Therapeutic high-dose vitamin D for vitamin D-deficient severe COVID-19 disease: randomized, double-blind, placebo-controlled study (SHADE-S).

BACKGROUND: efficacy of therapeutic cholecalciferol supplementation for severe COVID-19 is sparingly studied. OBJECTIVE: effect of single high-dose cholecalciferol supplementation on sequential organ failure assessment (SOFA) score in moderate-to-severe COVID-19. METHODS: participants with moderate to severe COVID-19 with PaO2/FiO2 ratio < 200 were randomized to 0.6 million IU cholecalciferol oral (intervention) or placebo. OUTCOMES: primary outcome was change in Day 7 SOFA score and pre-specified secondary outcomes were SOFA and 28-day all-cause mortality. RESULTS: in all, 90 patients (45 each group) were included for intention-to-treat analysis. 25(OH)D3 levels were 12 (10-16) and 13 (12-18) ng/ml (P = 0.06) at baseline; and 60 (55-65) ng/ml and 4 (1-7) ng/ml by Day 7 in vitamin D and placebo groups, respectively. The SOFA score on Day 7 was better in the vitamin D group [3 (95% CI, 2-5) versus 5 (95% CI, 3-7), P = 0.01, intergroup difference - 2 (95% CI, -4 to -0.01); r = 0.4]. A lower all-cause 28-day mortality [24% compared to 44% (P = 0.046)] was observed with vitamin D. CONCLUSIONS: single high-dose oral cholecalciferol supplementation on ICU admission can improve SOFA score at Day 7 and reduce in-hospital mortality in vitamin D-deficient COVID-19. ClinicalTrials.gov  id: NCT04952857 registered dated 7 July 2021. What is already known on this topic-vitamin D has immunomodulatory role. Observational and isolated intervention studies show some benefit in COVID-19. Targeted therapeutic vitamin D supplementation improve outcomes in severe COVID-19 is not studied in RCTs. What this study adds-high-dose vitamin D supplementation (0.6 Million IU) to increase 25(OH)D > 50 ng/ml is safe and reduces sequential organ failure assessment score, in-hospital mortality in moderate to severe COVID-19. How this study might affect research, practice or policy-vitamin D supplementation in vitamin D-deficient patients with severe COVID-19 is useful may be practiced.

Modified Enhanced Recovery After Surgery (ERAS) Protocol Versus Non-ERAS Protocol in Patients Undergoing Emergency Laparotomy for Acute Intestinal Obstruction: A Randomized Controlled Trial.

BACKGROUND: Enhanced Recovery After Surgery (ERAS) is a multimodal approach with promising results in improving patient outcome. Only recently, is evidence emerging highlighting how similar principles of care can be applied to patients undergoing emergency abdominal surgery. METHODS: A randomized controlled trial was conducted from November 2021 to April 2022 at PGIMER Chandigarh, which is a leading tertiary care hospital in northern India. 60 patients with acute intestinal obstruction requiring emergency laparotomy were randomized and assigned to ERAS or Non-ERAS group. ERAS protocol with some modifications was applied. Primary endpoints were post-operative hospital stay. Secondary end points were morbidity, 30-day readmission and mortality rate. Data analysis was done using SPSS 22.0. Independent t test or Mann-Whitney test and Chi-square or Fisher-exact test were used for analysis. RESULTS: A significant 3-day reduction in hospital stay was observed in ERAS compared to non-ERAS group (median (interquartile range) 5.50 (4.75-8.25) vs 8.0 (6.0-11.0) p = 0.003) with no difference in 30-day readmission rate, mortality rate and complication rate (according to Clavien-Dindo classification). ERAS group was associated with early recovery of gastrointestinal functions including time to first passage of flatus (p < 0.001), stools (p = 0.014), early ambulation (p < 0.001), time to first fluid diet (p < 0.001), solid diet (p = 0.001) and reduced nasogastric tube reinsertion rates (p = 0.01) despite its early removal. CONCLUSION: ERAS with some modifications can be applied in patients with intestinal obstruction. Thus, we can expedite post-operative recovery and early regain of gastrointestinal function with decreased hospital stay, comparable morbidity and mortality. Further studies are needed to assess ERAS role in emergency gastrointestinal surgeries. Trial registration Ctri.gov Identifier: CTRI/2022/04/042156.

Sustained Low Efficiency Dialysis in Critically Ill Children With Acute Kidney Injury: Single-Center Observational Cohort in a Resource-Limited Setting.

