of prevalence and prognosis of new onset organ failure in acutely ill undifferentiated patients, at arrival to hospital. The result of the review will assist physicians working in an ED, when assessing patients' risk of organ failure and their associated prognosis. METHODS The information sources used are electronic databases, PubMed, Cochrane Library, EMBASE, and CINAHL; references in included studies and review articles; and authors' personal files. One author will perform the title and abstract screening and exclude obviously ineligible studies. By an independent full-text screening, two authors will decide on the eligibility for the remaining studies. Eligible studies will include an unselected group of acutely ill adult patients at arrival to hospital, with one or more organ failures (respiratory, renal, cerebral, circulatory, hepatic, or coagulation failure). Included studies will have assessed the prevalence or prognosis, defined as mortality or ICU transfer, of new onset organ failure. From included studies, bibliographical and study description data, patient characteristics, and data related to prevalence of organ failure and prognosis will be extracted. We will assess risk of bias in included studies using the Quality in Prognosis Studies tool for prognostic studies and the Newcastle-Ottawa Scale for observational studies. We expect heterogeneity and to conduct a qualitative synthesis of the results. If, however, heterogeneity is low, we will conduct a random effects meta-analysis stratified by basic study design. DISCUSSION This review will summarize and analyze studies of prevalence and prognosis of acutely ill patients, with organ failure at arrival to hospital, assist ED physicians assessing the risk of organ failure in unselected patients, and guide recommendations for further research. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42017060871.


Ongoing TB testing during Covid-19 restrictions.


title: Imaging artifacts of Onyx and PHIL on conventional CT, cone-beam CT and MRI in an animal model.

text: BACKGROUND AND PURPOSE A frequently reported drawback of ethylene vinyl alcohol copolymer-based liquid embolic agents is the production of artifacts in diagnostic imaging. New embolic agents, such as Precipitating hydrophobic injectable liquid (PHIL; MicroVention, Tustin, CA, USA), are supposed to induce significantly fewer artifacts. The purpose of this study is to assess the degree of artifacts induced by the liquid embolic agents Onyx (Medtronic Neurovascular, Irvine, CA, USA) and PHIL in conventional computed tomography (CT), cone-beam CT and magnetic resonance imaging (MRI) in an experimental in vivo model. MATERIALS AND METHODS In 10 pigs the rete mirabile was embolized with Onyx ( n = 5) or PHIL ( n = 5). After embolization, conventional CT, cone-beam CT and MRI were performed. The degree of artifacts was graded qualitatively (five-point scale; for CT and MRI) and quantitatively (HUs of well-defined regions of interest (ROIs); for CT only). RESULTS Artifacts were significantly more severe for Onyx both in the qualitative (e.g. conventional CT: 2 versus 5 (medians); p = 0.008) and in the quantitative image analysis (e.g. cone-beam CT: standard deviation of a ROI near to the embolic agent cast, 94 HU versus 38 HU (medians); p = 0.008). Neither Onyx nor PHIL produced any apparent artifacts in MRI. CONCLUSION PHIL produces fewer artifacts than Onyx in conventional CT and cone-beam CT in an experimental in vivo model.


title: A strategic approach to COVID-19 vaccine R&D.

text: A public-private partnership and platform for harmonized clinical trials aims to accelerate licensure and distribution.


title: The armed forces medical services response to COVID-19.

text: The Indian Armed Forces have always responded to the Nation's call and the COVID-19 pandemic response has been no different. On instructions from the Government of India, the Armed Forces Medical Services (AFMS) pitched in right from the initial stages of the epidemic in India as part of a coordinated national response. Be it the execution of medical quarantine for Indian citizens evacuated from China and other COVID affected countries or establishing dedicated and mixed COVID hospitals for its own clientele as well as civilian patients, the AFMS worked in tandem with the national policies. The Armed Forces ensured force preservation and protection of its own troops and families by timely implementation of public health measures, even as it played its designated role in the national strategy. With vision, understanding and clarity, the AFMS continue to lend shoulder to India's response to this global public health challenge.


title: Recombinant Isfahan Virus and Vesicular Stomatitis Virus Vaccine Vectors Provide Durable, Multivalent, Single-Dose Protection against Lethal Alphavirus Challenge.

text: The demonstrated clinical efficacy of a recombinant vesicular stomatitis virus (rVSV) vaccine vector has stimulated the investigation of additional serologically distinct Vesiculovirus vectors as therapeutic and/or prophylactic vaccine vectors to combat emerging viral diseases. Among these viral threats are the encephalitic alphaviruses Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV), which have demonstrated potential for natural disease outbreaks, yet no licensed vaccines are available in the event of an epidemic. Here we report the rescue of recombinant Isfahan virus (rISFV) from genomic cDNA as a potential new vaccine vector platform. The rISFV genome was modified to attenuate virulence and express the VEEV and EEEV E2/E1 surface glycoproteins as vaccine antigens. A single dose of the rISFV vaccine vectors elicited neutralizing antibody responses and protected mice from lethal VEEV and EEEV challenges at 1 month postvaccination as well as lethal VEEV challenge at 8 months postvaccination. A mixture of rISFV vectors expressing the VEEV and EEEV E2/E1 glycoproteins also provided durable, single-dose protection from lethal VEEV and EEEV challenges, demonstrating the potential for a multivalent vaccine formulation. These findings were paralleled in studies with an attenuated form of rVSV expressing the VEEV E2/E1 glycoproteins. Both the rVSV and rISFV vectors were attenuated by using an approach that has demonstrated safety in human trials of an rVSV/HIV-1 vaccine. Vaccines based on either of these vaccine vector platforms may present a safe and effective approach to prevent alphavirus-induced disease in humans.IMPORTANCE This work introduces rISFV as a novel vaccine vector platform that is serologically distinct and phylogenetically distant from VSV. The rISFV vector has been attenuated by an approach used for an rVSV vector that has demonstrated safety in clinical studies. The vaccine potential of the rISFV vector was investigated in a well-established alphavirus disease model. The findings indicate the feasibility of producing a safe, efficacious, multivalent vaccine against the encephalitic alphaviruses VEEV and EEEV, both of which can cause fatal disease. This work also demonstrates the efficacy of an attenuated rVSV vector that has already demonstrated safety and immunogenicity in multiple HIV-1 phase I clinical studies. The absence of serological cross-reactivity between rVSV and rISFV and their phylogenetic divergence within the Vesiculovirus genus indicate potential for two stand-alone vaccine vector platforms that could be used to target multiple bacterial and/or viral agents in successive immunization campaigns or as heterologous prime-boost agents.


title: Combination guidance of contrast-enhanced US and fusion imaging in radiofrequency ablation for hepatocellular carcinoma with poor conspicuity on contrast-enhanced US/fusion imaging.

