title: Robotic Roux-en-Y Gastric Bypass, is it Safer than Laparoscopic Bypass?

text: BACKGROUND Along with the development of technology, robotic approach is being performed for laparoscopic Roux-en-Y gastric bypass (LRYGB). Some literatures reported same or better peri-operative outcomes with the robotic procedure. The aim of this study is to compare our experience in robot-assisted LRYGB (RA-LRYGB) with LRYGB in terms of peri-operative outcomes. METHODS From January 1, 2012 to April 30, 2014, a total of 270 patients underwent LRYGB by one surgeon at a single institution. Of these, 64 cases were done robotically. A retrospective review was performed for these patients, noting the outcomes and complications of the procedure. RESULTS The 64 RA-LRYGB patients had a mean age of 45.9 ± 10.0 years (range, 23-67) and a mean preoperative body mass index (BMI) of 48.4 ± 7.9 kg/m(2) (range, 33.8-76.4). The 207 LRYGB patients had a mean age of 45.0 ± 10.7 years (range, 21-67) and a mean preoperative BMI of 48.4 ± 8.1 kg/m(2) (range, 34.0-80.4). These two groups were clinically comparable. Mean length of hospital stay was 3.0 ± 4.1 days (range, 1-19) in RA-LRYGB patients, significantly longer than 1.6 ± 1.7 days (range, 1-17) in LRYGB patients (p < 0.01). Thirty-day readmission rate was 9.3% (n = 6) in the RA-LRYGB group and 6.8% (n = 14) in the LRYGB group. Higher leak rate was noticed in RA-LRYGB patients at 7.8% (n = 5), compared to 0.5% (n = 1) in LRYGB patients (p < 0.01). All the leaks occurred at the pouch level in the RA-LRYGB group, while one leak from the LRYGB group occurred at the gastrojejunal anastomosis site. CONCLUSIONS Robot-assisted Roux-en-Y gastric bypass may result in higher leak rate at the pouch level, when compared to that of laparoscopic procedures.


Recommendations for radiotherapy during the novel coronavirus pandemic.


Covid-19 current advice for pathologists.


title: Single-incision laparoscopic splenectomy: preliminary experience in consecutive patients and comparison to standard laparoscopic splenectomy.

text: BACKGROUND Since first being described in 2009, single-incision laparoscopic splenectomy has been described in a limited number of case reports and small case series. No studies have evaluated single-incision splenectomy in unselected patients, and outcomes of the procedure have not previously been compared to standard laparoscopy. METHODS A retrospective review was conducted to evaluate all single-incision splenectomies performed by a single surgeon between June 2010 and June 2011. Additionally, patients who underwent standard laparoscopic splenectomy by surgeons in the same tertiary referral surgical oncology group were evaluated to serve as a control group. Demographic data, operative parameters, and postoperative outcomes were assessed. RESULTS Eight patients underwent successful single-incision splenectomy during the study period without conversion to an open procedure or requiring additional ports. The median operative time was 92.5 min. There was 25 % morbidity and no mortality in the study group. Median length of stay was 4 days. Additionally, 18 patients who underwent standard laparoscopic splenectomy were evaluated for comparison. No significant differences were identified in the preoperative patient characteristics between the two groups. Single-incision splenectomy was associated with a shorter operative time (92.5 vs. 172 min, p = 0.003), lower conversion rate, equivalent length of stay, reduced mortality, similar morbidity, and comparable postoperative narcotic requirements. CONCLUSIONS Single-incision splenectomy is feasible, safe, and efficient in an unselected patient population in the hands of an experienced laparoscopic surgeon. The single-incision technique is comparable to standard laparoscopic splenectomy in terms of operative time and perioperative outcomes.


title: Laparoscopic gastrectomy for gastric cancer in the elderly patients.

text: BACKGROUND This study aimed to investigate the short-term surgical outcomes of laparoscopic gastrectomy for gastric cancer in elderly patients in order to determine the safety, feasibility, and risk factors for postoperative complications associated with this procedure. METHODS We retrospectively investigated 208 patients who underwent laparoscopic gastrectomy for gastric cancer between January 2007 and September 2014. After excluding 15 patients with unusual medical histories or surgical treatments, 193 were selected for this cohort study. We divided the patients into two cohorts: elderly patients (≥75 years old) and non-elderly patients (<74 years old). We compared these cohorts with respect to clinicopathological characteristics and intraoperative and postoperative parameters. RESULTS The overall complication rates were 11.4% (8 of 70 patients) in the elderly cohort and 8.1% (10 of 123 patients) in the non-elderly cohort (P = 0.449). In a univariate analysis, Charlson comorbidity index (CCI) of ≥3, American Society of Anesthesiologists (ASA) score of 3, operative time of ≥330 min, and intraoperative blood loss of ≥50 ml were found to correlate significantly with postoperative complications. In a multivariate analysis, CCI of ≥3 (P = 0.034), ASA score of 3 (P = 0.019), and intraoperative blood loss of ≥50 ml (P = 0.016) were found to be independent risk factors of postoperative complications. In contrast, age was not found to significantly affect the risk of postoperative complications. CONCLUSIONS Laparoscopic gastrectomy for gastric cancer can be successfully performed in elderly patients with an acceptable complication rate. This study suggested that high CCI, ASA score, and intraoperative blood loss volume were identified as independent predictors of postoperative complications after laparoscopic gastrectomy for gastric cancer.


Mechanical esophageal deviation: an approach for pulmonary vein reconnection attributed to esophageal heating.


title: Ebola virus disease in West Africa--the first 9 months of the epidemic and forward projections.

text: BACKGROUND On March 23, 2014, the World Health Organization (WHO) was notified of an outbreak of Ebola virus disease (EVD) in Guinea. On August 8, the WHO declared the epidemic to be a "public health emergency of international concern." METHODS By September 14, 2014, a total of 4507 probable and confirmed cases, including 2296 deaths from EVD (Zaire species) had been reported from five countries in West Africa--Guinea, Liberia, Nigeria, Senegal, and Sierra Leone. We analyzed a detailed subset of data on 3343 confirmed and 667 probable Ebola cases collected in Guinea, Liberia, Nigeria, and Sierra Leone as of September 14. RESULTS The majority of patients are 15 to 44 years of age (49.9% male), and we estimate that the case fatality rate is 70.8% (95% confidence interval [CI], 69 to 73) among persons with known clinical outcome of infection. The course of infection, including signs and symptoms, incubation period (11.4 days), and serial interval (15.3 days), is similar to that reported in previous outbreaks of EVD. On the basis of the initial periods of exponential growth, the estimated basic reproduction numbers (R0 ) are 1.71 (95% CI, 1.44 to 2.01) for Guinea, 1.83 (95% CI, 1.72 to 1.94) for Liberia, and 2.02 (95% CI, 1.79 to 2.26) for Sierra Leone. The estimated current reproduction numbers (R) are 1.81 (95% CI, 1.60 to 2.03) for Guinea, 1.51 (95% CI, 1.41 to 1.60) for Liberia, and 1.38 (95% CI, 1.27 to 1.51) for Sierra Leone; the corresponding doubling times are 15.7 days (95% CI, 12.9 to 20.3) for Guinea, 23.6 days (95% CI, 20.2 to 28.2) for Liberia, and 30.2 days (95% CI, 23.6 to 42.3) for Sierra Leone. Assuming no change in the control measures for this epidemic, by November 2, 2014, the cumulative reported numbers of confirmed and probable cases are predicted to be 5740 in Guinea, 9890 in Liberia, and 5000 in Sierra Leone, exceeding 20,000 in total. CONCLUSIONS These data indicate that without drastic improvements in control measures, the numbers of cases of and deaths from EVD are expected to continue increasing from hundreds to thousands per week in the coming months.


title: Hepatitis E virus enters liver cells through receptor-dependent clathrin-mediated endocytosis.

text: We investigated the virus-host interaction for hepatitis E virus (HEV) by performing competitive binding assays using in vitro assembled virus-like particles (VLPs). We used Escherichia coli expressed native capsid protein (pORF2) and its mutants with an attached Gly((5))-Ala (linker) reporter [enhanced green fluorescent protein (EGFP)/firefly luciferase (Fluc)]. Transmission electron microscopy and nanoparticle tracking showed near uniform particles of approximately 30-35 nm in diameter for pORF2 VLPs and 60-100 nm for reporter-linked VLPs. Binding of reporter-linked full-length (1-660aa) and N-terminal truncated (Δ1-112aa) pORF2 VLPs to Huh7 cell surfaces was found to be specific with 1.92 ± 0.065 × 10(5) sites per cell. Saturation binding indicated an equilibrium dissociation constant (K(d)) of 121.1 ± 23.83 and 123.8 ± 16.15 nm for pORF2-linker-EGFP and pORF2-linker-Fluc VLPs respectively. A similar binding pattern was observed for Δ1-112aa pORF2-linker-EGFP and Δ1-112aa pORF2-linker-Fluc VLPs with K(d) values of 123.6 ± 10.60 and 135.6 ± 16.19 nm respectively. The affinity (log K(i)) of pORF2 binding on Huh7 cells in the presence of EGFP-tagged and Fluc-tagged pORF2 VLPs was found to be approximately 2.0. However, no VLP formation or binding was observed with refolded C-terminal truncated (Δ458-660aa) pORF2. We investigated HEV internalization using fluorescent VLPs (EGFP-VLPs), which showed vesicle-mediated uptake starting at 5 min post-incubation. The uptake of VLPs could be stopped by inhibitors for clathrin-dependent endocytosis, but not by caveosome inhibitors. No binding and uptake of EGFP-VLPs were observed on non-hepatic cell lines (HeLa and SiHa). These findings suggest that HEV attaches to the host cell via a specific high affinity receptor and enters the cytoplasm by clathrin-mediated endocytosis.


title: Systematic assembly of a full-length infectious clone of human coronavirus NL63.

text: Historically, coronaviruses were predominantly associated with mild upper respiratory disease in humans. More recently, three novel coronaviruses associated with severe human respiratory disease were found, including (i) the severe acute respiratory syndrome coronavirus, associated with a significant atypical pneumonia and 10% mortality; (ii) HKU-1, associated with chronic pulmonary disease; and (iii) NL63, associated with both upper and lower respiratory tract disease in children and adults worldwide. These discoveries establish coronaviruses as important human pathogens and underscore the need for continued research toward the development of platforms that will enable genetic manipulation of the viral genome, allowing for rapid and rational development and testing of candidate vaccines, vaccine vectors, and therapeutics. In this report, we describe a reverse genetics system for NL63, whereby five contiguous cDNAs that span the entire genome were used to generate a full-length cDNA. Recombinant NL63 viruses which contained the expected marker mutations replicated as efficiently as the wild-type NL63 virus. In addition, we engineered the heterologous green fluorescent protein gene in place of open reading frame 3 (ORF3) of the NL63 clone, simultaneously creating a unique marker for NL63 infection and demonstrating that the ORF3 protein product is nonessential for the replication of NL63 in cell culture. The availability of the NL63 and NL63gfp clones and recombinant viruses provides powerful tools that will help advance our understanding of this important human pathogen.


