Search

Introduction: Sepsis is a global problem, which has a high mortality in cases of shock. Sepsis and its complications have been linked to acute stress response. Therefore, we hypothesized that decatecholaminization (i.e., reducing adrenergic stress) with dexmedetomidine would reduce mortality and improve the outcomes of septic shock. Methods and Analysis: This is a protocol for an open-label randomized controlled trial that aims to study the impact of heart rate (HR)-calibrated dexmedetomidine infusion on inhospital mortality, which is the study primary outcome, in cases of septic shock. We will use a dose range of 0.2–0.7 mcg/kg/h for 48 hours to keep the HR between 60 and 90 beats per minute (bpm). In ventilated patients, we will use the least conventional sedation that will enable the patients in both groups to tolerate the tube and ventilation. We plan to include 90 patients with sepsis and HR of > 90 bpm while on norepinephrine infusion. The main secondary outcomes are the mean dose of norepinephrine and the mean hemodynamic parameters over the first three days of inclusion or death. We will perform per-protocol and intension-to-treat analyses. The primary outcome will be analyzed using the Chi-square test, and we will report the risk ratio and 95% confidence interval. Thereafter, we will adjust for the confounders (i.e., age, sex, mechanical ventilation, and comorbidities) in a logistic regression. The level of statistical significance will be a p-value ≤ 0.05. Ethics and dissemination: We obtained the institutional review board approval (MS:22.02.1889) on March 19, 2022 at the Mansoura University, Faculty of Medicine. Written informed consent will be obtained from all patients or their relatives. We will publish the study results in a preprint registry and in conferences, with attempt to publish the report in a peer-reviewed journal. Trial registration: Clinical trial registration (https://clinicaltrials.gov/ct2/show/NCT05283083) on March 16, 2022

Background: COVID-19 is an abnormal host response to the SARS-CoV-2 infection, which is associated with endothelial dysfunction and multi-organ failure. Atorvastatin has been proposed to reduce COVID-19 severity and mortality. Methods: This randomized double-blind trial included 220 COVID-19 patients admitted to Mansoura University's isolation hospital in Egypt. One hundred and ten cases were given 40 mg of atorvastatin once daily for 28 days (group A), while 110 received a placebo (group B). All patients received treatment as per hospital protocol. The primary outcome is all-cause mortality at 28 days. We also tracked six-month mortality, time to clinical improvement, the risk of invasive mechanical ventilation, acute kidney injury, potential adverse events, and hospital and intensive care length of stay. Results: The 28-day all-cause mortality was 52/104 (50%) in group A vs. 54/103 (52.4%) in group B, odds ratio (OR) = 0.907 (0.526, 1.565), P = 0.727; adjusted OR = 0.773 (0.407, 1.47), P = 0.433. Six-month mortality occurred in 53/102 (52%) and 59/79 (60.8%) in group A vs. B, respectively, P = 0.208. Among hospital survivors in group A vs. group B, the median time to clinical improvement was 10 days (7–14) vs. 10 (7–15), P = 0.715; the duration of hospital stay was 10 days (7–14) vs. 10 (8–17), P = 0.378. Discontinuation was higher in group B (four vs. one), P = 0.369. Conclusions: In adults with severe or critical COVID-19, atorvastatin did not reduce the risk of 28-day or six-month mortality and did not improve other clinical outcomes. Trial registration: Clinical Trial Registry (NCT04952350) on July 1st, 2021. https://clinicaltrials.gov/ct2/show/NCT04952350

During liver transplantation, graft reperfusion triggers cerebral hyperemia, increases intracranial pressure, and disrupts the blood-brain barrier, thereby increasing the risk for immunosuppression neurotoxicity. Therefore, we tested the intraoperative optic nerve sheath diameter (ONSD) for predicting tacrolimus neurotoxicity after liver transplantation.We prospectively included 100 adult patients who underwent living donor liver transplantation. The ultrasonographic ONSD 5 min after reperfusion was used as the index test, whereas the occurrence of early tacrolimus neurotoxicity was used as the reference. The area under the receiver operating characteristic curve (AUROC) was used to estimate the ONSD prediction accuracy. We reported the specificity and sensitivity of ONSD 5 and 30 min after reperfusion. Cutoffs were derived from the ROC curves. In addition, we used regression to control for confounders while testing the association between the ONSD and tacrolimus neurotoxicity.The AUROC at T3 was 0.74 (95% confidence interval (CI), 0.63-0.85, P 0.001). An ONSD of ≥6.4 mm at T3 had an 86% sensitivity (95% CI, 68%-96%) and 53% specificity (95% CI, 41%-65%). An ONSD of ≥6.4 mm at T3 had an adjusted odds ratio for tacrolimus neurotoxicity of 6.3 (95% CI, 1.9-21, P = 0.003).This data indicates that intraoperative ultrasonic ONSD after reperfusion can predict tacrolimus neurotoxicity after liver transplantation.NCT03799770; registered on January 1st, 2019.

Background Clinical presentation and outcomes of COVID-19 infection during pregnancy remain limited and fragmented. Objectives To summarize the existing literature on COVID-19 infection during pregnancy and childbirth, particularly concerning clinical presentation and outcomes. Search strategy A systematic search of LitCovid, EBSCO MEDLINE, CENTRAL, CINAHL, Web of Science, and Scopus electronic databases. The references of relevant studies were also searched. Selection criteria Identified titles and abstracts were screened to select original reports and cross-checked for overlap of cases. Data collection and analysis A descriptive summary organized by aspects of clinical presentations (symptoms, imaging, and laboratory) and outcomes (maternal and perinatal). Main results We identified 33 studies reporting 385 pregnant women with COVID-19 infection: 368 (95.6%) mild; 14 (3.6%) severe; and 3 (0.8%) critical. Seventeen women were admitted to intensive care, including six who were mechanically ventilated and one maternal mortality. A total of 252 women gave birth, comprising 175 (69.4%) cesarean and 77 (30.6%) vaginal births. Outcomes for 256 newborns included four RT-PCR positive neonates, two stillbirths, and one neonatal death. Conclusion COVID-19 infection during pregnancy probably has a clinical presentation and severity resembling that in non-pregnant adults. It is probably not associated with poor maternal or perinatal outcomes.