text: PURPOSE The purpose of this study was to evaluate the usefulness of the combination guidance of contrast-enhanced US (CEUS) and fusion imaging in radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) with poor conspicuity on B-mode US and CEUS/fusion imaging. MATERIALS AND METHODS We conducted a retrospective cohort study, which included 356 patients with 556 HCCs that were inconspicuous on B-mode US. A total of 192 patients with 344 HCCs, 123 patients with 155 HCCs, and 37 patients with 57 HCCs underwent RFA under CEUS guidance, fusion imaging guidance, and the combination of CEUS and fusion imaging guidance. RESULTS The average number of treatment sessions was 1.1 (range: 1-2) in the CEUS guidance group, 1.1 (range: 1-2) in the fusion imaging guidance group, and 1.1 (range: 1-3) in the combination of CEUS and fusion imaging guidance group. Treatment analysis did not reveal significantly more RFA treatment sessions in the combination guidance group than in the other groups (p = 0.97, Student's t test). During the follow-up period (1.1-85.3 months, mean ± SD, 43.2 ± 59.5), the 3-year local tumor progression rates were 4.9, 7.2, and 5.9% in the CEUS guidance group, the fusion imaging guidance group, and the combination guidance group, respectively (p = 0.84, log-rank test). CONCLUSION In spite of selection bias, session frequency and local tumor progression were not different under the combination guidance with CEUS and fusion imaging in RFA. The combination of fusion imaging and CEUS guidance in RFA therapy is an effective treatment for HCC with poor conspicuity on B-mode US and CEUS/fusion imaging.


title: Endoscopic endonasal resection of skull base meningiomas: the significance of a "cortical cuff" and brain edema compared with careful case selection and surgical experience in predicting morbidity and extent of resection.

text: OBJECT This paper describes a consecutive series of skull base meningiomas resected using an endoscopic endonasal approach through various corridors at a single institution over 7 years. The impact of case selection and experience, the presence of a cortical cuff between the tumor and surrounding vessels, and brain edema on morbidity and rates of gross-total resection (GTR) were examined. METHODS A retrospective review of a series of 46 skull base meningiomas from a prospective database was conducted. The series of cases were divided by location: olfactory groove (n = 15), tuberculum and planum (n = 20), sellar/cavernous (n = 9) and petroclival (n = 2). Gross-total resection was never intended in the sellar/cavernous tumors, which generally invaded the cavernous sinus. Clinical charts, volumetric imaging, and pathology were reviewed to assess the extent of resection and complications. Cases were divided based on a time point in which surgical technique and case selection improved into Group 1 (surgery prior to June 2008; n = 21) and Group 2 (surgery after June 2008; n = 25) and into those with and without a cortical cuff and with and without brain edema. RESULTS Improved case selection had the greatest impact on extent of resection. For the entire cohort, rates of GTR went from 38% to 76% (p = 0.02), and for cases in which GTR was the intent, the rates went from 63% to 84% (not significant), which was mostly driven by the planum and tuberculum meningiomas, which went from 75% to 91.7 % (nonsignificant difference). The presence of a cortical cuff and brain edema had no impact on outcomes. There were 3 CSF leaks (6.5%) but all were in Group 1. Hence, CSF leak improved from 14.2% to 0% with surgical experience. Lessons learned for optimal case selection are discussed. CONCLUSIONS Surgical outcome for endonasal endoscopic resection of skull base meningiomas depends mostly on careful case selection and surgical experience. Imaging criteria such as the presence of a cortical cuff or brain edema are less important.


title: Expanding Indications of Transcatheter Heart Valve Interventions.

text: Transcatheter aortic valve replacement (TAVR) has been established as a less invasive alternative to open-heart surgery in inoperable or high-risk patients presenting with symptomatic severe aortic valve stenosis. The feasibility and efficacy of valve-in-valve implantation in degenerated surgical aortic bioprostheses have also been described and can currently be considered a valuable treatment option in patients deemed unsuitable for repeat cardiac surgery. However, the clinical use of TAVR devices is not limited to the treatment of the tricuspid stenotic aortic valve. Several additional indications including treatment of the bicuspid stenotic aortic valve, aortic regurgitation, and valve-in-valve or valve-in-ring implantation in the mitral or tricuspid position as well as treatment of pure mitral, tricuspid, or pulmonary regurgitation have been described. The purpose of the present review is to summarize the available evidence concerning the emerging off-label use of TAVR devices in current clinical practice. Case examples have been selected to highlight the main procedural steps of each particular intervention.


title: Tissue integration and inflammatory reaction in full-thickness abdominal wall repair using an innovative composite mesh.

text: PURPOSE When composite meshes are used in abdominal wall repair, seroma formation may persist and delay the desired integration leading to recurrence. This study compares tissue integration and inflammatory response in abdominal wall repair with composites with different absorbable synthetic barriers. METHODS Full-thickness defects created in the abdominal wall of rabbits were repaired using polypropylene prosthesis or the following composites: Physiomesh™ (Phy); Ventralight™ (Vent) and "new composite mesh" (Ncm) not yet used clinically in humans. The collected seroma was evaluated for IFN-γ/IL-4 by ELISA. Tissue integration, anti- (IL-13/TGFβ-1/IL-10/IL-4) and pro-inflammatory (TNF-α/IL-6/IFN-γ/VEGF) cytokine mRNA expression and TGFβ/VEGF immunolabeling were evaluated at 14 and 90 days post-implant. RESULTS Seroma was observed in 10 of 12 Phy/Vent and 4 of 12 Ncm. Wound fluid IFN-γ showed a time-dependent significant increase in Vent and tendency to decrease in Ncm, while all composites exhibited IL-4 upward trend. Prostheses were fully infiltrated by an organized connective tissue at end time although the area had shown prior seroma. A stable mesothelium was developed, except in adhesion areas. Vent/Phy displayed a significant increase in TNF-α/IFN-γ-mRNA over time. Significant decrease in VEGF mRNA was observed in Phy/Ncm, while a significant increase of TGFβ-1 mRNA was evident in all composites over time. Ncm exhibited the highest TGFβ protein expression area at short term and the greatest percentage of VEGF positive vessels at end time. CONCLUSION Ncm could be an appropriate candidate to improve clinical outcome showing the lower development of seroma and optimal tissue integration with minimal pro-inflammatory cytokine response over time and consistent pro-wound healing cytokine expression.


title: [Cardiac biomarkers and COVID-19 - Phenotypes and Interpretation].

text: Current pandemic caused by SARS-CoV-2 inducing viral COVID-19 pneumonia, is categorized in 3 stages. Some biomarkers could be assigned to one of these stages, showing a correlation to mortality in COVID-19 patients. Laboratory findings in COVID-19, especially when serially evaluated, may represent individual disease severity and prognosis. These may help planning and controlling therapeutic interventions. Biomarkers for myocardial injury (high sensitive cardiac troponin, hsTn) or hemodynamic stress (NTproBNP) may occur in COVID-19 pneumonia such as in other pneumonias, correlating with severity and prognosis of the underlying disease. In hospitalized COVID-19 patients' mild increases of hsTn or NTproBNP may be explained by cardiovascular comorbidities and direct or indirect cardiac damage or stress caused by or during COVID-19 pneumonia. In case of suspected NSTE-ACS and COVID-19, indications for echocardiography or reperfusion strategy should be carefully considered against the risk of contamination.


