title: The Effect of Product Safety Courses on the Adoption and Outcomes of LESS Surgery.

text: BACKGROUND AND OBJECTIVES As technology in surgery evolves, the medical instrument industry is inevitability involved in promoting the use and appropriate (ie, effective and safe) application of its products. This study was undertaken to evaluate industry-supported product safety courses in laparoendoscopic single-site (LESS) surgery, by using the metrics of surgeons' adoption of the technique, safety of the procedure, and surgeons' perception of the surgery. METHODS LESS surgery courses that involved didactic lectures, operative videos, operation observation, collaborative learning, and simulation, were attended by 226 surgeons. With Florida Hospital Tampa Institutional Review Board approval, the surgeons were queried before and immediately after the course, to assess their attitudes toward LESS surgery. Then, well after the course, the surgeons were contacted, repeatedly if necessary, to complete questionnaires. RESULTS Before the course, 82% of the surgeons undertook more than 10 laparoscopic operations per month. Immediately after the course, 86% were confident that they were prepared to perform LESS surgery. Months after the course, 77% of the respondents had adopted LESS surgery, primarily cholecystectomy; 59% had added 1 or more trocars in 0-20% of their procedures; and 73% held the opinion that operating room observation was the most helpful learning experience. Complications with LESS surgery were noted 12% of the time. Advantages of the technique were better cosmesis (58%) and patient satisfaction (38%). Disadvantages included risk of complications (37%) and higher technical demand (25%). Seventy-eight percent viewed LESS surgery as an advancement in surgical technique. CONCLUSION In multifaceted product safety courses, operating room observation is thought to provide the most helpful instruction for those wanting to undertake LESS surgery. The procedure has been safely adopted by surgeons who frequently perform laparoscopies. The tradeoff is in performing a more difficult technique to obtain better cosmesis for the patient. We must continue to conduct critical evaluations of product safety courses for the introduction of new technology in surgery.


COVID-19: are T lymphocytes simply watching?


title: Implementation of Preoperative Screening Protocols in Otolaryngology During the COVID-19 Pandemic.

text: OBJECTIVE To highlight emerging preoperative screening protocols and document workflow challenges and successes during the early weeks of the COVID-19 pandemic. METHODS This retrospective cohort study was conducted at a large urban tertiary care medical center. Thirty-two patients undergoing operative procedures during the COVID-19 pandemic were placed into 2 preoperative screening protocols. Early in the pandemic a "high-risk case protocol" was utilized to maximize available resources. As information and technology evolved, a "universal point-of-care protocol" was implemented. RESULTS Of 32 patients, 25 were screened prior to surgery. Three (12%) tested positive for COVID-19. In all 3 cases, the procedure was delayed, and patients were admitted for treatment or discharged under home quarantine. During this period, 86% of operative procedures were indicated for treatment of oncologic disease. There was no significant delay in arrival to the operating room for patients undergoing point-of-care screening immediately prior to their procedure (P = .92). DISCUSSION Currently, few studies address preoperative screening for COVID-19. A substantial proportion of individuals in this cohort tested positive, and both protocols identified positive cases. The major strengths of the point-of-care protocol are ease of administration, avoiding subsequent exposures after testing, and relieving strain on "COVID-19 clinics" or other community testing facilities. IMPLICATIONS FOR PRACTICE Preoperative screening is a critical aspect of safe surgical practice in the midst of the widespread pandemic. Rapid implementation of universal point-of-care screening is possible without major workflow adjustments or operative delays.


title: Approaches to conventional mechanical ventilation of the patient with acute respiratory distress syndrome.

text: To minimize ventilator-induced lung injury, attention should be directed toward avoidance of alveolar over-distention and cyclical opening and closure of alveoli. The most impressive study of mechanical ventilation to date is the Acute Respiratory Distress Syndrome (ARDS) Network study of higher versus lower tidal volume (V(T)), which reported a reduction in mortality from 39.8% to 31.0% with 6 mL/kg ideal body weight rather than 12 mL/kg ideal body weight (number-needed-to-treat of 12 patients). To achieve optimal lung protection, the lowest plateau pressure and V(T) possible should be selected. What is most important is limitation of V(T) and alveolar distending pressure, regardless of the mode set on the ventilator. Accumulating observational evidence suggests that V(T) should be limited in all mechanically ventilated patients-even those who do not have ALI/ARDS. Evidence does not support the use of pressure controlled inverse-ratio ventilation. Although zero PEEP is probably injurious, an area of considerable controversy is the optimal setting of PEEP. Available evidence does not support the use of higher PEEP, compared to lower PEEP, in unselected patients with acute lung injury (ALI)/ARDS. However, results of a meta-analysis using individual patients from 3 randomized controlled trials suggest that higher PEEP should be used for ARDS, whereas lower PEEP may be more appropriate in patients with ALI. PEEP should be set to maximize alveolar recruitment while avoiding over-distention. Many approaches for setting PEEP have been described, but evidence is lacking that any one approach is superior to any other. In most, if not all, cases of ALI/ARDS, conventional ventilation strategies can be used effectively to provide lung-protective ventilation strategies.


title: Mediterranean diet and depression among older individuals: The multinational MEDIS study.

text: BACKGROUND Depression has been linked to a large and growing economic and societal burden worldwide. In Europe, depression is one of the most frequent mental disorders across all age groups, but particularly in people aged 65 years and over, and higher depressive symptoms have been reported among individuals with chronic diseases (e.g., diabetes and heart disease). AIM To evaluate the role of adherence to the Mediterranean diet (MedDiet) in depression in a sample of older people living in the Mediterranean basin. METHODS Standard procedures were used to determine socio-demographic, lifestyle, and clinical characteristics of the participants, as well as their dietary habits, and depressive symptoms were evaluated using the Geriatric Depression Scale (GDS). Multi-adjusted logistic and linear regression analyses were carried out to evaluate the associations between participants' characteristics and depression. RESULTS Participants classified as having mild or severe depression were less educated and physically active, and more diabetic, and they reported less adherence to the MedDiet. Adherence to the MedDiet was associated with the absence of depression [(OR, 95% CI): 0.65, 0.50-0.85]. In addition, daily tea drinking was also related to the absence of depression [(OR, 95% CI): 0.51, 0.40-0.65]. CONCLUSIONS Greater adherence to the MedDiet and daily tea drinking seem to have a beneficial effect on depressive symptoms in older adults.


title: In vitro artefact assessment of a new MR-compatible microwave antenna and a standard MR-compatible radiofrequency ablation electrode for tumour ablation.

text: OBJECTIVE To evaluate and compare artefact configuration and diameters in a magnetic resonance (MR)-compatible prototype microwave (MW) applicator and a standard MR-compatible radiofrequency (RF) applicator for MR-guided tumour ablation. METHODS Both applicators were tested in a phantom study at 1.5T with three sequences: T1-weighted three-dimensional volume interpolated breath-hold examination (VIBE), T1-weighted fast low angle shot (FLASH), T2-weighted turbo spin echo (TSE). Applicator orientation to main magnetic field (B0) and slice orientation were varied. Needle tip location error (TLE) was assessed, and artefact diameters were calculated. Influence of imaging parameters on artefacts was assessed with analysis of variance (ANOVA) and post hoc testing. RESULTS MW applicator: the shaft artefact diameter measured 2.3 +/- 0.8 mm. Tip artefact diameter and length measured 2.2 ± 0.8 mm and 2.4 ± 1.3 mm, respectively. A prominent oval artefact (diameter: 16.5 +/- 1.8 mm, length: 19.1 +/- 2.5 mm) appeared close to the tip. TLE: - .3 +/- 0.6 mm. RF applicator: shaft and tip diameter measured 8.9 +/- 4.7 mm and 9.0 +/- .0 mm, respectively. TLE: -0.1 +/- 0.8 mm. Minimal artefacts were measured with RF applicator orientation parallel to B0 (P < 0.0001), whereas no such influence was found for MW applicator. For both applicators, significantly large artefacts were measured with T1 FLASH (P = 0.03). CONCLUSION The MW applicator's artefact is satisfactory and seems useable for MR-guided ablation procedures. KEY POINTS MW applicator's artefact appearance is independent of angulation to main magnetic field. MW applicator's prominent distal artefact may increase visibility under MR-guidance. RF and MW applicator's artefacts are precise concerning tip depiction. Largest artefact diameters are measured with T1-weighted fast low angle shot sequence.


title: Prospects of Targeting the Gastrin Releasing Peptide Receptor and Somatostatin Receptor 2 for Nuclear Imaging and Therapy in Metastatic Breast Cancer.

text: BACKGROUND The gastrin releasing peptide receptor (GRPR) and the somatostatin receptor 2 (SSTR2) are overexpressed on primary breast cancer (BC), making them ideal candidates for receptor-mediated nuclear imaging and therapy. The aim of this study was to determine whether these receptors are also suitable targets for metastatic BC. METHODS mRNA expression of human BC samples were studied by in vitro autoradiography and associated with radioligand binding. Next, GRPR and SSTR2 mRNA levels of 60 paired primary BCs and metastases from different sites were measured by quantitative reverse transcriptase polymerase chain reaction. Receptor mRNA expression levels were associated with clinico-pathological factors and expression levels of primary tumors and corresponding metastases were compared. RESULTS Binding of GRPR and SSTR radioligands to tumor tissue correlated significantly with receptor mRNA expression. High GRPR and SSTR2 mRNA levels were associated with estrogen receptor (ESR1)-positive tumors (p<0.001 for both receptors). There was no significant difference in GRPR mRNA expression of primary tumors versus paired metastases. Regarding SSTR2 mRNA expression, there was also no significant difference in the majority of cases, apart from liver and ovarian metastases which showed a significantly lower expression compared to the corresponding primary tumors (p = 0.02 and p = 0.03, respectively). CONCLUSION Targeting the GRPR and SSTR2 for nuclear imaging and/or treatment has the potential to improve BC care in primary as well as metastatic disease.


title: Nutritional Deficiencies in Patients after Roux-en-Y Gastric Bypass and Sleeve Gastrectomy during 12-Month Follow-Up.