title: Final results of the multicenter, prospective Axium MicroFX for Endovascular Repair of IntraCranial Aneurysm Study (AMERICA).

text: BACKGROUND We previously performed a multicenter prospective single-arm trial of 100 patients treated with Axium MicroFX Coils (ev3; Plymouth, Minnesota, USA), AMERICA: Axium MicroFX for Endovascular Repair of IntraCranial Aneurysm study. Initial angiographic and clinical outcomes were excellent. The final results are presented herein. METHODS AMERICA is a multicenter, prospective single-arm trial evaluating the safety and efficacy of the ev3 Axium MicroFX coil system in 100 separate aneurysms between April 2010 and October 2012. Trial endpoints were 3-6 month angiographic occlusion and clinical status, as reported by treatment center. RESULTS Mean follow-up was 157.9 days (median 153.5, range 1-445, SEM 9.3 days). At last follow-up imaging, 90.6% of all aneurysms, 90% of unruptured aneurysms, and 93.3% of ruptured aneurysms had Raymond grade I or II occlusion. Progression to further occlusion (lower Raymond occlusion grade) occurred in 29/85 aneurysms (34.1%). Aneurysm recurrence occurred in 11/85 aneurysms (12.9%). Ninety-nine per cent of patients treated electively and 68.7% of ruptured patients had a modified Rankin score of 0-2. Delayed adverse events (AEs), occurring after discharge and during the follow-up period, occurred in 10% of patients. In total, two AEs (one severe and one moderate) were potentially related to the device, thereby providing a 2% device-related AE rate. CONCLUSIONS In this prospective, multicenter series of 100 aneurysms treated with Axium MicroFX PGLA (polyglycolic/polylactic acid) coils, 3-6 month angiographic occlusion and clinical outcomes were excellent. This study suggests that Axium MicroFX PGLA coils are safe and effective in the treatment of intracranial aneurysms.


title: [Expert consensus on the management strategy of patients with hereditary ataxia during prevention and control of novel coronavirus pneumonia epidemic].

text: Since December 2019, a series of highly infectious cases of unexplained pneumonia have been discovered in Wuhan, Hubei Province, which have been confirmed as '2019 corona virus disease' caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 virus can invade many human systems including the lungs. Patients with central nervous system involvement may show a series of neurological symptoms, which is easy to be misdiagnosed and neglected, thereby increasing the risk of SARS-CoV-2 transmission. Hereditary ataxia is a large group of neurodegenerative diseases with great clinical and genetic heterogeneity and high mortality and disability. In view of the seriousness of the COVID-19 epidemic, a series of prevention and control measures adopted by the government have restricted the follow-up, diagnosis and treatment of patients by the hospitals, which has a great impact on their mental and physical health. In order to standardize the management of patients during the prevention and control of COVID-19 epidemic, the Specialized Committee of Neurogenetics of the Neurophysician Branch of Chinese Medical Doctor Association has formulated this consensus, with an aim to help patients to overcome the difficulties and pass the epidemic prevention period safely.


title: Degradability of poly(lactic acid)-containing nanoparticles: enzymatic access through a cross-linked shell barrier.

text: Comparative studies of bulk samples of hydrolytically degradable poly(lactic acid) (PLA) vs core-shell block copolymer micelles having PLA cores revealed remarkable acceleration in the proteinase K enzymatic hydrolysis of the nanoparticulate forms and demonstrated that even with amidation-based shell cross-linking the core domain remained accessible. Kinetic analyses by (1)H NMR spectroscopy showed less than 20% lactic acid released from enzymatically catalyzed hydrolysis of poly(l-lactic acid) in bulk, whereas ca. 70% of the core degraded within 48 h for block copolymer micelles of poly(N-(acryloyloxy)succinimide-copolymer-N-acryloylmorpholine)-block-poly(L-lactic acid) (P(NAS-co-NAM)-b-PLLA), with only a slight reduction to ca. 50% for the shell cross-linked derivatives. Rigorous characterization measurements by NMR spectroscopy, fluorescence spectroscopy, dynamic light scattering, atomic force microscopy, and transmission electron microscopy were employed to confirm core excavation. These studies provide important fundamental understanding of the effects of nanoscopic dimensions on protein-polymer interactions and polymer degradability, which will guide the development of these degradable nanoconstructs to reach their potential for controlled release of therapeutics and biological clearance.


title: Age-related presence of selected viral and bacterial pathogens in paraffin-embedded lung samples of dogs with pneumonia.

text: The aim of this retrospective study was to detect selected pathogens in pneumonic lung tissue of dogs of different age groups by immunohistochemistry (IHC), in situ hybridisation (ISH) or polymerase chain reaction (PCR) in order to get information about their involvement in pneumonia formation. In archived formalin-fixed and paraffin wax-embedded lung samples from 68 cases with the clinical and histologic diagnosis of pneumonia the histological pattern of pneumonia was re-evaluated and the samples were further investigated for the following infectious agents: canine distemper virus (CDV), canine adenovirus type 2 (CAV-2), canine respiratory coronavirus (CRCoV), Bordetella (B.) bronchiseptica, Pasteurella (P.) multocida, Mycoplasma spp., and Pneumocystis spp. In 47.1% of the samples at least one of the featured respiratory pathogens was detected. In 31.3% of these positive samples more than one pathogen could be found. The correct detection of CDV had been achieved in ten out of eleven positive cases (90.9%) upon initial investigation, but the presence of bacterial pathogens, like B. bronchiseptica (10 cases) and P. multocida (17 cases) had been missed in all but one case. While CDV and CRCoV infections were exclusively found in dogs younger than one year, the vast majority of infections with P. multocida and B. bronchiseptica were both common either in dogs younger than 4 months or older than one year. Thus, this retrospective approach yielded valuable data on the presence, absence and prevalence of certain respiratory pathogens in dogs with pneumonia.


"Banded bypass": the way to go?


title: Pathogenesis of type 2 turkey astroviruses with variant capsid genes in 2-day-old specific pathogen free poults.

text: The pathogenicity of three different type 2 turkey astroviruses (TAstV-2) was studied in specific pathogen free turkeys. These viruses differ based on sequence analysis of the capsid gene. Poults were inoculated at 2 days of age and examined during 14 days for clinical signs and virus shedding. All inoculated poults presented signs of enteric disease including diarrhoea and growth depression. Virus presence and shedding was detected by real-time reverse transcriptase-polymerase chain reaction from intestinal contents and cloacal swabs collected at 3, 7 and 14 days post-inoculation. Viraemia was also confirmed by this method. Common lesions observed at necropsy were dehydration; distended intestines filled with watery contents and undigested feed, and dilated caeca with foamy contents. Microscopic lesions present in the intestines consisted of mild crypt hyperplasia, villous atrophy and lymphocytic infiltration, and were most common in the jejunum. Presence of the viruses was demonstrated by immunohistochemistry and by in situ hybridization in both villi and crypt enterocytes in the jejunum and, less frequently, the duodenum, ileum and caeca. Mild lesions consisting mainly of lymphocytic infiltration were also observed in other organs including the pancreas, liver, spleen and kidneys. Mild to moderate bursal atrophy occurred in all TAstV-2-infected poults examined; however, no specific viral staining was observed in this organ or any other tissues examined apart from the intestines. In conclusion, TAstV-2 viruses with variant capsids produce a similar enteric disease in young turkeys and may also affect the immune system of the birds by causing bursal lymphoid depletion.


Telemedicine in the Era of the COVID-19 Pandemic: Implications in Facial Plastic Surgery.


title: Genomic analysis of two novel human enterovirus C genotypes found in respiratory samples from Peru.

text: We report the discovery of two enteroviruses detected in nasopharyngeal samples obtained from subjects with respiratory disease in Peru. Phylogenetic analysis indicated that both viruses belong to a clade within the species Human enterovirus C, which includes the recently characterized human enteroviruses 109 and 104. Members of this clade have undergone significant genomic rearrangement, as indicated by deletions in the hypervariable region of the 5' UTR and the VP1 protein, as well as recombination within the non-structural genes. Our findings and review of published sequences suggests that several novel human enterovirus C serotypes are currently circulating worldwide.


Smuggled wildlife products seized at US airports harbor zoonotic viruses.


title: Recombination between Vaccine and Field Strains of Porcine Reproductive and Respiratory Syndrome Virus.

text: We isolated and plaque purified IA76950-WT and IA70388-R, 2 porcine reproductive and respiratory syndrome viruses from pigs in the same herd in Iowa, USA, that exhibited coughing and had interstitial pneumonia. Phylogenetic and molecular evolutionary analysis indicated that IA70388-R is a natural recombinant from Fostera PRRSV vaccine and field strain IA76950-WT.


title: Serial viral infections in infants with recurrent respiratory illnesses.

text: To better understand the viral aetiology of recurrent and prolonged illnesses, nasal secretions were prospectively collected from 285 infants at increased risk of developing asthma. Of these, 27 infants had recurrent (at least five) moderate-to-severe respiratory illnesses (MSIs). The viral aetiology of the 150 MSIs and 86 scheduled visits was analysed by molecular diagnostics. The demographic and clinical data were compared with infants who had 0-4 MSIs. Frequently ill infants had higher exposure to other children and more wheezing illnesses than less symptomatic children. Viruses were detected in 136 (91%) out of 150 MSIs, 14 (67%) out of 21 mild illnesses and 29 (45%) out of 65 asymptomatic visits. Human rhinovirus was the most common aetiological agent (61, 43 and 35% in MSIs, mild illnesses and asymptomatic visits, respectively). Mixed viral infections were generally associated with more severe illnesses (27, 0 and 5%, respectively). Among the 27 frequently ill infants, only eight (5.3%) out of 150 MSIs were prolonged (> or =2 weeks duration). Considering all samples, detection of the same virus strain > or =2 weeks apart was unusual (5.3% of all 244 positive findings). Human rhinovirus infections occur early, pervasively and repetitively in these high-risk infants. Infants with prolonged or recurrent respiratory illnesses most often have a series of infections rather than persistent infection with one virus strain.


title: Dose rationale for favipiravir use in patients infected with SARS-CoV-2.