title: A prospective study comparing patient-reported outcomes in Crohn's disease.

text: BACKGROUND Patient reported outcomes are important in Crohn's disease. In this prospective cohort, we investigated the performance of the Bristol Stool Form Scale (BSFS) and a visual analog scale (VAS) for abdominal pain as outcome measures in Crohn's disease. METHODS Patients with active Crohn's disease starting glucocorticoids or anti-tumor necrosis factor were included. Before treatment and 10 weeks later we collected: clinical activity [Harvey Bradshaw Index (HBI) and Crohn's-Disease-Activity-Index (CDAI)], serum C-reactive protein (CRP) and fecal calprotectin, and BSFS (1-7) and a 100-mm VAS based on a 7-day diary. Clinical response was defined as a reduction by at least 3 and at least 100 of HBI and CDAI, respectively. Fecal calprotectin-response and CRP-response were defined as reduction of at least 50%. RESULTS Thirty-eight patients completed follow-up. At baseline, BSFS-parameters correlated more strongly with clinical activity (range: rs: 0.31-0.74) than with CRP (rs: -0.01 to 0.16) and fecal calprotectin (rs: 0.14-0.26). VAS scores correlated very weakly to moderately with clinical activity (rs: 0.18-0.45), and weakly to moderately with CRP (rs: 0.24-0.34) and fecal calprotectin (rs: 0.35-0.43). Changes in VAS scores correlated moderately to strongly (rs: 0.55-0.71) with changes in clinical activity, and weakly with changes in CRP and fecal calprotectin (rs: 0.21-0.35). Changes in BSFS parameters correlated weakly to moderately (rs: 0.23-0.53) with changes in clinical activity, and very weakly to weakly (rs: 0.01-0.35) with changes in CRP and fecal calprotectin. Responsiveness of VAS and BSFS was moderate to high (Guyatt's statistic 0.41-2.17) and highly dependent on the definition of response. CONCLUSIONS The BSFS and a VAS appear to be responsive with moderate-to-strong construct validity to monitor patients with Crohn's disease.


title: Virtual Surgical Fellowship Recruitment During COVID-19 and Its Implications for Resident/Fellow Recruitment in the Future

text: BACKGROUND: The COVID-19 pandemic has overlapped with the scheduled interview periods of over 20 surgical subspecialty fellowships, including the Complex General Surgical Oncology (CGSO) fellowships in the National Resident Matching Program and the Society of Surgical Oncology’s Breast Surgical Oncology fellowships. We outline the successful implementation of and processes behind a virtual interview day for CGSO fellowship recruitment after the start of the pandemic. METHODS: The virtual CGSO fellowship interview process at the University of Chicago Medicine and NorthShore University Health System was outlined and implemented. Separate voluntary, anonymous online secure feedback surveys were email distributed to interview applicants and faculty interviewers after the interview day concluded. RESULTS: Sixteen of 20 interview applicants (80.0%) and 12 of 13 faculty interviewers (92.3%) completed their respective feedback surveys. Seventy-five percent (12/16) of applicants and all faculty respondents (12/12) stated the interview process was ‘very seamless’ or ‘seamless’. Applicants and faculty highlighted decreased cost, time savings, and increased efficiency as some of the benefits to virtual interviewing. CONCLUSIONS: Current circumstances related to the COVID-19 pandemic require fellowship programs to adapt and conduct virtual interviews. Our report describes the successful implementation of a virtual interview process. This report describes the technical steps and pitfalls of organizing such an interview and provides insights into the experience of the interviewer and interviewee.


title: Penetrating Head Injury by a Nail Gun: Case Report, Review of the Literature, and Management Considerations.

text: Our objective is to discuss penetrating head injuries (PHIs) which, although rare, lead to considerable morbidity and mortality. One of the most significant culprits of PHI is the nail gun, which was introduced in 1959 and has gained substantial popularity. We describe our successful strategy for removing an 8-cm nail that penetrated through the orbit and middle cranial fossa, with the tip lodged within the posterior fossa. Vascular imaging and balloon test occlusion are imperative in circumstances where vessel sacrifice is necessary. In addition, positioning of balloons within large vessels that are in close proximity to the penetrating object is necessary to control bleeding that may occur during removal of the object. It is of paramount importance to have a multidisciplinary team participating in the management and eventual removal of foreign objects within the intracranial compartment. Included is a review of the literature and a discussion on management approaches to such injuries.


title: Validation of a pediatric single-port laparoscopic surgery simulator.

text: BACKGROUND This study aims to adapt an existing multiport pediatric laparoscopic surgery simulator to be suitable for pediatric single-port laparoscopy and to investigate construct validity for its use as a resource for skills training and assessment. METHODS An existing pediatric-sized box trainer was modified to accommodate a commercially available port. A total of 41 participants (18 novices, 16 intermediates and 7 experts) were recruited to complete four curriculum tasks via a single-port access approach. Objective task performance scores were evaluated. RESULTS Task completion times and performance scores were significantly different between novices and experts for the peg transfer (P = 0.02, P = 0.008 respectively), pattern cut (P < 0.001, P < 0.001 respectively) and ligating loop (P = 0.038, P = 0.035 respectively). There were significant differences in outcomes between novices and intermediates for all tasks, including the intracorporeal suture task (P ≤ 0.001). There were no significant differences in outcomes between intermediates and experts for all tasks. CONCLUSIONS The Pediatric Laparoscopic Surgery (PLS) simulator can be easily adapted for single-port laparoscopic surgery to be construct valid for the peg transfer, ligating loop and pattern cut tasks. There is scope for additional tasks to be developed that focus on the unique technical challenges and skills associated with single-port techniques.


title: Effect of adjusted cuff pressure of endotracheal tube during thyroidectomy on postoperative airway complications: prospective, randomized, and controlled trial.