text: INTRODUCTION Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) are the two most frequently performed bariatric operations. These two types of metabolic surgery alter the anatomy and function of digestive tract producing significant weight loss in morbidly obese patients but may lead to malnutrition. AIM Analysis of incidence and severity of malnutrition after bariatric surgery in patients submitted to RYGB or LSG during 12 months of follow-up. MATERIAL AND METHODS Retrospective study of 98 patients after RYGB (n = 47) or LSG (n = 51) assessed for nutritional deficiencies during 12 months after surgery was conducted. The differences in body mass index (BMI) and blood tests including erythrocytes, haemoglobin, total protein, albumin, iron, ferritin, transferrin, vitamin B12, folic acid, calcium and phosphorus concentrations were compared between groups before the operations and at 1 and 12 months. RESULTS Nutritional deficiencies were common before surgery with prevalence up to 19.6% for albumin in the LSG group. Median preoperative BMI levels and albumin concentrations were higher in the RYGB group compared to the LSG group, but there was no difference in percent excess weight loss (%EWL) at 1 and 12 months between LSG and RYGB. One month after LSG erythrocyte count, haemoglobin, iron, ferritin and transferrin levels were significantly higher than in the RYGB group. These differences subsided at 12 months. At 12 months, only the prevalence of vitamin B12 deficiency was significantly higher in the RYGB group. CONCLUSION Both RYGB and LSG lead to nutritional deficiencies despite different properties of operations and similar %EWL during follow-up.


title: Antenna coupling explains unintended thermal injury caused by common operating room monitoring devices.

text: INTRODUCTION Unintended thermal injury from patient monitoring devices (eg, electrocardiogram pads, neuromonitoring leads) results in third-degree burns. A mechanism for these injuries is not clear. The monopolar "bovie" emits radiofrequency energy that transfers to nearby, nonelectrically active cables or wires without direct contact by capacitive and antenna coupling. The purpose of this study was to determine if, and to what extent, radiofrequency energy couples to common patient monitoring devices. MATERIALS AND METHODS In an ex vivo porcine model, monopolar radiofrequency energy was delivered to a handheld "bovie" pencil. Nonelectrically active neuromonitoring and cardiac-monitoring leads were placed in proximity to the monopolar pencil and its cord. Temperature changes of tissue touched by the monitoring lead were measured using a thermal camera immediately after a 5-second activation. The energy-device cords were then separated by 15 cm, the power was reduced from 30 W coag to 15 W coag and different cord angulation was tested. An advanced bipolar device, a plasma-based device, and an ultrasonic device were also tested at standard settings. RESULTS The neuromonitoring lead increased tissue temperature at the insertion site by 39 ± 13°C (P<0.001) creating visible char at the skin. The electrocardiogram lead raised tissue temperature by 1.3 ± 0.5°C (P<0.001). Decreasing generator power from 30 W to 15 W and separating the bovie cord from the neuromonitoring cord by 15 cm significantly reduced the temperature change (39 ± 13°C vs. 26±5°C; P<0.001 and 39 ± 13°C vs. 10 ± 5°C; P<0.001, respectively). Lastly, monopolar energy increased tissue temperatures significantly more than argon beam energy (34 ± 15°C), advanced bipolar energy (0.2 ± 0.4°C), and ultrasonic energy (0 ± 0.3°C) (all P<0.001). CONCLUSIONS Stray energy couples to commonly used patient monitoring devices resulting in potentially significant thermal injury. The handheld bovie cord transfers energy via antenna coupling to neuromonitoring leads that can raise tissue temperatures over 100°F (39°C) using standard settings. The most effective ways to decrease this energy coupling is to reduce generator power, increase the separation between wires, or utilize lower voltage energy devices such as ultrasonic or bipolar energy.


title: Facial soft tissue trauma.

text: Traumatic facial soft tissue injuries are commonly encountered in the emergency department by plastic surgeons and other providers. Although rarely life-threatening, the treatment of these injuries can be complex and may have significant impact on the patient's facial function and aesthetics. This article provides a review of the relevant literature related to this topic and describes the authors' approach to the evaluation and management of the patient with facial soft tissue injuries.


The American College of Obstetricians and Gynecologists in 2020: A Clear Vision for the Future.


title: At a crossroads, wondering which way to go.

text: Having returned from travelling and working in Australia, the Covid-19 pandemic has given Anna Leach the chance to consider where she would like to take her career next.


title: Anterior and anterolateral resection for skull base malignancies: techniques and complication avoidance.

text: Combined anterior cranial base resection is the mainstay of therapy for skull base malignancies. Improvements in surgical techniques and reconstruction have led to a reduction in morbidity and overall better survival rates. Meticulous attention to dural and skull base reconstruction is essential for reducing the major complications, including cerebrospinal fluid leak and pneumocephalus. Complications can be devastating, but timely effective management can limit the severity.


title: Management of Incidental Pancreatic Cystic Lesions: Integrating Novel Diagnostic and Prognostic Factors With Current Clinical Guidelines.

text: Owing to increased detection rates, the diagnosis and management of incidental pancreatic cysts has become a common predicament. Up to 13% of patients undergoing cross-sectional imaging studies for other indications are found to have pancreatic cystic lesions. Although most cystic lesions are benign, the malignant potential of several types of pancreatic cysts makes accurate classification vital to directing therapy. To this end, advances in the last decade led to better characterization of pancreatic cyst morphology and hence enhanced the ability to predict underlying histopathology, and biological behavior. Although accurate classification remains a challenge, the utilization of complementary diagnostic tools is the optimal approach to dictate management. The following review includes a description of pancreatic cysts, a critical review of current and emerging diagnostic techniques and a review of recent guidelines in the management of incidental pancreatic cysts.


title: Repurposing Drugs for the Management of Patients with Confirmed Coronavirus Disease 2019 (COVID-19).

text: BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed coronavirus disease 2019 (COVID-19) by the World Health Organization, is a newly emerging zoonotic agent that emerged in China in December 2019. No specific treatment for COVID-19 is currently available. Usual palliative treatment includes maintaining hydration and nutrition and controlling fever and cough. The clinical severity and extent of transmission need to be determined, and therapeutic options need to be developed and optimized. METHODS The present review discusses the recent repurposing of drugs for COVID-19 treatment. RESULTS Several compounds, including remdesivir, lopinavir, ritonavir, interferon-β, ribavirin, chloroquine/hydroxychloroquine, azithromycin, tocilizumab, and ivermectin, have emerged as promising alternatives. They block the virus from entering host cells, prevent viral replication, and attenuate exacerbation of the host's immune response. CONCLUSION Although some evidence indicates the positive actions of different classes of compounds for the treatment of COVID-19, few clinical assays have been established to definitively demonstrate their therapeutic value in humans. Multicenter clinical studies are urgently needed to validate and standardize therapeutic regimens that involve these agents. Although science has not yet presented us with a specific drug against COVID-19, the repurposing of drugs appears to be promising in our fight against this devastating disease.


title: Single-port laparascopic cholecystectomy: scarless cholecystectomy.

text: Objective. Single-incision laparoscopic surgery is a new advanced technology to further minimize the invasiveness of laparoscopy through a single small incision hidden in the umbilicus. The objective is to describe short and long-term outcomes of SILS cholecystectomy. Methodology. Patients with gallbladder pathologies were unselectively enrolled and were prospectively studied between April 2009 and April 2010 and completed a post-operative follow-up for 12 months. Results. There were 22 women and 8 men. Mean age was 46 years. Twenty-one patients had biliary colic, seven had acute cholecystitis, one had gallbladder polyp, and another had resolving acute pancreatitis. Mean operative time was 104.3 ± 44 minutes. Mean BMI was 30.42 and the average pain score was 3.2 ± 1.1. One more port was inserted to help in finishing the procedure in one patient. There was no conversion to a standard laparoscopic or open technique. There was one post-operative bile collection from a missed cyctic duct of Luschka. Mean hospital stay was 1.2 days. Conclusion. Single-port laparoscopic cholecystectomy is feasible. Early conversion to a standard laparoscopic technique is advised to avoid serious complications. The procedure has an obvious cosmetic benefit. Additional prospective trials are necessary to define the benefits of single-port laparoscopic cholecystectomy.


title: Correction: Vol. 22, No. 6.

text: [This corrects the article on p. 993 in vol. 22, PMID: 27192395.].


title: Prognosis after surgical replacement with a bioprosthetic aortic valve in patients with severe symptomatic aortic stenosis: systematic review of observational studies.

text: OBJECTIVE To determine the frequency of survival, stroke, atrial fibrillation, structural valve deterioration, and length of hospital stay after surgical replacement of an aortic valve (SAVR) with a bioprosthetic valve in patients with severe symptomatic aortic stenosis. DESIGN Systematic review and meta-analysis of observational studies. DATA SOURCES Medline, Embase, PubMed (non-Medline records only), Cochrane Database of Systematic Reviews, and Cochrane CENTRAL from 2002 to June 2016. STUDY SELECTION Eligible observational studies followed patients after SAVR with a bioprosthetic valve for at least two years. METHODS Reviewers, independently and in duplicate, evaluated study eligibility, extracted data, and assessed risk of bias for patient important outcomes. We used the GRADE system to quantify absolute effects and quality of evidence. Published survival curves provided data for survival and freedom from structural valve deterioration, and random effect models provided the framework for estimates of pooled incidence rates of stroke, atrial fibrillation, and length of hospital stay. RESULTS In patients undergoing SAVR with a bioprosthetic valve, median survival was 16 years in those aged 65 or less, 12 years in those aged 65 to 75, seven years in those aged 75 to 85, and six years in those aged more than 85. The incidence rate of stroke was 0.25 per 100 patient years (95% confidence interval 0.06 to 0.54) and atrial fibrillation 2.90 per 100 patient years (1.78 to 4.79). Post-SAVR, freedom from structural valve deterioration was 94.0% at 10 years, 81.7% at 15 years, and 52% at 20 years, and mean length of hospital stay was 12 days (95% confidence interval 9 to 15). CONCLUSION Patients with severe symptomatic aortic stenosis undergoing SAVR with a bioprosthetic valve can expect only slightly lower survival than those without aortic stenosis, and a low incidence of stroke and, up to 10 years, of structural valve deterioration. The rate of deterioration increases rapidly after 10 years, and particularly after 15 years.


title: Radical hysterectomy in obese and morbidly obese women with cervical cancer.

