title: Patterns of recurrence after ablation of colorectal cancer liver metastases.

text: PURPOSE To determine the local recurrence rate and factors associated with recurrence after intraoperative ablation of colorectal cancer liver metastases. METHODS A retrospective analysis of a prospectively maintained database was performed for patients who underwent ablation of a hepatic colorectal cancer metastasis in the operating room from April 1996 to March 2010. Kaplan-Meier survival curves and Cox models were used to determine recurrence rates and assess significance. RESULTS Ablation was performed in 10% (n = 158 patients) of all cases during the study period. Seventy-eight percent were performed in conjunction with a liver resection. Of the 315 tumors ablated, most tumors were ≤ 1 cm in maximum diameter (53%). Radiofrequency ablation was used to treat most of the tumors (70%). Thirty-six tumors (11%) had local recurrence as part of their recurrence pattern. Disease recurred in the liver or systemically after 212 tumors (67%) were ablated. On univariate analysis, tumor size greater than 1 cm was associated with a significantly increased risk of local recurrence (hazard ratio 2.3, 95% confidence interval 1.2-4.5, P = 0.013). The 2 year ablation zone recurrence-free survival was 92% for tumors ≤ 1 cm compared to 81% for tumors >1 cm. On multivariate analysis, tumor size of >1 cm, lack of postoperative chemotherapy, and use of cryotherapy were significantly associated with a higher local recurrence rate. CONCLUSIONS Intraoperative ablation appears to be highly effective treatment for hepatic colorectal tumors ≤ 1 cm.


title: Patient-Related Factors Predicting Workspace Conditions during Laparoscopic Bariatric Surgery.

text: BACKGROUND Previous studies have focused on the role of deep neuromuscular blockade (NMB) in improving surgical conditions during laparoscopic bariatric surgery. However, a wide inter-individual variability has been noted. The aim of this study was to identify patient-related factors affecting surgeon satisfaction with the surgical space and surgery duration in laparoscopic bariatric surgery under deep NMB. METHODS One hundred eighty-five patients scheduled for laparoscopic gastric bypass were enrolled. Anesthesia was standardized. A deep NMB was maintained together with fixed patient positioning (30 reverse Trendelenburg) and constant pneumoperitoneum pressure (14 mmHg) during the whole surgical procedure. Immediately after surgery, the surgeon was invited to state his satisfaction with the surgical space through a verbal numeric scale (VNS) ranging from 0 (extremely poor) to 10 (optimal). RESULTS VNS score was negatively correlated with male gender (r = - 0.35; p = 0.0001), BMI (r = - 0.16; p = 0.03), and age (r = - 0.20; p = 0.008). Surgery duration was positively correlated with male gender (r = 0.27; p = 0.0003) and BMI (r = 0.22; p = 0.006). Multivariate linear regressions showed that lower VNS scores were predicted by male gender (p = 0.000001) and increased age (p = 0.009), and that a longer surgery duration was predicted by male gender (p = 0.0002). CONCLUSIONS Findings showed that male gender and higher patient age were independent predictors of lower surgeon satisfaction with the workspace during laparoscopic bariatric surgery. Male gender also had a significant role in predicting longer surgery duration. The role of android obesity, which is more frequently associated with male gender, in affecting surgeon-perceived workspace conditions needs further investigation.


title: Relationship Between Near-Infrared Spectroscopy-Derived Cerebral Oxygenation and Delirium in Critically Ill Patients: A Systematic Review.

text: BACKGROUND A common neurological complication of critical illness is delirium, defined as an acute change in level of consciousness, with impaired attention and disorganized thinking. Patients with delirium have increased risk of long-term cognitive dysfunction and mortality. The cause is unknown, which limits our ability to design therapeutic interventions. In patients undergoing surgery, low regional cerebral oxygenation (rSO2), as measured by near-infrared spectroscopy (NIRS), is associated with postoperative neurological dysfunction (eg delirium and long-term cognitive impairment). However, the relationship between NIRS-derived rSO2 and neurological outcomes in critically ill patients is unclear. The objective of this study was to assess the utilization of NIRS-derived rSO2 in critically ill patients outside the operating theater. We aimed to examine the relationship between rSO2 and neurological outcomes as well as to report rSO2 values in this population. METHODS The following databases were searched from inception to August 14, 2017: Ovid MedLine, Embase, Cochrane Library, and Web of Science. RESULTS Of 1410 articles identified by the search strategy, 8 were ultimately selected for final review. Most (7 of 8) were published since 2014. These studies included a total of 213 patients primarily with shock or respiratory failure. A variety of devices were used to measure rSO2, including INVOS and FORESIGHT. The duration of recording varied from 5 minutes to 72 hours. Four of the 8 studies reported on neurological outcomes. In all 4 studies, rSO2 was lower in critically ill patients who were delirious compared to controls, but this was only statistically significant in 2 of the studies. The heterogeneity in devices and duration of recording precluded meta-analysis. CONCLUSIONS There is limited literature describing rSO2 in critically ill patients outside the operating room. Although there may be a slight signal of an association between low rSO2 and delirium, more study is needed to explore this relationship.


title: Safety and feasibility of volumetric laser endomicroscopy in patients with Barrett's esophagus (with videos).

text: BACKGROUND Volumetric laser endomicroscopy (VLE) produces high-resolution, cross-sectional surface, and subsurface images for detecting neoplasia, targeting biopsies, and guiding real-time treatment. OBJECTIVE To evaluate the safety and feasibility of the Nvision VLE system. DESIGN Prospective, multicenter study. SETTING Tertiary-care medical centers. PATIENTS One hundred patients with suspected Barrett's esophagus, including 52 patients with prior endotherapy. INTERVENTIONS The first-generation Nvision VLE Imaging System, a balloon-centered, rotating optical probe provided images of the mucosa and submucosa through a 6-cm segment length and 360° scan of the distal esophagus. MAIN OUTCOME MEASUREMENTS Acquisition of a complete, 6-cm scan from the distal esophagus, demographic and procedural data, and final histologic diagnosis. RESULTS VLE imaging was successfully performed in 87 cases. After VLE imaging, biopsy specimens were obtained in 77 patients and mucosal resection was performed in 20 patients. The final pathologic diagnoses of the patients studied were adenocarcinoma (4 patients), high-grade dysplasia (10 patients), low-grade dysplasia (11 patients), indefinite (5 patients), intestinal metaplasia (29 patients), and normal squamous cells (18 patients). VLE was not completed in 13 of 100 (13%) because of optical probe and console issues. There were 2 minor adverse events (mucosal lacerations not requiring therapy). LIMITATIONS This was a feasibility study with a first-generation device. There was no direct histopathologic correlation with the VLE images or any comparative analysis with white-light endoscopy or narrow-band imaging findings. CONCLUSION VLE is a safe procedure for patients with suspected or confirmed Barrett's esophagus. Real-time VLE images enabled visualization of the mucosa and submucosa in 87% of cases. Further studies are needed to evaluate the in vivo diagnostic accuracy and clinical utility of VLE.


title: Clonality and intracellular polyploidy in virus evolution and pathogenesis.

text: In the present article we examine clonality in virus evolution. Most viruses retain an active recombination machinery as a potential means to initiate new levels of genetic exploration that go beyond those attainable solely by point mutations. However, despite abundant recombination that may be linked to molecular events essential for genome replication, herein we provide evidence that generation of recombinants with altered biological properties is not essential for the completion of the replication cycles of viruses, and that viral lineages (near-clades) can be defined. We distinguish mechanistically active but inconsequential recombination from evolutionarily relevant recombination, illustrated by episodes in the field and during experimental evolution. In the field, recombination has been at the origin of new viral pathogens, and has conferred fitness advantages to some viruses once the parental viruses have attained a sufficient degree of diversification by point mutations. In the laboratory, recombination mediated a salient genome segmentation of foot-and-mouth disease virus, an important animal pathogen whose genome in nature has always been characterized as unsegmented. We propose a model of continuous mutation and recombination, with punctuated, biologically relevant recombination events for the survival of viruses, both as disease agents and as promoters of cellular evolution. Thus, clonality is the standard evolutionary mode for viruses because recombination is largely inconsequential, since the decisive events for virus replication and survival are not dependent on the exchange of genetic material and formation of recombinant (mosaic) genomes.


title: Efficacy and safety of prophylactic use of ketamine for prevention of postanesthetic shivering: a systematic review and meta analysis.

text: BACKGROUND Postanesthetic shivering is a common complication of anesthesia, which accounts for much discomfort in postoperative patients and may increase postoperative complications in high-risk patients. Due to the lack of high-quality evidence, it is difficult to draw a conclusion about optimal anti-shivering medication. The main purpose of this meta-analysis was to analyze and evaluate the efficacy and safety of prophylactic use of ketamine for preventing postanesthetic shivering. METHODS We searched the following databases: Medline, Embase, and the Cochrane Central Register of Controlled Trails for randomized controlled trials. The primary outcome observed was the difference of the incidence rate of postanesthetic shivering between ketamine group and placebo group. The secondary outcomes were the sedation score and incidence of the side effects caused by ketamine and any other drugs utilized in the studies. RESULTS In this meta-analysis, we analyzed a total of 16 trials including 1485 patients. Ketamine reduced the incidence rate of postanesthetic shivering compared to a placebo (odds ratio [OR]: 0.13, 95% confidence interval [CI]: 0.06 to 0.26, P<0.01). Regarding side effects, there was no evident variability of the incidence of nausea and vomiting. Usage of ketamine was associated with a lower rate of hypotension and bradycardia when compared to a placebo. Hallucinations were more frequently observed in patients who received higher doses of ketamine. No significant difference was found in the incidence of postanesthetic shivering with ketamine versus other pharmacological interventions. CONCLUSIONS Ketamine can prevent postanesthetic shivering without severe side effects. However, ketamine shows no advantage over other anti-shivering drugs.


title: Parental Presence During Treatment of Ebola or Other Highly Consequential Infection.