text: BACKGROUND Postoperative sore throat (POST) is a common complaint after general anesthesia, especially following thyroidectomy. MATERIALS AND METHODS We examined the effect of adjusting the endotracheal tube cuff pressure during thyroidectomy on the incidence of airway complications. Ninety patients scheduled for elective thyroidectomy were randomized into two groups: control (group A, n = 45) and experimental (group B, n = 45). All patients underwent total intravenous anesthesia with propofol and remifentanil. In group A, the cuff pressure was set to 25 cm H2O initially and then monitored continuously without adjustment during thyroidectomy. In group B, the cuff pressure was maintained at approximately 25 cm H2O throughout the operation. The incidences and the severity of POST, hoarseness, dysphagia, and cough were recorded at 2 and 24 h postoperatively. RESULTS Cuff pressures in group A changed significantly over time (P < 0.05) and were higher than those of group B during thyroidectomy (P < 0.05). The incidences of POST were lower in group B than in group A at 2 and 24 h postoperatively (P < 0.05), and there was a significant difference in the severity of POST at 2 h postoperatively between the two groups. There were no differences in the incidences of hoarseness, dysphagia, and cough between the two study groups (P > 0.05). Adjusting the endotracheal cuff pressure during thyroidectomy decreased the incidence and degree of POST. CONCLUSIONS Intraoperative monitoring and adjustment of the cuff pressure can reduce POST in patients undergoing thyroidectomy.


title: Instant Abdominal Wall Reconstruction with Biologic Mesh following Resection of Locally Advanced Colonic Cancer.

text: We present a case of immediate abdominal wall reconstruction with biologic mesh following the resection of locally advanced colonic cancer. The tumor in the right colon did not respond to neoadjuvant chemotherapy. Surgical enbloc excision, including excision of the invasion in the abdominal wall, was achieved, and the defect was reconstructed with porcine dermal collagen mesh. The patient was discharged with no complication, and adaptation of the mesh was excellent at the six-month followup.


title: Prognosis of asymptomatic intracranial hemorrhage after endovascular treatment.

text: OBJECTIVE Asymptomatic intracranial hemorrhage (aSICH) is a common phenomenon after endovascular treatment of acute ischemic stroke, but its prognostic impacts remain unclear. This study evaluated functional outcomes of thrombectomy in patients with and without aSICH. METHODS Patients with acute ischemic stroke due to large artery occlusion in the anterior circulation who were treated with thrombectomy were enrolled in 21 centers. According to CT scans performed within 72 hours of endovascular procedures, patients with aSICH or without intracranial hemorrhage were included while patients with symptomatic intracranial hemorrhage (SICH) were excluded. Baseline data and functional outcomes were compared between patients with aSICH and those without intracranial hemorrhage. Logistic regression analysis was applied to evaluate the impacts of aSICH on functional outcomes. RESULTS Of the 632 patients with endovascular treatment, 101 (16.0%) were classified as having SICH, 212 (33.5%) as having aSICH, and 319 (50.5%) as being without intracranial hemorrhage. Patients with aSICH after endovascular treatment had a lower ratio of excellent outcome (mRS 0-1, OR 0.53; 95% CI 0.33 to 0.84, P=0.007) than those without intracranial hemorrhage. There were no significant differences concerning favorable outcome (mRS 0-2, OR 0.76; 95% CI 0.50 to 1.14, P=0.185) or mortality (OR 0.64; 95% CI 0.38 to 1.09, P=0.101) between patients with aSICH and those without intracranial hemorrhage. CONCLUSIONS In an Asian population, aSICH after thrombectomy may decrease the likelihood of an excellent functional outcome but does not influence a favorable outcome and mortality in patients with ischemic stroke due to large artery occlusion in the anterior circulation.


title: CYP1A1 and Cnr nitroreductase bioactivated niclosamide in vitro.

text: Niclosamide produces genotoxic effects, such as point mutations in Salmonella sp., sperm-head abnormalities in mice and clastogenic effects in human lymphocytes in vitro and in vivo. As cytochrome P450 could be involved in the bioactivation of niclosamide, we investigated which subfamily was involved. We used liver microsomal fractions from rats treated with phenobarbital/β-naphthoflavone (PB/β-NF), benzo[a]pyrene (BaP) or cyclohexanol, which are known to induce different cytochrome P450 subfamilies, such as CYP2B, CYP1A1, CYP1A2 and CYP2E1. We also inhibited CYP1A and CYP2E using α-NF and diethyldithiocarbamate to identify the cytochrome P450 involved. Liver-S9 fractions obtained from PB/β-NF- and BaP-treated rats significantly increased the number of revertants induced by niclosamide, while the CYP1A1 inhibitor α-NF decreased the number of revertants. The incubation of niclosamide with CYP1A1 Supersomes™ increased the number of revertants, suggesting that CYP1A1 is responsible for the bioactivation of niclosamide. Nitroreduction is also involved in niclosamide bioactivation, as the nitroreductase-deficient strain YG7132 did not respond to the niclosamide treatment. Our findings indicated that a metabolite, derived from the action of CYP1A1 and a nitroreduction-reaction process, has a key role in the bioactivation of niclosamide.


title: Laparoscopic Repair of Paraesophageal Hernias with a Falciform Ligament Buttress.

text: BACKGROUND Buttressing the crura in paraesophageal hernia (PEH) repairs with synthetic mesh may be associated with erosions and dysphagia, while biologic buttresses are expensive and do not decrease long-term recurrence rates. This study documents outcomes following laparoscopic PEH repairs using the falciform ligament as a buttress. METHODS This is a prospective study of laparoscopic PEH repairs with a falciform ligament buttress. Preoperatively and at 6 months follow-up, medications, radiologic studies and symptom scores were recorded. Patients included had a hiatal defect greater than 5 cm, while recurrent PEH or prior gastric surgery patients were excluded. RESULTS Thirty-four patients were included with a mean age of 61 years, and 33 patients completed postoperative evaluation with a mean follow-up of 7.1 months. The mean symptom severity decreased from 11.24 ± 1.71 to 3.24 ± 0.84, mean symptom frequency decreased from 11.62 ± 1.70 to 3.45 ± 0.85, and mean total symptom score decreased from 22.85 ± 3.40 to 6.69 ± 1.69 (p < 0.0001). Three patients had recurrences on the upper gastrointestinal (UGI) series. Only one required reoperation. CONCLUSIONS Laparoscopic PEH repair with a falciform ligament buttress is a viable option. Ongoing follow-up will demonstrate the utility of this approach to decrease morbidity and recurrence rates for paraesophageal hernia repairs.