text: OBJECTIVE To compare intraoperative and postoperative outcomes, pathologic findings, cancer recurrence, and death rates in normal-weight, overweight, obese, and morbidly obese women undergoing radical hysterectomy and pelvic lymphadenectomy for early-stage cervical cancer. METHODS A review of patients who underwent radical hysterectomy and pelvic lymphadenectomy for invasive cervical cancer between 1990 and 2006 was performed. On the basis of body mass index (BMI) (calculated as weight [kg]/[height (m)](2)), women were categorized as normal weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9), obese (BMI 30.0-34.9), or morbidly obese (BMI at least 35.0). RESULTS Four hundred eight women met the inclusion criteria. Of these, 155 (38%) were normal weight, 126 (31%) were overweight, 77 (19%) were obese, and 50 (12%) were morbidly obese. There were no statistically significant differences between these four groups in age, Charlson comorbidity score, smoking history, stage, histologic grade or subtype, tumor size, depth of invasion, transfusion rate, operative time, or intraoperative complications. Higher BMI was significantly correlated with higher estimated operative blood loss (P=.001). There were no statistically significant differences between the groups in pathologic findings, length of postoperative hospital stay, postoperative complications, readmission rate, or proportion of women receiving adjuvant radiotherapy. At a median follow-up time of 64 months, there were no differences between groups in rates of recurrence or death from disease. CONCLUSION Radical hysterectomy and pelvic lymphadenectomy is feasible for obese and morbidly obese women with cervical cancer. Obesity alone should not be a contraindication to radical hysterectomy in women with cervical cancer.


title: Predictors of mortality in Middle East respiratory syndrome (MERS).

text: We evaluated the clinical characteristics, cytokine/chemokine concentrations, viral shedding and antibody kinetics in 30 patients with Middle East respiratory syndrome (MERS), including 6 non-survivors admitted to 3 MERS-designated hospitals. Old age, low albumin, altered mentality and high pneumonia severity index score at admission were risk factors for mortality. In addition, severe signs of inflammation at initial presentation (at hospital days 1-4), such as high inducible protein-10 (p=0.0013), monocyte chemoattractant protein-1 (p=0.0007) and interleukin 6 (p=0.0007) concentrations, and poor viral control (high viral load at hospital days 5-10, p<0.001) without adequate antibody titres (low antibody titre at hospital days 11-16, p=0.07) during the course of disease, were associated with mortality.


Nasal Gene Expression of Angiotensin-Converting Enzyme 2 in Children and Adults.


title: Laparoscopic and robotic distal gastrectomy for gastrointestinal stromal tumour: case report.

text: BACKGROUND Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the digestive tract. The most frequent site of occurrence is the stomach. Due to the high potential for malignancy of GIST, resection should be the first-line treatment. Minimally invasive surgery may be used for surgical resection of GISTs. METHODS We describe a case of laparoscopic and robotic distal gastrectomy in a patient with diagnosis of GIST in the gastric antrum. Laparoscopy was useful for dissection and a da Vinci robot was used for Roux-en-Y reconstruction. RESULTS The postoperative course was uneventful. CONCLUSIONS Minimally invasive surgery offers benefits compared to open surgery, and laparoscopic and robot-assisted gastrectomy for the treatment of GIST could be technically feasible and safe because of the advantageous movements provided by the robotic arms.


title: ICU-acquired pneumonia with or without etiologic diagnosis: a comparison of outcomes.

text: OBJECTIVES The impact of ICU-acquired pneumonia without etiologic diagnosis on patients' outcomes is largely unknown. We compared the clinical characteristics, inflammatory response, and outcomes between patients with and without microbiologically confirmed ICU-acquired pneumonia. DESIGN Prospective observational study. SETTING ICUs of a university teaching hospital. PATIENTS We prospectively collected 270 consecutive patients with ICU-acquired pneumonia. Patients were clustered according to positive or negative microbiologic results. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS We compared the characteristics and outcomes between both groups. Negative microbiology was found in 82 patients (30%). Both groups had similar baseline severity scores. Patients with negative microbiology presented more frequently chronic renal failure (15 [18%] vs 11 [6%]; p=0.003), chronic heart disorders (35 [43%] vs 55 [29%]; p=0.044), less frequently previous intubation (44 [54%] vs 135 [72%]; p=0.006), more severe hypoxemia (PaO2/FIO2: 165±73 mm Hg vs 199±79 mm Hg; p=0.001), and shorter ICU stay before the onset of pneumonia (5±5 days vs 7±9 days; p=0.001) compared with patients with positive microbiology. The systemic inflammatory response was similar between both groups. Negative microbiology resulted in less changes of empiric treatment (33 [40%] vs 112 [60%]; p=0.005) and shorter total duration of antimicrobials (13±6 days vs 17±12 days; p=0.006) than positive microbiology. Following adjustment for potential confounders, patients with positive microbiology had higher hospital mortality (adjusted odds ratio 2.96, 95% confidence interval 1.24-7.04, p=0.014) and lower 90-day survival (adjusted hazard ratio 0.50, 95% confidence interval 0.27-0.94, p=0.031), with a nonsignificant lower 28-day survival. CONCLUSIONS Although the possible influence of previous intubation in mortality of both groups is not completely discarded, negative microbiologic findings in clinically suspected ICU-acquired pneumonia are associated with less frequent previous intubation, shorter duration of antimicrobial treatment, and better survival. Future studies should corroborate the presence of pneumonia in patients with suspected ICU-acquired pneumonia and negative microbiology.


Response to: 'Experience of telemedicine use in a big cohort of patients with rheumatoid arthritis during COVID-19 pandemic' by Santos-Moreno et al.


title: Outcomes of utilizing absorbable mesh as an adjunct to posterior sheath closure during complex posterior component separation.

text: BACKGROUND A minority of patients undergoing posterior component separation (PCS) have abdominal wall defects that preclude complete reconstruction of the visceral sac with native tissue. The use of absorbable mesh bridges (AMB) to span such defects has not been established. We hypothesized that AMB use during posterior sheath closure of PCS is safe and provides favorable outcomes. METHODS We performed a retrospective review of consecutive patients undergoing PCS with AMB at two hernia centers. Main outcome measures included demographics, comorbidities, and post-operative complications. RESULTS 36 patients were identified. Post-operative wound complications included five surgical site infections. At a median of 27 months, there were five recurrent hernias (13.9%), 2 of which were parastomal, but no episodes of intestinal obstruction/fistula. CONCLUSIONS Utilization of AMB for large posterior layer deficits results in acceptable rates of perioperative wound morbidity, effective PCS repairs, and does not increase intestinal morbidity or fistula formation.


title: Single-incision sleeve gastrectomy versus laparoscopic sleeve gastrectomy. A 2-year comparative analysis of 600 patients.

text: BACKGROUND This is a 2-year study to evaluate the feasibility; outcomes in terms of postoperative pain, weight loss, and complication rates; and cosmesis of the single-incision sleeve gastrectomy versus the conventional multiport sleeve gastrectomy. METHODS A prospective comparative analysis was done in 300 patients in each arm who underwent laparoscopic sleeve gastrectomy and single-incision sleeve gastrectomy from September 2009 till January 2012. Both groups were matched for age and BMI. Postoperative pain scoring was done using visual analogue scale. Outcomes in terms of pain score, scar satisfaction score, excess weight loss, resolution of co-morbidities, and complications were compared in both groups at the end of 6 months, 1 year, and 2 years. RESULTS Female patients preferred to undergo single-incision sleeve gastrectomy. Operating time and intraoperative blood loss were comparable in both groups. Visual analogue scale (VAS) scoring revealed lesser postoperative pain in the single-incision group. Excess weight loss and resolution of co-morbidities were also comparable in both groups at 6 months, 1 year, and 2 years. Incisional hernia was seen in 3 patients (1%) in the single-incision group. Leak rate was comparable. Cosmetic satisfaction was superior in patients who underwent single-incision surgery. CONCLUSIONS Surgical outcomes are comparable in both groups at the end of 2 years. The myth of high long-term incisional hernia rate after single-incision surgery has been dispelled. Single-incision surgery is less painful with better cosmesis. It has come of age and should no longer be considered as an experimental procedure.


title: Microembolism after Endovascular Treatment of Unruptured Cerebral Aneurysms: Reduction of its Incidence by Microcatheter Lumen Aspiration.

text: PURPOSE Diffusion-weighted MR images (DWI) obtained after endovascular treatment of cerebral aneurysms frequently show multiple high-signal intensity (HSI) dots. The purpose of this study was to see whether we could reduce their incidence after embolization of unruptured cerebral aneurysms by modification of our coiling technique, which involves the deliberate aspiration of the microcatheter lumen right after delivery of each detachable coil into the aneurysm sac. MATERIALS AND METHODS From January 2011 to June 2011, all 71 patients with unruptured cerebral aneurysms were treated using various endovascular methods. During the earlier period, 37 patients were treated using our conventional embolization technique (conventional period). Then 34 patients were treated with a modified coiling technique (modified period). DWI was obtained on the following day. We compared the occurrence of any DWI HSI lesions and the presence of the symptomatic lesions during the two time periods. RESULTS The incidence of the DWI HSI lesions differed significantly at 89.2% (33/37) during the conventional period and 26.5% (9/34) during the modified period (p < 0.0001). The incidence of symptomatic lesions differed between the two periods (29.7% during the conventional period vs. 2.9% during the modified period, p < 0.003). CONCLUSION Aspiration of the inner content of the microcatheter right after detachable coil delivery was helpful for the reduction of the incidence of microembolisms after endovascular coil embolization for the treatment of unruptured cerebral aneurysms.


title: SILK flow diverter for complex intracranial aneurysms: a Canadian registry.

text: INTRODUCTION The SILK flow diverter (SFD) is used for the treatment of complex intracranial aneurysms. Small case series have been reported in the literature but few studies with a large number of patients have been published. We present our experience with the SFD for the treatment of intracranial aneurysms in Canada. METHODS Centers across Canada using SFDs were contacted to fill out a case report form for patients treated with an SFD in their center. Individual centers were responsible for approval from their ethics committee. Image analysis was performed by individual operators. The case report forms were collected and the final analysis was performed. RESULTS A total of 92 patients were treated with SFDs in eight centers in Canada between January 2009 and August 2013. The aneurysms were located in the posterior circulation in 16 patients and in the anterior circulation in 76 patients. Most aneurysms (75%) were saccular in shape; 22% were fusiform and 3% were blister aneurysms. The size of the aneurysms varied from 2 to 60 mm with the neck varying from 2 to 60 mm. Perioperative morbidity and mortality were 8.7% and 2.2%, respectively. At the last available follow-up, 83.1% of the aneurysms were either completely or near-completely occluded. The rate of complications was higher for fusiform aneurysms (p<0.001). CONCLUSIONS The SFD appears to be an important tool for the treatment of complex intracranial aneurysms. Treatment outcomes and complication rates remain a problem, but should be considered in the context of available alternative interventions. Ongoing analysis of flow-diverting stents for radiographic and clinical performance is required.


title: Cryopreserved Human Allografts for the Reconstruction of Aortic and Peripheral Prosthetic Graft Infection.