OBJECTIVES: To evaluate use of sustained low efficiency dialysis (SLED) in critically ill children with acute kidney injury in a resource-limited setting. DESIGN: Observational database cohort study (December 2016 to January 2020). SETTING: PICU of a tertiary hospital in India. PATIENTS: Critically ill children undergoing SLED were included in the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical data, prescription variables, hemodynamic status, complications, kidney, and patient outcomes of all children undergoing SLED in the PICU were analyzed. A total of 33 children received 103 sessions of SLED. The median (interquartile range, IQR) age and weight of children who received SLED were 9 years (4.5-12.8 yr) and 26 kg (15.2-34 kg), respectively. The most common diagnosis was sepsis with septic shock in 17 patients, and the mean (± sd ) Pediatric Risk of Mortality III score at admission was 11.8 (±6.4). The median (IQR) number and mean (± sd ) duration of inotropes per session were 3 hours (2-4 hr) and 96 (±82) hours, respectively. Of 103 sessions, the most common indication for SLED was oligoanuria with fluid overload and the need for creating space for fluid and nutritional support in 45 sessions (44%). The mean (± sd ) duration of SLED was 6.4 (±1.3) hours with 72 of 103 sessions requiring priming. The mean (± sd ) ultrafiltration rate per session achieved was 4.6 (±3) mL/kg/hr. There was significant decrease in urea and creatinine by end of SLED compared with the start, with mean change in urea and serum creatinine being 32.36 mg/dL (95% CI, 18.53-46.18 mg/dL) ( p < 0.001) and 0.70 mg/dL (95% CI, 0.35-1.06 mg/dL) ( p < 0.001), respectively. Complications were observed in 44 of 103 sessions, most common being intradialytic hypotension (21/103) and bleeding at the catheter site (21/103). Despite complications in one third of the sessions, only nine sessions were prematurely stopped, and 23 of 33 patients receiving SLED survived. CONCLUSION: In critically ill children, our experience with SLED is that it is feasible and provides a viable form of kidney replacement therapy in a resource-limited setting.

Transurethral lidocaine (100 mg) bladder irrigation (TULI100) reduces the incidence of catheter related bladder discomfort in transurethral resection of bladder tumors: A randomized, double blind, controlled trial.

BACKGROUND: Transurethral resection of bladder tumors (TURBT) surgeries requires post-resection catheterization for continuous irrigation of the bladder. This indwelling catheter is associated with distressing catheter-related bladder discomfort (CRBD) and increases postoperative pain and agitation. OBJECTIVES: To prove the hypothesis that transurethral 100 mg lidocaine irrigation at the end of TURBT can reduce the frequency of moderate-to-severe postoperative CRBD. METHODS: 116 patients scheduled for TURBT were screened, 94 were recruited and completed the study. American Society of Anesthesiologists Physical Status I-II adult patients, 20-75 years of age undergoing elective TURBT surgery under general anesthesia were included. Transurethral normal saline with 0.01% lidocaine (100 mg in 1 L NS) was used for irrigation 30 min before the completion of surgery in group L, while only normal saline was used for transurethral irrigation in group N. The main outcomes were frequency of CRBD, pain and patient satisfaction at 0, 1, 2, and 6 h postoperatively. RESULTS: A total of 94 patients were analyzed in the study. The incidence of moderate-severe CRBD was significantly lower in group L as compared to group C at 0, 1, and 2 h (65.9% vs. 31.9%, p = 0.01; 31.9% vs. 10.6%, p = 0.012; 21.3% vs. 2.1%, p = 0.004, respectively). At the 6-h mark, the incidence of CRBD was lower in group L, although this did not achieve statistical significance (6.38% vs. 2.1%; p = 0.613). CONCLUSION: Irrigation with 0.01% lidocaine (100 mg) towards the end of TURBT reduces the incidence of moderate-severe CRBD by 52% and increases patient satisfaction.

Analysis of Predictors and Outcomes of COVID-19 Patients Requiring ICU Admission from COVID-19 Registry, India.