text: This clinical report offers guidance to health care providers and hospitals on options to consider regarding parental presence at the bedside while caring for a child with suspected or proven Ebola virus disease (Ebola) or other highly consequential infection. Options are presented to help meet the needs of the patient and the family while also posing the least risk to providers and health care organizations. The optimal way to minimize risk is to limit contact between the person under investigation or treatment and family members/caregivers whenever possible while working to meet the emotional support needs of both patient and family. At times, caregiver presence may be deemed to be in the best interest of the patient, and in such situations, a strong effort should be made to limit potential risks of exposure to the caregiver, health care providers, and the community. The decision to allow parental/caregiver presence should be made in consultation with a team including an infectious diseases expert and state and/or local public health authorities and should involve consideration of many factors, depending on the stage of investigation and management, including (1) a careful history, physical examination, and investigations to elucidate the likelihood of the diagnosis of Ebola or other highly consequential infection; (2) ability of the facility to offer appropriate isolation for the person under investigation and family members and to manage Ebola; (3) ability to recognize and exclude people at increased risk of worse outcomes (eg, pregnant women); and (4) ability of parent/caregiver to follow instructions, including appropriate donning and doffing of personal protective equipment.


title: Diphtheria Outbreak in Amerindian Communities, Wonken, Venezuela, 2016-2017.

text: In February 2017, a diphtheria outbreak occurred among Amerindians of the Pemón ethnic group in Wonken, Venezuela. A field investigation revealed ≈10 cases; clinical presentation did not include cutaneous or neurologic signs or symptoms. To prevent future outbreaks in Venezuela, Amerindian communities need better access to vaccination and healthcare.


title: Microglia are required for protection against lethal coronavirus encephalitis in mice.

text: Recent findings have highlighted the role of microglia in orchestrating normal development and refining neural network connectivity in the healthy CNS. Microglia are not only vital cells in maintaining CNS homeostasis, but also respond to injury, infection, and disease by undergoing proliferation and changes in transcription and morphology. A better understanding of the specific role of microglia in responding to viral infection is complicated by the presence of nonmicroglial myeloid cells with potentially overlapping function in the healthy brain and by the rapid infiltration of hematopoietic myeloid cells into the brain in diseased states. Here, we used an inhibitor of colony-stimulating factor 1 receptor (CSF1R) that depletes microglia to examine the specific roles of microglia in response to infection with the mouse hepatitis virus (MHV), a neurotropic coronavirus. Our results show that microglia were required during the early days after infection to limit MHV replication and subsequent morbidity and lethality. Additionally, microglia depletion resulted in ineffective T cell responses. These results reveal nonredundant, critical roles for microglia in the early innate and virus-specific T cell responses and for subsequent host protection from viral encephalitis.


title: Exercise performance by hemodialysis patients: a review of the literature.

text: Hemodialysis (HD) patients exhibit poor functional capacity and reduced quality of life as a result of the complications associated with end-stage renal disease (ESRD). A review of the literature indicates that regular physical activity can reduce the complications associated with ESRD by inducing adaptations in the cardiovascular, nervous, and musculoskeletal systems. In turn, this increases functional capacity and enhances quality of life in patients on HD. Hemodialysis patients can safely participate in a variety of exercise programs with minimal adverse effects. Intradialytic exercise programs that can incorporate aerobic and resistance exercise promote exercise adherence and should be encouraged on dialysis units.


COVID-19 Impacts on Child and Youth Anxiety and Depression: Challenges and Opportunities.


title: COVID-19 pandemic and the impact on dental education: discussing current and future perspectives.

text: Due to the COVID-19 pandemic crisis, many dental schools and instructors are rethinking the way they teach and interact with students. New perspectives regarding a change in face-to-face activities, social isolation and the reformulation of clinical activities result in a transition toward e-learning and e-teaching processes. In this review, we discuss some favorable aspects and difficulties associated with virtual teaching and learning, searching for available tools and techniques as well as new perspectives.


title: α-Defensins and hsCRP levels in inflammatory response of standard and laparoendoscopic single-site cholecystectomy.

text: BACKGROUND Laparoendoscopic single-site (LESS) surgery is an evolution of laparoscopic surgery aiming at decreasing the patient's parietal trauma associated with abdominal operations. LESS has been found so far to be efficient and have the same good results as the standard four-port laparoscopic cholecystectomy. α-Defensins are antimicrobial peptides of the organism. They are the first cell components against pathogens. Cytokines are also mediators in the response to trauma. The aim of this study was to compare the inflammatory reaction in LESS and four-port laparoscopic cholecystectomy. METHODS Forty patients with noncomplicated cholelithiasis were randomly assigned into one of two groups. Group A included the patients who would undergo four-port laparoscopic cholecystectomy and group B included the patients who would undergo LESS cholecystectomy. These patients had a BMI < 30, were ASA I or II, and had no previous upper-GI surgery. Blood was taken preoperatively and 6 and 24 h postoperatively. hsCRP (with automated analyzer) and α-defensins (using ELISA) were calculated for each sample. The same postoperative protocol was followed for both groups. Mann-Whitney U test was used to analyze the results. Pain was calculated with a visual analog scale (VAS) for shoulder and abdomen at 6 and 24 h. Hospital stay, nausea, and pain medication needed was noted. RESULTS The α-defensins value was statistically significantly higher in the 24-h samples (P < 0.001) for LESS cholecystectomy. No statistically significant difference was shown for hsCRP, even though P = 0.05 for the 24-h samples with the values of LESS higher. No LESS was converted to a classical laparoscopic cholecystectomy, and none of the patients of either group needed conversion to open cholecystectomy. Pain was statistically significantly less for the LESS group at the 24-h interval (P < 0.0001). Less medication was needed for LESS patients after the 6th postoperative hour (P = 0.007). CONCLUSION Higher inflammatory reaction in LESS cholecystectomy could be the result of greater tension on the tissues. More studies are needed to conclude if this has a significant clinical expression.


title: Automated identification of abnormal respiratory ciliary motion in nasal biopsies.

text: Motile cilia lining the nasal and bronchial passages beat synchronously to clear mucus and foreign matter from the respiratory tract. This mucociliary defense mechanism is essential for pulmonary health, because respiratory ciliary motion defects, such as those in patients with primary ciliary dyskinesia (PCD) or congenital heart disease, can cause severe sinopulmonary disease necessitating organ transplant. The visual examination of nasal or bronchial biopsies is critical for the diagnosis of ciliary motion defects, but these analyses are highly subjective and error-prone. Although ciliary beat frequency can be computed, this metric cannot sensitively characterize ciliary motion defects. Furthermore, PCD can present without any ultrastructural defects, limiting the use of other detection methods, such as electron microscopy. Therefore, an unbiased, computational method for analyzing ciliary motion is clinically compelling. We present a computational pipeline using algorithms from computer vision and machine learning to decompose ciliary motion into quantitative elemental components. Using this framework, we constructed digital signatures for ciliary motion recognition and quantified specific properties of the ciliary motion that allowed high-throughput classification of ciliary motion as normal or abnormal. We achieved >90% classification accuracy in two independent data cohorts composed of patients with congenital heart disease, PCD, or heterotaxy, as well as healthy controls. Clinicians without specialized knowledge in machine learning or computer vision can operate this pipeline as a "black box" toolkit to evaluate ciliary motion.


Error in methods.


title: A new surgical technique for spontaneous esophagopleural fistula after pneumonectomy: cervical esophagogastrostomy via presternal and subcutaneous route, using a thoracic esophageal mucosal stripping.

text: We report a new surgical technique for spontaneous esophagopleural fistula after pneumonectomy. A 67-year-old man underwent right pneumonectomy for tuberculosis-destroyed lung 30 years previously and a right Eloesser window for empyema without any evidence of fistula 4 years previously. He presented to our hospital for food material spillage out of the Eloesser window when he was eating. The esophagopleural fistula was observed from the upper thoracic esophagus to the right postpneumonectomy dead space. He underwent left cervical esophagogastrostomy via a presternal subcutaneous route, using thoracic esophageal mucosal stripping. He was discharged without complications on postoperative day 12.


Type of sport activities during COVID-19 crisis among Bavarian students.


Parainfluenza virus 4 presenting with pericardial effusion in an immunocompetent child.


title: Does routine use of ultrasound result in additional thyroid procedures in patients with primary hyperparathyroidism?

text: BACKGROUND Minimally invasive parathyroidectomy for primary hyperparathyroidism depends on accurate preoperative imaging. Cervical ultrasound is commonly used to localize parathyroid adenomas, but can lead to discovery of concomitant thyroid gland pathology requiring modification of the operative approach. How the identification of incidental thyroid lesions affects patient management is unclear. STUDY DESIGN A prospective database of patients undergoing parathyroidectomy was analyzed for thyroid pathology discovered by ultrasound. Lesions were biopsied if indicated, and operative management was adjusted accordingly. Clinical data were correlated with operative decision-making. RESULTS Between July 2002 and November 2009, 310 patients with primary hyperparathyroidism underwent ultrasound. Concomitant thyroid pathology was noted in 89 (29%) patients. Thirty-seven patients (42% of pathology) underwent fine-needle aspiration of a thyroid nodule. Thirteen patients (4% of all patients) underwent a thyroid operation not related to parathyroid disease: 9 thyroid lobectomies for presumably benign nodules and 4 total thyroidectomies for malignancy. Two were for confirmed papillary thyroid cancer, and the other 2 were for an indeterminate biopsy that later proved to be papillary thyroid cancer. One lobectomy discovered microscopic papillary thyroid cancer independent of the biopsied nodule. In total, 5 (2% of all patients) malignancies were discovered. CONCLUSIONS Twenty-nine percent of patients with primary hyperparathyroidism had concomitant thyroid pathology on ultrasound. Forty-two percent of these patients underwent biopsy, and 2% had malignant pathology. Routine use of ultrasound in patients with primary hyperparathyroidism leads to discovery of unrecognized thyroid pathology and cancer.


BIOSECURITY. Flu study raises questions about U.S. ban.


Climate action and poverty alleviation must go hand-in-hand.


Update in Viral Infections 2014.


title: Development of a large-volume human-derived adipose acellular allogenic flap by perfusion decellularization.

text: In reconstructive surgery, transfer of patients' tissue (autologous flaps) is routinely used to repair large soft tissue defects caused by surgery, trauma, chronic diseases, or malformations; unfortunately, this strategy is not always possible and often creates a secondary defect in the donor site of the tissue. Tissue-engineered synthetic flaps are currently unable to repair clinically-relevant, large-volume defects; allogenic flaps from cadaveric donors could provide a ready-to-use biological alternative if treated with methods to avoid the immune-rejection of the donor's cells. Here, we describe the successful decellularization of a large (> 800 cc) human-derived adipose flap through a perfusion apparatus; we demonstrate the complete removal of the immunogenic cellular components of the flap with the retention of its structural components and vascular network. Our aim is to obtain a universally compatible, off-the-shelf acellular allogenic flap that could be recellularized with cells from recipient patients to provide a tissue-engineered allogenic/autologous alternative for reconstruction of large-volume soft-tissue defects.


