Genome-wide loss-of-function screen using human pluripotent stem cells to study virus-host interactions for SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019, has become a global health concern. Therefore, there is an immense need to understand the network of virus-host interactions by using human disease-relevant cells. We have thus conducted a loss-of-function genome-wide screen using haploid human embryonic stem cells (hESCs) to identify genes involved in SARS-CoV-2 infection. Although the undifferentiated hESCs are resistant to SARS-CoV-2, their differentiated definitive endoderm (DE) progenies, which express high levels of ACE2, are highly sensitive to the virus. Our genetic screening was able to identify the well-established entry receptor ACE2 as a host factor, along with additional potential novel modulators of SARS-CoV-2. Two such novel screen hits, the transcription factor MAFG and the transmembrane protein TMEM86A, were further validated as conferring resistance against SARS-CoV-2 by using CRISPR-mediated mutagenesis in hESCs, followed by differentiation of mutant lines into DE cells and infection by SARS-CoV-2. Our genome-wide genetic screening investigated SARS-CoV-2 host factors in non-cancerous human cells with endogenous ACE2 expression, providing a unique platform to identify novel modulators of SARS-CoV-2 cytopathology in human cells.

Does endoscopy at the time of revisional bariatric surgery decrease complication rates? an analysis of the NSQIP database.

BACKGROUND: Endoscopy is performed routinely during bariatric surgery. It is often used for provocative testing and intraluminal inspection during Roux-en-Y gastric bypass (RNYGB) and sleeve gastrectomy (SG). Recent publications would indicate about one-quarter of bariatric cases are performed with concurrent endoscopy, resulting in a slight increase in time but no increase in complications within 30 days compared with cases where no endoscopy is performed. Do these results persist for endoscopy during revisional bariatric surgery (RBS)? METHODS: An analysis of the American College of Surgeons National Surgical Quality Initiative Program (NSQIP) was conducted for the years 2005-2017. Seventeen postoperative outcomes were analyzed in this database. A 1:1 propensity score matching analysis was completed for 13 patient comorbidities and demographics. A McNemar's test for paired categorical variables and a paired t-test for continuous variables were completed, with a significant P value of 0.05. The results were reported as the frequency and percentage for categorical variables and the mean (± standard deviation) for continuous variables. RESULTS: A total of 7249 RBS cases were identified. After propensity score matching for patient comorbidities and demographics 2329 cases remained. Esophagogastroduodenoscopy (EGD) was performed in 375 (16%) of these patients. There were no differences in complication rates between the two groups. CONCLUSIONS: Similar to non-revisional bariatric surgery, there is no difference in 30-day postoperative complications when endoscopy is performed in RBS. Endoscopy is performed in about one-sixth of RBS cases.

SARS-CoV-2 Omicron Induces Enhanced Mucosal Interferon Response Compared to other Variants of Concern, Associated with Restricted Replication in Human Lung Tissues.

SARS-CoV-2 Omicron variant has been characterized by decreased clinical severity, raising the question of whether early variant-specific interactions within the mucosal surfaces of the respiratory tract could mediate its attenuated pathogenicity. Here, we employed ex vivo infection of native human nasal and lung tissues to investigate the local-mucosal susceptibility and innate immune response to Omicron compared to Delta and earlier SARS-CoV-2 variants of concern (VOC). We show that the replication of Omicron in lung tissues is highly restricted compared to other VOC, whereas it remains relatively unchanged in nasal tissues. Mechanistically, Omicron induced a much stronger antiviral interferon response in infected tissues compared to Delta and earlier VOC-a difference, which was most striking in the lung tissues, where the innate immune response to all other SARS-CoV-2 VOC was blunted. Notably, blocking the innate immune signaling restored Omicron replication in the lung tissues. Our data provide new insights to the reduced lung involvement and clinical severity of Omicron.

Evaluating the change in patterns of traumatic injury in the setting of pandemic and social distancing restrictions: An analysis of a level 1 trauma center.

BACKGROUND: Social distancing measures and quarantine during the COVID-19 pandemic have led to reported changes in traumatic injury patterns. We set to examine the effects of these restrictive guidelines in our trauma center. METHODS: This is a retrospective chart review of all patients evaluated for traumatic injuries at a Level 1 trauma center during two time periods: March-June 2020 (COVID) and March-June 2019 (Pre-COVID). RESULTS: Overall trauma volume did not differ significantly between the two time periods. Changes seen during COVID included increases in penetrating injuries (12.5% vs 6.7%, p < 0.001), particularly those due to firearms (7.5% vs 3.7%, p < 0.001). Hospital length of stay, intensive care unit length of stay, and days on the ventilator remained consistent between the two groups. Trends toward increased injuries in the home and non-accidental trauma were not statistically significant. CONCLUSION: Traumatic injury patterns have changed as a result of social distancing in both the adult and pediatric trauma populations. Analyzing the effects of social distancing on trauma can lead to a better development of preventive strategies.

Is fundoplication necessary after paraesophageal hernia repair? A meta-analysis and systematic review.