text: Background: This study aimed to present cases with cryopreserved human allografts (CHAs) for vascular reconstruction in both aortic and peripheral infected prosthetic grafts. Materials and Methods: This is a single center, observational descriptive study with retrospective analysis. In all cases, the infected prosthetic graft material was completely removed. At discharge, patients were administered anticoagulants. Follow-up examinations included clinical visits, echo-color-Doppler ultrasounds, or computed tomography angiography within 30 days and at 3, 6, and 12 months after the treatment, and then twice per year. Results: We treated 21 patients (90% men, n=19) with the mean age of 71±12 years and mean interval between the initial operation and replacement with CHA of 30 months [range, 1-216; interquartile range (IQR), 2-36]. In-hospital mortality was 14% (n=3); no CHA-related complication led to death. Limb salvage was 100%. No patient was lost at the median follow-up of 14 months (range, 2-61; IQR, 6-39). No rupture, aneurysmal degeneration, or re-infection occurred. Estimated freedom from CHA-related adverse events (95% confidence interval, 43-63) was 95% at 3 years. Conclusion: In our experience, CHAs are a viable option for prosthetic graft infections and provide satisfactory clinical results and favorable stability because of a very low rate of CHA-related adverse events during follow-up.


title: Efficacy and Safety of Ablative Therapy in the Treatment of Patients with Metastatic Pheochromocytoma and Paraganglioma.

text: Metastatic pheochromocytoma and paraganglioma (PPGL) are incurable neuroendocrine tumors. The goals of treatment include palliating symptoms and reducing tumor burden. Little is known about the use of radiofrequency ablation (RFA), cryoablation (CRYO), and percutaneous ethanol injection (PEI) to treat metastatic PPGL. We performed a retrospective study of patients age 17 years and older with metastatic PPGL who were treated with ablative therapy at Mayo Clinic, USA, between June 14, 1999 and November 14, 2017. Our outcomes measures were radiographic response, procedure-related complications, and symptomatic improvement. Thirty-one patients with metastatic PPGL had 123 lesions treated during 42 RFA, 23 CRYO, and 4 PEI procedures. The median duration of follow-up was 60 months (range, 0⁻163 months) for non-deceased patients. Radiographic local control was achieved in 69/80 (86%) lesions. Improvement in metastasis-related pain or symptoms of catecholamine excess was achieved in 12/13 (92%) procedures. Thirty-three (67%) procedures had no known complications. Clavien-Dindo Grade I, II, IV, and V complications occurred after 7 (14%), 7 (14%), 1 (2%), and 1 (2%) of the procedures, respectively. In patients with metastatic PPGL, ablative therapy can effectively achieve local control and palliate symptoms.


title: The Preceding Surgeon Factor in Bariatric Surgery: a Positive Influence on the Learning Curve of Subsequent Surgeons.

text: BACKGROUND The learning curve of laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery has been well investigated. The learning curve is defined by complications and/or by duration of surgery (DOS). Previous studies report an inverse relationship between patient outcome and patient volume. In this study, we investigate whether the learning curve of preceding bariatric surgeons is of additional influence for surgeons who start to perform LRYGB in the same centre. MATERIALS AND METHODS We retrospectively analysed the records of all 713 consecutive primary LRYGB patients operated in our centre from December 2007 until July 2012. Surgeon 1 and 3 had previous laparoscopic bariatric experience whilst Surgeon 2 and 4 had not. We stratified the data between the four surgeons with different levels of experience and in a chronology of 50 cases. RESULTS Sixty-seven (9.4 %) complications occurred in the study period. Surgeon 1 had more complications occurring within the first 50 cases than Surgeon 4 (10 versus 1, p < 0.05). There was no difference in complication rate between groups of 50 consecutive cases. None of the patients died. DOS decreased for every consecutive surgeon, irrespective of their experience. The learning curve defined by DOS was steepest for Surgeon 1, followed by Surgeon 2, 3 and 4. CONCLUSION In this study, we show that the learning curve of the preceding surgeon positively influences the learning curve of latter surgeons, irrespective of their experience. Therefore, the 'preceding surgeon factor' should be taken in account in addition to volume requirements when starting new bariatric facilities.


title: COVID-19: Understanding and mitigating trauma in ICU survivors.

text: The spread of coronavirus disease 2019 (COVID-19) has placed many individuals in need of critical care, with a high proportion of hospitalized patients being admitted to intensive care units (ICU) to treat acute outcomes of COVID-19 (e.g., respiratory failure via mechanical ventilation). The ICU is known to be a setting where individuals are at a high risk of experiencing significant psychological difficulties, and patients with COVID-19 are particularly susceptible to such experiences, which can impact their recovery process (e.g., postintensive care syndrome). This article seeks to highlight the intersection between critical care related to trauma and COVID-19 and point providers toward opportunities for anticipating and managing secondary effects in effort to promote psychological adaptation. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: First molecular identification of 'Candidatus mycoplasma haemominutum' from a cat with fatal haemolytic anaemia in Hungary.

text: Although haemobartonellosis was previously reported in Hungary, until now the diagnosis (based on morphological identification in blood smears) has only been suggestive of the occurrence of the large species, recently reclassified as Mycoplasma haemofelis. However, in July 2007 a cat was presented at a small animal clinic with severe haemolytic anaemia, icterus and haemoglobinuria. While biochemical parameters were within the reference range, the cat had leukocytosis and rapidly decreasing haematocrit values, and eventually died 7 days after the sudden onset of aggravating clinical signs. From blood samples of the cat 'Candidatus Mycoplasma haemominutum' was identified by molecular methods, according to its 100% 16S rRNA gene sequence homology with two Swiss isolates and one isolate from the UK. The rapid termination of the disease and the high pathogenicity of the causative agent observed in this case are unusual, taking into account that PCR results were negative for immunosuppressive viruses. This is the first record of this feline haemoplasma species in Hungary.


title: Strangulated ileostomy evisceration following lateralizing mesh repair of parastomal hernia.

text: Parastomal hernia formation and ostomy prolapse are relatively common complications of intestinal ostomy construction. Underlay mesh placement with lateralization of the stoma limb appears to be the method of repair with the lowest recurrence rate. Prophylaxis of new stomas with mesh is advocated by many authors. We report the case of an 81-year-old man with chronic steroid-dependent COPD who presented to the emergency department with strangulated small bowel evisceration 9 days following completion abdominal colectomy, and creation of an end ileostomy reinforced with intraperitoneal mesh. This rare complication was related to this patient's risk factors for poor healing including poor nutrition, age, chronic COPD and coughing and steroid dependence with immunosuppression.


title: The unmet needs of informal carers of stroke survivors: a protocol for a systematic review of quantitative and qualitative studies.

text: INTRODUCTION Stroke events deeply affect not only the stroke survivor but also often the quality of life and physical and psychological health of the family and friends who care for them. There is a need for further information about the unmet needs of these informal carers in order to develop support services and interventions. The primary objective of this review is to report and synthesise the research describing the unmet needs of carers of stroke survivors. METHODS AND ANALYSIS A systematic review of quantitative and qualitative studies that report on the unmet needs of carers will be conducted. The following databases will be searched for relevant articles: MEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsycINFO, EMBASE, Allied and Complementary Medicine Database and Scopus. No publication date constraints will be applied. Studies will be limited to those published in English and conducted among humans. Eligible studies will report on the unmet needs of informal carers of stroke survivors, defined as family members, friends and other unpaid caregivers. Studies which focus on formal, clinical or medical caregivers will be excluded. A narrative synthesis and pooled analysis of the main outcomes will be reported. ETHICS AND DISSEMINATION This review will be submitted to a peer-reviewed journal. Our findings are expected to provide new insights into the unmet needs of stroke survivors' carers. Knowledge about the unmet needs of carers will inform the development and refinement of interventions and services to address these needs and better support carers of stroke survivors. The findings of this systematic review will be disseminated publicly and in peer-reviewed journals and may be the topic of research presentations. TRIAL REGISTRATION NUMBER CRD42017067391.


Pandemic brings mass vaccinations to a halt.


title: Intrapericardial cystic hematoma in a dog treated by thoracoscopic subtotal pericardectomy.

text: CASE DESCRIPTION A 2-year-old castrated male mixed-breed dog was evaluated because of a 1-week history of respiratory distress and abdominal distension. Thoracic radiography and echocardiography at that time revealed an enlarged cardiac silhouette and pericardial effusion; abdominal radiography and ultrasonography revealed ascites. CLINICAL FINDINGS At the initial referral examination 5 weeks later, the dog weighed 37.5 kg (82.5 lb) and appeared clinically normal. The only abnormality detected was a grade I/VI systolic murmur on the left side of the thorax. Echocardiography revealed a large fat- and fluid-filled cystic structure located next to the right ventricle with scant pericardial effusion. Computed tomography revealed a bilobed peripherally contrast-enhancing structure within the right ventral aspect of the pericardium; the right ventricle appeared compressed by the cyst. TREATMENT AND OUTCOME Initial treatment consisted of pericardiocentesis and abdominocentesis to alleviate clinical signs. Thoracoscopic subtotal pericardectomy was performed 6 weeks after the initial treatment. The cyst was completely excised, and multiple adhesions between the visceral and parietal pericardium were transected, without surgical or anesthetic complications. Histologic examination of the cyst revealed chronic inflammation with histiocytic infiltration, suggesting possible foreign body reaction or chronic inflammation and hemorrhage. These findings supported a diagnosis of cystic hematoma of the pericardium. The dog remained clinically normal for at least 16 months after surgery. CLINICAL RELEVANCE This report represents a rare case of intrapericardial cystic hematoma in a dog. Minimally invasive surgery was performed without complications, suggesting that thoracoscopic subtotal pericardectomy is a feasible treatment option for affected dogs.


title: The relationship between the psychological stress of adolescents in school and the prevalence of chronic low back pain: a cross-sectional study in China.

text: Background Accumulating evidence supports an association between an unhealthy mental state and low back pain (LBP). However, the degree of the association between mental health and chronic low back pain (CLBP) in the general population is poorly understood. The objective of this study was to analyze the incidence of CLBP in Chinese college students and to examine the association between students' unhealthy mental states and the prevalence of CLBP. Methods This is a cross-sectional study. A total of 10,000 questionnaires were distributed in the second semester of the 2017-2018 academic year by the School of Medicine, Shanghai JiaoTong University. Eligible participants were students aged ≥ 18 years from randomly selected Chinese colleges. Participants completed a questionnaire survey that included items from the Symptom Checklist-90 (SCL-90) and items on demographic factors, LBP prevalence, quality of life at their university, study-related stress and interpersonal relationships. The evaluation of students' mental states in the survey was divided into two major parts: direct and indirect indicators. A multivariate logistic regression model was mainly used to explore the relationship between CLBP and the students' mental health. Results There was a high incidence of CLBP in the college students. Multiple logistic regression analysis indicated that the risk of CLBP increased with increasing scores on the SCL-90, and a clinically unhealthy mental state (scores greater than 3) was significantly associated with CLBP (adjusted odds ratios for depression, anxiety, coercion, paranoia, and interpersonal sensitivity were 7.209, 6.593, 3.959, 4.465, and 4.283, respectively; p < 0.001). Participants who had poor living habits or uncomfortable campus lives and those who experienced heavy academic pressure also showed a higher positive association with CLBP compared with the full sample. Conclusions Unhealthy psychological conditions, which may be attributed to unsatisfying school lives, excessive learning pressure, and uncomfortable interpersonal relationships, represent a risk factor for CLBP in college students.