2019 Subject Index.


title: An alphavirus replicon-derived candidate vaccine against Rift Valley fever virus.

text: Rift Valley fever virus (RVFV) is a mosquito-transmitted bunyavirus (genus Phlebovirus) associated with severe disease in livestock and fatal encephalitis or haemorrhagic fever in a proportion of infected humans. Although live attenuated and inactivated vaccines have been used in livestock, and on a limited scale in humans, there is a need for improved anti-RVFV vaccines. Towards this goal, Sindbis virus replicon vectors expressing the RVFV Gn and Gc glycoproteins, as well as the non-structural nsM protein, were constructed and evaluated for their ability to induce protective immune responses against RVFV. These replicon vectors were shown to produce the RVFV glycoproteins to high levels in vitro and to induce systemic anti-RVFV antibody responses in immunized mice, as determined by RVFV-specific ELISA, fluorescent antibody tests, and demonstration of a neutralizing antibody response. Replicon vaccination also provided 100% protection against lethal RVFV challenge by either the intraperitoneal or intranasal route. Furthermore, preliminary results indicate that the replicon vectors elicit RVFV-specific neutralizing antibody responses in vaccinated sheep. These results suggest that alphavirus-based replicon vectors can induce protective immunity against RVFV, and that this approach merits further investigation into its potential utility as a RVFV vaccine.


title: Differences in neutralizing antigenicity between laboratory and clinical isolates of HCoV-229E isolated in Japan in 2004-2008 depend on the S1 region sequence of the spike protein.

text: Human coronavirus (HCoV) is a causative agent of the common cold. Although HCoV is highly prevalent in the world, studies of the genomic and antigenic details of circulating HCoV strains have been limited. In this study, we compared four Japanese isolates with the standard HCoV-229E strain obtained from ATCC (ATCC-VR740) by focusing on the spike (S) protein, a major determinant of neutralizing antigen and pathogenicity. The isolates were found to have nucleotide deletions and a number of sequence differences in the S1 region of the S protein. We compared two of the Japanese isolates with the ATCC-VR740 strain by using virus-neutralizing assays consisting of infectious HCoV-229E particles and vesicular stomatitis virus (VSV)-pseudotyped virus carrying the HCoV-229E S protein. The two clinical isolates (Sendai-H/1121/04 and Niigata/01/08) did not react with antiserum to the ATCC-VR740 strain via the neutralizing test. We then constructed a pseudotype VSV-harboured chimeric S protein with the ATCC S1 and Sendai S2 regions or that with Sendai S1 and ATCC S2 regions and compared them by a neutralization test. The results revealed that the difference in the neutralizing antigenicity depends on the S1 region. This different antigenic phenotype was also confirmed by a neutralizing test with clinically isolated human sera. These results suggest that the HCoV-229E viruses prevalent in Japan are quite different from the laboratory strain ATCC-VR740 in terms of the S sequence and neutralization antigenicity, which is attributed to the difference in the S1 region.


title: Current status and evolution of robotic-assisted thoracic surgery in Germany-results from a nationwide survey.

text: Background Robot-assisted surgery has made a significant entry into surgical practice within Germany, including thoracic surgery. As no published data exists regarding robotic-assisted thoracic surgery (RATS), we conducted a survey to investigate its current status. Methods We performed a nationwide survey of all centers active in RATS, using a standardized questionnaire. The annual number of operations, mean duration of surgery, docking time, length of hospital stay(s), conversions, chest tube duration, the RATS program start date, robot system used, operating room capacity, and staplers and instruments used were recorded. Results Of the 22 centers contacted, 14 responded. In total, 786 RATS interventions were recorded. Most were anatomical lung resections, comprising 372 (bi-) lobectomies and 80 segmentectomies. During the study period, eight bronchoplastic procedures were performed robotically. There were 93 wedge lung resections, 148 thymectomies, 26 sympathectomies, and 59 other RATS procedures, and a single-center series of around 1,000 RATS thymectomies (excluded from statistical analysis). The average incision-suture time of the RATS lobectomy was 245 (range, 80-419) minutes, average residence time seven days. The conversion rate was 6.7% across all interventions, with significant inter-intervention differences. All surveyed centers plan to further expand RATS, with OR capacity being a frequent impediment. Five RATS interventions were performed in Germany in 2013, versus 320 in 2018. Conclusions Overall, RATS is becoming more established in everyday clinical practice in Germany. The number of operations, active centers, and trained RATS surgeons has increased steadily since 2013. A German-speaking operation course for entry into RATS already exists. Even extended resections can be carried out safely, and RATS has become standard procedure in some centers.


title: The required sample size in vaccination-challenge experiments with infectious bronchitis virus, a meta-analysis.

text: For statistical, animal welfare and financial reasons the choice of the number of chickens per group in experiments is important. This estimation, together with the number of tracheal organ cultures (TOCs) that need to be examined from each chicken in order to assess protection, should be based on the difference in level of protection that one would like to be able to detect (effect size), the expected variability of the results between and within the chickens, the desired confidence level and the power of the study. To obtain data that would facilitate this estimation, a meta-analysis was performed on the data from 18 infectious bronchitis virus (IBV) vaccination-challenge experiments performed at the Dutch Animal Health Service Deventer, the Netherlands (GD) in order to determine and quantify the source of variation in the mean level of protection of different groups. For the calculations, 137 groups of chickens were subdivided into 10 clusters based on age (young or adult), vaccination (none, homologous or heterologous), challenge (IBV or mock infected) and location of vaccination (isolator at GD or in the field). The results were used to estimate the required number of chickens per group for the different clusters using 2, 5 or 10 TOCs per chicken to be able to detect effect sizes of 6.25%, 12.5%, 25% and 50% between groups of chickens with 95% confidence (P<0.05) and 80% power. The number of chickens that was required for the mentioned effect sizes varied greatly from 2 to 650. This meta-analysis provided data that allow research workers to estimate the number of chickens that should be included in each group in order to obtain reliable results based on particular combinations of infectious bronchitis vaccination and challenge strains as defined by the presented clusters.


Preparing for a Surge of Coronavirus Cases.


title: [The keypoints in treatment of the critical novel coronavirus pneumonia patient].

text: The novel coronavirus pneumonia (new coronavirus pneumonia) (NCP) has been prevalent in Wuhan and spread rapidly to all of our country. Some cases can develop into ARDS, or even death. We will share the treatment experience of severe NCP with the first-line treatment experience. The best respiratory support mode should be selected, but the timing of intubation and protection during intubation are two difficulties; patients with high level peep and poor effect in prone position can be given ECMO support. For NCP patients with mechanical ventilation, reasonable sedation and analgesia strategies should be formulated; delirium should not be ignored. In addition, there is up regulation of inflammatory factors in patients with severe NCP, but the effect of renal replacement therapy needs to be further confirmed by clinical research.


title: Pediatric invasive disease due to Haemophilus influenzae serogroup A in Riyadh, Saudi Arabia: case series.

text: UNLABELLED We describe the first two cases of invasive disease caused by Haemophilus influenzae serotype A in Saudi Arabia. This is the first known reported invasive Haemophilus influenzae serotype A from Saudi Arabia. CASE PRESENTATION A ten-month-old and three-month-old male not known to have any past history of any medical illness and who had received H. influenzae type b (Hib) vaccine presented to our hospital mainly with fever of few days' duration. A provisional diagnosis of meningitis with sepsis was made and laboratory tests were requested. The chest radiograph was normal. The laboratory results revealed leukocytosis, but leukopenia was noticed in the younger infant. Blood culture and cerebrospinal fluid specimens yielded a pure culture of Haemophilus influenzae and serotyping showed the isolates to be serogroup A. Both patients were started on vancomycin and third-generation cephalosporin. On receiving the blood culture result, vancomycin was stopped. Fever subsided after 48 hours, while in the second case, it continued for 12 days from the admission date. The repeat blood cultures were negative. Antibiotic therapy was given for 10 days for the first case with an unremarkable hospital course, while the second case was complicated by seizure and received a longer duration of antibiotics. Both infants were discharged home in good condition. CONCLUSIONS Invasive non-typeable H. influenzae strains are emerging and there is a need for surveillance of this disease. This has implications in future vaccine development.


title: NICTABA and UDA, two GlcNAc-binding lectins with unique antiviral activity profiles.

text: OBJECTIVES This study aimed to assess the antiviral properties of a unique lectin (NICTABA) produced by the tobacco plant, Nicotiana tabacum. METHODS Cellular assays were used to investigate the antiviral activity of NICTABA and Urtica dioica agglutinin (UDA). Surface plasmon resonance (SPR) studies were performed to study the sugar specificity and the interactions of both lectins with the envelope glycoproteins of HIV-1. RESULTS The N-acetyl-d-glucosamine (GlcNAc)-binding lectins exhibited broad-spectrum activity against several families of enveloped viruses including influenza A/B, Dengue virus type 2, herpes simplex virus types 1 and 2 and HIV-1/2. The IC50 of NICTABA for various HIV-1 strains, clinical isolates and HIV-2 assessed in PBMCs ranged from 5 to 30 nM. Furthermore, NICTABA inhibited syncytium formation between persistently HIV-1-infected T cells and uninfected CD4+ T lymphocytes and prevented DC-SIGN-mediated HIV-1 transmission to CD4+ target T lymphocytes. However, unlike many other antiviral carbohydrate-binding agents (CBAs) described so far, NICTABA did not block HIV-1 capture to DC-SIGN+ cells and it did not interfere with the binding of the human monoclonal antibody 2G12 to gp120. SPR studies with HIV-1 envelope glycoproteins showed that the affinity of NICTABA for gp120 and gp41 was in the low nanomolar range. The specific binding of NICTABA to gp120 could be prevented in the presence of a GlcNAc trimer, but not in the presence of mannose trimers. NICTABA displayed no antiviral activity against non-enveloped viruses. CONCLUSIONS Since CBAs possess a high genetic barrier for the development of viral resistance and NICTABA shows a broad antiviral activity profile, this CBA may qualify as a potential antiviral candidate with a pleiotropic mode of action aimed at targeting the entry of enveloped viruses.