text: We read with a great interest the paper by Du et Chen suggesting dosing regimen of favipiravir in COVID-191 . We would like to complement their observations with our PK/PD experience of favipiravir against Ebola virus (EBOV). The drug EC50 against EBOV and SARS-CoV-2 are 10-60 µg/ml and 9.4 µg/ml4 , respectively. However results obtained by our working group suggest a higher value of EC50 , in the range 40-80 µg/ml (X. de Lamballerie & F. Touret, unpublished results). We therefore use the conservative assumption that the drug EC50 against SARS-CoV-2 is in the same range as against EBOV.


title: Outcomes of robotic partial nephrectomy for renal masses with nephrometry score of ≥7.

text: OBJECTIVES To evaluate the safety and feasibility of robotic partial nephrectomy for patients with complex renal masses. METHODS We reviewed the data for 164 consecutive patients who had undergone transperitoneal robotic partial nephrectomy at a tertiary care center from February 2007 to June 2010. Of the 112 patients who had available imaging studies to review, 67 were identified and classified as having a moderately or highly complex renal mass according to the R.E.N.A.L. nephrometry score (≥7) (tumor size-[R]adius, location and depth-[E]xophytic or endophytic; nearness to the renal sinus fat or collecting system [N]; anterior or posterior position [A], and polar vs non-polar location [L]). The preoperative, perioperative, pathologic, and functional outcomes data were analyzed. RESULTS The median body mass index was 29.6 kg/m(2) (range 19.9-44.8). Of the 67 patients, 32 were men and 35 were women, with 32 right-sided masses and 35 left-sided masses. The median tumor size was 3.7 cm (range 1.2-11), and the median operative time was 180 minutes (range 150-180). The median estimated blood loss was 200 mL (range 100-375), and the warm ischemia time was 19.0 minutes (range 15-26). The median hospital stay was 3.0 days (range 3-4). The estimated glomerular filtration rate was calculated at a median decrease of 11.1 mL/min/1.73 m(2) (range 9-1.3). According to the Clavien-Dindo classification of surgical complications, 2 grade 1, 12 grade 2, and 1 grade 3 complication occurred. All margins were pathologically negative, except for 1, and, after a mean follow-up of 10 months, no recurrences had developed. CONCLUSIONS Robotic partial nephrectomy is a safe and feasible option for moderately or highly complex renal masses determined by the R.E.N.A.L. nephrometry score. The warm ischemia time, blood loss, and complications were increased with highly complex masses.


How is biomedical research funding faring during the COVID-19 lockdown?


title: The growing role of noninvasive ventilation in patients requiring prolonged mechanical ventilation.

text: For many patients with chronic respiratory failure requiring ventilator support, noninvasive ventilation (NIV) is preferable to invasive support by tracheostomy. Currently available evidence does not support the use of nocturnal NIV in unselected patients with stable COPD. Several European studies have reported benefit for high intensity NIV, in which setting of inspiratory pressure and respiratory rate are selected to achieve normocapnia. There have also been studies reporting benefit for the use of NIV as an adjunct to exercise training. NIV may be useful as an adjunct to airway clearance techniques in patients with cystic fibrosis. Accumulating evidence supports the use of NIV in patients with obesity hypoventilation syndrome. There is considerable observational evidence supporting the use of NIV in patients with chronic respiratory failure related to neuromuscular disease, and one randomized controlled trial reported that the use of NIV was life-prolonging in patients with amyotrophic lateral sclerosis. A variety of interfaces can be used to provide NIV in patients with stable chronic respiratory failure. The mouthpiece is an interface that is unique in this patient population, and has been used with success in patients with neuromuscular disease. Bi-level pressure ventilators are commonly used for NIV, although there are now a new generation of intermediate ventilators that are portable, have a long battery life, and can be used for NIV and invasive applications. Pressure support ventilation, pressure controlled ventilation, and volume controlled ventilation have been used successfully for chronic applications of NIV. New modes have recently become available, but their benefits await evidence to support their widespread use. The success of NIV in a given patient population depends on selection of an appropriate patient, selection of an appropriate interface, selection of an appropriate ventilator and ventilator settings, the skills of the clinician, the motivation of the patient, and the support of the family.


title: Gastric tube necrosis following minimally invasive oesophagectomy is a learning curve issue.

text: INTRODUCTION Gastric tube necrosis following oesophagectomy is thought to have an increased association with a minimally invasive technique. Some suggest gastric ischaemic preconditioning may reduce ischaemic complications. We discuss our series of 155 consecutive minimally invasive oesophagectomies (MIOs), including a number of cases of gastric tube ischaemia, of which 4 (2.6%) developed conduit necrosis. METHODS Data were collected prospectively of MIOs carried out by a single surgeon between 2005 and 2011. Cases of gastric tube necrosis were identified. RESULTS Overall, 155 patients were identified. The inpatient mortality rate was 2.6%. Gastric tube necrosis occurred in four patients (2.6%). An ultrasonic dissector injury to the gastroepiploic arcade had occurred in two cases. In another case, the gastric tube was strangulated in the hiatus. In the remaining case, no clear mechanical cause was identified. All 4 cases occurred within the first 73 cases. The gastric tube necrosis rate of the first 50 cases versus cases 51-155 was 4% and 2% respectively (p=0.5948). The anastomotic leak rate in these two cohorts was 18% and 7% respectively (p=0.0457). There was a significant reduction in overall gastric tube complications from 22% to 10% following the learning curve of the initial 50 cases (p=0.0447). CONCLUSIONS In our series, gastric tube necrosis appears to be a learning curve issue. Prophylactic measures such as ischaemic preconditioning become less relevant as the operating surgeon's experience increases. Instead, meticulous attention to preserving the gastroepiploic arcade, avoidance of tension in the tube and careful positioning of the gastric conduit through an adequately sized hiatus are key factors.


title: Patient feedback to improve quality of patient-centred care in public hospitals: a systematic review of the evidence.

text: BACKGROUND To review systematically the published literature relating to interventions informed by patient feedback for improvement to quality of care in hospital settings. METHODS A systematic search was performed in the CINAHL, EMBASE, PsyInfo, MEDLINE, Cochrane Libraries, SCOPUS and Web of Science databases for English-language publications from January 2008 till October 2018 using a combination of MeSH-terms and keywords related to patient feedback, quality of health care, patient-centred care, program evaluation and public hospitals. The quality appraisal of the studies was conducted with the MMAT and the review protocol was published on PROSPERO. Narrative synthesis was used for evaluation of the effectiveness of the interventions on patient-centred quality of care. RESULTS Twenty papers reporting 20 studies met the inclusion criteria, of these, there was one cluster RCT, three before and after studies, four cross-sectional studies and 12 organisational case studies. In the quality appraisal, 11 studies were rated low, five medium and only two of high methodological quality. Two studies could not be appraised because insufficient information was provided. The papers reported on interventions to improve communication with patients, professional practices in continuity of care and care transitions, responsiveness to patients, patient education, the physical hospital environment, use of patient feedback by staff and on quality improvement projects. However, quantitative outcomes were only provided for interventions in the areas of communication, professional practices in continuity of care and care transitions and responsiveness to patients. Multi-component interventions which targeted both individual and organisational levels were more effective than single interventions. Outcome measures reported in the studies were patient experiences across various diverse dimensions including, communication, responsiveness, coordination of and access to care, or patient satisfaction with waiting times, physical environment and staff courtesy. CONCLUSION Overall, it was found that there is limited evidence on the effectiveness of interventions, because few have been tested in well-designed trials, very few papers described the theoretical basis on which the intervention had been developed. Further research is needed to understand the choice and mechanism of action of the interventions used to improve patient experience.


title: Meta-analysis of prophylactic mesh to prevent parastomal hernia.

text: BACKGROUND Rates of parastomal hernia following stoma formation remain high. Previous systematic reviews suggested that prophylactic mesh reduces the rate of parastomal hernia; however, a larger trial has recently called this into question. The aim was to determine whether mesh placed at the time of primary stoma creation prevents parastomal hernia. METHODS The Cochrane Central Register of Controlled Trials, MEDLINE, Embase and CINAHL were searched using medical subject headings for parastomal hernia, mesh and prevention. Reference lists of identified studies, clinicaltrials.gov and the WHO International Clinical Trials Registry were also searched. All randomized clinical trials were included. Two authors extracted data from each study independently using a purpose-designed sheet. Risk of bias was assessed by a tool based on that developed by Cochrane. RESULTS Ten randomized trials were identified among 150 studies screened. In total 649 patients were included in the analysis (324 received mesh). Overall the rates of parastomal hernia were 53 of 324 (16·4 per cent) in the mesh group and 119 of 325 (36·6 per cent) in the non-mesh group (odds ratio 0·24, 95 per cent c.i. 0·12 to 0·50; P < 0·001). Mesh reduced the rate of parastomal hernia repair by 65 (95 per cent c.i. 28 to 85) per cent (P = 0·02). There were no differences in rates of parastomal infection, stomal stenosis or necrosis. Mesh type and position, and study quality did not have an independent effect on this relationship. CONCLUSION Mesh placed prophylactically at the time of stoma creation reduced the rate of parastomal hernia, without an increase in mesh-related complications.


title: The p64 Flow Diverter-Mid-term and Long-term Results from a Single Center.

text: BACKGROUND AND PURPOSE The p64 is a flow modulation device designed to be used in endovascular treatment of intracranial aneurysms. There is limited data on the long-term effectiveness of the device. This study sought to determine the safety and long-term efficacy of this device. METHODS A retrospective review of a prospectively maintained database was performed to identify all patients treated with a p64 between March 2015 and November 2018 at University Hospital St. Ivan Rilski. Anatomical features, intraprocedural complications, clinical, and angiographic outcomes were also taken into account and reviewed. RESULTS A total of 72 patients with 72 aneurysms who met the inclusion criteria were identified. Device placement was successful in all patients. Follow-up angiographic imaging at 6 months showed complete occlusion (O'Kelly-Marotta scale [OKM] D) in 55 (76.3%) patients, subtotal aneurysmal filling (OKM B) in 10 (13.8%) patients, and neck remnant (OKM C) in 7 (9.7%) patients. Catheter angiography at 12 months was available for 70 patients (97.2%) and of these patients 91.4% of the aneurysms were completely occluded (OKM D) (64/72). Delayed angiography at 24 months was available for 68 patients (94.4%) and of these 98.5% (67/68) had completely occluded aneurysms. A 36-month angiography was available for 61 patients (84.4%) by which point all aneurysms had been completely occluded (100%). Permanent morbidity due to delayed aneurysmal rupture occurred in one patient (1.38%). The mortality rate was 0%. Self-limiting mild intimal hyperplasia was seen in 2 patients (2.72%). CONCLUSION Treatment of intracranial aneurysms with a p64 flow modulation device is safe and effective with a high success rate and only infrequent complications.