Background: Patients admitted to intensive care units (ICUs) with severe coronavirus disease (COVID-19) are associated with high mortality. The present retrospective, multicenter study describes the predictors and outcomes of COVID-19 patients requiring ICU admission from COVID-19 Registry of Indian Council of Medical Research (ICMR), India. Materials and methods: Prospectively collected data from participating institutions were entered into the electronic National Clinical Registry of COVID-19. We enrolled patients aged >18 years with COVID-19 pneumonia requiring ICU admission between March 2020 and August 2021. Exclusion criteria were negative in RT-PCR report, death within 24 hours of ICU admission, or incomplete data. Their demographic and laboratory variables, ICU severity indices, treatment strategies, and outcomes were analyzed. Results: A total of 5,865 patients were enrolled. Overall mortality was 43.2%. Non-survivors were older (58.2 ± 15.4 vs 53.6 ± 14.7 years; p = 0.001), had multiple comorbidities (33.2% vs 29.5%, p = 0.001), had higher median D-dimer (1.56 vs 1.37, p = 0.015), higher CT severity index (16.8 ± 5.2 vs 13.5 ± 5.47, p = 0.001) and longer median hospital stay (10 vs 8 days, p = 0.001) and ICU stay (5 vs 4 days, p = 0.001), compared with survivors.On multivariate analysis, high CRP (HR 1.008, 95% CI: 1.006-1.010, p = 0.001) and high D-dimer (HR 1.089, 95% CI: 1.065-1.113, p < 0.001) were associated with invasive mechanical ventilation while older age (HR 1.19, CI: 1.001-1.038, p = 0.039) and high D-dimer (HR-1.121, CI: 1.072-1.172, p = 0.001) were independently associated with mortality and while the use of prophylactic low molecular weight heparin (LMWH) (HR 0.647, CI: 0.527-0.794, p = 0.001) lowered mortality. Conclusion: Among 5,865 COVID-19 patients admitted to ICU, mortality was 43.5%. High CRP and D-dimers were independently associated with the need for invasive mechanical ventilation while older age and high D-dimer were associated with higher mortality. The use of prophylactic LMWH independently reduced mortality. How to cite this article: Kajal K, Singla K, Puri GD, Bhalla A, Mukherjee A, Kumar G, et al. Analysis of Predictors and Outcomes of COVID-19 Patients Requiring ICU Admission from COVID-19 Registry, India. Indian J Crit Care Med 2023;27(8):552-562.

Clinical profile and outcome of arteriovenous fistulae in children on maintenance hemodialysis from a low-resource setting.

INTRODUCTION: Arteriovenous fistula (AVF) is the recommended access of choice in children on maintenance hemodialysis. The challenges of creating and maintaining a fistula in children are many. The objective of our study was to describe the clinical profile and outcomes of AVFs in children from a resource-limited setting. METHODS: A retrospective analysis of children who have had an AVF for maintenance hemodialysis from 2010 to 2020 was performed. The center protocol for creation and management of complications was followed. Failure of fistula to mature was defined as primary failure. Primary patency was defined as the time from creation of access to the first complication requiring intervention. The primary failure rate, duration of primary patency and associated risk factors, and 1- and 3-year primary fistula patency rates were studied. RESULTS: Thirty-six children (38 AVFs) with the median (interquartile range) age of 11 (8, 13) years were included. Brachiocephalic anastomosis was the most common site (75%) of AVF. The primary failure rate was 5.5% (2 of 36). The mean (95% confidence interval) duration of primary patency was 42.3 (29.9, 54.7) months. There were no particular factors associated with the duration of primary patency. The 1- and 3-year primary patency rate was 91% and 73%, respectively. CONCLUSIONS: In resource-limited settings, AVF had good primary patency and is a feasible and durable access for maintenance hemodialysis in children.

Incidence & outcomes of clinically significant bleeding events in critically ill COVID-19 patients receiving Therapeutic dose AntiCoagulanTs: A retrospective cohort study (INTerACT study).