title: Urgent need for individual mobile phone and institutional reporting of at home, hospitalized, and intensive care unit cases of SARS-CoV-2 (COVID-19) infection.

text: Approximately 90 days of the SARS-CoV-2 (COVID-19) spreading originally from Wuhan, China, and across the globe has led to a widespread chain of events with imminent threats to the fragile relationship between community health and economic health. Despite near hourly reporting on this crisis, there has been no regular, updated, or accurate reporting of hospitalizations for COVID-19. It is known that many test-positive individuals may not develop symptoms or have a mild self-limited viral syndrome consisting of fever, malaise, dry cough, and constitutional symptoms. However some individuals develop a more fulminant syndrome including viral pneumonia, respiratory failure requiring oxygen, acute respiratory distress syndrome requiring mechanical ventilation, and in substantial fractions leading to death attributable to COVID-19. The pandemic is evolving in a clustered, non-inform fashion resulting in many hospitals with preparedness but few or no cases, and others that are completely overwhelmed. Thus, a considerable risk of spread when personal protection equipment becomes exhausted and a large fraction of mortality in those not offered mechanical ventilation are both attributable to a crisis due to maldistribution of resources. The pandemic is amenable to self-reporting through a mobile phone application that could obtain critical information on suspected cases and report on the results of self testing and actions taken. The only method to understand the clustering and the immediate hospital resource needs is mandatory, uniform, daily reporting of hospital censuses of COVID-19 cases admitted to hospital wards and intensive care units. Current reports of hospitalizations are delayed, uncertain, and wholly inadequate. This paper urges all the relevant stakeholders to take up self-reporting and reporting of hospitalizations of COVID-19 as an urgent task in combating this devastating pandemic.


Microwave ablation with percutaneous approach for the treatment of pancreatic adenocarcinoma.


title: Minimally invasive versus open pancreatoduodenectomy (LEOPARD-2): study protocol for a randomized controlled trial.

text: BACKGROUND Data from observational studies suggest that minimally invasive pancreatoduodenectomy (MIPD) is superior to open pancreatoduodenectomy regarding intraoperative blood loss, postoperative morbidity, and length of hospital stay, without increasing total costs. However, several case-matched studies failed to demonstrate superiority of MIPD, and large registry studies from the USA even suggested increased mortality for MIPDs performed in low-volume (<10 MIPDs annually) centers. Randomized controlled multicenter trials are lacking but clearly required. We hypothesize that time to functional recovery is shorter after MIPD compared with open pancreatoduodenectomy, even in an enhanced recovery setting. METHODS/DESIGN LEOPARD-2 is a randomized controlled, parallel-group, patient-blinded, multicenter, phase 2/3, superiority trial in centers that completed the Dutch Pancreatic Cancer Group LAELAPS-2 training program for laparoscopic pancreatoduodenectomy or LAELAPS-3 training program for robot-assisted pancreatoduodenectomy and have performed ≥ 20 MIPDs. A total of 136 patients with symptomatic benign, premalignant, or malignant disease will be randomly assigned to undergo minimally invasive or open pancreatoduodenectomy in an enhanced recovery setting. After the first 40 patients (phase 2), the data safety monitoring board will assess safety outcomes (not blinded for treatment allocation) and decide on continuation to phase 3. Patients from phase 2 will then be included in phase 3. The primary outcome measure is time (days) to functional recovery. All patients will be blinded for the surgical approach, at least until postoperative day 5, but preferably until functional recovery has been attained. Secondary outcome measures are operative and postoperative outcomes, including clinically relevant complications, mortality, quality of life, and costs. DISCUSSION The LEOPARD-2 trial is designed to assess whether MIPD reduces time to functional recovery, as compared with open pancreatoduodenectomy in an enhanced recovery setting. TRIAL REGISTRATION Netherlands Trial Register, NTR5689 . Registered on 2 March 2016.


title: Association of Public Health Interventions With the Epidemiology of the COVID-19 Outbreak in Wuhan, China.

text: Importance Coronavirus disease 2019 (COVID-19) has become a pandemic, and it is unknown whether a combination of public health interventions can improve control of the outbreak. Objective To evaluate the association of public health interventions with the epidemiological features of the COVID-19 outbreak in Wuhan by 5 periods according to key events and interventions. Design, Setting, and Participants In this cohort study, individual-level data on 32 583 laboratory-confirmed COVID-19 cases reported between December 8, 2019, and March 8, 2020, were extracted from the municipal Notifiable Disease Report System, including patients' age, sex, residential location, occupation, and severity classification. Exposures Nonpharmaceutical public health interventions including cordons sanitaire, traffic restriction, social distancing, home confinement, centralized quarantine, and universal symptom survey. Main Outcomes and Measures Rates of laboratory-confirmed COVID-19 infections (defined as the number of cases per day per million people), across age, sex, and geographic locations were calculated across 5 periods: December 8 to January 9 (no intervention), January 10 to 22 (massive human movement due to the Chinese New Year holiday), January 23 to February 1 (cordons sanitaire, traffic restriction and home quarantine), February 2 to 16 (centralized quarantine and treatment), and February 17 to March 8 (universal symptom survey). The effective reproduction number of SARS-CoV-2 (an indicator of secondary transmission) was also calculated over the periods. Results Among 32 583 laboratory-confirmed COVID-19 cases, the median patient age was 56.7 years (range, 0-103; interquartile range, 43.4-66.8) and 16 817 (51.6%) were women. The daily confirmed case rate peaked in the third period and declined afterward across geographic regions and sex and age groups, except for children and adolescents, whose rate of confirmed cases continued to increase. The daily confirmed case rate over the whole period in local health care workers (130.5 per million people [95% CI, 123.9-137.2]) was higher than that in the general population (41.5 per million people [95% CI, 41.0-41.9]). The proportion of severe and critical cases decreased from 53.1% to 10.3% over the 5 periods. The severity risk increased with age: compared with those aged 20 to 39 years (proportion of severe and critical cases, 12.1%), elderly people (≥80 years) had a higher risk of having severe or critical disease (proportion, 41.3%; risk ratio, 3.61 [95% CI, 3.31-3.95]) while younger people (<20 years) had a lower risk (proportion, 4.1%; risk ratio, 0.47 [95% CI, 0.31-0.70]). The effective reproduction number fluctuated above 3.0 before January 26, decreased to below 1.0 after February 6, and decreased further to less than 0.3 after March 1. Conclusions and Relevance A series of multifaceted public health interventions was temporally associated with improved control of the COVID-19 outbreak in Wuhan, China. These findings may inform public health policy in other countries and regions.


title: Ligation of the rectum with an extracorporeal sliding knot facilitating laparoscopic cross-stapling: a procedure revisited.

text: BACKGROUND Multiple stapler firings during distal rectal division were associated with unduly long stapler line and anastomotic leakage after laparoscopic rectal resection. A simple and relatively easy technique to perform a safe transection of rectum is presented. MATERIALS AND METHODS The extracorporeal ligation of the rectum just proximal to the cut end of the rectum before applying the linear stapling stapler facilitates the procedure and requires only a few firings of the stapler during the laparoscopic rectal resections. RESULTS Ten patients with a median age of 72 years underwent rectal transection with this technique. The procedure was performed with a single 60-mm cartridge in 3 patients, and two firings of the Endo GIA™ (Covidien LLC, Mansfield, MA) with a 45-mm cartridge were necessary for cross-stapling at the level of the pelvic floor in the remaining patients. There were no intraoperative complications. Postoperative complications were seen in 2 patients. CONCLUSIONS This simple technique theoretically seems safer than the conventional approach and should be considered as an additional option for rectal transection.


title: Effect of delay in diagnosis on transmission of COVID-19.

text: The outbreak of COVID-19 caused by SARS-CoV-2 in Wuhan and other cities of China is a growing global concern. Delay in diagnosis and limited hospital resources lead to a rapid spread of COVID-19. In this study, we investigate the effect of delay in diagnosis on the disease transmission with a new formulated dynamic model. Sensitivity analyses and numerical simulations reveal that, improving the proportion of timely diagnosis and shortening the waiting time for diagnosis can not eliminate COVID-19 but can effectively decrease the basic reproduction number, significantly reduce the transmission risk, and effectively prevent the endemic of COVID-19, e.g., shorten the peak time and reduce the peak value of new confirmed cases and new infection, decrease the cumulative number of confirmed cases and total infection. More rigorous prevention measures and better treatment of patients are needed to control its further spread, e.g., increasing available hospital beds, shortening the period from symptom onset to isolation of patients, quarantining and isolating the suspected cases as well as all confirmed patients.


title: Accumulation of autophagosomes in Semliki Forest virus-infected cells is dependent on expression of the viral glycoproteins.

text: Autophagy is a cellular process that sequesters cargo in double-membraned vesicles termed autophagosomes and delivers this cargo to lysosomes to be degraded. It is enhanced during nutrient starvation to increase the rate of amino acid turnover. Diverse roles for autophagy have been reported for viral infections, including the assembly of viral replication complexes on autophagic membranes and protection of host cells from cell death. Here, we show that autophagosomes accumulate in Semliki Forest virus (SFV)-infected cells. Despite this, disruption of autophagy had no effect on the viral replication rate or formation of viral replication complexes. Also, viral proteins rarely colocalized with autophagosome markers, suggesting that SFV did not utilize autophagic membranes for its replication. Further, we found that SFV infection, unlike nutrient starvation, did not inactivate the constitutive negative regulator of autophagosome formation, mammalian target of rapamycin, suggesting that SFV-dependent accumulation of autophagosomes was not a result of enhanced autophagosome formation. In starved cells, addition of NH(4)Cl, an inhibitor of lysosomal acidification, caused a dramatic accumulation of starvation-induced autophagosomes, while in SFV-infected cells, NH(4)Cl did not further increase levels of autophagosomes. These results suggest that accumulation of autophagosomes in SFV-infected cells is due to an inhibition of autophagosome degradation rather than enhanced rates of autophagosome formation. Finally, we show that the accumulation of autophagosomes in SFV-infected cells is dependent on the expression of the viral glycoprotein spike complex.


title: Complications of lower urinary tract surgery in small animals.