Covid-19: Are chest compressions an aerosol generating procedure or not?


title: Massive plasmablast response elicited in the acute phase of hantavirus pulmonary syndrome.

text: Beside its key diagnostic value, the humoral immune response is thought to play a protective role in hantavirus pulmonary syndrome. However, little is known about the cell source of these antibodies during ongoing human infection. Herein we characterized B-cell subsets circulating in Andes-virus-infected patients. A notable potent plasmablast (PB) response that increased 100-fold over the baseline levels was observed around 1 week after the onset of symptoms. These PB present a CD3neg CD19low CD20neg CD38hi CD27hi CD138+/- IgA+/- surface phenotype together with the presence of cytoplasmic functional immunoglobulins. They are large lymphocytes (lymphoblasts) morphologically coincident with the 'immunoblast-like' cells that have been previously described during blood cytology examinations of hantavirus-infected patients. Immunoreactivity analysis of white blood cell lysates suggests that some circulating PB are virus-specific but we also observed a significant increase of reactivity against virus-unrelated antigens, which suggests a possible bystander effect by polyclonal B-cell activation. The presence of this large and transient PB response raises the question as to whether these cells might have a protective or pathological role during the ongoing hantavirus pulmonary syndrome and suggest their practical application as a diagnostic/prognostic biomarker.


title: Outcomes of laparoscopic versus open colectomy in elective surgery for diverticulitis.

text: BACKGROUND The role of laparoscopy in the management of diverticular disease is evolving. Concerns were raised in the past because laparoscopic resection for diverticulitis is often difficult and occasionally hazardous. This study was undertaken to evaluate the difference in overall outcomes between elective open and laparoscopic surgery with or without anastomosis for diverticulitis. METHODS Using the National Inpatient Sample (NIS) database, clinical data of patients who underwent elective open and laparoscopic surgery (lap) for diverticulitis from 2002 to 2007 were collected and analyzed. Patients who underwent emergent surgery were excluded. RESULTS A total of 124,734 patients underwent elective surgery for diverticulitis: open, 110,172 (88.3%); lap, 14,562 (11.7%). The overall intraoperative complication rate was significantly lower in the laparoscopy group (0.63% vs. 1.15%, P < 0.01). However, there was no significant difference observed in ureteral injury between groups (open, 0.17%; lap, 0.12%, P = 0.15). All evaluated postoperative complications (ileus, abdominal abscess, leak, wound infection, bowel obstruction, urinary tract infection, pneumonia, respiratory failure, venous thromboembolism) were significantly higher for the open procedures. The laparoscopy group had a shorter mean hospital stay (lap, 5.06 days; open, 6.68 days, P < 0.01) and lower total hospital charges (lap, $36,389; open, $39,406, P < 0.01) than the open group. Also, mortality was four times higher in the open group (open, 0.54%; lap, 0.13%, P < 0.01). CONCLUSIONS The laparoscopic operation was associated with lower morbidity, lower mortality, shorter hospital stay, and lower hospital charges compared to the open operation for diverticulitis. Elective laparoscopic surgery for diverticulitis is safe and can be considered the preferred operative option.


title: Portal vein arterialization promotes liver regeneration after extended partial hepatectomy in a rat model.

text: In the current study, we sought to establish a novel rat model of portal vein arterialization (PVA) and evaluate its impact on liver regeneration after extended partial hepatectomy (PH). A total of 105 Sprague-Dawley rats were randomly assigned to three groups: 68% hepatectomy (the PH group), portal arterialization after 68% hepatectomy (the PVA group), and right nephrectomy only (the control group). Liver regeneration rate (LRR), 5-bromo-2-deoxyuridine (BrdU) labeling index, and liver functions were assessed on postoperative day 2, 7, 14 and 28. The 28-day survival rates were compared among the three groups. The 28-day survival rates were similar in all groups (P = 0.331), and the anastomotic patency was 100%. The LRR in the PVA group was significantly higher than that of the PH group within postoperative 14 days (P < 0.05). The PVA and PH group had increased serum alanine aminotransferase levels (232 ± 61 U/L and 212 ± 53 U/L, respectively) compared with the control group (101 ± 13 U/L) on postoperative day 2, whereas from postoperative day 7 to day 28 there were no differences among the three groups. Serum albumin values were higher after the PVA procedure within postoperative day 14, which gradually became comparable on postoperative day 28 among the three groups. The peaks of BrdU labeling index appeared on postoperative day 2 in all rats, and the PVA procedure was associated with increased BrdU labeling index from postoperative day 7 to 28. The 28-day survival of the PVA rats was comparable. Our findings demonstrate that the PVA procedure utilizing portal vein trunk-renal artery microvascular reconstruction promotes remnant liver regeneration and confers beneficial effects on maintaining and even optimizing liver function after extended partial hepatectomy in rats.


WHO's Blueprint List of Priority Diseases.


title: Endovascular Treatment of Post-thrombotic Venous Ilio-Femoral Occlusions: Prognostic Value of Venous Lesions Caudal to the Common Femoral Vein.

text: OBJECTIVES To propose a scale of severity for post-thrombotic venous lesions (PTVLs) after ilio-femoral deep venous thrombosis and to compare the grade with the results of endovascular treatment of ilio-femoral PTVLs. METHODS In this retrospective monocentric observational study, we included 95 patients treated for ilio-femoral PTVLs. We proposed a four-grade scale evaluating the severity of PTVLS caudal to the common femoral vein based on CT phlebography and per-operative phlebography. For most patients, venous patency was assessed with color duplex ultrasonography and the clinical efficacy of the intervention using the Villalta and CIVIQ scores. RESULTS Recanalization was successful in 100% of patients with a morbidity rate of 4%. After a mean follow-up of 21 months, the overall primary patency was 75%, the assisted primary patency 82%, and the secondary patency 93%. Secondary patency was 100% for grade 0-1, 90% for grade 2, and 63% for grade 3 (p < 0.002). There was no correlation between the extension of stenting caudally of the common femoral vein and venous patency. The mean improvements in the Villalta and CIVIQ-20 scores were, respectively, 4.6 (p < 0.0001) and 18 (p < 0.0001); scores were not correlated with the grade of PTVLs in the thigh. CONCLUSION Venous patency after endovascular treatment of ilio-femoral PTVLs was strongly linked to the severity of PTVLs caudal to the common femoral vein but not to the extent of stenting.


title: The utility of bioactive coils in the embolization of aneurysms.

text: There has been an exponential growth in the endovascular treatment of intracranial aneurysms over the past three decades and it is now the primary mode of treatment in the cerebrovascular community. Despite the proven safety and efficacy of bare platinum coils, criticism of the durability of endovascular coiling with respect to traditional open surgical clipping persists. In order to overcome this criticism, several newer generations of coils have been introduced with the purpose of enhancing the durability of the initial endovascular treatment. These 'bioactive' coils have an additional material [polyglycolic acid (PGA), polyglycolic/polylactic acid (PGLA), or hydrogel)] added to the bare platinum coil in order to induce an inflammatory response and/or increase packing density within the aneurysm. While comparable safety profiles have been proven, a review of the multiple trials and clinical series published on this topic provides no clear evidence to suggest that the current bioactive coil iterations provide any sustained benefit over bare platinum coils.


title: Otolaryngologists' Role in Redeployment During the COVID-19 Pandemic: A Commentary.

text: As otolaryngologists, we identify as subspecialists and fellowship-trained surgeons and may even identify as "super-subspecialists." The likelihood of being redeployed and drawing from knowledge learned during our postgraduate year 1 training seemed exceedingly unlikely until physician resources became scarce in some health care systems during the COVID-19 pandemic. More now than ever, it is evident that our broad training is valuable in helping patients and allowing the otolaryngologist to meaningfully contribute to the larger health care community, especially while the majority (70%-95%) of elective care is delayed. With our skill set, otolaryngologists are poised to support various aspects of hospital wards, intensive care units, emergency departments, and beyond.


title: Comparison of Graft Length Changes During Knee Motion Among 5 Different Anatomic Single-Bundle Anterior Cruciate Ligament Reconstruction Approaches: A Biomechanical Study.

text: Background In several anatomic single-bundle anterior cruciate ligament (ACL) reconstruction (ASB-ACLR) procedures, the femoral and tibial tunnel apertures are created at different locations within the native ACL attachment area. Hypothesis Graft length changes during knee motion will be different among ASB-ACLR procedures with different femoral and tibial tunnel aperture locations. Study Design Controlled laboratory study. Methods A total of 12 cadaveric knees were used in this study. In each knee, 4 and 3 thin tunnels were created within the ACL attachment area on the femur and the tibia, respectively. Using 1 of 5 different combinations of femoral and tibial tunnel aperture location, 5 ASB-ACLRs were performed on each knee. In each reconstruction approach, a strong thread was used in place of the tendon graft, and the tibial graft end was tethered to a custom-made isometric positioner at 0° of knee flexion, with an approximately 12-N load applied to the thread. Then, each specimen underwent 5 cycles of knee flexion-extension motion in a range between 0° and 120°, and graft length changes were determined for each SB-ACLR approach. Results The length changes of the graft were significantly different among the 5 ASB-ACLRs. The maximum length change values of the 3 grafts that were implanted between the femoral and tibial centers of the posterolateral bundle attachments or implanted into the femoral tunnel created at the center of the fanlike extension fiber attachment were significantly greater than those of the graft implanted between the centers of the anteromedial bundle attachments (P < .0001) and of the graft implanted between the centers of the whole ACL attachments (P < .0001). Conclusion The length changes of the graft during knee motion were significantly different among the 5 ASB-ACLR approaches, even though all of the tunnel apertures were created within the femoral and tibial attachments of the native ACL. Clinical Relevance The grafts in the first 3 graft locations may be so relaxed during knee flexion that they cannot resist anterior drawer loads exerted on the tibia.


Lessons learnt during the first 100 days of COVID-19 pandemic in India.


Covid-19: Africa records over 10 000 cases as lockdowns take hold.


title: Shedding a new light on Huntington's disease: how blood can both propagate and ameliorate disease pathology.

text: Huntington's disease (HD) is a monogenic neurodegenerative disorder resulting from a mutation in the huntingtin gene. This leads to the expression of the mutant huntingtin protein (mHTT) which provokes pathological changes in both the central nervous system (CNS) and periphery. Accumulating evidence suggests that mHTT can spread between cells of the CNS but here, we explored the possibility that mHTT could also propagate and cause pathology via the bloodstream. For this, we used a parabiosis approach to join the circulatory systems of wild-type (WT) and zQ175 mice. After surgery, we observed mHTT in the plasma and circulating blood cells of WT mice and post-mortem analyses revealed the presence of mHTT aggregates in several organs including the liver, kidney, muscle and brain. The presence of mHTT in the brain was accompanied by vascular abnormalities, such as a reduction of Collagen IV signal intensity and altered vessel diameter in the striatum, and changes in expression of Glutamic acid decarboxylase 65/67 (GAD65-67) in the cortex. Conversely, we measured reduced pathology in zQ175 mice by decreased mitochondrial impairments in peripheral organs, restored vessel diameter in the cortex and improved expression of Dopamine- and cAMP-regulated phosphoprotein 32 (DARPP32) in striatal neurons. Collectively, these results demonstrate that circulating mHTT can disseminate disease, but importantly, that healthy blood can dilute pathology. These findings have significant implications for the development of therapies in HD.


