Core warming of coronavirus disease 2019 (COVID-19) patients undergoing mechanical ventilation - a pilot study (preprint)

Fever is a recognized protective factor in patients with sepsis, and growing data suggest beneficial effects on outcomes in sepsis with elevated temperature, with a recent pilot randomized controlled trial showing lower mortality by warming afebrile sepsis patients in the intensive care unit. The objective of this prospective single-site randomized controlled trial was to determine if core warming improves respiratory physiology of mechanically ventilated patients with COVID-19, allowing earlier weaning from ventilation, and greater overall survival. A total of 19 patients with mean age of 60.5 ({+/-}12.5) years, 37% female, mean weight 95.1 ({+/-}18.6) kg, and mean BMI 34.5 ({+/-}5.9) kg/m2 with COVID-19 requiring mechanical ventilation were enrolled from September 2020 through February 2022. Patients were randomized 1:1 to standard-of-care or to receive core warming for 72 hours via an esophageal heat exchanger commonly utilized in critical care and surgical patients. The maximum target temperature was 39.8 {degrees}C. A total of 10 patients received usual care and 9 patients received esophageal core warming. After 72 hours of warming, PaO2/FiO2 ratios were 197 ({+/-}32) and 134 ({+/-}13.4), Cycle Thresholds were 30.8 ({+/-}6.4) and 31.4 ({+/-}3.2), ICU mortality was 40% and 44%, 30-day mortality was 30% and 22%, and mean 30-day ventilator-free days were 11.9 ({+/-}12.6) and 6.8 ({+/-}10.2) for standard-of-care and warmed patients, respectively (p=NS). This pilot study suggests that core warming of patients with COVID-19 undergoing mechanical ventilation is feasible and appears safe. Optimizing time to achieve febrile-range temperature may require a multimodal temperature management strategy to further evaluate effects on outcome.

Comprehensive Bioinformatics analysis of angiotensin-converting enzyme 2 (ACE2) (preprint)

ACE2, a member of the angiotensin converting enzyme family, plays an irreplaceable role in the renin-angiotensin system. And the variations of ACE2 are regarded as the key factor to human diseases such as the novel coronavirus pneumonia, cardiovascular disease, and tumors. Here, we summarized the mutation, expression, modification and function of the human ACE2 based on comprehensive bioinformatics analysis. Especially, the relationship between ACE2 expression and diseases, especially tumor was further discussed. ACE2 is highly conserved in different genera and families. We explored the correlation between ACE2 and disease based on the datasets of GCBI and GEO (Gene expression omnibus), and found the expression of ACE2 is related to heart failure. High prevalence of ACE2 mutations is observed in diffuse large B-cell lymphoma, uterine carcinosarcoma (UCS), and stomach adenocarcinoma (STAD). We first identified that highly expressed of ACE2 was linked to poor prognosis of overall survival for tumors of brain lower grade glioma (LGG). Specially, the expression level of ACE2 in kidney-related tumor tissues is much higher than that of normal kidney tissues. ACE2 is negatively correlated with the infiltration level of cancer-associated fibroblasts in most kinds of cancers, such as uterine corpus endometrial carcinoma (UCEC), esophageal carcinoma (ESCA), ovarian serous cystadenocarcinoma (OV) and kidney renal clear cell carcinoma (KIRC); positively correlation in testicular germ cell tumors (TGCT). The different phosphorylation sites of ACE2 were analyzed in CPTAC dataset, and the DNA methylation of ACE2 in colon adenocarcinoma (COAD), kidney renal papillary cell carcinoma (KIRP), and rectum adenocarcinoma (READ) was lower than that of normal control by using SMART database. Moreover, we summarized the interaction proteins and targeted miRNAs of ACE2 through bioinformatics. Then we found the endocrine process and the regulation of systemic arterial blood pressure were involved in the functional mechanisms of ACE2 by using KEGG and GO analysis. Our study offers a relatively comprehensive understanding of ACE2.

Patients’ experiences undergoing cancer surgery during the COVID-19 pandemic: a qualitative study (preprint)

Purpose: This study aimed to understand patients’ experiences undergoing cancer surgery during the COVID-19 pandemic. In response to COVID-19, many elective cancer surgeries were delayed creating a massive backlog of cases. Patients’ experiences with surgical delays may inform healthcare systems’ responses to the backlog of cases and guide preparations for future healthcare emergencies. Methods: This was a qualitative description study. Patients undergoing general surgery for cancer at two university-affiliated hospitals between March 2020 and January 2021 were invited to one-to-one interviews. Patients were purposefully selected using quota sampling until interviews produced no new information (i.e., thematic saturation). Interviews were conducted using a semi-structured guide and analyzed according to inductive thematic analysis. Results: Twenty patients were included [mean age 64±12.9; male (n=10); surgical delay (n=14); cancer sites: breast (n=8), skin (n=4), hepato-pancreato-biliary (n=4), colorectal (n=2), and gastro-esophageal (n=2)]. When determining their willingness to undergo surgery, patients weighed the risk of COVID-19 infection against the urgency of their disease. Changes to the hospital environment (e.g., COVID-19 preventative measures) and deviations from expected treatment (e.g., alternative treatments, remote consultations, rescheduled care) caused diverse psychological responses, ranging from increased satisfaction to severe distress. Patients employed several coping strategies to mitigate distress, including eliciting reassurance from care providers, seeking information from unconventional sources, and reframing care interruptions. Conclusions: Changes in care during the pandemic elicited diverse psychological responses from patients undergoing cancer surgery. Coping was facilitated by consistent communication with providers, emphasizing the importance of patient-centered expectation setting as we prepare for the future within and beyond the pandemic.