text: Surgical procedures of the lower urinary tract are commonly performed in small animal practice. Cystotomy for removal of uroliths and urethrostomy diverting urine outflow due to urethral obstruction are the most commonly performed surgical procedures of the bladder and urethra respectively. Surgical procedures of the lower urinary tract are typically associated with few complications, including leakage of urine, loss of luminal diameter (stricture or stenosis), urine outflow obstruction, tissue devitalization, denervation, urinary incontinence, urinary tract infection, and death. Complications can result from inappropriate or inadequate diagnosis, localization, and surgical planning; failure to respect regional anatomy, and other causes.


title: Does the learning curve during laparoscopic colectomy adversely affect costs?

text: BACKGROUND This study aimed to investigate whether the learning curve during laparoscopic colectomy is associated with increased costs compared with the procedure after the learning curve has been achieved. METHODS The direct costs for patients undergoing laparoscopic colectomy during the learning curve (group A) and after the attainment of proficiency by two colorectal surgeons performing the procedure (group B) between 2001 and 2007 were compared. The learning curve was defined as the first 40 laparoscopic colectomy cases for each surgeon. The distribution of cases for the surgeons ensured that cost-related differences were not influenced by lead time bias of cases performed during the learning curve. RESULTS The study involved 80 group A and 74 group B patients. Groups A and B were similar in terms of age (P = 0.7), gender (P = 0.5), American Society of Anesthesiologists (ASA) score (P = 0.5), body mass index (P = 0.3), diagnosis (P = 0.8), previous abdominal surgery (P = 0.07), and comorbidity (P = 0.4). The two groups also were similar with regard to performance of anastomosis (P = 0.2) or resection (P = 0.6), conversion to open surgery (P = 0.7), postoperative morbidity (P = 0.6), readmission (P = 0.1), reoperation rate (P = 0.6), and hospital length of stay (P = 0.6). The operation time was significantly longer for group A (P = 0.01). The total direct costs (P = 0.7) and the operating room (P = 0.6), nursing (P = 0.7), pharmacy (P = 0.9), radiology (P = 1), and professional (P = 0.051) costs were however similar between the two groups. CONCLUSIONS As expected, laparoscopic colectomy during the learning curve period is associated with prolonged operating time. Concerns pertaining to increased conversions, complications, and direct costs during this period were not substantiated in this study.


title: [Initial experience of a program of clipping the sympathetic nervous system for the treatment of hyperhidrosis and facial flush].

text: INTRODUCTION AND OBJECTIVE To evaluate the results of our program of clipping the thoracic sympathetic nervous system (TSNS) for the treatment of facial flush and/or hyperhidrosis (HH), and to compare the methodology-results of the program development phase (A: January 2007-April 2009) and its consolidation phase (B: May 2009-March 2010). MATERIAL AND METHODS The program included a total of 44 patients (88 procedures) subjected to videothoracoscopy and clipping of the TSNS in a one day surgery unit. Data were collected and analysed retrospectively, and a descriptive and comparative statistical analysis was performed between the two periods (A and B). RESULTS The overall morbidity was 5 cases (11.3%). The post-surgical occurrence rate of HH was 4.54% (2 cases), and the incidence of compensatory sweating was 65.9% (minimal in 26 of the 29 cases). On comparing period B with period A, there was a significant decrease in surgical time, disappearance of recurrence of HH, a decrease of 30% in morbidity, reduction by half in the incidence of moderate to severe compensatory sweating, and an increase in the level of satisfaction. The clamps were removed in one of the poorly tolerated compensatory sweating cases, resulting in its disappearance. CONCLUSIONS Clipping the TSNS is a safe technique in the one day surgery unit, with a short learning curve (20 cases) after which comparable, or even better, results are obtained than those of sympatholysis. These results, together with their potential reversibility, makes it, in our opinion, the technique of choice in the surgery of the TSNS.


Highlight - viruses and signaling.


Ventilation and airway management during Cardiopulmonary Resuscitation in COVID-19 era.


title: Choice of fluid in acute illness: what should be given? An international consensus.

text: Fluid management during critical illness is a dynamic process that may be conceptualized as occurring in four phases: rescue, optimization, stabilization, and de-escalation (mobilization). The selection and administration of resuscitation fluids is one component of this complex physiological sequence directed at restoring depleted intravascular volume. Presently, the selection of i.v. fluid is usually dictated more by local practice patterns than by evidence. The debate on fluid choice has primarily focused on evaluating outcome differences between 'crystalloids vs colloids'. More recently, however, there is interest in examining outcome differences based on the chloride content of crystalloid solutions. New insights into the conventional Starling model of microvascular fluid exchange may explain that the efficacy of colloids in restoring and maintaining depleted intravascular volume is only moderately better than crystalloids. A number of investigator-initiated, high-quality, randomized controlled trials have demonstrated that modest improvements in short-term physiological endpoints with colloids have not translated into better patient-centred outcomes. In addition, there is substantial evidence that certain types of fluids may independently worsen patient-centred outcomes. These include hydroxyethyl starch and albumin solutions in selected patient populations. There is no evidence to support the use of other colloids. The use of balanced salt solutions in preference to 0.9% saline is supported by the absence of harm in large observational studies. However, there is no compelling randomized trial-based evidence demonstrating improved clinical outcomes with the use of balanced salt solutions compared with 0.9% saline at this time.


title: Genomic Analysis of Early SARS-CoV-2 Variants Introduced in Mexico.

text: The COVID-19 pandemic has affected most countries in the world. Studying the evolution and transmission patterns in different countries is crucial to implement effective strategies for disease control and prevention. In this work, we present the full genome sequence for 17 SARS-CoV-2 isolates corresponding to the earliest sampled cases in Mexico. Global and local phylogenomics, coupled with mutational analysis, consistently revealed that these viral sequences are distributed within 2 known lineages, the SARS-CoV-2 lineage A/G, containing mostly sequences from North America, and the lineage B/S containing mainly sequences from Europe. Based on the exposure history of the cases and on the phylogenomic analysis, we characterized fourteen independent introduction events. Additionally, three cases with no travel history were identified. We found evidence that two of these cases represent local transmission cases occurring in Mexico during mid-March 2020, denoting the earliest events described for the country. Within this local transmission cluster, we also identified the H49Y amino acid change in the Spike protein. This mutation is a homoplasy occurring independently through time and space, and may function as a molecular marker to follow on any further spread of these viral variants throughout the country. Our results depict the general picture of the SARS-CoV-2 variants introduced at the beginning of the outbreak in Mexico, setting the foundation for future surveillance efforts.IMPORTANCE Understanding the introduction, spread and establishment of SARS-CoV-2 within distinct human populations is crucial to implement effective control strategies as well as the evolution of the pandemics. In this work, we describe that the initial virus strains introduced in Mexico came from Europe and the United States and the virus was circulating locally in the country as early as mid-March. We also found evidence for early local transmission of strains having the mutation H49Y in the Spike protein, that could be further used as a molecular marker to follow viral spread within the country and the region.


Ethical decision making in a pandemic: where are the voices of vulnerable people?


title: Axis-specific analysis and predictors of endocrine recovery and deficits for non-functioning pituitary adenomas undergoing endoscopic transsphenoidal surgery.

text: PURPOSE Endoscopic transsphenoidal surgery (ETSS) is a well-established treatment for patients with nonfunctioning pituitary adenomas (NFPAs). Data on the rates of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS and the predictors of endocrine function before and after ETSS are scarce. This study is purposed to analyze the comprehensive changes in hormonal function and identify factors that predict recovery or worsening of hormonal axes following ETSS for NFPA. METHODS A retrospective review of 601 consecutive patients who underwent ETSS between 2010 and 2018 at one institution was performed. Recovery or development of new hypopituitarism was analyzed in 209 NFPA patients who underwent ETSS. RESULTS Patients with preoperative endocrine deficits (59.8%) in one or more pituitary axes had larger tumor volumes (P = 0.001) than those without preoperative deficits. Recovery of preoperative pituitary deficit occurred in all four axes, with overall mean recovery of 29.7%. The cortisol axis showed the highest recovery whereas the thyroid axis showed the lowest, with 1-year cumulative recovery rates of 44.3% and 6.1%, respectively. Postoperative hypopituitarism occurred overall in 17.2%, most frequently in the thyroid axis (24.3%, 27/111) and least frequently in the cortisol axis (9.7%, 16/165). Axis-specific predictors of post-operative recovery and deficiency were identified. CONCLUSIONS Dynamic alterations in pituitary hormones were observed in a proportion of patients following ETSS in NFPA patients. Postoperative endocrine vulnerability, recovery, and factors that predicted recovery or loss of endocrine function depended on the hormonal system, necessitating an axis-specific surveillance strategy postoperatively.


title: Preferential cytolysis of peripheral memory CD4+ T cells by in vitro X4-tropic human immunodeficiency virus type 1 infection before the completion of reverse transcription.

text: CD4+ T-cell depletion is the hallmark of AIDS pathogenesis. Multiple mechanisms may contribute to the death of productively infected CD4+ T cells and innocent-bystander cells. In this study, we characterize a novel mechanism in which human immunodeficiency virus type 1 (HIV-1) infection preferentially depletes peripheral memory CD4+ T cells before the completion of reverse transcription. Using a recombinant HIV-1 carrying the green fluorescent protein reporter gene, we demonstrate that memory CD4+ T cells were susceptible to infection-induced cell death at a low multiplicity of infection. Infected memory CD4+ T cells underwent rapid necrotic cell death. Killing of host cells was dependent on X4 envelope-mediated viral fusion, but not on virion-associated Vpr or Nef. In contrast to peripheral resting CD4+ T cells, CD4+ T cells stimulated by mitogen or certain cytokines were resistant to HIV-1-induced early cell death. These results demonstrate that early steps in HIV-1 infection have a detrimental effect on certain subsets of CD4+ T cells. The early cell death may serve as a selective disadvantage for X4-tropic HIV-1 in acute infection but may play a role in accelerated disease progression, which is associated with the emergence of X4-tropic HIV-1 in the late stage of AIDS.