Current opinions on selected respiratory infections causing global morbidity and mortality.


title: American College of Physicians Ethics Manual: sixth edition.

text: Medicine, law, and social values are not static. Reexamining the ethical tenets of medicine and their application in new circumstances is a necessary exercise. The sixth edition of the American College of Physicians (ACP) Ethics Manual covers emerging issues in medical ethics and revisits older ones that are still very pertinent. It reflects on many of the ethical tensions in medicine and attempts to shed light on how existing principles extend to emerging concerns. In addition, by reiterating ethical principles that have provided guidance in resolving past ethical problems, the Manual may help physicians avert future problems. The Manual is not a substitute for the experience and integrity of individual physicians, but it may serve as a reminder of the shared duties of the medical profession.


title: Intentional leaks in industrial masks have a significant impact on efficacy of bilevel noninvasive ventilation: a bench test study.

text: BACKGROUND During noninvasive ventilation, nonintentional leaks have a detrimental effect on the efficacy of ventilation. A wide range of industrial masks are available, with intentional leaks of different importance. The potential impact of this variability in intentional leaks on performances of bilevel ventilators has not been assessed. OBJECTIVE To measure intentional leaks in seven different industrial masks and determine whether higher leaks modify ventilator performance and quality of ventilation. METHODS Seven interfaces connected to four ventilators, the VPAP III ST (ResMed; NorthRyde, Australia), the BiPAP Harmony (Respironics; Monroeville, PA), the SmartAir ST (Covidien/Airox; Pau, France), and the GoodKnight 425 ST Bilevel (Covidien/Tyco-Nellcor/Puritan Bennett; Pleasanton, CA), were adapted on a mannequin connected to a lung model (ASL5000, IngMar Medical; Pittsburgh, PA). Inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure were 14 and 4 cm H(2)O, respectively. The lung model was set with a respiratory rate of 15 cycles per min and a duration of inspiration of 1 s in three simulated conditions (normal, restrictive, and obstructive). Inspiratory trigger delay and effort, capacity to achieve and maintain IPAP, expiratory cycling and tidal volume were analyzed for all masks and ventilators in the three simulated lung conditions. RESULTS The level of intentional leaks in the seven masks ranged from 30 to 45 L/min for an IPAP of 14 cm H(2)O. Importance of leaks did not influence trigger performances. However, capacity to achieve and maintain IPAP was significantly decreased with all ventilators and in all simulated lung conditions when intentional leaks increased. This led to a maximum reduction in delivered tidal volume of 48 mL. Expiratory cycling was not affected by the level of intentional leaks except in obstructive lung conditions. CONCLUSION Mask intentional leaks can impair efficacy of ventilation, especially when > 40 L/min.


Decreasing the Incidence of Tuohy-Borst Clamp Connector Disconnections From Perineural Catheters: A Quality Improvement Study.


Impact of coronavirus disease 2019 on healthcare workers: beyond the risk of exposure.


title: Radiofrequency Ablation of Hepatocellular Carcinoma with a "Nodule-in-Nodule" Appearance: Long-Term Follow-up and Clinical Implications.

text: PURPOSE Hepatocellular carcinoma (HCC) with a "nodule-in-nodule" (NIN) appearance has unique histological characteristics as an early HCC. We assessed long-term therapeutic outcomes of radiofrequency ablation (RFA) in HCC patients considering this appearance. MATERIALS AND METHODS Our Institutional Review Board approved this retrospective study, and the requirement for written informed consent was waived. Between May 2006 and April 2012, a total of 572 patients underwent RFA for single HCC as a first-line treatment. Patients were divided into a NIN HCC group (n = 22) and a non-NIN HCC group (n = 550), according to the NIN feature on pretreatment imaging studies. Local tumor progression (LTP) and disease-free survival (DFS) were compared. Prognostic factors for LTP and DFS were assessed using a Cox proportional hazards model. RESULTS The cumulative LTP rates were 4.6 and 4.6% at 3 and 5 years, respectively, in the NIN HCC group, and 15.9 and 20.5% in the non-NIN HCC group, with borderline statistical significance (p = 0.085). The corresponding DFS rates were 53.8 and 37.7% in the NIN HCC group and 44.0 and 31.7% in the non-NIN HCC group, with no significant difference (p = 0.318). Although on multivariate analysis only tumor size was a significant prognostic factor for LTP, there was a trend bordering on the significance for the NIN feature [hazard ratio (HR) = 0.19; p = 0.099]. However, it was not a significant factor for DFS (HR = 0.18; p = 0.682). CONCLUSIONS The NIN appearance, a rare (4%, 22/550) but unique feature of early HCC, may be a favorable prognostic factor for RFA in terms of local tumor control.


title: Potential pro-arrhythmic effects of pharmacotherapy against SARS-CoV-2.

text: The pandemic caused by the SARS-COV-2 or COVID-19 virus has been a global challenge given its high rate of transmission and lack of effective therapy or vaccine. This scenario has led to the use of various drugs that have demonstrated a potential effect against the virus in vitro. However, time has not been enough to properly evaluate their clinical effectiveness. The use of chloroquine/hydroxychloroquine, azithromycin and antiviral treatment and has been proposed by various groups, supported by in-vitro studies and limited patient series, without the adequate scientific rigor that precedes drug prescription. Although it may represent the only hope for many patients, it is important to know the main adverse effects associated with the use of these drugs and to better select patients who may benefit from them.


title: Global and regional estimates of the prevalence of root caries - Systematic review and meta-analysis.

text: Aim To evaluate the pooled prevalence of root caries through a systematic review and meta-analysis. Methods A keyword search was done in Scopus, Pubmed and CINAHL databases using all the synonyms of root caries in the published literature (till January 1st, 2018). The search was supplemented with standard Boolean operators and other keywords like prevalence, epidemiology in the title, abstract and MeSH terms. Data was extracted and exported to Covidence software for screening and removal of duplicates. Results The search revealed a total of 492 documents from Scopus (n = 95), Pubmed (n = 220) and CINAHL (n = 177). Random effects model was used as there was a high degree of heterogeneity was seen among the studies published (I2 = 99.62%). A total of 74 publications were included in the analysis of the pooled prevalence of root caries which yielded a prevalence of 41.5 (36.9-46.1). Conclusion Root caries is a significant problem, and four out of ten adults might be affected.


title: Bereavement in the Time of Coronavirus: Unprecedented Challenges Demand Novel Interventions.

text: COVID-19 fatalities exemplify "bad deaths" and are distinguished by physical discomfort, difficulty breathing, social isolation, psychological distress, and care that may be discordant with the patient's preferences. Each of these death attributes is a well-documented correlate of bereaved survivors' symptoms of depression, anxiety, and anger. Yet the grief experienced by survivors of COVID-related deaths is compounded by the erosion of coping resources like social support, contemporaneous stressors including social isolation, financial precarity, uncertainty about the future, lack of routine, and the loss of face-to-face mourning rituals that provide a sense of community and uplift. National efforts to enhance advance care planning may help dying patients to receive care that is concordant with the preferences of them and their families. Virtual funeral services, pairing bereaved elders with a telephone companion, remote counseling, and encouraging "continuing bonds" may help older adults adapt to loss in the time of pandemic.


title: The effects of heat-killed wild-type Lactobacillus casei Shirota on allergic immune responses in an allergy mouse model.

text: BACKGROUND Probiotics are used as a management strategy for allergic diseases, but their effects on allergic responses in sensitized allergic individuals remain unclear. This study explored the immunomodulatory effects of probiotics on allergen-specific allergic reactions in an allergy mouse model. METHODS C57BL/6 mice were presensitized by epicutaneous patching with recombinant Der p 2, and were subsequently administered orally with either heat-killed wild-type Lactobacillus casei or NaHCO(3) buffer for 5 weeks (n=6 per group). All mice then received 2 subcutaneous immunizations of Der p 2 to mimic allergen immunotherapy, followed by aerosol challenge with Der p 2 a week later. RESULTS The Der p 2-sensitized mice fed L. casei showed significantly lower Der p 2-specific IgE and IgG1 after subcutaneous immunizations and airway challenge with Der p 2 compared to the control, unfed group. Splenic T cells of mice fed L. casei showed suppression of Th-2 (IL-5, IL-13, IL-10 and IL-4) and proinflammatory (TNF-alpha, IFN-gamma) cytokines. Following airway allergen challenge, the mice fed L. casei showed histological evidence of attenuation of lung inflammation, as well as reductions in the total cell count and Th2 and proinflammatory cytokines in bronchoalveolar lavage fluid, compared to controls. Taken together, these results suggest that the oral administration of heat-killed L. casei could effectively downregulate the pre-existing Th-2 allergic responses and pulmonary inflammatory responses upon subcutaneous and airway allergen challenge. CONCLUSIONS L. casei has intrinsic adjuvant and immunomodulatory properties that could potentially be exploited for secondary prevention or treatment of allergic respiratory diseases.


title: Resuscitation of preterm infants with different inspired oxygen fractions.

text: OBJECTIVE To test the hypothesis that an initial fraction of inspired oxygen (FiO2) of 30% during resuscitation of preterm infants results in less oxidative stress and is associated with improved clinical outcomes compared with an FiO2 of 65%. STUDY DESIGN Preterm infants of gestational age <32 weeks (n = 193) were randomized to start resuscitation with either 30% oxygen (low-oxygen group) or 65% oxygen (high-oxygen group), after which the FiO2 was adjusted based on oxygen saturation values. The primary outcome was bronchopulmonary dysplasia (BPD) assessed at 36 weeks postmenstrual age. Secondary outcomes included major neonatal illnesses and markers of oxidative stress. RESULTS The median gestational age of included infants was 28(6)/7 weeks (IQR, 26(5)/7-30(3)/7 weeks). The incidence of BPD was not significantly different between the low-oxygen and high-oxygen groups (24% vs. 17%; P = .15). The FiO2 in both groups was adjusted to a mean of 40% by 7 minutes in the low-oxygen group and by 11 minutes in the high-oxygen group. No differences in markers of oxidative stress were noted between groups. CONCLUSION Initial supplementation of preterm infants with 30% oxygen during the fetal-to-neonatal transition is as safe as 65% oxygen, with no differences in oxidative stress markers or BPD.