title: Treatment of psychotic symptoms in bipolar disorder with aripiprazole monotherapy: a meta-analysis.

text: BACKGROUND We present a systematic review and meta-analysis of the available clinical trials concerning the usefulness of aripiprazole in the treatment of the psychotic symptoms in bipolar disorder. METHODS A systematic MEDLINE and repository search concerning clinical trials for aripiprazole in bipolar disorder was conducted. RESULTS The meta-analysis of four randomised controlled trials (RCTs) on acute mania suggests that the effect size of aripiprazole versus placebo was equal to 0.14 but a more reliable and accurate estimation is 0.18 for the total Positive and Negative Syndrome Scale (PANSS) score. The effect was higher for the PANSS-positive subscale (0.28), PANSS-hostility subscale (0.24) and PANSS-cognitive subscale (0.20), and lower for the PANSS-negative subscale (0.12). No data on the depressive phase of bipolar illness exist, while there are some data in favour of aripiprazole concerning the maintenance phase, where at week 26 all except the total PANSS score showed a significant superiority of aripiprazole over placebo (d = 0.28 for positive, d = 0.38 for the cognitive and d = 0.71 for the hostility subscales) and at week 100 the results were similar (d = 0.42, 0.63 and 0.48, respectively). CONCLUSION The data analysed for the current study support the usefulness of aripiprazole against psychotic symptoms during the acute manic and maintenance phases of bipolar illness.


Highlights From the Circulation Family of Journals.


Benefit v. risk when using chloroquine in patients with severe COVID-19 disease.


title: Radiofrequency Ablation Combined with Hepatic Arterial Chemoembolization Using Degradable Starch Microsphere Mixed with Mitomycin C for the Treatment of Liver Metastasis from Colorectal Cancer: A Prospective Multicenter Study.

text: PURPOSE This phase II prospective study investigates possible benefits of radiofrequency ablation (RFA) combined with hepatic arterial chemoembolization using degradable starch microsphere (DSM) mixed with mitomycin C (MMC) in non-surgical candidates with colorectal liver metastases. MATERIALS AND METHODS This study, approved by the respective institutional review board, included non-surgical candidates with 3 or fewer liver tumors of 3 cm or smaller, or a single lesion 5 cm or smaller. Percutaneous RFA was performed immediately after chemoembolization using DSM-MMC. Primary and secondary endpoints were the local tumor control rate, safety, and 2-year recurrence-free and overall survival rates. RESULTS This study examined 25 patients (22 males, 3 females) with 38 tumors of mean maximum diameter of 2.2 ± 0.9 cm (standard deviation) (range 1.0-4.2 cm). Their mean age was 70.2 ± 8.2 years (range 55-82 years). Local tumor progression developed in 3 tumors (7.9%, 3/38) of 3 patients (12%, 3/25) during the mean follow-up of 34.9 ± 9.2 months (range 18.3-50.1 months). The 2-year local tumor control rates were 92.0% [95% confidence interval (CI), 81.4-100%] on a patient basis and 94.6% (95% CI, 87.3-100%) on a tumor basis. The respective 2-year overall and recurrence-free survival rates were 88.0% (95% CI, 75.3-98.5%) and 63.3% (95% CI, 44.2-82.5%), with median survival time of 48.4 months. Fever was the only adverse event requiring treatments in 2 patients (8%). CONCLUSIONS This combination therapy is safe, exhibiting strong anticancer effects on colorectal liver metastasis, which might contribute to patient survival.


title: Successful retrieval of a retained capsule endoscope with single incision laparoscopic surgery.

text: Capsule endoscopy (CE) is commonly used for examining and diagnosing gastrointestinal disease, especially small bowel disease. Capsule retention is a well-known and significant complication of CE and requires surgical or endoscopic removal. Most reports described the retrieval of retained CE via laparotomy. We report a case of successful retrieval of the capsule using single incision laparoscopic surgery.


title: Characterization and Demonstration of the Value of a Lethal Mouse Model of Middle East Respiratory Syndrome Coronavirus Infection and Disease.

text: UNLABELLED Characterized animal models are needed for studying the pathogenesis of and evaluating medical countermeasures for persisting Middle East respiratory syndrome-coronavirus (MERS-CoV) infections. Here, we further characterized a lethal transgenic mouse model of MERS-CoV infection and disease that globally expresses human CD26 (hCD26)/DPP4. The 50% infectious dose (ID50) and lethal dose (LD50) of virus were estimated to be <1 and 10 TCID50 of MERS-CoV, respectively. Neutralizing antibody developed in the surviving mice from the ID50/LD50 determinations, and all were fully immune to challenge with 100 LD50 of MERS-CoV. The tissue distribution and histopathology in mice challenged with a potential working dose of 10 LD50 of MERS-CoV were subsequently evaluated. In contrast to the overwhelming infection seen in the mice challenged with 10(5) LD50 of MERS-CoV, we were able to recover infectious virus from these mice only infrequently, although quantitative reverse transcription-PCR (qRT-PCR) tests indicated early and persistent lung infection and delayed occurrence of brain infection. Persistent inflammatory infiltrates were seen in the lungs and brain stems at day 2 and day 6 after infection, respectively. While focal infiltrates were also noted in the liver, definite pathology was not seen in other tissues. Finally, using a receptor binding domain protein vaccine and a MERS-CoV fusion inhibitor, we demonstrated the value of this model for evaluating vaccines and antivirals against MERS. As outcomes of MERS-CoV infection in patients differ greatly, ranging from asymptomatic to overwhelming disease and death, having available both an infection model and a lethal model makes this transgenic mouse model relevant for advancing MERS research. IMPORTANCE Fully characterized animal models are essential for studying pathogenesis and for preclinical screening of vaccines and drugs against MERS-CoV infection and disease. When given a high dose of MERS-CoV, our transgenic mice expressing hCD26/DPP4 viral receptor uniformly succumbed to death within 6 days, making it difficult to evaluate host responses to infection and disease. We further characterized this model by determining both the ID50 and the LD50 of MERS-CoV in order to establish both an infection model and a lethal model for MERS and followed this by investigating the antibody responses and immunity of the mice that survived MERS-CoV infection. Using the estimated LD50 and ID50 data, we dissected the kinetics of viral tissue distribution and pathology in mice challenged with 10 LD50 of virus and utilized the model for preclinical evaluation of a vaccine and drug for treatment of MERS-CoV infection. This further-characterized transgenic mouse model will be useful for advancing MERS research.


title: Identification of adenoviruses in fecal specimens from wild chimpanzees (Pan trogylodytes schweinfurthii) in western Tanzania.

text: DNA of two distinctive adenoviruses was detected in wild chimpanzees in western Tanzania that showed clinical signs of acute, upper respiratory disease, notably coughing. The amplified sequences from part of the capsid hexon gene suggests that one virus is a novel adenovirus serotype candidate and the other virus is a species C adenovirus most closely related to recent isolates from captive chimpanzees in the United States, Simian AdV 37 with 86% nucleic acid identity and Simian AdV 40 with 95% nucleic acid identity, respectively. The species C adenovirus sequences suggest possible recombination with a human adenovirus. The source of these viruses and disease association is not known.


title: Virtual Dysphagia Evaluation: Practical Guidelines for Dysphagia Management in the Context of the COVID-19 Pandemic.

text: With encouraging signs of pandemic containment nationwide, the promise of return to a full range of clinical practice is on the horizon. Clinicians are starting to prepare for a transition from limited evaluation of emergent and urgent complaints to resumption of elective surgical procedures and routine office visits within the next few weeks to months. Otolaryngology as a specialty faces unique challenges when it comes to the COVID-19 pandemic due to the fact that a comprehensive head and neck examination requires aerosol-generating endoscopic procedures. Since the COVID-19 pandemic is far from being over and the future may hold other highly communicable infectious threats that may require similar precautions, standard approaches to the clinical evaluation of common otolaryngology complaints will have to be modified. In this communication, we present practical recommendations for dysphagia evaluation with modifications to allow a safe and comprehensive assessment.


Infection control strategies of patient diversion in response to COVID-19.


title: The ns12.9 Accessory Protein of Human Coronavirus OC43 Is a Viroporin Involved in Virion Morphogenesis and Pathogenesis.

text: UNLABELLED An accessory gene between the S and E gene loci is contained in all coronaviruses (CoVs), and its function has been studied in some coronaviruses. This gene locus in human coronavirus OC43 (HCoV-OC43) encodes the ns12.9 accessory protein; however, its function during viral infection remains unknown. Here, we engineered a recombinant mutant virus lacking the ns12.9 protein (HCoV-OC43-Δns12.9) to characterize the contributions of ns12.9 in HCoV-OC43 replication. The ns12.9 accessory protein is a transmembrane protein and forms ion channels in both Xenopus oocytes and yeast through homo-oligomerization, suggesting that ns12.9 is a newly recognized viroporin. HCoV-OC43-Δns12.9 presented at least 10-fold reduction of viral titer in vitro and in vivo. Intriguingly, exogenous ns12.9 and heterologous viroporins with ion channel activity could compensate for the production of HCoV-OC43-Δns12.9, indicating that the ion channel activity of ns12.9 plays a significant role in the production of infectious virions. Systematic dissection of single-cycle replication revealed that ns12.9 protein had no measurable effect on virus entry, subgenomic mRNA (sgmRNA) synthesis, and protein expression. Further characterization revealed that HCoV-OC43-Δns12.9 was less efficient in virion morphogenesis than recombinant wild-type virus (HCoV-OC43-WT). Moreover, reduced viral replication, inflammatory response, and virulence in HCoV-OC43-Δns12.9-infected mice were observed compared to the levels for HCoV-OC43-WT-infected mice. Taken together, our results demonstrated that the ns12.9 accessory protein functions as a viroporin and is involved in virion morphogenesis and the pathogenesis of HCoV-OC43 infection. IMPORTANCE HCoV-OC43 was isolated in the 1960s and is a major agent of the common cold. The functions of HCoV-OC43 structural proteins have been well studied, but few studies have focused on its accessory proteins. In the present study, we demonstrated that the ns12.9 protein is a newly recognized viroporin, and the ns12.9 gene knockout virus (HCoV-OC43-Δns12.9) presents a growth defect in vitro and in vivo. We identified the important functions of the ns12.9 viroporin in virion morphogenesis during HCoV-OC43 infection. Furthermore, mice infected with HCoV-OC43-Δns12.9 exhibited reduced inflammation and virulence accompanied by a lower titer in the brain than that of wild-type-infected mice, suggesting the ns12.9 viroporin influences virus pathogenesis. Therefore, our findings revealed that the ns12.9 viroporin facilitates virion morphogenesis to enhance viral production, and these results provided a deeper understanding of HCoV-OC43 pathogenesis.