Covid-19: Easing lockdown could risk second spike, say public health doctors.


title: Building multidevice pipeline constructs of favorable metal coverage: a practical guide.

text: BACKGROUND AND PURPOSE The advent of low-porosity endoluminal devices, also known as flow diverters, exemplified by the Pipeline in the United States, produced the greatest paradigm shift in cerebral aneurysm treatment since the introduction of detachable coils. Despite robust evidence of efficacy and safety, key questions regarding the manner of their use remain unanswered. Recent studies demonstrated that the Pipeline device geometry can dramatically affect its metal coverage, emphasizing the negative effects of oversizing the device relative to its target vessels. This follow-up investigation focuses on the geometry and coverage of multidevice constructs. MATERIALS AND METHODS A number of Pipeline devices were deployed in tubes of known diameters and photographed, and the resultant coverage was determined by image segmentation. Multidevice segmentation images were created to study the effects of telescoped devices and provide an estimate of coverages resulting from device overlap. RESULTS Double overlap yields a range of metal coverage, rather than a single value, determined by the diameters of both devices, the size of the recipient artery, and the degree to which strands of the overlapped devices are coregistered with each other. The potential variation in coverage is greatest during overlap of identical-diameter devices, for example, ranging from 24% to 41% for two 3.75-mm devices deployed in a 3.5-mm vessel. Overlapping devices of progressively different diameters produce correspondingly more uniform ranges of coverage, though reducing the maximum achievable value, for example, yielding a 33%-34% range for 3.75- and 4.75-mm devices deployed in the same 3.5-mm vessel. CONCLUSIONS Rational strategies for building multidevice constructs can achieve favorable geometric outcomes.


title: Pre-Procedural Surveillance Testing for SARS-CoV-2 in an Asymptomatic Population in the Seattle Region Shows Low Rates of Positivity.

text: Seattle region hospitals have been impacted for several months by community spread of the coronavirus disease of 2019 (COVID-19).….


title: Coagulopathy in COVID-19.

text: COVID-19-associated coagulopathy is common in patients with COVID-19, causing high rates of thrombotic complications that increase the morbidity and mortality. Markedly elevated levels of D-dimer with normal fibrinogen levels are the hallmark laboratory findings and correlate with severity of illness and risk of thrombosis. Aggressive VTE prophylaxis is paramount for all patients with COVID-19. Patients with very high D-dimer levels (6 times the upper limit of normal, greater than 3,000 ng/mL) have the greatest risk of thrombosis and may benefit from active screening and more intensive VTE prophylaxis.


When can professional sport recommence safely during the COVID-19 pandemic? Risk assessment and factors to consider.


title: Closed-loop control of mechanical ventilation: description and classification of targeting schemes.

text: There has been a dramatic increase in the number and complexity of new ventilation modes over the last 30 years. The impetus for this has been the desire to improve the safety, efficiency, and synchrony of ventilator-patient interaction. Unfortunately, the proliferation of names for ventilation modes has made understanding mode capabilities problematic. New modes are generally based on increasingly sophisticated closed-loop control systems or targeting schemes. We describe the 6 basic targeting schemes used in commercially available ventilators today: set-point, dual, servo, adaptive, optimal, and intelligent. These control systems are designed to serve the 3 primary goals of mechanical ventilation: safety, comfort, and liberation. The basic operations of these schemes may be understood by clinicians without any engineering background, and they provide the basis for understanding the wide variety of ventilation modes and their relative advantages for improving patient-ventilator synchrony. Conversely, their descriptions may provide engineers with a means to better communicate to end users.


title: Reduction en masse can be treated using pure laparoscopic transabdominal preperitoneal hernioplasty following early CT diagnosis: report of a case.

text: Reduction en masse refers to the rare occurrence of an incarcerated inguinal hernia arising from the manual reduction of a hernia. Such a condition constitutes a medical emergency because the hernia contents, such as the small bowel, remain strangulated in the preperitoneal space. Therefore, an early and accurate diagnosis, with early treatment, is important. A 61-year-old Japanese man presented with an irreducible lump over his left groin, leading to the reduction of an incarcerated inguinal hernia by a doctor at another hospital. Later, he was admitted to our hospital with vomiting and abdominal pain. Computed tomography showed a ball-like lesion containing an incarcerated bowel loop over his left pelvis. The patient was diagnosed with an incarcerated small bowel obstruction due to a reduction en masse; a laparoscopic transabdominal preperitoneal (TAPP) hernioplasty was performed. TAPP hernioplasty is a safe method for treating reductions en masse that allows confirmation of bowel viability.


title: An alternate pathophysiologic paradigm of sepsis and septic shock: implications for optimizing antimicrobial therapy.

text: The advent of modern antimicrobial therapy following the discovery of penicillin during the 1940s yielded remarkable improvements in case fatality rate of serious infections including septic shock. Since then, pathogens have continuously evolved under selective antimicrobial pressure resulting in a lack of significant improvement in clinical effectiveness in the antimicrobial therapy of septic shock despite ever more broad-spectrum and potent drugs. In addition, although substantial effort and money has been expended on the development novel non-antimicrobial therapies of sepsis in the past 30 years, clinical progress in this regard has been limited. This review explores the possibility that the current pathophysiologic paradigm of septic shock fails to appropriately consider the primacy of the microbial burden of infection as the primary driver of septic organ dysfunction. An alternate paradigm is offered that suggests that has substantial implications for optimizing antimicrobial therapy in septic shock. This model of disease progression suggests the key to significant improvement in the outcome of septic shock may lie, in great part, with improvements in delivery of existing antimicrobials and other anti-infectious strategies. Recognition of the role of delays in administration of antimicrobial therapy in the poor outcomes of septic shock is central to this effort. However, therapeutic strategies that improve the degree of antimicrobial cidality likely also have a crucial role.


COVID-19 Infection: Early Lessons.


title: Inflamed symptomatic sellar arachnoid cyst: case report.

text: Sellar arachnoid cysts are rare; an infected arachnoid cyst is extremely rare as only one case has been reported to date in the literature. Here, we report a patient with an infected or inflamed sellar arachnoid cyst that was successfully treated with transsphenoidal surgery (TSA). A 53-year-old female with a history of chronic sinusitis developed a headache 5 months ago, and one month before admission polyuria, polydipsia, and abnormal vaginal bleeding occurred. The magnetic resonance imaging (MRI) showed a sellar cystic mass with a thickened pituitary stalk. Preoperative hormonal study revealed normal pituitary hormone levels except for a moderate elevation of prolactin. She was diagnosed with diabetes insipidus of the central nervous system origin based on a water-deprivation test. TSA was performed under an impression of symptomatic Rathke's cleft cyst according to the MRI findings. Intraoperative findings showed confirmation of turbid intracystic contents, but micro-organisms were unidentified on microbial culture. Pathology of the cyst wall revealed inflamed meningoepithelial lining cells compatible with an arachnoid cyst.


title: Laparoscopic transthoracic liver resection.

text: INTRODUCTION Minimally invasive laparoscopic liver surgery is being performed with increased frequency. Lesions located on the anterior and lateral liver segments are easier to approach through laparoscopy. On the other hand, laparoscopic access to posterior and superior segments is less frequent and technically demanding. AIM Technical description for laparoscopic transthoracic access employed on hepatic wedge resection. TECHNIQUE Laparoscopic transthoracic hepatic wedge resection on segment 8. CONCLUSION Transthoracic approach allows access to the posterior and superior segments of the liver, and should be considered for oddly located tumors and in patients with numerous previous abdominal interventions.


title: Proteomic analysis of endothelial cell autoantigens recognized by anti-dengue virus nonstructural protein 1 antibodies.

text: We previously showed the occurrence of autoimmune responses in dengue virus (DV) infection, which has potential implications for the pathogenesis of dengue hemorrhagic syndrome. In the present study, we have used a proteomic analysis to identify several candidate proteins on HMEC-1 endothelial cells recognized by anti-DV nonstructural protein 1 (NS1) antibodies. The target proteins, including ATP synthase beta chain, protein disulfide isomerase, vimentin, and heat shock protein 60, co-localize with anti-NS1 binding sites on nonfixed HMEC-1 cells using immunohistochemical double staining and confocal microscopy. The cross-reactivity of anti-target protein antibodies with HMEC-1 cells was inhibited by NS1 protein pre-absorption. Furthermore, a cross-reactive epitope on NS1 amino acid residues 311-330 (P311-330) was predicted using homologous sequence alignment. The reactivity of dengue hemorrhagic patient sera with HMEC-1 cells was blocked by synthetic peptide P311-330 pre-absorption. Taken together, our results identify putative targets on endothelial cells recognized by anti-DV NS1 antibodies, where NS1 P311-330 possesses the shared epitope.


title: Validation and Investigation of the Operating Characteristics of the Ulcerative Colitis Endoscopic Index of Severity.

text: BACKGROUND The Ulcerative Colitis Endoscopic Index of Severity (UCEIS) is a novel instrument to evaluate endoscopic disease activity. It has been demonstrated to outperform the more widely used Mayo endoscopic score (MES) in predicting long-term prognosis, including the need for colectomy. Despite its potential benefits, many clinicians still prefer to use MES because its operating characteristics are better defined and its grades are more readily applicable to clinical decision-making. The aims of our study were to quantify the UCEIS cutoff most closely associated with the need for treatment escalation and to perform a validation exercise using MES and clinical, biochemical, and histological measures of disease activity. METHODS Endoscopies performed in UC patients between November 2016 and January 2018 were retrospectively reviewed. Agreement between the UCEIS and MES was quantified using Kappa (κ) statistics. A UCEIS cutoff for treatment escalation was calculated using chi-square, receiver operating characteristic curve, and area under the curve (AUC) analyses. The Pearson correlation coefficient was used to compare linear relationships between UCEIS and clinical (Simple Clinical Colitis Activity Index [SCCAI]), biochemical (C-reactive protein [CRP]), and histological (Nancy Histological Index [NHI]) activity. RESULTS Two hundred one (56%) procedures documented both UCEIS and MES, demonstrating substantial agreement (κ = 0.713; P < 0.001). Treatment was escalated after 199 (56%) procedures. Receiver operating characteristic curve analysis of need for treatment escalation showed the highest sensitivity and specificity for UCEIS ≥4 (0.80 and 0.93, respectively; AUC, 0.93). Of 170 patients with a UCEIS ≥4, treatment was escalated in 159 (94%), but not for 11 (6%). Of 185 patients with a UCEIS ≤3, 40 (22%) were escalated, whereas 145 (78%) were not (P < 0.001). UCEIS correlated strongly with NHI (0.723; P < 0.001), moderately with SCCAI (0.671; P < 0.001), and weakly with CRP (0.279; P < 0.001). CONCLUSIONS A UCEIS ≥4 was significantly associated with treatment escalation. This cutoff could therefore be used to support clinical decision-making based on endoscopic findings. Strong and moderate correlations were found between UCEIS and histological and clinical disease activity, respectively, whereas a weak correlation was found with CRP. 10.1093/ibd/izy325_Video_1 izy325.video1 5849933952001.


title: ACE2, COVID-19, and ACE Inhibitor and ARB Use during the Pandemic: The Pediatric Perspective.

text: Potential but unconfirmed risk factors for coronavirus disease 2019 in adults and children may include hypertension, cardiovascular disease, and chronic kidney disease, as well as the medications commonly prescribed for these conditions, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. Coronavirus binding to angiotensin-converting enzyme 2, a crucial component of the renin-angiotensin-aldosterone system, underlies much of this concern. Children are uniquely impacted by the coronavirus but the reasons are unclear. This review will highlight the relationship of coronavirus disease 2019 with hypertension, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, and lifetime risk of cardiovascular disease from the pediatric perspective. We briefly summarize the renin-angiotensin-aldosterone system and comprehensively review the literature pertaining to the angiotensin-converting enzyme 2/angiotensin-(1-7) pathway in children and the clinical evidence for how angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers affect this important pathway. Given the importance of the angiotensin-converting enzyme 2/angiotensin-(1-7) pathway and the potential differences between adults and children, it is crucial that children are included in coronavirus-related research, as this may shed light on potential mechanisms for why children are at decreased risk of severe coronavirus disease 2019.