Future directions in IAT: better studies, better selection, better timing and better techniques.


title: The impact of COVID-19 lockdown on admission to gynecological emergency departments: Results from a multicenter Italian study.

text: OBJECTIVE To evaluate the impact of the COVID-19 lockdown on admissions to gynecological emergency departments (ED) of three Italian university hospitals with different rates of COVID-19 incidence. METHODS A retrospective study was conducted in the gynecological EDs of Modena (Emilia-Romagna), Sassari and Cagliari (Sardinia) regarding all admissions to gynecological EDs during November 1 to 30, 2019, and March 11 to April 9, 2020 (lockdown period). RESULTS A total of 691 women (mean age 38.3±14.3 years) who were admitted to the gynecological EDs were included. The relative decrease in women evaluated from March 11 to April 9, 2020, was -56.6% (95% confidence interval [CI] 52.2-61.1). Time spent in the ED was also significantly shorter during this period (P=0.02) in comparison to November 1 to 30, 2019. The most evident decrease was observed for pelvic pain (-68.9% [95% CI 60.3-76.7]; -91 cases). The management of women suggests a more effective use of the ED, with higher rates of hospitalization (P=0.001) and recourse to emergent surgeries (P=0.005) and lower rates of discharge to home (P=0.03). CONCLUSION The COVID-19 lockdown greatly reduced the rate of admission to gynecological EDs, but the real emergencies were filtered from the more deferrable ones.


title: Antibiotic regimens for the empirical treatment of newborn infants with necrotising enterocolitis.

text: BACKGROUND Although the exact aetiology of necrotising enterocolitis (NEC) remains unknown, research suggests that it is multifactorial; suspected pathophysiological mechanisms include immaturity, intestinal ischaemia, disruption of intestinal mucosal integrity, formula feeding, hyperosmolar load to the intestine, infection and bacterial translocation. Various antibiotic regimens have been widely used in the treatment of NEC. OBJECTIVES To compare the efficacy of different antibiotic regimens on mortality and the need for surgery in neonates with NEC. SEARCH METHODS Searches were made of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2012), Oxford Database of Perinatal Trials, MEDLINE (1966 to February 2012), EMBASE (1980 to February 2012) and CINAHL (1982 to February 2012). SELECTION CRITERIA All randomised and quasi-randomised controlled trials where antibiotic regimens were used for treatment of NEC. DATA COLLECTION AND ANALYSIS Eligibility of studies for inclusion was assessed independently by each review author. The criteria and standard methods of the Cochrane Neonatal Review Group were used to assess the methodological quality of the included trials. MAIN RESULTS Two trials met the inclusion criteria. Faix 1988 randomised 42 premature infants with radiological diagnosis of NEC. Infants were randomised to receive either intravenous ampicillin and gentamicin or ampicillin, gentamicin and clindamycin. Hansen 1980 randomised 20 infants with NEC to receive intravenous ampicillin and gentamicin with or without enteral gentamicin.In the study by Faix 1988, there were no statistical differences in mortality (RR 1.10; 95% CI 0.32 to 3.83) or bowel perforation (RR 2.20; 95% CI 0.45 to 10.74) between the two groups although there was a trend towards higher rate of strictures in the group that received clindamycin (RR 7.20; 95% CI 0.97 to 53.36).The Hansen 1980 study showed no statistically significant difference in death, bowel perforation or development of strictures. AUTHORS' CONCLUSIONS There was insufficient evidence to recommend a particular antibiotic regimen for the treatment of NEC. There were concerns about adverse effects following the usage of clindamycin, related to the development of strictures. To address this issue a large randomised controlled trial needs to be performed.


A hidden danger of COVID-19.


title: First US experience with Pipeline Flex with Shield Technology using aspirin as antiplatelet monotherapy.

text: Flow diversion has revolutionised the treatment of intracranial aneurysms, and the Pipeline Embolization Device (PED) remains the only flow diverter (FD) approved in the USA. However, thromboembolic events remain an issue for FDs. Attempting to minimise these incidents, a newer PED has been developed with the use of covalent bonding of phosphorylcholine onto the Pipeline device that has been known as Shield Technology (PED Shield), which in vitro has demonstrated a significant reduction in material thrombogenicity. We report the first US experience of the PED Shield in the treatment of a ruptured fusiform aneurysm located in the right vertebral artery in an attempt to mitigate complications related to the use of dual-antiplatelet therapy and discuss our rationale for using the new FD, using aspirin only as the antiplatelet regimen.


title: Cationic polypeptides contribute to the anti-HIV-1 activity of human seminal plasma.

text: Mucosal surfaces of the reproductive tract as well as their secretions have important roles in preventing sexual transmission of HIV-1. In the current study, the majority of the intrinsic anti-HIV-1 activity of human seminal plasma (SP) was determined to reside in the cationic polypeptide fraction. Antiviral assays utilizing luciferase reporter cells and lymphocytic cells revealed the ability of whole SP to prevent HIV-1 infection, even when SP was diluted 3200-fold. Subsequent fractionation by continuous flow acid-urea (AU)-PAGE and antiviral testing revealed that cationic polypeptides within SP were responsible for the majority of anti-HIV-1 activity. A proteomic approach was utilized to resolve and identify 52 individual cationic polypeptides that contribute to the aggregate anti-HIV-1 activity of SP. One peptide fragment of semenogelin I, termed SG-1, was purified from SP by a multistep chromatographic approach, protein sequenced, and determined to exhibit anti-HIV-1 activity against HIV-1. Anti-HIV-1 activity was transient, as whole SP incubated for prolonged time intervals exhibited a proportional decrease in anti-HIV-1 activity that was directly attributed to the degradation of semenogelin I peptides. Collectively, these results indicate that the cationic polypeptide fraction of SP is active against HIV-1, and that semenogelin-derived peptides contribute to the intrinsic anti-HIV-1 activity of SP.


title: Perflubron Distribution During Transition From Gas to Total Liquid Ventilation.

text: Total liquid ventilation (TLV) using perfluorocarbons has shown promising results for the management of neonatal respiratory distress. However, one important safety consideration for TLV is a better understanding of the early events during the transition to TLV, especially regarding the fate of residual air in the non-dependent-lung regions. Our objective was to assess perflubron distribution during transition to TLV using electrical impedance tomography, complemented by fluoroscopy, in a neonatal lamb model of induced surfactant deficiency. Eight lambs were anesthetized and ventilated in supine position. Surfactant deficit was induced by saline lung lavage. After deflation, lungs were filled with 25 ml/kg perflubron over 18 s, and TLV was initiated. Electrical impedance tomography data was recorded from electrodes placed around the chest, during the first 10 and at 120 min of TLV. Lung perfusion was also assessed using hypertonic saline injection during apnea. In addition, fluoroscopic sequences were recorded during initial lung filling with perfluorocarbons, then at 10 and 60 min of TLV. Twelve lambs were used as controls for histological comparisons. Transition to TLV involved a short period of increased total lung volume (p = 0.01) secondary to recruitment of the dependent lung regions. Histological analysis shows that TLV was protective of these same regions when compared to gas-ventilated lambs (p = 0.03). The non-dependent lung regions filled with perflubron over at least 10 min, without showing signs of overdistention. Tidal volume distribution was more homogenous in TLV than during the preceding gas ventilation. Perflubron filling was associated with a non-significant increase in the anterior distribution of the blood perfusion signal, from 46 ± 17% to 53 ± 6% (p = 0.4). However, combined to the effects on ventilation, TLV had an instantaneous effect on ventilation-perfusion relationship (p = 0.03), suggesting better coupling. Conclusion: transition to TLV requires at least 10 min, and involves air evacuation or dissolution in perflubron, dependent lung recruitment and rapid ventilation-perfusion coupling modifications. During that time interval, the total lung volume transiently increases. Considering the potential deleterious effect of high lung volumes, one must manage this transition phase with care and, we suggest using a real-time monitoring system such as electrical impedance tomography.


title: Dichotomizing Level of Pial Collaterals on Multiphase CT Angiography for Endovascular Treatment in Acute Ischemic Stroke: Should It Be Refined for 6-Hour Time Window?

text: PURPOSE Although endovascular treatment is currently thought to only be suitable for patients who have pial arterial filling scores >3 as determined by multiphase computed tomography angiography (mpCTA), a cut-off score of 3 was determined by a study, including patients within 12 hours after symptom onset. We aimed to investigate whether a cut-off score of 3 for endovascular treatment within 6 hours of symptom onset is an appropriate predictor of good functional outcome at 3 months. MATERIALS AND METHODS From April 2015 to January 2016, acute ischemic stroke patients treated with mechanical thrombectomy within 6 hours of symptom onset were enrolled into this study. Pial arterial filling scores were semi-quantitatively assessed using mpCTA, and clinical and radiological parameters were compared between patients with favorable and unfavorable outcomes. Multivariate logistic regression analysis was then performed to investigate the independent association between clinical outcome and pial collateral score, with the predictive power of the latter assessed using C-statistics. RESULTS Of the 38 patients enrolled, 20 (52.6%) had a favorable outcome and 18 had an unfavorable outcome, with the latter group showing a lower mean pial arterial filling score (3.6±0.8 vs. 2.4±1.2, P=0.002). After adjusting for variables with a P-value of <0.1 in univariate analysis (i.e., age and National Institutes of Health Stroke Scale score at admission), pial arterial filling scores higher than a cut-off of 2 were found to be independently associated with favorable clinical outcomes (P=0.012). C-statistic analysis confirmed that our model had the highest prediction power when pial arterial filling scores were dichotomized at >2 vs. ≤2. CONCLUSION A pial arterial filling cut-off score of 2 as determined by mpCTA appears to be more suitable for predicting clinical outcomes following endovascular treatment within 6 hours of symptom onset than the cut-off of 3 that had been previously suggested.


title: Percutaneous CT-Guided Ablation in the Hepatic Dome: Artificially Induced Pneumothorax for Safe Transpleural Access.

text: Ablative therapies have become a great alternative to surgical treatment of hepatic nodules. Some technical difficulties may negatively influence the effectiveness of this therapy, such as lesions located near the diaphragm. The transthoracic approach is commonly used to access these lesions. However, it is associated with an increased risk of complications, such as pneumothorax, hemothorax, alveolar bleeding, and others. We report a case of a radiofrequency ablation of a lesion in the hepatic dome, where an artificially induced pneumothorax was performed to guarantee a safe and effective access. The air was easily injected by a spinal needle and later aspirated by a single-lumen catheter. Induced pneumothorax shoud be considered in ablation of hepatic dome lesions, mainly when the transhepatic access is not appropriate.