Lockdowns due to COVID-19 threaten PhD students' and early-career researchers' careers.


title: Response to comment on "Oestrogen-induced angiogenesis and implantation contribute to the development of parasitic myomas after laparoscopic morcellation".

text: According to the literature review, CO2 insufflation on parasitic myoma implantation is not well studied, and we concur that our study is related to "Morcellation-induced parasitic myomas." We did not compare CO2 insufflation to non-insufflation in our study. The reason is the efficacy of gasless laparoscopic myomectomy and morcellation is not well established and this modality is seldom performed. Moreover, the effects of pneumoperitoneum on mesothelial cells and the role of the entire peritoneal cavity as a cofactor in adhesion formation have become well established, the role of CO2 insufflation in the establishment of parasitic myomas has not yet been studied. As such, more in-depth and well-designed studies for the role of CO2 insufflation are needed.


title: Easy Advancement of a Large-Profile Microcatheter (Excelsior XT27™) by Parallel Use of Two Microguidewires For Stent Delivery.

text: PURPOSE In the endovascular treatment of cerebral aneurysms, navigating a large-bore microcatheter for delivery of an open-cell stent can be challenging, especially in wide-necked bifurcation aneurysms. We were able to overcome this difficulty by parallel use of two microguidewires through the stent-delivery microcatheter. MATERIALS AND METHODS From December 2014 to April 2015, we treated 15 patients with wide-necked bifurcation aneurysms. For stent delivery, we used a 300-cm 0.014-in microguidewire (Transend), which was placed into the target branch using an exchange technique. A 0.027-in microcatheter (Excelsior XT-27), which was designed for the stent, was advanced over the exchange microguidewire. If we had trouble in advancing the microcatheter over the exchange microguidewire, we inserted a regular microguidewire (Traxcess), into the microcatheter lumen in a parallel fashion. We also analyzed the mechanism underlying microcatheter positioning failure and the success rate of the 'parallel-wire technique'. RESULTS Among the 15 cases, we faced with navigation difficulty in five patients. In those five cases, we could advance the microcatheter successfully by applying the parallel-wire technique. There were no procedure-related complications. CONCLUSION Simply by using another microguidewire together with pre-existing microguidewire in a parallel fashion, the stent-delivery microcatheter can be easily navigated into the target location in case of any advancement difficulty.


Pearls and Oy-sters: Facial nerve palsy as a neurological manifestation of Covid-19 infection.


title: Activation of the chicken type I interferon response by infectious bronchitis coronavirus.

text: UNLABELLED Coronaviruses from both the Alphacoronavirus and Betacoronavirus genera interfere with the type I interferon (IFN) response in various ways, ensuring the limited activation of the IFN response in most cell types. Of the gammacoronaviruses that mainly infect birds, little is known about the activation of the host immune response. We show that the prototypical Gammacoronavirus, infectious bronchitis virus (IBV), induces a delayed activation of the IFN response in primary renal cells, tracheal epithelial cells, and a chicken cell line. In fact, Ifnβ expression is delayed with respect to the peak of viral replication and the accompanying accumulation of double-stranded RNA (dsRNA). In addition, we demonstrate that MDA5 is the primary sensor for Gammacoronavirus infections in chicken cells. Furthermore, we provide evidence that accessory proteins 3a and 3b of IBV modulate the response at the transcriptional and translational levels. Finally, we show that, despite the lack of activation of the IFN response during the early phase of IBV infection, the signaling of nonself dsRNA through both MDA5 and TLR3 remains intact in IBV-infected cells. Taken together, this study provides the first comprehensive analysis of host-virus interactions of a Gammacoronavirus with avian innate immune responses. IMPORTANCE Our results demonstrate that IBV has evolved multiple strategies to avoid the activation of the type I interferon response. Taken together, the present study closes a gap in the understanding of host-IBV interaction and paves the way for further characterization of the mechanisms underlying immune evasion strategies as well as the pathogenesis of gammacoronaviruses.


title: Navigating the Ethics of COVID-19 in Otolaryngology.

text: The COVID-19 pandemic has dramatically altered how otolaryngologists contemplate and assume their roles in health care delivery. The ethical implications of this pandemic upon our practice are formidable and distinct from other surgical fields. The salient ethical issues of public health stewardship and safety, distributive justice, and nonabandonment are distilled for the practicing otolaryngologist.


title: Beyond the "B": a new concept of the surgical staple enabling miniature staplers.

text: BACKGROUND Surgical staplers currently all rely on the same staple form-the "B" which necessitates a high delivery profile (12 mm). A novel "D" shape staple allows for an extremely low profile of the applicator. The acute and long-term efficacy of a D-shaped staple (Cardica, Redwood City, CA, USA) was compared to conventional B-form staples (Covidien, Norwalk, CN, USA) in an animal model for intestinal transections and anastomoses. METHODS Jejunojejunal anastomoses (JJ) were performed via mini-laparotomy in a swine model. White & blue D- and B-shaped staples were studied in three groups (planned survival 14-84 days). Intraoperative assessment included completeness of staple line, hemostasis, and need for intervention. Postoperatively, animals were evaluated for complications. At the time of sacrifice, gross pathological and histological assessments were performed. RESULTS Twenty-three animals had 40 anastomoses (23 "D" and 17 "B" staple anastomoses) with no intraoperative mortalities. One "D" staple application required a manual extension of the cut. Acute hemostasis was 100%. Group 1 (n = 5) compared white staples in JJs (D staple n = 5; B staple n = 5; 14-day survival = 100%). Group 2 (n = 12) compared white staples in JJs (D staple n = 12; B staple n = 6; 34-day survival = 92 %). One animal died on day 4 for a non-staple related cause. Group 3 (n = 6) compared blue staples in JJs (D staple n = 6; B staple n = 6; 84 day survival = 84%). One animal died on day 18 due to an obstruction at the B staple JJ caused by stricture. There were no other bleeding, leaks or strictures in any of the groups. Gross pathology and histology were unremarkable in all JJs. CONCLUSIONS This study showed no difference in intraoperative performance and the chronic healing response in JJs between D- and B-shaped staples. Based on these findings, the D-shaped staple elicits a normal healing response in jejunostomies and offers the possibility of clinical use of this advance in staple design.


title: The effect of a handwashing intervention on preschool educator beliefs, attitudes, knowledge and self-efficacy.

text: This paper describes the effect of a preschool hygiene intervention program on psychosocial measures of educators regarding handwashing and communicable pediatric disease. A cluster-randomized trial, with randomization at the level of the preschool, was run in 40 Jerusalem preschool classrooms. Eighty preschool educators participated. The program used a multipronged approach which included elements aimed at staff, children, parents, school nurses and the classroom environment. Frontal lectures by medical, epidemiological and educational experts, along with printed materials and experiential learning, were provided to staff. Responses from a validated survey instrument were used to build four scales for each respondent regarding beliefs, attitudes, self-efficacy and knowledge. The scales were built on a Likert-type 1-7 scale (1 = minimum, 7 = maximum). The effect of the intervention was tested using mixed model analysis of variance. Response was received from 92.5% of educators. Educators believed that handwashing could affect health (mean = 5.5, SD = 1.1), had high levels of self-efficacy (mean = 6.1, SD = 0.9) and had positive attitudes toward handwashing (mean = 5.7, SD = 1.2). Knowledge was affected by the intervention (intervention: mean = 6.2, SD = 0.7; control: mean = 5.8, SD = 0.8). The combination of positive attitudes toward handwashing among educators and the program's effectiveness in imparting knowledge helped to create a sustained social norm of handwashing among many children in disparate locations.


title: Stroke intervention: catheter-based therapy for acute ischemic stroke.

