Lymphopenia associated with survivin and its downstream pathway in COVID-19 serving as a potential route in COVID-19 pathogenesis.

PURPOSE: Starting in 2019, coronavirus disease 2019 (COVID-19) caused an epidemic that was growing rapidly and has harmed millions of people globally. It has been demonstrated that survivin regulates lymphocyte survival, a main route involved in COVID-19 pathogenesis. Survivin belongs to the inhibitor of apoptosis protein (IAP) family, and its primary functions comprise regulating mitosis and inhibiting apoptosis. Since lower survivin expression has been shown to increase the sensitivity of lymphocytes to apoptotic induction, we looked into the function of survivin and its corresponding pathways in COVID-19 pathogenesis. MATERIALS AND METHODS: The expression of survivin, X-linked inhibitor of apoptosis protein (XIAP), caspases 3, 7, 9, and poly (ADP-ribose) polymerase (PARP) was evaluated at both mRNA and protein levels in peripheral blood mononuclear cells (PBMCs) derived from healthy donors and patients with severe and moderate COVID-19 by qRT-PCR and Western blotting, respectively. Then, we enforced apoptosis to COVID-19 patient-derived lymphocytes, and the percent was assessed by flow cytometry. RESULTS: Survivin and XIAP were less expressed in PBMCs derived from COVID-19 patients as apoptosis inhibitors than PARP, cleaved-PARP, caspase 9, and cleaved caspases 3 and 7, according to the results of real-time PCR and Western blot analysis. Additionally, according to the flow cytometry results, the down-regulation of survivin served as a potential factor in the lymphocyte depletion observed in patients with COVID-19. CONCLUSION: The role of survivin and its related pathway was first discovered in the development of COVID-19 and may serve as a potential prognostic and therapeutic target.

Comparing the Effect of Neostigmine and Metoclopramide on Gastric Residual Volume of Mechanically Ventilated Patients in Intensive Care Unit: A Double-Blind Randomized Clinical Trial.

INTRODUCTION: The gastric residual volume (GRV) monitoring in patients with mechanical ventilation (MV) is a common and important challenge. The purpose of this study was to compare the effect of neostigmine and metoclopramide on GRV among MV patients in the intensive care unit (ICU). METHODS: In a double-blind randomized clinical trial, a total of 200 mechanically ventilated ICU patients with GRV > 120 ml (6 hours after the last gavage) were randomly assigned into two groups (A and B) with 100 patients in each group. Patients in groups A and B received intravenous infusion of neostigmine at a dose of 2.5 mg/100 ml normal saline and metoclopramide at a dose of 10 mg/100 ml normal saline, within 30 minutes, respectively. GRV was evaluated 5 times for each patient, once before the intervention and 4 times (at 3, 6, 9, and 12 hours) after the intervention. In addition, demographic characteristics including age and gender, as well as severity illness based on the sequential organ failure assessment score (SOFA), were initially recorded for all patients. RESULTS: After adjusting of demographic and clinical characteristics (age, gender, and SOFA score), the generalized estimating equation (GEE) model revealed that neostigmine treatment increased odds of GRV improvement compared to the metoclopramide group (OR = 2.45, 95% CI: 1.60-3.76, P < 0.001). However, there is a statistically significant time trend (within-subject differences or time effect) regardless of treatment groups (P < 0.001). CONCLUSION: According to the results, although neostigmine treatment significantly improved GRV in more patients in less time, within 12 hours of treatment, all patients in both groups had complete recovery. Considering that there was no significant difference between the two groups in terms of side effects, it seems that both drugs are effective in improving the GRV of ICU patients.

Effect of High-Dose Vitamin D on Duration of Mechanical Ventilation in ICU Patients.

The relationship of vitamin D3 with the duration of mechanical ventilation and mortality is still unknown. Therefore, this study aimed to determine the effect of using high-dose vitamin D on the duration of mechanical ventilation among the patients admitted to the intensive care unit. The current double-blinded clinical trial was performed on 44 mechanically ventilated, adult patients. Using permuted block randomization, the patients were recruited in intervention and placebo arms. In the placebo group, four patients were excluded due to death before 72 h. The vitamin D level was measured in both groups on entrance and 7th day of the study. The intervention and placebo groups received intramuscular injection of 300000 IU vitamin D and identical placebo, respectively. SOFA and CPIS score were evaluated daily for 7 days and on 14th and 28th days of the study. Also duration of mechanical ventilation and mortality rate were recorded. Fourteen males and 8 females were recruited in the intervention group, as well as 13 males and 5 females in the control group. There was no significant difference in baseline characteristics of the patients including gender and age. The mean duration of the mechanical ventilation was 17.63 ± 14 days in the intervention group versus 27.72 ± 22.48 days in the control group (p = 0.06). Mortality rate in control and intervention groups was 61.1% versus 36.3% (p = 0.00), respectively. Administration of high-dose vitamin D could reduce mortality in mechanically ventilated patients. Despite decrease of 10 days in duration of mechanical ventilation, the difference was not statistically significant. Larger studies are recommended.

The Effect of a Single Dose Oral Pregabalin on Hemodynamic Changes and Duration of Analgesia after Spinal Anesthesia in Orthopedic Surgeries of Tibial Fractures.

Treatment of acute pain and hemodynamic changes after surgery is extremely important. Various drugs for pain relief after surgery have been studied. The aim of this study was to evaluate the effect of a single dose of oral pregabalin on hemodynamic changes and duration of analgesia after spinal anesthesia in orthopedic surgeries of tibia fractures. This clinical trial was carried out on 120 patients with fractures of the tibia bone in 2014 in city of Zahedan. Sampling was conducted using randomized blocks and patients were placed into pregabalin (150 mg PO 1 h before anesthesia) and placebo groups. Duration of analgesia, severity of anxiety, mean arterial pressure, and pulse rate were evaluated in both groups. The mean age of the patients was 34.8 ± 21.7 years and 84 patients (70%) were male and 36 (30%) were female. There were no significant differences at baseline characteristics of the patients in two arms of the study. After surgery, mean arterial pressure, pulse rate and anxiety, were significantly lower in intervention group. Also the duration of analgesia was significantly longer in intervention arm (185.3 ± 4.9 vs 36.9 ± 13.9, P < 0.01). Dizziness as a side effect of pregabalin was observed in 21 and 11 subjects in intervention and placebo groups, respectively (P < 0.01). The present study showed that a single dose of oral pregabalin increases the duration of analgesia and maintains hemodynamic stability in orthopedic surgery patients.