Evaluation of the susceptibility of mice & hamsters to SARS-CoV-2 infection.


Don't panic: five minutes with . . . Kai Zacharowski.


title: First-in-man experience with the ReVive PV peripheral thrombectomy device for the revascularization of below-the-knee embolic occlusions.

text: PURPOSE To report the initial use of a novel thrombectomy device for revascularization of below-the-knee thromboembolic occlusions encountered during proximal revascularization procedures. CASE REPORTS The ReVive PV Peripheral Thrombectomy Device is a non-detachable, self-expanding stent-like device recently approved for peripheral thrombectomy. Four patients (3 women; mean age 68.8 years) undergoing proximal revascularization procedures experienced embolic occlusions of all 3 trifurcation vessels in 1 patient, the tibioperoneal trunk alone in 2 cases, and the peroneal artery alone in the last patient. In all cases, the involved arteries represented the primary or sole vessel(s) providing outflow to the lower extremity. In each case, the ReVive PV device was used to successfully extract the thrombus and restore flow to the distal extremity. No complications were encountered during any of the procedures. CONCLUSION The ReVive PV peripheral thrombectomy device may facilitate the safe and efficient revascularization of distal arterial embolic occlusions.


title: Dexmedetomidine pharmacokinetic-pharmacodynamic modelling in healthy volunteers: 1. Influence of arousal on bispectral index and sedation.

text: Background Dexmedetomidine, a selective α 2 -adrenoreceptor agonist, has unique characteristics, such as maintained respiratory drive and production of arousable sedation. We describe development of a pharmacokinetic-pharmacodynamic model of the sedative properties of dexmedetomidine, taking into account the effect of stimulation on its sedative properties. Methods In a two-period, randomized study in 18 healthy volunteers, dexmedetomidine was delivered in a step-up fashion by means of target-controlled infusion using the Dyck model. Volunteers were randomized to a session without background noise and a session with pre-recorded looped operating room background noise. Exploratory pharmacokinetic-pharmacodynamic modelling and covariate analysis were conducted in NONMEM using bispectral index (BIS) monitoring of processed EEG. Results We found that both stimulation at the time of Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale scoring and the presence or absence of ambient noise had an effect on the sedative properties of dexmedetomidine. The stimuli associated with MOAA/S scoring increased the BIS of sedated volunteers because of a transient 170% increase in the effect-site concentration necessary to reach half of the maximal effect. In contrast, volunteers deprived of ambient noise were more resistant to dexmedetomidine and required, on average, 32% higher effect-site concentrations for the same effect as subjects who were exposed to background operating room noise. Conclusions The new pharmacokinetic-pharmacodynamic models might be used for effect-site rather than plasma concentration target-controlled infusion for dexmedetomidine in clinical practice, thereby allowing tighter control over the desired level of sedation. Clinical trial registration NCT01879865.


Antivaccine forces gaining online.


title: Transanal Total Mesorectal Excision: Is There a Real Advantage? The Baltic View.

text: Background The novel surgical procedure transanal total mesorectal excision (taTME) has rapidly become an interest of research in order to overcome the shortcomings of laparoscopic surgery in the treatment of middle and low rectal cancer. taTME is a new natural orifice transluminal endoscopic surgery modality combining three rectal surgery techniques. Methods A retrospective clinical study was conducted in a single centre for a period of 3 years, and herein we report on our first 25 taTME procedures in patients with middle and lower third rectal adenocarcinoma. Results The main demographics were evaluated. The mean age of patients was 64 ± 12 years. There were predominantly males (72%) and 7 female patients (28%) with an average body mass index of 29 ± 4.8 kg/m2. High blood pressure, obesity, chronic heart insufficiency, chronic atrial fibrillation, and diabetes mellitus were commonly diagnosed in all patients. A circumferential resection margin >1 mm was achieved in 16% (n = 4), >2 mm in 40% (n = 10), and >3 mm in 44% (n = 11) of operated patients. The average CRM was 1.8 ± 0.9 cm. In 24% of cases, the distance of a tumour from the mesorectal fascia (MRF) was <1 mm; meanwhile, for 76% of patients, the tumour margin was >1 mm from the MRF. Recovery to flatus was 3 ± 1 days. The average length of hospital stay was 11 ± 3 days. The overall postoperative morbidity was 8%, i.e. one (4%) complication classified as Clavien-Dindo degree I and one (4%) major (IIIb) complication. Subsequently, all patients successfully recovered and were discharged from hospital. During the follow-up period no cancer recurrence was observed. Conclusion Our results nicely demonstrate that taTME can be safely performed with acceptable perioperative complications in patients with middle or lower third rectal cancer. In addition, the perioperative morbidity is also acceptable. However, taTME remains a technically highly demanding operation but is feasible and safe after the appropriate experience is gained. Nevertheless, larger multi-centre prospective randomised studies are ongoing to confirm the safety and to verify oncological results when compared to laparoscopic rectal surgery.


title: Reduction in Wound Complications After Total Ankle Arthroplasty Using a Compression Wrap Protocol.

text: BACKGROUND The purpose of this study was to evaluate the clinical differences in wound complications after total ankle arthroplasty (TAA) between a cohort of patients that received a compression wrap protocol and a historical control group treated with cast immobilization. METHODS Patient charts and postoperative wound pictures were reviewed for 42 patients who underwent a compression wrap protocol and 50 patients who underwent circumferential casting after primary TAA from 2008 to 2013. A blinded reviewer graded each wound using a novel postoperative wound classification system, and recorded whether the wound was completely healed by or after 3 months. A second blinded review was performed to determine intraobserver reliability. Mean patient age was 55 years (range, 24-80) and all patients had at least 6-month follow-up. RESULTS There were significantly more total wound complications (P = .02) and mild wound complications (P = .02) in the casted group compared to the compression wrap group. There were no significant differences in the number of moderate and severe complications between each group. A significantly higher proportion of TAA incisions took longer than 3 months to heal in the casted group (P = .02). CONCLUSIONS Based on our clinical experience with postoperative wound care after TAA, use of a compression wrap protocol was safe and effective at reducing wound-related complications, and well tolerated by patients. Further prospective, randomized clinical trials are warranted to evaluate the utility and cost-effectiveness of a compression wrap protocol after TAA.


title: Robotic NOTES (Natural Orifice Translumenal Endoscopic Surgery) in reconstructive urology: initial laboratory experience.

text: OBJECTIVES To present an initial experience with robotic natural orifice translumenal surgery (R-NOTES) in reconstructive urology using the da Vinci surgical system. METHODS In 10 female farm pigs (mean weight, 34.5 kg), 10 pyeloplasties (right 5, left 5), 10 partial nephrectomies (right 5, left 5), and 10 radical nephrectomies (right 5, left 5) were performed. The robot telescope and the first robotic arm were placed through a single 2-cm umbilical incision, and the second robotic arm was placed through the vagina. RESULTS All 30 R-NOTES procedures were performed successfully without any addition of laparoscopic port or open conversion. Mean length of the umbilical incision was 2.6 cm. Mean operative time was 154 minutes, and mean estimated total blood loss was 72 mL. Mean warm ischemia time in the partial nephrectomy group was 25.4 minutes. There were no intraoperative complications. There were no robotic system failures during the entire experiment. We did not find any significant difference when comparing right-side and left-side procedures. When analyzing the learning curve, only robot preparation time reached a statistically significant inverse correlation with increasing number of cases (r = -0.72, P = .018). CONCLUSIONS Robotic NOTES pyeloplasty, partial nephrectomy, and radical nephrectomy are feasible and safe in the porcine model. This approach has the potential for a less morbid and scarless outcome. Intracorporeal suturing is significantly enhanced using the robot, especially through the challenging translumenal natural orifice approach. Further development of robots adaptive to NOTES would boost efforts toward clinical NOTES applications.


title: Replication-Competent Influenza Virus and Respiratory Syncytial Virus Luciferase Reporter Strains Engineered for Co-Infections Identify Antiviral Compounds in Combination Screens.

text: Myxoviruses such as influenza A virus (IAV) and respiratory syncytial virus (RSV) are major human pathogens, mandating the development of novel therapeutics. To establish a high-throughput screening protocol for the simultaneous identification of pathogen- and host-targeted hit candidates against either pathogen or both, we have attempted co-infection of cells with IAV and RSV. However, viral replication kinetics were incompatible, RSV signal window was low, and an IAV-driven minireplicon reporter assay used in initial screens narrowed the host cell range and restricted the assay to single-cycle infections. To overcome these limitations, we developed an RSV strain carrying firefly luciferase fused to an innovative universal small-molecule assisted shut-off domain, which boosted assay signal window, and a hyperactive fusion protein that synchronized IAV and RSV reporter expression kinetics and suppressed the identification of RSV entry inhibitors sensitive to a recently reported RSV pan-resistance mechanism. Combined with a replication-competent recombinant IAV strain harboring nanoluciferase, the assay performed well on a human respiratory cell line and supports multicycle infections. Miniaturized to 384-well format, the protocol was validated through screening of a set of the National Institutes of Health Clinical Collection (NCC) in quadruplicate. These test screens demonstrated favorable assay parameters and reproducibility. Application to a LOPAC library of bioactive compounds in a proof-of-concept campaign detected licensed antimyxovirus therapeutics, ribavirin and the neuraminidase inhibitor zanamivir, and identified two unexpected RSV-specific hit candidates, Fenretinide and the opioid receptor antagonist BNTX-7. Hits were evaluated in direct and orthogonal dose-response counterscreens using a standard recRSV reporter strain expressing Renilla luciferase.


title: LAPAROSCOPIC RESECTION OF GASTROINTESTINAL STROMAL TUMORS (GIST).

text: BACKGROUND Gastrointestinal mesenchymal or stromal tumors (GIST) are lesions originated on digestive tract walls, which are treated by surgical resection. Several laparoscopic techniques, from gastrectomies to segmental resections, have been used successfully. AIM Describe a single center experience on laparoscopic GIST resection. METHOD Charts of 15 operated patients were retrospectively reviewed. Thirteen had gastric lesions, of which ten were sub epithelial, ranging from 2-8 cm; and three were pure exofitic growing lesions. The remaining two patients had small bowel lesions. Surgical laparoscopic treatment consisted of two distal gastrectomies, 11 wedge gastric resections and two segmental enterectomies. Mechanical suture was used in the majority of patients except on six, which underwent resection and closure using manual absorbable sutures. There were no conversions to open technique. RESULTS Mean operative time was 1h 29 min±92 (40-420 min). Average lenght of hospital stay was three days (2-6 days). There were no leaks, postoperative bleeding or need for reintervention. Mean postoperative follow-up was 38±17 months (6-60 months). Three patients underwent adjuvant Imatinib treatment, one for recurrence five months postoperatively and two for tumors with moderate risk for recurrence . CONCLUSION Laparoscopic GIST resection, not only for small lesions but also for tumors above 5 cm, is safe and acceptable technique.