text: The majority (>80%) of the three-quarters of a million strokes that will occur in the United States this year are ischemic in nature. The treatment of acute ischemic stroke is very similar to acute myocardial infarction, which requires timely reperfusion therapy for optimal results. The majority of patients with acute ischemic stroke do not receive any form of reperfusion therapy, unlike patients with acute myocardial infarction. Improving outcomes for acute stroke will require patient education to encourage early presentation, an aggressive expansion of qualified hospitals, and willing providers and early imaging strategies to match patients with their best options for reperfusion therapy to minimize complications.


title: Fetoscopic two-layer closure of open neural tube defects.

text: OBJECTIVE Fetoscopy for closure of open neural tube defects (NTD) remains controversial, as the use of patches or single-layer closure is not considered to meet the standards of good neurosurgical reconstruction. In this study, we describe a fetoscopic two-layer (myofascial and skin) closure technique for the treatment of NTD in five patients and report the preliminary anatomical outcome at birth. METHODS From February to September 2017, five pregnant women with a fetus with a NTD, including three cases of myelomeningocele and two cases of myelocele, were operated on using a fetoscopic two-layer closure technique. In this technique, with the uterus exteriorized and using three 10-Fr ports, the placode is dissected from the surrounding tissue and detethered, removing the cystic tissue. The skin is undermined by blunt dissection and the defect is sutured to the midline in two layers (myofascial and skin) using a running 4/0 resorbable barbed suture. RESULTS Median gestational age at the procedure was 24 + 3 (range, 23 + 5 to 27 + 3) weeks. Surgery was successful in all cases, without any intraoperative complications. Median time in surgery was 180 (range, 140-180) min and median time for fetoscopy was 105 (range, 65-120) min. In terms of obstetric complications, three cases of premature rupture of membranes and one case of chorioamnionitis were recorded. Median gestational age at delivery was 34 + 1 (range, 25 + 4 to 37 + 2) weeks and two patients delivered vaginally. The closed defect was watertight with good quality tissue in all cases. CONCLUSION Fetoscopic two-layer closure of NTD may improve the quality of the tissue covering the defect, diminishing the need for postnatal surgical revision, and preserving the well-documented beneficial effects of prenatal closure on the neural tissue and hindbrain herniation. However, this technique may not be appropriate for those cases with wide diastasis of the myofascial layer or with a low quantity of available tissue. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.


title: Early outcomes of robotic-assisted inguinal hernia repair in obese patients: a multi-institutional, retrospective study.

text: BACKGROUND Minimally invasive inguinal hernia repair (IHR) in general and particularly in obese patients has not been widely adopted, potentially due to the perceived technical challenges and the well-documented learning curve associated with laparoscopic repair. Outcomes in robotic-assisted IHR in obese (BMI ≥ 30 kg/m2) patients have not been described and warrant study. METHODS Seven surgeons conducted a multicenter retrospective chart review of their early robotic-assisted IHR (RHR) cases and compared them with their open IHR (OHR) cases. Demographics, operative characteristics, and perioperative morbidity were compared for unadjusted and propensity-matched populations. RESULTS 651 robotic-assisted cases and 593 open cases were collected. The outcomes of 148 RHRs to 113 OHRs in obese patients were compared. For obese populations-whether unadjusted (robotic-assisted, n = 148; open, n = 113) or matched (1:1) (robotic-assisted, n = 95; open, n = 93)-the robotic-assisted and open cohorts were comparable in terms of demographics and baseline characteristics. Significantly higher percentages of OHR patients experienced postoperative complications post-discharge (unadjusted: 11.5% vs. 2.7%, p = 0.005; and matched: 10.8% vs. 3.2%, p = 0.047). More concomitant procedures and bilateral repairs were conducted in obese RHR patients than in obese OHR patients (unadjusted 29.7% vs. 16.8%, p = 0.019; and unadjusted 35.1% vs. 11.5%, p < 0.0001-respectively). Prior laparoscopic IHR experience did not affect 30-day outcomes. CONCLUSIONS Obese patients who undergo RHR have a lower rate of postoperative complications compared to obese patients who undergo OHR. Previous laparoscopic IHR experience, more bilateral repairs, and more concomitant procedures were not associated with increased complications in RHR patients. These outcomes may facilitate increased adoption of minimally invasive IHR approaches in the obese population.


title: Update with level 1 studies of the European Hernia Society guidelines on the treatment of inguinal hernia in adult patients.

text: PURPOSE In 2009, the European Hernia Society published the EHS Guidelines for the Treatment of Inguinal Hernia in Adult Patients. The Guidelines contain recommendations for the treatment of inguinal hernia from diagnosis till aftercare. The guidelines expired January 1, 2012. To keep them updated, a revision of the guidelines was planned including new level 1 evidence. METHODS The original Oxford Centre for Evidence-Based Medicine ranking was used. All relevant level 1A and level 1B literature from May 2008 to June 2010 was searched (Medline and Cochrane) by the Working Group members. All chapters were attributed to the two responsible authors in the initial guidelines document. One new chapter on fixation techniques was added. The quality was assessed by the Working Group members during a 2-day meeting and the data were analysed, especially with respect to any change in the level and/or text of any of the conclusions or recommendations of the initial guidelines. In the end, all relevant references published until January 1, 2013 were included. The final text was approved by all Working Group members. RESULTS For the following topics, the conclusions and/or recommendations have been changed: indications for treatment, treatment of inguinal hernia, day surgery, antibiotic prophylaxis, training, postoperative pain control and chronic pain. The addendum contains all current level 1 conclusions, Grade A recommendations and new Grade B recommendations based on new level 1 evidence (with the changes in bold). CONCLUSIONS Despite the fact that the Working Group responsible for it tried to represent most kinds of surgeons treating inguinal hernias, such general guidelines inevitably must be fitted to the daily practice of every individual surgeon treating his/her patients. There is no doubt that the future of guideline implementation will strongly depend on the development of easy to use decision support algorithms tailored to the individual patient and on evaluating the effect of guideline implementation on surgical outcome. At the 35th International Congress of the EHS in Gdansk, Poland (May 12-15, 2013), it was decided that the EHS, IEHS and EAES will collaborate from now on with the final goal to publish new joint guidelines, most likely in 2015.