Background & objectives: The high mortality associated with the thrombotic events in hospitalized COVID-19 patients resulted in the usage of anticoagulants in varying doses. Whether high-dose anticoagulants have led to better outcomes or higher incidence of clinically significant bleeding events is debatable. Thus, this study was conducted to find the incidence of clinically significant bleeding events in moderate-to-severe COVID-19 ARDS (acute respiratory distress syndrome) patients on therapeutic anticoagulation and their outcomes. Methods: In this retrospective, single-centre study of 155 critically ill COVID-19 patients, the incidence of clinically significant bleeding was observed. Multivariate regression models were used to evaluate the association between anticoagulant regimen, coagulation and inflammatory markers with the incidence of bleeding and thrombotic events. Results: The incidence of clinically relevant non-major bleeding was 33.54 per cent (26.17-41.46%) and major bleeding was 9.03 per cent (5.02-14.69%). The anticoagulation intensity at baseline had a high odds of major bleeding when enoxaparin and dual antiplatelet therapy were used together [adjusted odds ratio OR of 434.09 (3.81-49502.95), P<0.05]. At admission, bleeders had a poorer PaO2/FiO2 ratio with more patients on invasive ventilation. At the time of bleeding, the bleeders had a higher D-dimer, ferritin, C-reactive protein and procalcitonin compared to non-bleeders. The subhazard ratio for death in bleeders was 3.35 (95% confidence interval, 1.97-5.65; P<0.001). Interpretation & conclusions: The incidence of bleeding in critically ill COVID-19 patients on therapeutic anticoagulation may increase with the severity of the disease as well as with concurrent use of dual antiplatelets. Major bleeding may also contribute to higher mortality.

Reporting adverse events of ChAdOx1 nCoV-19 coronavirus vaccine (Recombinant) among the vaccinated healthcare professionals: A cross-sectional survey.

Background & objectives: The safety of the ChAdOx1 nCoV-19 vaccine is a cause of concern for many who have been vaccinated. The people have multiple concerns and fear regarding the adverse events of the vaccine. Thus, this study was undertaken to establish the safety profile of ChAdOx1 nCoV-19 Corona Virus Vaccine (Recombinant) among the healthcare professionals. Methods: This was a descriptive cross-sectional survey. After taking clearance from the institutional ethics committee 1500 healthcare professionals, who had their vaccination in the past two weeks were selected. They were provided with an online survey proforma regarding adverse events following immunization (AEFIs) of COVID-19 vaccine developed using google forms with an informed consent form affixed to it. Results: A total of 1036 individuals participated in the study. The mean and median (inter quartile range) age of the participants was 37.7 ±11.25 and 35 (29-46) yr, respectively. Of these, 52.1 per cent were female, 29.3 per cent were doctors, 33.4 per cent were nurses and 9.5 per cent were paramedical staff. Forty six per cent participants experienced one or more minor AEFIs such as pain, tenderness, redness, etc. at the injection site. Fatigue (31.75%), generalized feeling of unwell (28.57%), muscle pain (23.16%) and fever (21.71%) were the most commonly reported systemic AEFIs followed by headache (20.07%), dizziness (10.03%) and joint pains (15.25%). Most of them experienced these AEFIs within 24 h of the first dose of administration. About 42 per cent of the participants took oral antipyretics/analgesics for managing the AEFIs. Interpretation & conclusions: ChAdOx1 nCoV-19 Corona Virus Vaccine was found to be associated with mild local and systemic AEFIs that were more common after the first dose as compared to the second dose. There adverse events could be dealt with oral over-the-counter medications, with no requirement of hospitalization.

Sub-optimal gain in vision in retinal vein occlusion due to under-treatment in the real world: results from an open-label prospective study of Intravitreal Ranibizumab.

BACKGROUND: Macular edema secondary to retinal vein occlusion (RVO) is an important cause of loss of vision. Intravitreal injections (IVI) of anti-vascular endothelial growth factor (VEGF) are the standard of care in this disease, as shown in numerous randomized controlled trials. The purpose of this study was to study the efficacy and safety of ranibizumab, an anti-VEGF agent, in the real-world setting. METHODS: This was 48 weeks, open-label, prospective, multicentre, observational study. Patients diagnosed with ME secondary to RVO were treated with IVI of Ranibizumab 0.5 mg in real-world conditions. Efficacy was measured by improvement seen in best-corrected visual acuity (BCVA) in terms of Early Treatment of Diabetic Retinopathy Study (ETDRS) Letter Scores and change in central retinal thickness (CRT) measured by optical coherence tomography. RESULTS: One hundred eyes of 100 patients (79 with branch retinal vein occlusion and 21 with central retinal vein occlusion) were recruited in the study. The mean (standard deviation, SD) BCVA was 52.8 (21.99) letters at baseline and 62.3 (24.40) letters at week 48. From baseline, there was a significant improvement in BCVA by 7.7 letters (p = 0.001) at 48 weeks. The mean (SD) of CRT was 479.9 (216.25) µm at baseline and it decreased significantly to 284.9 (171.35) µm at week 48 (p < 0.001). During the study period, the average number of intravitreal injections was 3.5 per patient. There was no report of endophthalmitis in any eye. CONCLUSIONS: Ranibizumab is well tolerated and effective in treating macular edema secondary to RVO in real-world clinical settings. However, there is under-treatment compared to controlled clinical trials, and the gain in vision is sub-optimal with under-treatment. TRIAL REGISTRATION: Clinical Trials Registry - India: CTRI/2015/07/005985 .