A pan-cancer analysis of the oncogenic role of COVID-19 risk gene Leucine Zipper Transcription Factor-Like Protein 1 (LZTFL1) in human tumors (preprint)

Population-based studies showed that COVID-19 infection causes higher death rate in cancer patients. However, the molecular mechanism of COVID-19 with cancer is still largely unknown. Here we analyzed the Leucine Zipper Transcription Factor-Like Protein 1 (LZTFL1) which is the most significant gene associated with COVID-19. First, we explored the potential oncogenic roles of LZTFL1 through transcriptome data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. LZTFL1 is significantly low expressed in 11 of 34 kinds of cancers we analyzed. Consistent with the mRNA expression data, the protein expression of LZTFL1 in lung adenocarcinoma (LUAD), clear cell renal cell carcinoma (ccRCC), Uterine corpus endometrial carcinoma (UCEC), and ovarian cancer (OV) patients are significantly decreased compared to healthy tissues. The survival analysis from the Kidney renal clear cell carcinoma (KIRC), Rectum adenocarcinoma (READ), and Uveal Melanoma (UVM), the LZTFL1 high expression group have a significantly higher survival rate compared to the low expression group. Taken together, LZTFL1 acts as a cancer suppressor gene for several cancers. Moreover, LZTFL1 expression was associated with the cancer-associated fibroblast infiltration in several tumors including Bladder Urothelial Carcinoma (BLCA), Breast invasive carcinoma (BRCA), Esophageal carcinoma (ESCA), Head and Neck squamous cell carcinoma (HNSC), Lung squamous cell carcinoma (LUSC), and Pancreatic adenocarcinoma (PAAD). Gene ontology analysis showed that cilium organization, positive regulation of establishment of protein localization to telomere and SRP-dependent cotranslational protein targeting to the membrane were involved in the function mechanisms related to LZTFL1. Our studies offer a relatively comprehensive understanding of the oncogenic roles of LZTFL1 across different kinds of tumors.

Effect of laparoscopic sleeve gastrectomy vs laparoscopic sleeve + Rossetti fundoplication on weight loss and de novo GERD in patients affected by morbid obesity: a randomized clinical study.

PURPOSE: To compare sleeve gastrectomy (SG) to SG associated with Rossetti fundoplication (SG + RF) in terms of de novo gastro-esophageal reflux disease (GERD) after surgery, weight loss, and postoperative complications. MATERIALS AND METHODS: Patients affected by morbid obesity, without symptoms of GERD, who were never in therapy with proton pump inhibitors (PPIs), were randomized into two groups. One group underwent SG and the other SG + RF. The study was stopped on February 2020 due to the COVID pandemic. RESULTS: A total of 278 patients of the programmed number of 404 patients were enrolled (68.8%). De novo esophagitis was considered in those patients who had both pre- and postoperative gastroscopy (97/278, 34.9%). Two hundred fifty-one patients (90.3%) had completed clinical follow-up at 12 months. SG + RF resulted in an adequate weight loss, similar to classic SG at 12-month follow-up (%TWL = 35. 4 ± 7.2%) with a significantly better outcome in terms of GERD development. One year after surgery, PPIs were necessary in 4.3% SG + RF patients compared to 17.1% SG patients (p = 0.001). Esophagitis was present in 2.0% of SG + RF patients versus 23.4% SG patients (p = 0.002). The main complication after SG + RF was wrap perforation (4.3%), which improved with the surgeon's learning curve. CONCLUSION: SG + RF seemed to be an effective alternative to classic SG in preventing de novo GERD. More studies are needed to establish that an adequate learning curve decreases the higher percentage of short-term complications in the SG + RF group.

Comparison of endoscopic activity before and during the covid pandemic at a tertiary care hospital in South Punjab (preprint)