Does Age Matter? The Relationship between Sleep-disordered Breathing and Incident Atrial Fibrillation in Older Men.


title: ASGE guideline on the role of endoscopy in the evaluation and management of choledocholithiasis.

text: Each year choledocholithiasis results in biliary obstruction, cholangitis, and pancreatitis in a significant number of patients. The primary treatment, ERCP, is minimally invasive but associated with adverse events in 6% to 15%. This American Society for Gastrointestinal Endoscopy (ASGE) Standard of Practice (SOP) Guideline provides evidence-based recommendations for the endoscopic evaluation and treatment of choledocholithiasis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework was used to rigorously review and synthesize the contemporary literature regarding the following topics: EUS versus MRCP for diagnosis, the role of early ERCP in gallstone pancreatitis, endoscopic papillary dilation after sphincterotomy versus sphincterotomy alone for large bile duct stones, and impact of ERCP-guided intraductal therapy for large and difficult choledocholithiasis. Comprehensive systematic reviews were also performed to assess the following: same-admission cholecystectomy for gallstone pancreatitis, clinical predictors of choledocholithiasis, optimal timing of ERCP vis-à-vis cholecystectomy, management of Mirizzi syndrome and hepatolithiasis, and biliary stent therapy for choledocholithiasis. Core clinical questions were derived using an iterative process by the ASGE SOP Committee. This body developed all recommendations founded on the certainty of the evidence, balance of risks and harms, consideration of stakeholder preferences, resource utilization, and cost-effectiveness.


title: Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection: epidemiology, pathogenesis and clinical characteristics.

text: OBJECTIVE Middle East Respiratory Syndrome Coronavirus-(MERS-CoV) infection is an evolving worldwide health crisis. The early diagnosis and management of the disease remains a major challenge. This study designed to discuss the epidemiology, pathogenesis and clinical appearances of MERS-CoV infections. MATERIALS AND METHODS We conducted a broad search of the English-language literature in "PubMed" "Medline" "Web of knowledge", "EMBASE" and "Google Scholar" World Health Organization-WHO" using the key words "Middle East Respiratory Syndrome", "MERS", "MERS-CoV" "Epidemiology" "Transmission" "Pathogenesis" "Clinical Characteristics". We reviewed the literature on epidemiology, pathogenesis and clinical appearances of MERS-CoV infection and the required information was documented. RESULTS The global prevalence of MERS-CoV infection from June 2012 to April 2018 is 2206 people. The number of cases reported from Saudi Arabia is 1831 (83%) with mortality rate of 787 (35.67%). The main clinical manifestations are fever, chills, generalized myalgia, cough, shortness of breath, nausea, vomiting and diarrhea. The age-allied prevalence of MERS-CoV was highest amongst elderly people with chronic debilitating diseases such as pulmonary diseases, end-stage renal illness, diabetes mellitus and malignancy. CONCLUSIONS MERS-CoV infection is an emerging global health concern, affected people in 27 countries in the various continents. MERS-CoV infection has been identified mainly in the Middle East, Europe, Africa, Asia and North America. Early detection and management of MERS-CoV infection is of critical importance to minimize the burden of the disease.


title: MAPK pathway mutations in head and neck cancer affect immune microenvironments and ErbB3 signaling.

text: MAPK pathway mutations affect one-fifth of head and neck squamous cell carcinoma (HNSCC). Unexpectedly, MAPK pathway aberrations are associated with remarkably long patient survival, even among patients with TP53 mutations (median ∼14 yr). We explored underlying outcome-favoring mechanisms with omics followed by preclinical models. Strikingly, multiple hotspot and non-hotspot MAPK mutations (A/BRAF, HRAS, MAPK1, and MAP2K1/2) all abrogated ErbB3 activation, a well-established HNSCC progression signal. Inhibitor studies functionally defined ERK activity negatively regulating phospho-ErbB3 in MAPK-mutants. Furthermore, pan-pathway immunoprofiling investigations identified MAPK-mutant tumors as the only "CD8+ T-cell-inflamed" tumors inherently bearing high-immunoreactive, constitutive cytolytic tumor microenvironments. Immunocompetent MAPK-mutant HNSCC models displayed active cell death and massive CD8+ T-cell recruitment in situ. Consistent with CD8+ T-inflamed phenotypes, MAPK-mutant HNSCC patients, independent of tumor-mutational burden, survived 3.3-4 times longer than WT patients with anti-PD1/PD-L1 immunotherapies. Similar prognosticity was noted in pan-cancers. We uncovered clinical, signaling, and immunological uniqueness of MAPK-mutant HNSCC with potential biomarker utilities predicting favorable patient survival.


The surgeon makes the difference, not the instrument used.


title: The protocol of low-impact laparoscopic cholecystectomy: the combination of mini-laparoscopy and low-pressure pneumoperitoneum.

text: Low-impact laparoscopic (LIL) cholecystectomy is an innovative surgical protocol that combines the use of mini-laparoscopic instruments (3-mm ports) under a low- and stable-pressure pneumoperitoneum (8 mmHg), with the aim of minimizing the surgical invasiveness and the risks related to CO2 insufflation on the peritoneal environment. In day-surgery settings, LIL may contribute to increase the surgical success due to several potential benefits in terms of postoperative pain intensity and time to full recovery. In 14 consecutive patients requiring cholecystectomy for uncomplicated cholelithiasis, LIL was carried out uneventfully. No conversion, intra-operative or postoperative complications occurred. All patients were discharged the same day of surgery. Postoperative pain was well tolerated with no need of prolonged opioid therapy. Technical aspects and indications for LIL cholecystectomy are detailed.


title: Addressing cultural, racial and ethnic discrepancies in guideline discordant gestational weight gain: a systematic review and meta-analysis.

text: Objective To systematically review the literature and describe the discrepancies in achieving the 2009 Institute of Medicine (IOM) gestational weight gain (GWG) guidelines across cultures. Methods Ten databases were searched from inception to April 2018. Observational cohort studies were included that examined adult women; reported on a measure of culture; compared cultural groups, and reported on GWG. Articles were broken down into papers that used the current 2009 IOM GWG guidelines and those that used others. A meta-analysis was conducted for studies using the 2009 guidelines examining the prevalence of discordant GWG across cultural groups. Results The review included 86 studies. Overall, 69% of women experienced discordant GWG irrespective of culture. White women experienced excessive GWG most often, and significantly more than Asian and Hispanic women; Black women had a higher prevalence of excessive GWG than Hispanic and Asian women; however, this difference was not significant. Conclusions The majority of women experience excessive GWG, with White women experiencing this most often. Culturally diverse GWG guidelines are needed to individualize antenatal care and promote optimal maternal-fetal health outcomes across cultural groups.


title: Molecular diagnostics of infectious diseases.

text: PURPOSE OF REVIEW The purpose of this article is to review the molecular methods commonly used in medical microbiology as well as to update the clinician as to newer molecular technologies that show promise in the identification of microorganisms as well as evaluation of the presence of virulence factors and antibiotic resistance determinants. RECENT FINDINGS Numerous molecular assays have been developed recently using a variety of technologies. Direct hybridization techniques have allowed analysis of blood culture bottles for organisms such as methicillin-resistant Staphylococcus aureus. Target amplification methods allow postamplification analysis using a variety of technologies depending on the clinical needs for the assay. Postamplification analysis includes methods such as Sanger sequencing, pyrosequencing, reverse hybridization, and Luminex analysis, which are becoming more widely utilized. In the future, whole genome sequencing, mass spectrometry, and microarray analysis may provide a wealth of information that can be used to specifically tailor the treatment of infectious diseases. SUMMARY The implications of current trends in molecular infectious diseases are moving towards high-throughput, simple, array-type technologies that will provide a wealth of data regarding types of organisms present in a sample and the virulence factors/resistance determinants that influence the severity of disease. As a result of these developments, infectious diseases will be more accurately and effectively treated.