Scope of artificial intelligence in airway management.

The evolution of artificial intelligence (AI) systems in the field of anaesthesiology owes to notable advancements in data processing, databases, algorithmic programs, and computation power. Over the past decades, its accelerated progression has enhanced safety in anaesthesia by improving the efficiency of equipment, perioperative risk assessments, monitoring, and drug administration systems. AI in the field of anaesthesia aims to improve patient safety, optimise resources, and improve the quality of anaesthesia management in all phases of perioperative care. The use of AI is likely to impact difficult airway management and patient safety considerably. AI has been explored to predict difficult intubation to outperform conventional airway examinations by integrating subjective factors, such as facial appearance, speech features, habitus, and other poorly known features. This narrative review delves into the status of AI in airway management, the most recent developments in this field, and its future clinical applications.

South Asian medical cohorts reveal strong founder effects and high rates of homozygosity.

The benefits of large-scale genetic studies for healthcare of the populations studied are well documented, but these genetic studies have traditionally ignored people from some parts of the world, such as South Asia. Here we describe whole genome sequence (WGS) data from 4806 individuals recruited from the healthcare delivery systems of Pakistan, India and Bangladesh, combined with WGS from 927 individuals from isolated South Asian populations. We characterize population structure in South Asia and describe a genotyping array (SARGAM) and imputation reference panel that are optimized for South Asian genomes. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of rare homozygotes that reach 100 times that seen in outbred populations. Founder effects increase the power to associate functional variants with disease processes and make South Asia a uniquely powerful place for population-scale genetic studies.

Primary Aortoesophageal Fistula Presenting as Upper Gastrointestinal Bleed.

Aortoenteric fistula is a rare condition that can be primary or secondary. The primary type is less common than the secondary. The secondary aortoenteric fistula is an uncommon fatal complication after reconstructive surgery for an aortic aneurysm or other aortic diseases. Here we present a case of a 59-year-old man who presented to our emergency department with sudden onset of massive hematemesis. Imaging studies were done and the patient was diagnosed to have aortoesophageal fistula. Upper gastrointestinal endoscopy showed an intraluminal bulge in the posterior wall of the esophagus with an ulcer and hematoma. The patient was planned for emergency surgical intervention, but the patient had recurrent bouts of hematemesis and, unfortunately, expired. Hence patients presenting with massive hematemesis, aortoenteric fistula can be the underlying cause, and all surgeons should be aware of such conditions and the need for emergent surgical intervention.

Neurosurgical Emergency in an Adult With Single Ventricle Physiology: A Case Report.

The anesthetic management of a patient with uncorrected congenital heart disease presenting for noncardiac surgery is quite challenging. When this becomes a neurosurgical emergency, the need to balance cerebral and complex circulatory physiologies tests the anesthesiologist's preparedness. The principal clinical challenges we faced were preventing increases in intracranial pressure while maintaining the circulatory physiology using the "cardiac grid" approach to hemodynamic management in a case of acyanotic double outlet right ventricle with a posterior fossa space-occupying lesion. Point of care preoperative echocardiography enabled us to understand the altered circulatory physiology and successfully manage this patient.

Small Cell Carcinoma of Gallbladder With Nodal Metastasis Mimicking As Synchronous Malignancy in Gallbladder and Common Bile Duct.

Small cell carcinoma of the gallbladder is an extremely rare disease. Even with current aggressive and diverse treatments, small cell carcinoma of the gallbladder has an extremely poor prognosis. The presence of synchronous malignancies in the gallbladder and the biliary tract is even rare. Synchronous malignancy can be due to either local spread or metastasis. It can also occur due to field change in the extrahepatic malignancy or can arise de novo as multifocal malignancy. Small cell carcinoma of gallbladder with nodal metastasis mimicking as synchronous malignancy in the gallbladder and distal common bile duct is rare. We report a 74-year-old male who presented with abdominal pain and jaundice. Initial imaging studies were suggestive of the possibility of synchronous malignancy in the gallbladder and common bile duct. However, further imaging studies showed that carcinoma of the gallbladder had metastasis to the lymph nodes, causing external compression to the common bile duct rather than synchronous malignancy. Cytology was diagnostic of small cell carcinoma of the gallbladder. The patient had metastasis to other sites also. The patient underwent endoscopic retrograde cholangiopancreatography with stenting and started on palliative platinum-based chemotherapy with cisplatin and gemcitabine, and he is under regular follow-up.