title: A study to compare circulating flunixin, meloxicam and gabapentin concentrations with prostaglandin E₂ levels in calves undergoing dehorning.

text: The purpose of this study was to investigate the pharmacokinetics of intravenous flunixin (2.2 mg/kg b.w.), oral meloxicam (1mg/kg b.w.), oral gabapentin (15 mg/kg b.w.) alone or co-administrated with meloxicam as well as the effects of these compounds on prostaglandin E2 (PGE2) synthesis in calves subjected to surgical dehorning. Plasma samples collected up to 24h after drug administration were analyzed by liquid chromatography/mass spectrometry, whereas blood PGE2 levels were measured by immunoenzymatic assay. In plasma, the terminal half-live of flunixin, meloxicam and gabapentin were 6.0 h (range, 3.4-11.0 h), 16.7h (range, 13.7-21.3h) and 15.3h (range, 11-32.9h), respectively. The co-administration of single doses of gabapentin and meloxicam did not seem to affect the pharmacokinetic profile of the two drugs except for gabapentin that reached significantly (P<0.05) higher maximum serum concentration (Cmax) when co-administered with meloxicam, than when administered alone. At 5, 360 and 720 min after dehorning, a significant (P<0.01) decrease in PGE2 concentration was observed in flunixin-treated animals compared with control calves. Moreover, circulating log PGE2 concentrations were inversely proportional to log flunixin concentrations (R(2)=0.75; P<0.0001). None of the other drugs significantly affected blood PGE2 levels. Further assessment of oral meloxicam and gabapentin in established pain models is required to formulate science based analgesic recommendations to enhance animal well-being after dehorning.


title: The Cough Cylinder: a tool to study measures against airborne spread of (myco-) bacteria.

text: BACKGROUND 'Covering your cough' reduces droplet number, but its effect on airborne pathogen transmission is less clear. The World Health Organization specifically recommends cough etiquette to prevent the spread of Mycobacterium tuberculosis, but implementation is generally poor and evidence supporting its value is lacking. METHODS We constructed a model to assess 'real life' transmission risk by counting viable pathogens from aerosols produced by coughing patients, thus allowing the assessment of outward protection measures in a standardised fashion. During the validation process, we focused on rod-shaped bacteria as surrogates for M. tuberculosis. RESULTS The Cough Cylinder enabled us to sample Pseudomonas aeruginosa, Escherichia coli and mycobacteria from aerosols produced by patients with cystic fibrosis, primary ciliary dyskinesia and tuberculosis. Pathogens in droplets and in airborne particles could be sampled. Delayed air sampling allowed specific measurement of persistent airborne particles. CONCLUSION This novel experimental system allows measurement of aerosol pathogen spread in a highly standardised fashion. It also offers the possibility to assess the impact of different interventions to limit aerosol transmission.


title: Comparative Evaluation of the Biodistribution Profiles of a Series of Nonpeptidic Neurotensin Receptor-1 Antagonists Reveals a Promising Candidate for Theranostic Applications.

text: UNLABELLED Neurotensin receptor-1 (NTR1) is a promising target for diagnostic imaging and targeted radionuclide therapy. The aim of this study was to evaluate the biodistribution profiles of a series of newly developed diarylpyrazole-based NTR1 antagonists regarding their suitability as diagnostic and potentially radiotherapeutic agents. METHODS 3BP-227, 3BP-228, and 3BP-483 were labeled with (111)In and injected intravenously into NTR1-positive HT29 xenograft-bearing nude mice. At 3, 6, 12, and 24 h after administration, SPECT/CT images were acquired or mice were sacrificed for ex vivo determination of tissue-associated radioactivity. RESULTS High-contrast tumor visualization in SPECT/CT images was achieved using the 3 compounds of this study. Ex vivo biodistribution studies confirmed a high and persistent tumor uptake, peaking at 6 h after injection for (111)In-3BP-227 (8.4 ± 3.1 percentage injected dose per gram [%ID/g]) and at 3 h after injection for (111)In-3BP-228 (10.2 ± 5.3 %ID/g) and (111)In-3BP-483 (1.9 ± 0.8 %ID/g). Tumor-to-normal-tissue ratios obtained with (111)In-3BP-227 and (111)In-3BP-228 were consistently greater than 1. CONCLUSION On the basis of the superior biodistribution profile compared with previously reported radiolabeled NTR1 ligands, (111)In-3BP-227 is an ideal candidate for further development as a theranostic tracer.


Three-dimensional endoscopic sinus surgery: feasibility and technical aspects.


title: Rapid Validation of Telepathology by an Academic Neuropathology Practice During the COVID-19 Pandemic.

text: CONTEXT The coronavirus disease 19 (COVID-19) pandemic is placing unparalleled burdens on regional and institutional resources in medical facilities across the globe. This disruption is causing unprecedented downstream effects to traditionally established channels of patient care delivery, including those of essential anatomic pathology services. With Washington state being the initial North American COVID-19 epicenter, the University of Washington in Seattle has been at the forefront of conceptualizing and implementing innovative solutions in order to provide uninterrupted quality patient care amidst this growing crisis. OBJECTIVE To conduct a rapid validation study assessing our ability to reliably provide diagnostic Neuropathology services via a whole slide imaging (WSI) platform as part of our departmental COVID-19 planning response. DESIGN This retrospective study assessed diagnostic concordance of neuropathological diagnoses rendered via WSI as compared to those originally established via traditional histopathology in a cohort of 30 cases encompassing a broad range of neurosurgical and neuromuscular entities. This study included the digitalization of 93 slide preparations, which were independently examined by groups of board-certified neuropathologists and neuropathology fellows. RESULTS There were no major or minor diagnostic discrepancies identified in either the attending neuropathologist or neuropathology trainee groups for either the neurosurgical or neuromuscular case cohorts. CONCLUSIONS Our study demonstrates that accuracy of neuropathological diagnoses and interpretation of ancillary preparations via WSI are not inferior to those generated via traditional microscopy. This study provides a framework for rapid subspecialty validation and deployment of WSI for diagnostic purposes during a pandemic event.


Coronavirus fears cancel world's biggest physics meeting.


title: Thoracoscopic pneumonectomy: an 11-year experience.

text: BACKGROUND It is unclear whether thoracoscopic (video-assisted thoracoscopic surgery [VATS]) pneumonectomy improves outcomes compared with open approaches. METHODS One hundred seven consecutive pneumonectomies performed at an experienced center from January 2002 to December 2012 were studied retrospectively. Forty cases were open, and 50 successful VATS and 17 conversions were combined (intent-to-treat [ITT] analysis). RESULTS The VATS cohort had more preoperative comorbidities (three vs two, P = .003), women (57% vs 30%, P = .009), and older ages (65 years vs 63 years, P = .07). Although advanced clinical stage was less for VATS (26% vs 50% stage III, P = .035), final pathologic staging was similar (25% vs 38%, P = .77). Pursuing a VATS approach yielded similar complications (two vs two, median, P = .73) with no catastrophic intraoperative events like bleeding. Successful VATS pneumonectomy rates rose from 50%-82% by the second half of the series (P < .001). Completion pneumonectomy cases (13.4% VATS, 7.5% open) had similar outcomes. Having similar initial discomforts as patients undergoing open surgery, more patients undergoing VATS were pain-free at 1 year (53% vs 19%, P = .03). Conversions resulted in longer ICU stays (4 days vs 2 days, P = .01). Advanced clinical stage (III-IV) ITT VATS had longer median overall survival (OS) (42 months vs 13 months, log-rank P = .042). Successful VATS cases with early pathologic stage (0-II) had a median OS of 80 vs 16 months for converted and 28 months for open (log rank = 0.083). CONCLUSIONS Attempting thoracoscopic pneumonectomy at an experienced center appears safe but does not yield the early pain/complication reductions observed for VATS lobectomy. There may be long-term pain/survival advantages for certain stages that warrant further study and refinement of this approach.


title: Mathematical models of infection transmission in healthcare settings: recent advances from the use of network structured data.

text: PURPOSE OF REVIEW Mathematical modeling approaches have brought important contributions to the study of pathogen spread in healthcare settings over the last 20 years. Here, we conduct a comprehensive systematic review of mathematical models of disease transmission in healthcare settings and assess the application of contact and patient transfer network data over time and their impact on our understanding of transmission dynamics of infections. RECENT FINDINGS Recently, with the increasing availability of data on the structure of interindividual and interinstitution networks, models incorporating this type of information have been proposed, with the aim of providing more realistic predictions of disease transmission in healthcare settings. Models incorporating realistic data on individual or facility networks often remain limited to a few settings and a few pathogens (mostly methicillin-resistant Staphylococcus aureus). SUMMARY To respond to the objectives of creating improved infection prevention and control measures and better understanding of healthcare-associated infections transmission dynamics, further innovations in data collection and parameter estimation in modeling is required.


title: Clinical reasoning in feline spinal disease: which combination of clinical information is useful?

text: OBJECTIVES The aim of this study was to evaluate if a combination of discrete clinical characteristics can be used to identify the most likely differential diagnoses in cats with spinal disease. METHODS Two hundred and twenty-one cats referred for further evaluation of spinal disease were included and categorised as follows: non-lymphoid neoplasia (n = 44); intervertebral disc disease (n = 42); fracture/luxation (n = 34); ischaemic myelopathy (n = 22); feline infectious peritonitis virus myelitis (n = 18); lymphoma (n = 16); thoracic vertebral canal stenosis (n = 11); acute non-compressive nucleus pulposus extrusion (n = 11); traumatic spinal cord contusion (n = 8); spinal arachnoid diverticula (n = 7); lumbosacral stenosis (n = 5); and spinal empyema (n = 3). Information retrieved from the medical records included signalment, clinical history and clinical presentation. Univariate analyses of variables (clinical history, breed, age, sex, general physical examination findings, onset, progression, spinal hyperaesthesia, asymmetry, ambulatory status and neuroanatomical location) were performed, and variables were retained in a multivariate logistic regression model if P <0.05. RESULTS Multivariate logistic regression revealed that intervertebral disc disease most often occurred in middle-aged, purebred cats with a normal general physical examination and an acute onset of painful and progressive clinical signs. Ischaemic myelopathy occurred most often in older cats with a stable or improving, non-painful, lateralising, C6-T2 myelopathy. Spinal fracture/luxation occurred most often in younger cats and resulted most often in a peracute onset, painful, non-ambulatory neurological status. Concurrent systemic abnormalities or abnormal findings detected on general physical examination were significantly associated with feline infectious peritonitis virus myelitis, spinal lymphoma or spinal empyema. CONCLUSIONS AND RELEVANCE This study suggests that using easily identifiable characteristics from the history and clinical examination can assist in obtaining a preliminary differential diagnosis when evaluating cats with spinal disease. This information could aid veterinary practitioners in clinical decision-making.