title: Patient visits to an emergency department in anticipation of the COVID-19 pandemic.

text: BACKGROUND The Emergency Department in Trondheim has prepared for a large influx of patients infected with the SARS-CoV-2 virus. We conducted a study comparing patients in the Emergency Department in the first weeks of the pandemic in Norway (weeks 11 and 12) with the average number of patient visits. MATERIAL AND METHOD Data from patients at the Emergency Department of St Olav's Hospital in the period 6 January 2020-22 March 2020 were retrieved from the Emergency Department's database. Logistical patient data concerning patient numbers, chief complaints, length of stay in the Emergency Department, acuity level, isolation status, and treatment level were analysed. RESULTS In week 12, 331 patients were referred to the Emergency Department, a reduction of 39 % compared with the average of 541 patients in weeks 2-10. There was a general reduction in all patient groups, but particularly those discharged from the Emergency Department. In week 12 there were 56 more patients isolated with suspected/potentially infectious disease (187 %) compared with the average for weeks 2-10, and these patients spent almost two hours longer in the Emergency Department than other patients. INTERPRETATION There was a reduction in patient visits to the Emergency Department in the first weeks of the pandemic. The percentage of patients isolated for infection control increased, and the time spent in the Emergency Department for these patients was greater than for other patients. The reduction in the inflow of patients is expected to be temporary, and the Emergency Department at St Olav's Hospital expects a large influx of patients with suspected COVID-19 disease.


title: Local immunomodulation combined to radiofrequency ablation results in a complete cure of local and distant colorectal carcinoma.

text: Radiofrequency ablation (RFA) of colorectal liver metastases activates a specific T-cell response that is ineffective in avoiding recurrence. Recently, local immunomodulation garnered interests as a way to improve the immune response. We were interested in improving the RFA immune response priming to propose a curative treatment of colorectal cancer (CRC) based on antitumor immunity. First, we demonstrated that the RFA did not increase the tumor infiltrating lymphocytes in secondary distant tumors of patients and in mice model and could not avoid relapse. Remarkably, RFA and in situ immunomodulation with GM-CSF-BCG hydrogel induced complete cure of microscopic secondary lesions in mice, related to a strong specific immune response. Then, we demonstrated that the immune escape of large secondary lesions was reversed by addition of the systemic PD-1 blockade to the in situ immunomodulation. The lack of an effective distant immune response in patients treated with RFA confirmed the relevance of this new combination strategy. Increasing the in situ priming response of radiofrequency ablation provides effective adjuvants to induce an abscopal effect. In the case of large lesions, synergy between PD1 blockade inhibitor, ineffective alone or after single RFA, with in situ immunomodulation, could lead to reconsideration of the use of checkpoint inhibition in metastatic MSS CRC.


title: The impact of technology on treatment of iatrogenic cervicothoracic vascular traumas: a study of two cases three decades apart and a review of the literature.

text: Complications such as pseudoaneurysms (PA) related to cervicothoracic venous access can be devastating. In this article, we present two similar cases in which technological advances impacted diagnosis, treatment, and results. Both patients developed massive PA after deep venous puncture attempts. The first case occurred in 1993 and was diagnosed by a duplex scan that revealed a large PA originating from the right subclavian artery. The artery was approached by median sternotomy with supraclavicular extension. The PA originated from the thyrocervical trunk and was treated with simple ligation. The second case was in 2017. Angiotomography revealed a PA originating in the vertebral artery, which was treated with endovascular techniques, maintaining vessel patency. Both patients progressed satisfactorily, despite quite different approaches. Cervicothoracic vascular lesions represent a diagnostic and therapeutic challenge, where the risk of rupture is high. Technological advances have reduced the risks involved in management of vascular injuries with difficult surgical access.


title: Comparison of the Eragen Multi-Code Respiratory Virus Panel with conventional viral testing and real-time multiplex PCR assays for detection of respiratory viruses.

text: High-throughput multiplex assays for respiratory viruses are an important step forward in diagnostic virology. We compared one such assay, the PLx Multi-Code Respiratory Virus Panel (PLx-RVP), manufactured by Eragen Biosciences, Inc. (Madison, WI), with conventional virologic testing, consisting of fluorescent-antibody staining plus testing with the R-mix system and fibroblast tube cultures. The test set consisted of 410 archived respiratory specimens, mostly nasopharyngeal swabs, including 210 that had been positive by conventional testing for a balanced selection of common respiratory viruses. Specimens yielding discrepant results were evaluated using a panel of respiratory virus PCR assays developed, characterized, and validated with clinical specimens. PLx-RVP increased the total rate of detection of viruses by 35.8%, and there was a 25.7% increase in the rate of detection of positive specimens. Reference PCR assay results corroborated the PLx-RVP result for 54 (82%) of 66 discrepancies with conventional testing. Of the 12 specimens with discrepancies between PLx-RVp and the reference PCRs, 6 were positive for rhinovirus by PLx-RVP and the presence of rhinovirus was confirmed by nucleotide sequencing. The remaining six specimens included five in which the PLx-RVP failed to detect parainfluenza virus and one in which the detection of influenza A virus by PLx-RVP could not be confirmed by the reference PCR. Taking the results of the reference PCR assay results into account, the sensitivities of the PLx-RVP for individual viruses ranged from 94 to 100% and the specificities ranged from 99 to 100%. We conclude that PLx-RVP is a highly accurate system for the detection of respiratory viruses and significantly improves the rate of detection of these viruses compared to that by conventional virologic testing.


title: Left paralumbar laparoscopic bilateral ovariectomy in mares.

text: OBJECTIVE To develop a novel technique for left paralumbar laparoscopic bilateral ovariectomy in standing, sedated mares. STUDY DESIGN Prospective descriptive clinical study. ANIMALS Twelve client-owned mares. METHODS Healthy mares with normal ovarian palpation and ultrasonographic appearance were enrolled. Horses were restrained in standing stocks and administered a variable rate infusion of sedation. A left paralumbar bilateral ovariectomy was performed with 1 laparoscopic and 3 instrument portals. Access to the right ovary was facilitated by retracting the descending colon and associated mesentery with a fan retractor. Ovaries were removed with traumatic forceps, and a blunt tip vessel sealing device. A laparoscopic portal within the 17th intercostal space provided good visualization of the right ovary and reduced interference between instrumentation. Complications were recorded during hospitalization. In addition, an owner follow-up questionnaire was used to determine complications after discharge from the hospital. RESULTS Left paralumbar bilateral ovariectomy was successful in all 12 mares, with a mean surgical time of 76 ± 8 minutes. Postoperative complications occurred in 4/12 (33%) mares and included fever, mild colic, incisional swelling, and azotemia. Complications resolved and mares returned to full activity, with complete owner satisfaction. CONCLUSIONS Bilateral ovariectomy can be successfully achieved with minimal morbidity in standing mares with normal ovarian ultrasonographic appearance via left paralumbar laparoscopy.


Ebola Virus Disease Preparations Do Not Protect the United States Against Other Infectious Outbreaks.


title: Evidence of Muller's ratchet in herpes simplex virus type 1.

text: Population bottlenecks can have major effects in the evolution of RNA viruses, but their possible influence in the evolution of DNA viruses is largely unknown. Genetic and biological variation of herpes simplex virus type 1 (HSV-1) has been studied by subjecting 23 biological clones of the virus to 10 plaque-to-plaque transfers. In contrast to large population passages, plaque transfers led to a decrease in replicative capacity of HSV-1. Two out of a total of 23 clones did not survive to the last transfer in 143 TK(-) cells. DNA from three genomic regions (DNA polymerase, glycoprotein gD and thymidine kinase) from the initial and passaged clones was sequenced. Nucleotide substitutions were detected in the TK and gD genes, but not in the DNA polymerase gene. Assuming a uniform distribution of mutations along the genome, the average rate of fixation of mutations was about five mutations per viral genome and plaque transfer. This value is comparable to the range of values calculated for RNA viruses. Four plaque-transferred populations lost neurovirulence for mice, as compared with the corresponding initial clones. LD(50) values obtained with the populations subjected to serial bottlenecks were 4- to 67-fold higher than for their parental clones. These results equate HSV-1 with RNA viruses regarding fitness decrease as a result of plaque-to-plaque transfers, and show that population bottlenecks can modify the pathogenic potential of HSV-1. Implications for the evolution of complex DNA viruses are discussed.


title: Niclosamide ethanolamine inhibits artery constriction.

text: We previously demonstrated that the typical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited artery constriction, but CCCP was used only as a pharmacological tool. Niclosamide is an anthelmintic drug approved by FDA. Niclosamide ethanolamine (NEN) is a salt form of niclosamide and has been demonstrated to uncouple mitochondrial oxidative phosphorylation. The aim of the present study was to elucidate the vasoactivity of NEN and the potential mechanisms. Isometric tension of rat mesenteric artery and thoracic aorta was recorded by using multi-wire myograph system. The protein levels were measured by using western blot techniques. Niclosamide ethanolamine (NEN) treatment relaxed phenylephrine (PE)- and high K+ (KPSS)-induced constriction, and pre-treatment with NEN inhibited PE- and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, NEN also showed antagonism against PE- and KPSS-induced constriction. NEN induced increase of cellular ADP/ATP ratio in vascular smooth muscle cells (A10) and activated AMP-activated protein kinase (AMPK) in A10 cells and rat thoracic aorta. NEN-induced aorta relaxation was attenuated in AMPKα1 knockout (-/-) mice. SERCA inhibitors cyclopiazonic acid and thapsigargin, but not KATP channel blockers glibenclamide and 5-hydroxydecanoic acid, attenuated NEN-induced vasorelaxation in rat mesenteric arteries. NEN treatment increased cytosolic [Ca2+]i and depolarized mitochondrial membrane potential in vascular smooth muscle cells (A10). Niclosamide in non-salt form showed the similar vasoactivity as NEN in rat mesenteric arteries. Niclosamide ethanolamine inhibits artery constriction, indicating that it would be promising to be developed as an anti-hypertensive drug or it would induce vasodilation-related side effects when absorbed in vivo.


Drug-Eluting Stents Are the Default Strategy for Superficial Femoral Artery Intervention Now.


title: How to support the quality of life of people living with cognitive disorders? A (k)new challenge in the post-Covid World.

text: Currently more than five million confirmed cases and over 300,000 deaths due to COVID-19 infection have occurred worldwide (1). In the absence of a vaccine, effective prophylaxis or treatment, containment relies on restrictive lockdown measures, as has occurred in most European countries.