title: The acetyl-esterase activity of the hemagglutinin-esterase protein of human coronavirus OC43 strongly enhances the production of infectious virus.

text: Most betacoronaviruses possess an hemagglutinin-esterase (HE) protein, which appears to play a role in binding to or release from the target cell. Since this HE protein possesses an acetyl-esterase activity that removes acetyl groups from O-acetylated sialic acid, a role as a receptor-destroying enzyme has been postulated. However, the precise function of HE and of its enzymatic activity remains poorly understood. Making use of neutralizing antibody and of molecular clones of recombinant human coronavirus OC43 (HCoV-OC43), our results suggest that the HE protein of this HCoV could be associated with infection of target cells and, most notably, is important in the production of infectious viral particles. Indeed, after transfecting BHK-21 cells with various cDNA infectious clones of HCoV-OC43, either lacking the HE protein or bearing an HE protein with a nonfunctional acetyl-esterase enzymatic activity, we were reproducibly unable to detect recombinant infectious viruses compared to the reference infectious HCoV-OC43 clone pBAC-OC43(FL). Complementation experiments, using BHK-21 cells expressing wild-type HE, either transiently or in a stable ectopic expression, demonstrate that this protein plays a very significant role in the production of infectious recombinant coronaviral particles that can subsequently more efficiently infect susceptible epithelial and neuronal cells. Even though the S protein is the main viral factor influencing coronavirus infection of susceptible cells, our results taken together indicate that a functionally active HE protein enhances the infectious properties of HCoV-OC43 and contributes to efficient virus dissemination in cell culture.


title: Inactivation of coxsackievirus B4, feline calicivirus and herpes simplex virus type 1: unexpected virucidal effect of a disinfectant on a non-enveloped virus applied onto a surface.

text: OBJECTIVE To evaluate the effect of a disinfectant onto viruses in suspension on the one hand and applied onto a surface on the other. METHODS A system combining flocked swabs to recover viruses dried onto stainless steel carriers and gel filtration to eliminate cytotoxic products has been developed to study the virucidal effect of a quaternary ammonium-based disinfectant towards herpes simplex virus type 1 (HSV-1), coxsackievirus B4 (CVB4) and feline calicivirus F9 (FCV). The recovery of FCV has been estimated by RT real-time PCR. RESULTS HSV-1, CVB4 and FCV had a titer over 10(4) TCID50 · ml(-1) after 2 h drying and were recovered from the carriers using flocked swabs. HSV-1 was inactivated in suspension and on stainless steel carriers by the disinfectant (a reduction factor of 4 and 2.83 log, respectively) whereas CVB4 was resistant. The reduction of infectious titer was moderate, 1.5 log in 30 min, when FCV was in suspension, whereas it was up to 4 log in 10 min when the virus was dried on a carrier. Dried FCV was efficiently recovered from carriers as demonstrated by RT real-time PCR. CONCLUSION A non-enveloped virus, FCV, applied on a surface, but not in suspension, was inactivated by a quaternary ammonium-based disinfectant. The resistance of viruses applied onto a surface to the effect of disinfectants should be investigated further.


title: Outcomes of slit mesh in laparoscopic totally extraperitoneal inguinal hernia repair: Does it affect recurrence?

text: INTRODUCTION The aim of this study was to compare outcomes between slit and non-slit mesh placement in laparoscopic totally extraperitoneal inguinal hernia repair. METHODS This is a retrospective study of 113 patients who underwent laparoscopic totally extraperitoneal inguinal hernia repair with Ultrapro mesh between January 2010 and December 2011. Sixty-two and 82 hernias were operated on in the slit mesh and non-slit mesh groups, respectively. Postoperative complications, recurrence, and patient satisfaction levels were evaluated. RESULTS One hernia in the slit mesh group (1/62, 1.6%) and one in the non-slit mesh group (1/82, 1.2%) developed recurrence (P = 1.00). The incidence of postoperative neuralgia was 4/62 (6.5%) and 7/82 (8.5%) in the slit mesh and non-slit mesh groups, respectively (P = 0.76). Satisfaction rates in the slit mesh and non-slit mesh groups were similar at 60/62 (96.8%) and 80/82 (97.6%), respectively (P = 1.00). CONCLUSION No significant differences in outcomes were found between slit and non-slit mesh placement. Both have low complication rates, low recurrence rates, and high satisfaction levels.


title: Feasibility of single-incision laparoscopic appendectomy in a small hospital.

text: PURPOSE This study aimed to compare clinical outcomes for single-incision laparoscopic appendectomy (SILA) and conventional laparoscopic appendectomy (CLA) for the treatment of acute appendicitis and to assess the feasibility of performing SILA in a small hospital with limited surgical instruments and staff experience. METHODS Retrospective record review identified 133 patients who underwent laparoscopic appendectomy from December 2013 to April 2015. Patients were categorized according to the type of appendectomy performed (SILA or CLA). Patient characteristics and surgical outcomes were compared between the 2 groups. Postoperative complication rates were compared using the Clavien-Dindo classification. Postoperative pain was assessed using a visual analog scale immediately postsurgery; at 12, 24, 36, and 48 hours postoperatively, and at 7 days postoperatively. RESULTS Record review identified 38 patients who had undergone SILA and 95 patients who had undergone CLA. No significant differences in clinical characteristics were found between the 2 groups. There were no significant differences in operation time, time to flatus, or length of hospital stay. Overall complication rates were not significantly different between the 2 groups. No complications worse than grade IIIa occurred in the SILA group. Postoperative pain scores were not significantly different between the 2 groups at any time point. CONCLUSION We found comparable surgical outcomes for SILA compared to CLA. Even in a small hospital with limited surgical instruments and staff experience, SILA may be a feasible and safe technique.


title: Totally extraperitoneal repair of inguinal hernia: techniques and pitfalls of a challenging procedure.

text: Inguinal hernia repair is the most common procedure performed worldwide in general surgery. Since the turn of the 21st century, the minimally invasive approach and in particular totally extraperitoneal (TEP) repair has gained in popularity. The concept of the TEP approach combines the advantages of anterior tension-free mesh repair (Lichtenstein repair) and the open preperitoneal approach championed by Stoppa. TEP repair uses a prosthetic mesh significantly bigger than in open herniorrhaphy, offering a complete overlap of the myopectineal orifice. TEP repair is a challenging technique with unfamiliar anatomy, a limited operative field, and long learning curve. This article provides an experienced opinion on the practical aspects of the TEP approach. Some of these steps have already been discussed in the surgical literature, while others are the fruit of a personal expertise grasped over the years with more than 1,000 TEP repairs performed.