Life and Death, Hope and Despair in the Era of Coronavirus Disease 2019.


title: Simultaneous mechanical ventilation of several patients with a single ventilator.

text: Introduction Simultaneous mechanical ventilation of several patients with a single ventilator might reduce the deficit of these devices for the care of patients with acute respiratory failure due to Covid-19. Objective To communicate the results of a mechanical ventilation exercise with a ventilator in a lung simulator, and simultaneously in two and four. Results No statistically significant differences were observed between programmed, recorded and measured positive end-expiratory pressure, mean airway pressure and peak pressure, except when simultaneously ventilating four lung simulators. Conclusions Simultaneous mechanical ventilation should be implemented by medical personnel with experience in the procedure, be restricted to two patients and carried out in the intensive care unit.


A Survey on Physical and Mental Distress among Cancer Patients during the COVID-19 Epidemic in Wuhan, China.


title: Retrosigmoid Versus Traditional Ileal Conduit for Urinary Diversion After Radical Cystectomy.

text: BACKGROUND Ureteroileal anastomotic stricture (UAS) after ileal conduit diversion occurs in a non-negligible proportion of patients undergoing radical cystectomy (RC). Surgical techniques aimed at preventing this potential complication are sought. OBJECTIVE To describe our surgical technique of retrosigmoid ileal conduit, and to assess perioperative outcomes and postoperative complications with a focus on UAS rate. DESIGN, SETTING, AND PARTICIPANTS A prospective single-centre, single-surgeon cohort of 67 consecutive patients undergoing open RC with ileal conduit urinary diversion between July 2013 and April 2017 was analysed. A study group of 30 patients receiving retrosigmoid ileal conduit was compared with a control group of 37 patients receiving standard Wallace ileal conduit. SURGICAL PROCEDURE Retrosigmoid versus Wallace ileal conduit diversion after open RC. MEASUREMENTS Operative room (OR) time, estimated blood loss (EBL), transfusion rate, and 90-d postoperative complications were recorded and compared between the two groups. In particular, rate of UAS, defined as upper collecting system dilatation requiring endourological or surgical management, was assessed and compared. RESULTS AND LIMITATIONS The two groups were comparable with regard to all demographic, clinical, and pathological variables. No differences were observed in terms of OR time (p=0.35), EBL (p=0.12), and transfusion rate (p=0.81). Ninety-day postoperative complications were observed in 11 (36.7%) patients who underwent a retrosigmoid ileal conduit and 20 (54.1%) patients who received a traditional ileal conduit (p=0.32). Major complications (grade 3-4) were observed in three (10%) cases in the former group and in 12 (32.4%) cases in the latter group (p=0.08). Mean (standard deviation) follow-up time was 10.8±4.0 mo in the study group and 27.5±9.5 mo in the control group (p<0.001). No single case of UAS was observed in the study group, whereas six (16.2%) cases of UAS occurred in the control group (p=0.02). The main limitation is a nonrandomised comparison of a relatively small cohort with short-term follow-up. CONCLUSIONS In our study, we observed a significantly reduced rate of UAS and no increase in postoperative complications with the retrosigmoid ileal conduit diversion compared with standard Wallace ileal conduit diversion after open RC. PATIENT SUMMARY We describe our surgical technique of retrosigmoid ileal conduit as urinary diversion after open radical cystectomy. Compared with traditional techniques, our technique for ileal conduit was found to be safe and reduce the risk of ureteric strictures.


title: Comparison of incisional complications between skin closures using a simple continuous or intradermal pattern: a pilot study in horses undergoing ventral median celiotomy.

text: Background Development of incisional complications following ventral median celiotomy might depend on suture pattern for skin closure. Methods In this prospective study, 21 healthy male horses underwent celiotomy. Skin closure was either performed via a continuous percutaneous pattern (CO group; 5 warmbloods/5 ponies) or an intradermal pattern (ID group; 5 warmbloods/6 ponies). Follow-up examination of the incisional site included daily monitoring for edema, dehiscence, and drainage. Transcutaneous ultrasound was performed at Days 3, 6, and 10 as well as on Week 8 and 12 to evaluate size of edema and presence or absence of sinus formation, and hernia formation. Prevalence of incisional infection on base of positive microbiological analysis at any time up to Day 10 was evaluated and compared between ID and CO group. Furthermore, edema size was analysed by a linear mixed-effect model for group and time dependency. Results Observed incisional complications included edema (9/10 in CO, 10/11 in ID), suture sinus formation (2/10 in CO, 1/11 in ID), surgical site infection (2/10 in CO, 0/11 in ID), and incisional hernia (1/10 in CO, 0/11 in ID). The overall prevalence of incisional infection was 9.5% without significant differences between both groups (20% in CO, 0% in ID; p = 0.214). Edema size was not dependent on time or group (p = 0.545 and p = 0.627, respectively). Discussion CO and ID suture pattern are appropriate for skin closure following ventral median celiotomy in horses. None of the animals in the continuous ID group developed surgical site infections, even without the use of antibiotics.


title: Fistula Following Laparoscopic Sleeve Gastrectomy: a Proposed Classification and Algorithm for Optimal Management.

text: BACKGROUND Laparoscopic sleeve gastrectomy (LSG) is an accepted restrictive procedure with a hormonal component. There is no definitive course of treatment for post-LSG fistula; it remains a feared complication. We aimed to classify post-LSG fistulas and propose an algorithm to optimize their treatment. METHODS Following primary and revisional LSG in obese patients, a retrospective observational study of fistulas was undertaken. Radiological studies were performed to identify anatomically distinct types of fistulas. An algorithm was elaborated for the classification and evolving treatment of each type of fistula. RESULTS Twenty post-LSG fistulas were studied (13 [2.5%] from our center, 7 referred) with a mean body mass index of 43.1 ± 10.2 kg/m2 (32.0-76.0) and mean age of 33.1 ± 11.4 years (20.0-56.0). In all cases, the clinically suspected diagnosis was radiologically confirmed by water-soluble upper gastrointestinal series and double-contrast abdomino-pelvic CT scan. Three anatomical fistula types were characterized: type I, a small leak with no collection; type II, a leak with associated intra-abdominal abscess; and type III, a leak with multiple internal or external abscesses, a complex fistula. In accord with our algorithm, patients without sepsis received conservative treatment initially; this was sufficient for type I leaks. Type II abscesses received internal or external percutaneous drainage, and in some cases, stenting or endoprosthesis. Surgery was reserved for failure of conservative options and type III fistula. In cases of sepsis, surgery was mandatory. CONCLUSION A radiologically defined, anatomically based classification system and treatment algorithm proved effective in clinical management of post-LSG fistula.


Antiplatelet Therapy Following Percutaneous Coronary Intervention in Patients Complicated by COVID-19: Implications from Clinical Features to Pathological Findings.


Novel Tools, Biomarkers, and Disease Entities in Esophageal Disorders.


title: Human cytochrome P450 4F3: structure, functions, and prospects.

text: Cytochrome P450 4F3 (CYP4F3), originally identified as one of the leukotriene B4 ω-hydroxylases, belongs to a CYP gene family that comprises several members, which participate in the metabolism of various endobiotics, as well as some xenobiotics. The CYP4F gene family is clustered in a 0.5-Mb stretch of genomic DNA on the p13 region of chromosome 19. Apart from the ω-hydroxylation of leukotriene B4 and prostaglandins, CYP4F3 is the main catalyst in the oxidation of fatty acid epoxides. CYP4F3 expression results from the synthesis of two distinct enzymes, CYP4F3A and CYP4F3B, which originate from the alternative splicing of a single pre-mRNA precursor molecule. Remarkably, the selection of either isoform is part of a tissue-specific control through which CYP3F3A is mostly expressed in leukocytes and CYP4F3B mostly in the liver. Recently, CYP4F3 single nucleotide polymorphisms have been incriminated in the onset of pathologies, including celiac or Crohn's diseases. Although much has been discovered in the regulation and function of CYP4F2, the closest CYP4F subfamily member, analyses of CYP4F3 enzymes lag somewhat behind in the field of our knowledge. In this short review, emphasis will be placed on the regulation and the functional roles of human CYP4F3.


title: Nutrients in prevention, treatment, and management of viral infections; special focus on Coronavirus.

text: BACKGROUND The coronavirus disease 2019 (COVID-19) is a pandemic caused by coronavirus with mild to severe respiratory symptoms. This paper aimed to investigate the effect of nutrients on the immune system and their possible roles in the prevention, treatment, and management of COVID-19 in adults. METHODS This Systematic review was designed based on the guideline of the Preferred Reporting for Systematic Reviews (PRISMA). The articles that focussed on nutrition, immune system, viral infection, and coronaviruses were collected by searching databases for both published papers and accepted manuscripts from 1990 to 2020. Irrelevant papers and articles without English abstract were excluded from the review process. RESULTS Some nutrients are actively involved in the proper functioning and strengthening of the human immune system against viral infections including dietary protein, omega-3 fatty acids, vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B6, vitamin B12, vitamin C, iron, zinc, and selenium. Few studies were done on the effect of dietary components on prevention of COVID-19, but supplementation with these nutrients may be effective in improving the health status of patients with viral infections. CONCLUSION Following a balanced diet and supplementation with proper nutrients may play a vital role in prevention, treatment, and management of COVID-19. However, further clinical trials are needed to confirm these findings and presenting the strong recommendations against this pandemic.