Introduction: Coronavirus disease 2019 (COVID-19) has resulted in dramatic changes to healthcare delivery. Endoscopic activity has had frequent disruptions during this pandemic. The objective of the study was to see the influence of pandemic over the endoscopic activity. Methods: This retrospective analysis of endoscopic activity was undertaken at Nishtar Hospital Multan. Procedural analysis was done in the three months immediately after covid lockdown (1st April till 30th June 2020) and was compared to a similar period one year back. Results: Five hundred and fifty-four (68.5%) patients underwent endoscopic procedures during the three months of pre-COVID era, while this number reduced to half (n=255, 31.5%) patients during the covid pandemic. Even though the absolute number of Esophagogastroduodenoscopies (EGDs) reduced during the pandemic, patients were more likely to undergo EGDs during the COVID pandemic in contrast to the era before the pandemic (79% versus 66%, p = 0.002). The most common indication for EGD was upper gastrointestinal bleeding (UGIB). The percentage of EGDs done for UGIB rose from almost 60% to 80% during the covid pandemic (p < 0.001). The most common findings were esophageal varices and portal gastropathy (non-significant difference during and before the pandemic). Percentage of ERCPs done for obstructive jaundice doubled during the COVID pandemic (33% versus 65%, p = 0.002).The most common indication for sigmoidoscopy or colonoscopy was lower gastrointestinal bleeding. However, no significant difference was found before and during the covid pandemic (41.7% and 45.8% respectively, p=0.72). Internal hemorrhoids were the most common endoscopic finding. Colon cancer diagnosis reduced from 10% to undetected during the pandemic period. Conclusion: COVID pandemic resulted in a considerable reduction in all types of endoscopic procedures. The majority of procedures were done for emergency indications like gastrointestinal bleeding. Rates of cancer detection were significantly reduced. MeSH: Endoscopy, COVID-19, Gastroenterology

Novel method of transpulmonary pressure measurement with an air-filled esophageal catheter (preprint)

Background There is a strong rationale for proposing transpulmonary pressure-guided protective ventilation in acute respiratory distress syndrome (ARDS). The reference esophageal balloon catheter method requires complex in vivo calibration and dedicated ventilator with auxiliary pressure port. A simple, inexpensive, accurate and reproducible method of measuring esophageal pressure would greatly facilitate the measure of transpulmonary pressure to individualize protective ventilation in the intensive care unit.Results We propose an air-filled esophageal catheter method without balloon, using disposable catheter and transducer that allows reproducible esophageal pressure measurements, and that does not require any specific ventilator equipment. We use a 49 cm-long thin low compliance polyvinyl 10 Fr suction catheter, positioned in the lower third of the esophagus and connected to an air-filled disposable blood pressure transducer bound to the monitor. To guarantee air transmission, the transducer is pressurized by an air-filled infusion bag allowing its integrated flush device to deliver continuous air flow and to obtain a stable esophageal waveform. Calibration requires simple zeroing the transducer open to atmospheric pressure. Esophageal pressures recorded on the monitoring are expressed in mmHg and need to be converted in cmH2O. We tested our novel method in 10 consecutive intubated patients with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. We calculated the target transpulmonary pressures for protective lung and diaphragm ventilation, both in passive and spontaneously breathing conditions. Esophageal to airway pressure change ratio was close to one in both conditions (median [P25;P75] = 0.94 [0.92;1.00] and 0.98 [0.96;1.01]). We adjusted ventilator settings towards recommended pressure targets to limit atelectrauma, barotrauma, inspiratory effort and lung stress, by modifying positive end-expiratory pressure, tidal volume, or inspiratory pressure accordingly.Conclusions We propose a simple, inexpensive and reproducible method for esophageal pressure monitoring with an air-filled esophageal catheter without balloon. It holds the promise of widespread bedside use of transpulmonary pressure-guided protective ventilation in patients with ARDS.

Transjugular Intrahepatic Portosystemic Shunt In COVID-19 Patient: A Case Report (preprint)

Transjugular intrahepatic portosystemic shunt (TIPS) should be considered in all liver transplant candidates, besides being a life-saving procedure in bleeding from esophageal or gastric varices. In this case, we describe the management of a patient with diagnosis of coronavirus (COVID-19) with variceal bleeding in an emergency situation with worsening of pulmonary function.

The transmembrane serine protease inhibitors are potential antiviral drugs for 2019-nCoV targeting the insertion sequence-induced viral infectivity enhancement (preprint)

At the end of 2019, the SARS-CoV-2 induces an ongoing outbreak of pneumonia in China1, even more spread than SARS-CoV infection2. The entry of SARS-CoV into host cells mainly depends on the cell receptor (ACE2) recognition and spike protein cleavage-induced cell membrane fusion3,4. The spike protein of SARS-CoV-2 also binds to ACE2 with a similar affinity, whereas its spike protein cleavage remains unclear5,6. Here we show that an insertion sequence in the spike protein of SARS-CoV-2 enhances the cleavage efficiency, and besides pulmonary alveoli, intestinal and esophagus epithelium were also the target tissues of SARS-CoV-2. Compared with SARS-CoV, we found a SPRR insertion in the S1/S2 protease cleavage sites of SARS-CoV-2 spike protein increasing the cleavage efficiency by the protein sequence aligment and furin score calculation. Additionally, the insertion sequence facilitates the formation of an extended loop which was more suitable for protease recognition by the homology modeling and molicular docking. Furthermore, the single-cell transcriptomes identified that ACE2 and TMPRSSs are highly coexpressed in AT2 cells of lung, along with esophageal upper epithelial cells and absorptive enterocytes. Our results provide the bioinformatics evidence for the increased spike protein cleavage of SARS-CoV-2 and indicate its potential target cells.