A Radiation Mitigator as a Potential Treatment for COVID-19.


At the Heart of the Matter: Unmasking and Addressing COVID-19's Toll on Diverse Populations.


COLLISION Trial Seeks to Answer Time-Honored Question: "Thermal Ablation or Surgery for Colorectal Liver Metastases?"


title: A Phase IV Study of Thromboembolic and Bleeding Events Following Hip and Knee Arthroplasty Using Oral Factor Xa Inhibitor.

text: BACKGROUND Multiple randomized controlled trials have documented the effectiveness of rivaroxaban in the prevention of venous thromboembolism up to 1-month following total joint arthroplasty. However, the effectiveness and safety of rivaroxaban in the real-world setting, outside of the strict protocols used by randomized clinical trials, are unknown. METHODS This was a prospective, observational, noninterventional, phase IV study of 3914 consecutive patients who underwent total joint arthroplasty from June 2010 to December 2012. Patients were treated with rivaroxaban 10 mg by mouth daily starting postoperative day 1 and continued for 15 days. Participants were followed up in clinic at 6 weeks and contacted by telephone at 12 weeks. The primary outcome of interest was symptomatic venous thromboembolism; secondary outcomes included bleeding events, transfusion requirements, and death. RESULTS The incidence of symptomatic deep venous thrombosis at 3 months was 0.5% (n = 18). Only 1 deep venous thrombosis event occurred within 7 days of surgery. The incidence of symptomatic pulmonary embolism (PE) at 3 months was 0.7% (n = 28). Thirteen PEs (46%) occurred within 7 days of surgery. The rate of major bleeding while on prophylaxis was 0.1%. Only 5% of patients received a blood transfusion. No deaths were attributed to thromboembolic events. CONCLUSION This prospective, observational, phase IV study demonstrates that rivaroxaban appears to protect patients against symptomatic PE and is not associated with major bleeding events when used in a real-world setting as described.


title: Failure of a vaccine using immunogenic recombinant proteins rNcSAG4 and rNcGRA7 against neosporosis in mice.

text: The development of an effective vaccine against Neospora caninum infection in cattle is an important issue due to the significant economic impact of this parasitic disease worldwide. In this work, the immune response, safety and efficacy of different vaccine formulations using the N. caninum recombinant proteins rNcSAG4 (the first bradyzoite-specific protein assayed as a vaccine) and rNcGRA7 were evaluated in mouse models. The survival curves of pups from all vaccinated groups showed a slight delay in time to death compared to control groups; this difference was statistically significant for rNcSAG4+adjuvant group. Immune response of mice vaccinated with rNcSAG4 was characterized by reduced specific IgG and cytokine levels with an equilibrated IFN-gamma/IL-10 balance. Regarding mice vaccinated with rNcGRA7, a very strong humoral and cellular immune response was generated characterized by a hyper-production of IFN-gamma. This response was not accompanied by significant protection. Vaccination with a mixture of both recombinant proteins reduced infection in lung and brain during acute and chronic infection, respectively, although it was not statistically significant. In summary, no significant protection was obtained with these vaccine formulations in the present mouse models. However, the study reveals some positive results on immune response and efficacy for both recombinant proteins; these results are being discussed in order to suggest new approaches with new chronic infection mouse models and adjuvants.


title: Malignant melanotic Xp11 neoplasms exhibit a clinicopathological spectrum and gene expression profiling akin to alveolar soft part sarcoma: a proposal for reclassification.

text: The classification of the distinct group of mesenchymal neoplasms, first described as 'Xp11 translocation perivascular epithelioid cell tumor (PEComa)' and for which recently the term 'melanotic Xp11 neoplasm' or 'Xp11 neoplasm with melanocytic differentiation' has been proposed, remains challenging and controversial. We collected 27 melanotic Xp11 neoplasms, the largest series to date, for a comprehensive evaluation. Fourteen of the cases, along with 8 alveolar soft part sarcomas (ASPS), 9 conventional PEComas, and a control group of 7 normal tissues were submitted to RNA sequencing. Follow-up available in 22 patients showed 5-year overall survival (OS) and 5-year disease-free survival (DFS) of 47.6 and 35.7% respectively, which were similar to ASPS and significantly worse than conventional PEComa. Univariate analysis of location (occurring in the kidney versus not kidney), infiltrative growth pattern, nuclear pleomorphism, mitotic activity ≥2/50 HPF, necrosis, and lymphovascular invasion were found to be associated with OS and/or DFS. Multivariate analysis identified that location was the only factor found to independently correlate with DFS. More importantly, RNA sequencing-based clustering analysis segregated melanotic Xp11 neoplasm and ASPS, clearly from other tumors including conventional PEComa and Xp11 translocation renal cell carcinoma (RCC) and formed a compact cluster representative of the largely similar expression signature. In this study, we first clearly define the true biologic nature that melanotic Xp11 neoplasms are distinctive malignant mesenchymal tumors, rather than simply PEComa variants with occasionally unpredictable behavior. Meanwhile, melanotic Xp11 neoplasm and ASPS more likely represent phenotypic variants of the same entity, which is distinct from conventional PEComa and Xp11 translocation RCC. Based on these important findings, melanotic Xp11 neoplasm might be reclassified into a distinctive entity together with ASPS, independent from PEComa, in the future revisions of the current World Health Organization categories of tumors of soft tissue and bone for the improved reclassification. This article is protected by copyright. All rights reserved.


title: Exploring failure of antimicrobial prophylaxis and pre-emptive therapy for transplant recipients: a systematic review.

text: OBJECTIVES Infections remain a threat for solid organ and stem cell transplant recipients. Antimicrobial prophylaxis and pre-emptive therapy have improved survival of these patients; however, the failure rates of prophylaxis are not negligible. The aim of this systematic review is to explore the reasons behind failure of antimicrobial prophylaxis and pre-emptive therapy. SETTING This systematic review included prospective randomised controlled trials and prospective single-arm studies. PARTICIPANTS The studies included were on prophylaxis and pre-emptive therapy of opportunistic infections in transplant recipients. Studies were included from databases MEDLINE, CENTRAL and Embase published until October first 2018. PRIMARY AND SECONDARY OUTCOME MEASURES Primary outcome measures were breakthrough infections, adverse events leading to stopping of treatment, switching medication or dose reduction. Secondary outcome measures were acquired resistance to antimicrobials, antifungals or antivirals and death. RESULTS From 3317 identified records, 30 records from 24 studies with 2851 patients were included in the systematic review. Seventeen focused on prophylactic and pre-emptive treatment of cytomegalovirus and seven studies on invasive fungal infection. The main reasons for failure of prophylaxis and pre-emptive therapy were adverse events and breakthrough infections, which were described in 54% (13 studies) and 38% (9 studies) of the included studies, respectively. In 25%, six of the studies, a detailed description of patients who experienced failure of prophylaxis or pre-emptive therapy was unclear or lacking. CONCLUSIONS Our results show that although failure is reported in the studies, the level of detail prohibits a detailed analysis of failure of prophylaxis and pre-emptive therapy. Clearly reporting on patients with a negative outcome should be improved. We have provided guidance on how to detect failure early in a clinical setting in accordance to the results from this systematic review. PROSPERO REGISTRATION NUMBER CRD42017077606.


title: A randomized trial comparing vaginal and laparoscopic hysterectomy vs robot-assisted hysterectomy.

text: STUDY OBJECTIVE To investigate the hospital cost and short-term clinical outcome of traditional minimally invasive hysterectomy vs robot-assisted hysterectomy in women primarily not considered candidates for vaginal surgery. DESIGN Randomized controlled trial (Canadian Task Force classification I). SETTING University Hospital in Sweden. PATIENTS One hundred twenty-two women with uterine size ≤ 16 gestational weeks scheduled to undergo minimally invasive hysterectomy because of benign disease. INTERVENTIONS Robot-assisted hysterectomy or traditional vaginal or laparoscopic minimally invasive hysterectomy. MEASUREMENTS AND MAIN RESULTS All women underwent surgery as randomized. There were no demographic differences between the 2 groups. Vaginal hysterectomy was possible in 41% in the traditional minimally invasive group, at a mean hospital cost of $4579 compared with $7059 for traditional laparoscopic hysterectomy. This was reflected in a mean hospital cost of $993 more per robotic-assisted hysterectomy than for traditional minimally invasive hysterectomy when the robot was a preexisting investment. This hospital cost increased by $1607 when including investments and cost of maintenance. A per-protocol subanalysis comparing laparoscopy and robotics demonstrated similar hospital cost when the robot was a preexisting investment ($7059 vs $7016). Robotic-assisted hysterectomy was associated with less blood loss and fewer postoperative complications. CONCLUSION A similar hospital cost can be attained for laparoscopy and robotics when the robot is a preexisting investment. From the perspective of hospital costs, robotic-assisted hysterectomy is not advantageous for treating benign conditions when a vaginal approach is feasible in a high proportion of patients.


title: Design of Novel HIV-1/2 Fusion Inhibitors with High Therapeutic Efficacy in Rhesus Monkey Models.