title: Fentanyl enhances the excitability of rapidly adapting receptors to cause cough via the enhancement of histamine release in the airways.

text: UNLABELLED BACKGROUND Although the mechanism of fentanyl-induced cough is unclear, several lines of evidence suggest that allergic mediators, such as histamine, may play a role in the production of fentanyl-induced coughs. The aim of this study was to explore the effects of fentanyl on cough sensitivity to inhaled citric acid and on histamine release in BALF in mice. METHODS The cough reflex was induced by the inhalation of citric acid. Male ICR mice were exposed to a nebulized solution of citric acid at a concentration of 0.1 M under conscious and identical conditions using a body plethysmograph. The number of coughs produced per 3-min period of exposure to citric acid was counted. Histamine content in BALF was analyzed by HPLC post-column derivatization and fluorescence detection. RESULTS Intravenous administration of fentanyl increased the number of citric acid-induced coughs. The fentanyl-induced enhancement of the number of citric acid-induced coughs was abolished in mice that had been pretreated with moguisteine, a rapidly adapting receptor (RAR) antagonist or fexofenadine, a histamine H1 receptor antagonist. Fentanyl significantly increased the concentration of histamine in BALF. CONCLUSION The results of this study suggest that fentanyl enhances the excitability of RARs to cause cough, and enhancement of histamine release in the airways may some how be related to this change.


title: Comparison of Universal Versus Age-Restricted Screening of Colorectal Tumors for Lynch Syndrome Using Mismatch Repair Immunohistochemistry: A Cohort Study.

text: Background Guidelines recommend screening all patients with newly diagnosed colorectal cancer (CRC) for Lynch syndrome (LS). However, the efficiency of universal LS screening in elderly populations has not been well studied. Objective To compare the performance of age-restricted and universal LS screening using reflex mismatch repair (MMR) immunohistochemistry (IHC) of CRC tumors. Design Retrospective cohort study. Setting A large, diverse, community-based health care system. Participants 3891 persons with newly diagnosed CRC who had LS screening between 2011 and 2016. Measurements Diagnostic yield of different LS screening strategies. Results Sixty-three LS cases (diagnostic yield, 1.62%) were identified by universal screening, with only 5 (7.9%) detected after age 70 years and 1 (1.6%) detected after age 80 years. When all patients with CRC who had universal screening were used as the denominator, 58 LS cases (diagnostic yield, 1.49% [95% CI, 1.13% to 1.92%]) were identified in patients with CRC diagnosed at or before age 70 years, 60 LS cases (diagnostic yield, 1.54% [CI, 1.18% to 1.98%]) were identified in those with CRC diagnosed at or before age 75 years, and 62 LS cases (diagnostic yield, 1.59% [CI, 1.22% to 2.04%]) were identified in those with CRC diagnosed at or before age 80 years. Using 75 years as the upper age limit for screening missed 3 of 63 (4.8%) LS cases but resulted in 1053 (27.1%) fewer cases requiring tumor MMR IHC. Using 80 years as the upper age limit missed 1 of 63 (1.6%) LS cases and resulted in 668 (17.2%) fewer cases requiring tumor MMR IHC. Limitation Persons who were eligible for but did not complete germline analysis were excluded from calculations of performance characteristics. Conclusion The incremental diagnostic yield decreased substantially after age 70 to 75 years. Stopping reflex CRC screening for LS after age 80 years may be reasonable because of very low efficiency, particularly in resource-limited settings, but this merits further investigation. Studies evaluating the effect of diagnosing LS in elderly persons on their family members are needed. Primary Funding Source Kaiser Permanente Northern California Division of Research.


title: Imaging for infection: from visualization of inflammation to visualization of microbes.

text: BACKGROUND With the development of high-resolution cross-sectional imaging, anatomic identification of most areas of infection has become routine. Imaging a site of infection allows for diagnosis and treatment. In the past, molecular imaging for infection involved mainly the use of radiolabeled leukocytes for functional targeting at infection sites. With the recent development of functional nuclear imaging, bacterial and viral metabolism can also be imaged directly for potential identification of early infection. METHODS Review of pertinent English-language literature. RESULTS Cross-sectional imaging is used routinely to identify and treat sources of infection in patients with fever, leukocytosis, or unexplained hemodynamic instability. Although ultrasound is preferred for the identification of biliary or hepatic sepsis, computed tomography (CT) has proved to be accurate for the identification and treatment of intra-abdominal fluid collections and abscesses. Biologic imaging is a non-invasive technique that identifies sites of infection in cases in which no definite abnormality is identified via cross-sectional imaging. This is made possible by imaging the accumulation of radioisotopes that have been attached to white blood cells or glucose. Biologic imaging is useful for the identification of anatomic sites where there is inflammation or high metabolic demand. However, a drawback of biologic imaging is that it is not specific for infection. Techniques that image microbes directly increase the specificity of imaging results significantly and can be used to quantify and track infectious processes. For example, radiolabeling of antimicrobial proteins and antibiotics is one technique that has been demonstrated to identify areas of infection accurately in animals but is not currently being used clinically in humans. With the advent of gene therapy, many researchers are inserting the herpes viral thymidine kinase gene into both viruses and bacteria. This allows for tracking of the infectious process by imaging the accumulation of radiolabeled thymidine analogues. CONCLUSION This review summarizes standard imaging for infection as it is currently practiced clinically. We will also explore the promising new methods of microbial imaging that are likely to become standards in clinical care in the near future.


title: Emerging paradigms in anti-infective drug design.

text: The need for new drugs to treat microbial infections is pressing. The great progress made in the middle part of the twentieth Century was followed by a period of relative inactivity as the medical needs relating to infectious disease in the wealthier nations receded. Growing realisation that anti-infectives are needed in many parts of the world, to treat neglected diseases as well as to combat the burgeoning risk of resistance to existing drugs, has galvanised a new wave of research into anti-microbial drugs. The transfer of knowledge from the Pharmaceutical industry relating to the importance of understanding how to target drugs successfully within the body, and improved understanding of how pathogens interact with their hosts, is driving a series of new paradigms in anti-infective drug design. Here we provide an overview of those processes as an introduction to a series of articles from experts in this area that emerged from a meeting entitled "Emerging Paradigms in Anti-Infective Drug Design" held in London on the 17th and 18th September 2012. The symposium was organised jointly by British Society for Parasitology (BSP) and the Biological & Medicinal Chemistry sector of the Royal Society of Chemistry (RSC) and held at the London School of Hygiene & Tropical Medicine. The symposium set out to cover all aspects of the identification of new therapeutic modalities for the treatment of neglected and tropical diseases. We aimed to bring together leading scientists from all the disciplines working in this field and cover the pharmacology, medicinal chemistry and drug delivery of potential new medicines. Sessions were held on: "Target diseases and targets for drugs", "Target based medicinal chemistry", "Bioavailability and chemistry", "Targeting intracellular microbes", "Alternative approaches and models", and "New anti-infectives - how do we get there?" This symposium was organised by Simon Croft (LSHTM) and Mike Barrett (University of Glasgow) for the BSP, and David Alker (David Alker Associates) and Andrew Stachulski (University of Liverpool) for the Biological & Medicinal Chemistry sector of the RSC.


title: Risk of infection associated with intravenous iron preparations: protocol for updating a systematic review.

text: INTRODUCTION The benefits and risk of intravenous iron have been documented in previous systematic reviews and continue to be the subject of randomised controlled trials (RCTs). An ongoing issue that continues to be raised is the relationship between administering iron and developing infection. This is supported by biological plausibility from animal models. We propose an update of a previously published systematic review and meta-analysis with the primary focus being infection. METHODS AND ANALYSIS We will include RCTs and non-randomised studies (NRS) in this review update. We will search the relevant electronic databases. Two reviewers will independently extract data. Risk of bias for RCTs and NRS will be assessed using the relevant tools recommended by The Cochrane Collaboration. Data extracted from RCTs and NRS will be analysed and reported separately. Pooled data from RCTs will be analysed using a random effects model. We will also conduct subgroup analyses to identify any patient populations that may be at increased risk of developing infection. We will provide a narrative synthesis on the definitions, sources and responsible pathogens for infection in the included studies. Overall quality of evidence on the safety outcomes of mortality and infection will be assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION This systematic review will only investigate published studies and therefore ethical approval is not required. The results will be broadly distributed through conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER PROSPERO (CRD42018096023).


title: Transumbilical sleeve gastrectomy with an accessory lateral port: surgical results in 237 patients and 1-year follow-up.

text: BACKGROUND The transumbilical approach has recently been shown to be safe for several surgical procedures. Case series of sleeve gastrectomy (SG) with a transumbilical approach (TUSG) has been reported with various techniques. The objective of this report is to present the technique, surgical results, and 1-year follow-up results of simplified TUSG using rigid instruments. METHODS All of the patients who had undergone SG since July 2010 were offered a transumbilical approach. The operative technique involves a transumbilical incision and the introduction of a SILS® or GelPoint® multiport and a 5-mm metallic accessory trocar laterally in the left flank. Rigid instruments were used in all patients. Gastric transection was made 4-5 cm proximal to the pylorus, calibrated with a 36-Fr bougie. Selected hemostasis to the staple line was achieved with metallic clips. RESULTS A total of 237 patients underwent TUSG. Patient body mass index ranged from 30 to 46 kg/m(2). The mean operative time was 49.5 ± 14.9 min. Six patients presented with early complications, including hemoperitoneum in three cases, antral leak in one case, intestinal perforation in one case, and portal vein thrombosis in one case. Conversion to the multitrocar technique was required in one patient. There were no mortalities. The mean length of hospital stay was 2.2 ± 1 days. The cosmetic result was satisfactory for all of the patients. CONCLUSIONS TUSG is a safe and feasible procedure using the described technique. The insertion of a 5-mm assistance trocar simplifies the procedure, allowing the use of rigid instruments.


title: A virtual postgraduate community of practice.

text: During the COVID-19 lockdown one community of homeworkers at risk of being overlooked in contingency planning is that of postgraduate student researchers, known to suffer from higher levels of mental ill-health than the general population. Physical distance from a supportive network of supervisors, peers and colleagues holds the potential to negatively impact postgraduates' health.