Background: Although mass vaccination has reduced the severity of COVID-19, mortality is still high among hospitalized patients. Being a sepsis-like disease, an anti-inflammatory drug as atorvastatin would reduce mortality and severity in COVID-19. Methods: We designed a randomized clinical trial that recruited 220 COVID-19 patients admitted in the COVID-19 isolation hospital at Mansoura University, Egypt. 110 cases were assigned to receive 40 mg Atorvastatin once daily for 28 days and 110 were assigned to receive placebo. Delta Pharm company supported the study with the drug and the placebo, which mimics the drug as regards the drug package, the tablet color, consistency, and size. All patients received the standard treatment as per the hospital protocol. The Institutional Review Board approval and the informed consent from all participants were obtained. The primary outcome is the 28-day all-cause mortality. Additionally, we will collect the in-hospital mortality, the need for mechanical ventilation, time to clinical improvement, in-hospital thrombo-embolic events, acute kidney injury, and the hospital and the intensive care duration of stay. We plan to follow the patients up for 6 months for reporting mortality and long-term neurological, psychological, and respiratory consequences. We will report the un-adjusted 28-mortality using X2. Then, we will report the adjusted odds ratio with a pre-planned multiple logistic regression model. We will report our results using the point estimate and the 95% confidence interval and the P-value. Discussion: After summarizing the main results of the study, we will discuss the outcomes with the current evidence. In addition to the planned regression model results, we would report any potential effect modifications after the planned subgroup analysis by the disease severity and the invasive mechanical ventilation status. In the end, we will conclude the risk reduction of atorvastatin on the 28-day all-cause mortality and the main secondary outcomes. Trial registration: The study was registered at the Clinical Trial Registry (NCT04952350) on July 1st , 2021. https://clinicaltrials.gov/ct2/show/NCT04952350

BackgroundManagement of COVID-19 in transplant patients is a big challenge. Data on immunosuppression management, clinical picture, and outcomes are lacking.ObjectivesTo summarize the current literature on COVID-19 in transplant patients especially the data regarding the immunosuppression protocols, clinical presentation, and outcomes.Search strategyA systematic search of MEDLINE, EBSCO, CENTRAL, CINAHL, LitCovid, Web of Science, and Scopus electronic databases. The references of the relevant studies were also searched. The search was last updated on June 3, 2020.Selection CriteriaPrimary reports of solid organ transplant patients who developed COVID-19. An overlap of cases in different reports was checked.Data collection and analysisA descriptive summary of immunosuppression therapy (before and after COVID-19), clinical presentation (symptoms, imaging, laboratory, and disease severity), management (oxygen therapy, antiviral, and antibacterial), major outcomes (Intensive care admission, invasive mechanical ventilation, acute kidney injury), and mortality.Main resultsWe identified 74 studies reporting 823 cases of solid organ transplantation with COVID-19. Among 372 patients, 114 (30.6%) were mild COVID-19, 101 (27.2%) moderate, and 157 (42.2%) severe or critical.Major outcomes included intensive care unit admission, invasive ventilation, and acute kidney injury, which occurred in 121 (14.7%), 97 (11.8%), and 63 (7.7%) of patients, respectively. Mortality was reported in 160 (19.4%) patients. Missing individual data hindered making clinical correlations.ConclusionCOVID-19 in solid organ transplant patients probably has a more disease severity, worse major outcomes (Intensive care admission, invasive ventilation, acute kidney injury), and higher mortality than in non-transplant patients.

Sağır, Özlem (Balikesir Author), Introduction More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. Methods and analysis EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. Ethics and dissemination EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369. ©

Highlights • Biliary reconstruction is a cornerstone of LDLT. • The use of trans-anastomotic biliary catheters is controversial. • We describe a rare case of intestinal obstruction due to internal herniation around biliary catheter. • Awareness of this complication plus early surgical intervention can prevent postoperative morbidity and mortality., Introduction Biliary reconstruction is a cornerstone of living-donor liver transplantation (LDLT). The routine uses of trans-anastomotic biliary catheters in biliary reconstruction had been a controversial issue. We describe a rare complication related to the use of trans-anastomotic biliary catheter after LDLT. In this case, intestinal obstruction occurred early after LDLT due to internal herniation of the small bowel around trans-anastomotic biliary catheter. Presentation A 42 years male patient with end stage liver disease underwent LDLT utilizing a right hemi-liver graft. Biliary reconstruction was done by single duct-to-duct anastomosis over trans-anastomotic biliary catheter. The patient was doing well apart from early postoperative ascites that was managed medically. Three weeks after surgery, the patient developed severe agonizing central abdominal pain not responding to anti-spasmodics and analgesics. The decision was to proceed for surgical exploration. Exploration revealed internal herniation of the small bowel loops around the trans-anastomotic biliary catheter without strangulation. Reduction of the internal hernia was done by releasing the fixation of the biliary catheter from the anterior abdominal wall. Small bowel resection was not required. The patient had smooth postoperative course and was discharged 10 days after surgery. Discussion Awareness regarding this rare complication plus early surgical intervention can prevent the development of postoperative morbidity and mortality. To the best of our knowledge this is the first report to describe such are complication after LDLT. Conclusion We report the first case of internal herniation of small bowel around biliary catheter early after LDLT.