text: T-20 (enfuvirtide) is the only approved viral fusion inhibitor that is used for the treatment of human immunodeficiency virus type 1 (HIV-1) infection; however, it has relatively low antiviral activity and easily induces drug resistance. We recently reported a T-20-based lipopeptide fusion inhibitor (LP-40) showing improved anti-HIV activity (X. Ding et al., J Virol 91:e00831-17, 2017, https://doi.org/10.1128/JVI.00831-17). In this study, we designed LP-50 and LP-51 by refining the structure and function of LP-40. The two new lipopeptides showed dramatically enhanced secondary structure and binding stability and were exceptionally potent inhibitors of HIV-1, HIV-2, simian immunodeficiency virus (SIV), and chimeric simian-human immunodeficiency virus (SHIV), with mean 50% inhibitory concentrations (IC50s) in the very low picomolar range. They also exhibited dramatically increased potencies in inhibiting a panel of T-20- and LP-40-resistant mutant viruses. In line with their in vitro data, LP-50 and LP-51 exhibited extremely potent and long-lasting ex vivo anti-HIV activities in rhesus monkeys: serum dilution peaks that inhibited 50% of virus infection were >15,200-fold higher than those for T-20 and LP-40. Low-dose, short-term monotherapy of LP-51 could sharply reduce viral loads to undetectable levels in acutely and chronically SHIV infected monkey models. To our knowledge, LP-50 and LP-51 are the most potent and broad HIV-1/2 and SIV fusion inhibitors, which can be developed for clinical use and can serve as tools for exploration of the mechanisms of viral entry and inhibition.IMPORTANCE T-20 remains the only membrane fusion inhibitor available for the treatment of viral infection, but its relatively low anti-HIV activity and genetic barrier for drug resistance have significantly limited its clinical application. Here we report two new lipopeptide-based fusion inhibitors (LP-50 and LP-51) showing extremely potent inhibitory activities against diverse HIV-1, HIV-2, SIV, and T-20-resistant variants. Promisingly, both inhibitors exhibited potent and long-lasting ex vivo anti-HIV activity and could efficiently suppress viral loads to undetectable levels in SHIV-infected monkey models. We believe that LP-50 and LP-51 are the most potent and broad-spectrum fusion inhibitors known to date and thus have high potential for clinical development.


title: Comparison of the performance of direct fluorescent antibody staining, a point-of-care rapid antigen test and virus isolation with that of RT-PCR for the detection of novel 2009 influenza A (H1N1) virus in respiratory specimens.

text: Although infections with the novel pandemic 2009 influenza A (H1N1) virus (A/H1N1/2009) appeared to be relatively mild during the first summer of circulation ('off season'), there has been significant morbidity and hospitalization and several fatal cases. Thus, rapid detection of A/H1N1/2009 is crucial for efficient treatment and infection control measures. In contrast to seasonal influenza, where point-of-care (POC) rapid antigen tests and direct fluorescent antibody (DFA) staining ensure rapid detection, diagnosis of A/H1N1/2009 has so far been based on RT-PCR. This study retrospectively compared the performance of the Quidel QuickVue POC test, DFA staining and virus isolation with that of RT-PCR for A/H1N1/2009 detection in 526 respiratory specimens collected during the first wave of the outbreak from May to September 2009. A/H1N1/2009 was detected in 9.1% (48/526) of samples. One hundred and thirty-seven of the A/H1N1/2009 PCR-negative samples were additionally tested using a RealAccurate Respiratory RT-PCR panel, revealing other respiratory viruses (mainly entero/rhino- and adenoviruses) in 42.3% (58/137). All methods analysed detected A/H1N1/2009 with excellent specificity but different sensitivities (POC test: 18.2%; DFA staining: 38.7%; virus isolation: 45.7%). Therefore, the POC test was not suitable for diagnosis, detecting A/H1N1/2009 only if present in high concentrations (corresponding median Ct value=19.0; range=16.5-21.4). DFA staining was also able to detect A/H1N1/2009 in specimens with a lower virus concentration (median Ct value=24.0; range=16.5-29.8). Virus isolation, which was positive after a median time of 7.5 days, was too time-consuming. In summary, DFA staining is superior to POC testing and may be appropriate for patients expected to have a rather high level of virus replication. Nevertheless, in DFA-negative specimens, A/H1N1/2009 should be excluded by RT-PCR.


title: The potential of adenoviral vaccine vectors with altered antigen presentation capabilities.

text: INTRODUCTION Despite their appeal as vaccine vectors, adenoviral vectors are yet unable to induce protective immune responses against some weakly immunogenic antigens. Additionally, the maximum doses of adenovirus-based vaccines are limited by vector-induced toxicity, causing vector elimination and diminished immune responses against the target antigen. In order to increase immune responses to the transgene, while maintaining a moderate vector dose, new technologies for improved transgene presentation have been developed for adenoviral vaccine vectors.Areas covered:This review provides an overview of different genetic-fusion adjuvant technologies that aim to improve antigen presentation in the context of adenoviral vector-based vaccines. The influence on both T cell and B cell responses are discussed, with a main focus on two technologies: MHC class II-associated invariant chain and virus-like-vaccines.Expert opinion:Different strategies have been tested to improve adenovirus-based vaccinations with varying degrees of success. The reviewed genetic adjuvants were designed to increase antigen processing and MHC presentation, or promote humoral immune responses with an improved conformational antigen display. While none of the introduced technologies is universally applicable, this review shall give an overview to identify potential improvements for future vaccination approaches.


title: De novo designed peptides for biological applications.

text: In recent years our ability to design and assemble peptide-based materials and objects de novo (i.e. from first principles) has improved considerably. This brings us to a point where the resulting assemblies are quite sophisticated and amenable to engineering in new functions. Whilst such systems could be used in a variety of ways, biological applications are of particular interest because of the demand for biocompatible, readily produced systems with potential as drug-delivery agents, components of biosensors and scaffolds for 3D cell and tissue culture. This tutorial review describes the building blocks (or tectons) that are being used in peptide assembly, highlights a range of materials and objects that have been produced, notably hydrogels and virus-like particles, and introduces a number of potential applications for the designs.


title: Effect of Roux-en-Y gastric bypass surgery on bile acid metabolism in normal and obese diabetic rats.

text: In addition to classic functions of facilitating hepatobiliary secretion and intestinal absorption of lipophilic nutrients, bile acids (BA) are also endocrine factors and regulate glucose and lipid metabolism. Recent data indicate that antiobesity bariatric procedures e.g. Roux-en-Y gastric bypass surgery (RYGB), which also remit diabetes, increase plasma BAs in humans, leading to the hypothesis that BAs may play a role in diabetes resolution following surgery. To investigate the effect of RYGB on BA physiology and its relationship with glucose homeostasis, we undertook RYGB and SHAM surgery in Zucker diabetic fatty (ZDF) and normoglycemic Sprague Dawley (SD) rats and measured plasma and fecal BA levels, as well as plasma glucose, insulin, Glucagon like peptide 1 (GLP-1) and Peptide YY (PYY), 2 days before and 3, 7, 14 and 28 days after surgery. RYGB decreased body weight and increased plasma GLP-1 in both SD and ZDF rats while decreasing plasma insulin and glucose in ZDF rats starting from the first week. Compared to SHAM groups, both SD-RYGB and ZDF-RYGB groups started to have increases in plasma total BAs in the second week, which might not contribute to early post-surgery metabolic changes. While there was no significant difference in fecal BA excretion between SD-RYGB and SD-SHAM groups, the ZDF-RYGB group had a transient 4.2-fold increase (P<0.001) in 24-hour fecal BA excretion on post-operative day 3 compared to ZDF-SHAM, which paralleled a significant increase in plasma PYY. Ratios of plasma and fecal cholic acid/chenodeoxycholic acid derived BAs were decreased in RYGB groups. In addition, tissue mRNA expression analysis suggested early intestinal BA reabsorption and potentially reduced hepatic cholic acid production in RYGB groups. In summary, we present novel data on RYGB-mediated changes in BA metabolism to further understand the role of BAs in RYGB-induced metabolic effects in humans.


title: Experience and dissection device are more relevant than patient-related factors for operation time in laparoscopic sigmoid resection-a retrospective 8-year observational study.

text: PURPOSE Surgical outcome is influenced by multiple patient-specific factors and operative expertise of the surgeon. Clinical relevance of medical technical innovations often remains unclear even though laparoscopic surgical procedures are characterized by continual advancement of various devices. Lately, in dissection and sealing technology, fast-cutting ultrasonic scissors are combined with simultaneous bipolar coagulation (bimodal dissection device (BDD)). We investigated how this new technology, operative expertise, and patient-specific factors (body mass index, age) influence operation time in laparoscopic-assisted sigmoid resection. METHODS Between 2008 and 2016, 161 laparoscopic sigmoid resections (52% conventional dissection device (CDD); 48% BDD) performed in a single center were retrospectively evaluated. Biometric patient data, complication rates, and surgery duration, reflecting the learning curve, were analyzed. Operations were performed by experienced surgeons (n = 3) and trainees (n = 4). RESULTS Minor postoperative complications (e.g., impaired wound healing, non-revisional secondary bleeding) occurred in 11 cases (6.8%). Major complications (e.g., bleeding requiring revision, anastomotic leakage) were observed in 3.7%. No heat-related coagulation damage was observed. BDD reduced operation time for both experienced (CDD 150 min, BDD 125 min; p < 0.001) and trainee surgeons (CDD 169 min, BDD 135 min; p = 0.036). Reduction of operation time (indicative of a learning curve in progress) was observed for all surgeons. The curve was steeper using BDD. CONCLUSIONS Patient-specific factors did not have a significant effect on operation time. Even taking the learning curve into account, a combination of ultrasonic dissection and simultaneous bipolar coagulation reduces operation time of laparoscopic-assisted sigmoid resection, regardless of surgeon's expertise.


title: A noninvasive neuroprosthesis augments hand grasp force in individuals with cervical spinal cord injury: the functional and therapeutic effects.

text: OBJECTIVES The primary purpose of this study was to evaluate myoelectrically controlled functional electrical stimulation (MeCFES) for enhancing the tenodesis grip in people with tetraplegia. The second aim was to estimate the potential number of candidates for the MeCFES device. The application of MeCFES provides the user with direct control of the grasp force as opposed to triggered FES systems. METHODS Screening 253 medical records of C5 to C7 spinal cord injury resulted in 27 participants who trained activities of daily living for 12 × 2 hours, using the MeCFES. Hand function was evaluated by the Action Research Arm Test (ARAT). Primary outcome was the ARAT change score with/without the device, before/after the intervention period. Secondary outcome was the number of positive or clinically relevant change scores with respect to the cohort. RESULTS The MeCFES improved hand test score in 63% of the subjects at first application. Training resulted in a significant therapeutic effect, which resulted in an overall increase of hand function in 89% of the participants and 30% experienced a clinically relevant change (6 points or more). CONCLUSIONS Clinical relevance was found both as an assistive aid and as a therapeutic tool in rehabilitation. The therapeutic effect deserves further investigation in clinical studies.