INTRODUCTION: Paraesophageal hernias are often asymptomatic, but when symptomatic they should be fixed laparoscopically. A cruroplasty of the diaphragmatic pillars is performed and a fundoplication is usually performed at the time. However, there are times, especially in emergency cases, where it is not always possible to perform a fundoplication. We hypothesized there would be no difference in outcomes whether or not a fundoplication is performed as part of a paraesophageal hernia repair. METHODS: A literature review of available clinical databases was performed using PubMed, Clinical Key and Google Scholar. Our search terms were: "paraesophageal hernia" "paraesophageal hernia repair" "fundoplication" "emergency surgery" "no fundoplication" We excluded studies that were in languages other than English, abstracts and small case series. RESULTS: Our search criteria yielded a total of 22 studies published between 1997 and 2020. There were a total of 8600 subjects enrolled into this study. The overall pooled prevalence of fundoplication were estimated as 69% (95% CI: 59%-78%). In patients who underwent fundoplication, the risk of gastroesophageal reflux disease (GERD) was reduced as compared to patients who did not undergo fundoplication (RR: 0.64, 95% CI: 0.40-1.04, p = 0.069, I2 = 47.2%). A similar trend was also observed in recurrence (RR: 0.53, 95% CI: 0.27-1.03, p = 0.061, I2 = 0.0%) and reoperations (RR: 0.25, 95% CI: 0.02-2.69, p = 0.25, I2 = 56.7%). However, patients who underwent fundoplication had an increased risk of dysphagia (RR: 1.68, 95% CI: 0.59-4.81, p = 0.83, I2 = 42%). CONCLUSIONS: There is a higher rate of recurrence of gastroesophageal reflux disease, recurrence of hernia and reoperation when no fundoplication is performed during a paraesophageal hernia repair but a lower risk of dysphagia, but none of these reached statistical significance.(Comment 1) Paraesophageal hernia repair with fundoplication should be performed, but it is acceptable to not do it in certain situations.

Adult-onset perianal Langerhans cell histiocytosis presenting as pruritus ani: a case report and review of the literature.

BACKGROUND: Langerhans cells belong to the histiocytic system and give rise to two tumors: Langerhans cell histiocytosis and Langerhans cell sarcoma. Clinical aggressiveness and degree of atypia distinguish the two neoplasms. Langerhans cell histiocytosis can infiltrate a single or multiple organ systems and particularly affects bone, skin, and lymph nodes. Perianal cutaneous Langerhans cell histiocytosis is a rare condition in adults, with 15 cases reported in the literature. CASE: We present the case of a 50-year-old hispanic man who presented with a 9-month history of pruritus ani and a personal history of diabetes insipidus. Punch biopsy confirmed a lesion of Langerhans cells origin but could not exclude Langerhans cell sarcoma because of limited sample size. An additional biopsy was planned as well as a positron emission tomography scan to determine the extent of disease spread. While the patient failed to follow up for repeat biopsy, the positron emission tomography scan was performed and was negative for metastatic disease. A stable perianal lesion of Langerhans cell histiocytosis with benign clinical features in a 50-year-old male despite lack of treatment is extremely rare and has not been described in the literature so far. Here, we review the presentation and workup of patients with Langerhans cell histiocytosis, review the relevant literature, and discuss treatment planning. CONCLUSION: Perianal Langerhans cell histiocytosis is rare, and there should be a high index of suspicion with chronic or new perianal lesions, especially in a patient with a history of diabetes insipidus. It is also important to consider the patient's full clinical course when it is not possible to reach a definitive pathological diagnosis before management.

Homeostasis and Defense at the Surface of the Eye. The Conjunctival Microbiota.

The literature on ocular microbiome has grown tremendously over the past decade, and our knowledge of the different aspects and roles in homeostasis and protection is continuously growing. The development of 16 S rRNA sequencing has allowed the field to characterize communities of bacteria in health and ocular disease. Efforts should continue to further elucidate the interplay between microbiome and key players, such as age, comorbidities, and contact lens usage in order to have better control of the sight-threatening complications.

Magnetic sphincter augmentation at the time of bariatric surgery: an analysis of the MBSAQIP.

BACKGROUND: Magnetic sphincter augmentation (MSA) has gained popularity as a treatment for gastroesophageal reflux disease (GERD). The role of MSA in treating GERD in metabolic and bariatric surgery (MBS) patients at the time of primary MBS is unknown. OBJECTIVE: To determine the short-term outcomes of MSA placed at the time of MBS. SETTING: National database, United States. METHODS: We queried the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database for MSA performed at time of the sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) for the years 2017-2018. A propensity adjusted analysis was performed to assess 30-day outcomes of patients who had MSA placed versus those who did not. RESULTS: There were 319,580 patients who underwent MBS in the study period. Twenty-four patients had MSA at time of surgery. These patients did not have a higher reported rate of preoperative GERD (P = .93). Six patients (25%) with MSA had a RYGB; the other 18 patients (75%) patients had SG (P < .001). Operative times were similar between the groups and there was no difference in length of stay. After propensity matched analysis (with 24 patients in each arm), patients who underwent an MSA had shorter discharge times (1.4 days [.8] versus 2.0 [.9], P = .012). CONCLUSION: MSA is safe in the short term in MBS. There is no difference in major morbidity or mortality and operative times are similar in MSA patients. The long-term efficacy of this practice is unknown.