High-Dose Dexamethasone Versus Tocilizumab in Moderate to Severe COVID-19 Pneumonia: A Randomized Controlled Trial.

Background and objectives Recent randomized controlled trials (RCTs) have indicated potential therapeutic benefits with high-dose dexamethasone (HDD) or tocilizumab (TCZ) plus standard care in moderate to severe coronavirus disease 2019 (COVID-19) with acute respiratory distress syndrome (ARDS). No study has compared these two against each other. We aimed to compare the efficacy and safety of HDD against TCZ in moderate to severe COVID-ARDS. Methods Patients admitted with moderate to severe COVID-19 ARDS with clinical worsening within 48 hours of standard care were randomly assigned to receive either HDD or TCZ plus standard care. The primary outcome was ventilator-free days (VFDs) at 28 days. The main secondary outcomes were 28-day all-cause mortality and the incidence of adverse events. Our initial plan was to perform an interim analysis of the first 42 patients. Results VFDs were significantly lower in the HDD arm (median difference: 28 days; 95% confidence interval (CI): 19.35-36.65; Cohen's d = 1.14;p < 0.001). We stopped the trial at the first interim analysis due to high 28-day mortality in the HDD arm (relative risk (RR) of death: 6.5; p = 0.007; NNT (harm) = 1.91). The incidence of secondary infections was also significantly high in the HDD arm (RR: 5.5; p = 0.015; NNT (harm) = 2.33). Conclusions In our study population, HDD was associated with a very high rate of mortality and adverse events. We would not recommend HDD to mitigate the cytokine storm in moderate to severe COVID-19 ARDS. TCZ appears to be a much better and safer alternative.

Pulmonary Function, Mental and Physical Health in Recovered COVID-19 Patients Requiring Invasive Versus Non-invasive Oxygen Therapy: A Prospective Follow-Up Study Post-ICU Discharge.

Background Survivors of COVID-19 pneumonia may have residual lung injury and poor physical and mental health even after discharge. We hypothesized that COVID-19 severe acute respiratory distress syndrome (ARDS) patients needing mechanical ventilation may be at a greater risk of deterioration in pulmonary function, mental health, and quality of life (QOL). This study analyses the differences in pulmonary function, mental health, and QOL after recovery, in patients having received non-invasive oxygen therapy versus invasive mechanical ventilation during ICU stay. Methods Patients aged >18 years, who had completed 3 months post ICU discharge, with moderate to severe COVID-19 ARDS, were consecutively enrolled from May 1 to July 31, 2021. Patients were allocated into Group A - having required high flow nasal cannula (HFNC)/non-invasive ventilation (NIV) and Group B - having received invasive mechanical ventilation. Pulmonary function tests, 6-minute walk test (6-MWT), and health-related quality of life were compared. Results Of the 145 eligible patients, 31 were lost to follow-up and 21 died. Seventy-four patients were allocated into Groups A (57 patients) and B (17 patients). In Group A, abnormal forced expiratory volume in first second (FEV1), forced vital capacity (FVC), forced expiratory flow in mid-half of FVC (FEF25-75), and peak expiratory flow rate (PEFR) values were obtained in 27 (47.37%), 43 (75.44%), 11 (19.3%), and 25 (43.86%) patients, and in Group B, in 13 (76.47%), 17 (100%), 1 (5.88%), and 8 (47%) patients, respectively. No patient had abnormal FEV1/FVC. All Group B patients had a restrictive pattern in spirometry as compared to 77% in Group A. Group B had a lower arterial partial pressure of oxygen (PaO2) (p=0.0019), % predicted FVC (p<0.0001), % predicted FEV1 (p=0.001), and 6-MWT distance (p<0.001). The physical component score in the short-form survey 12 questionnaire was higher in group A, p<0.001, whereas the mental component score was comparable. Conclusions Patients requiring invasive mechanical ventilation (MV) have a greater risk of impaired pulmonary function and reduced QOL post-ICU discharge. This warrants a greater need for following these patients for better rehabilitation.

ßA1-crystallin regulates glucose metabolism and mitochondrial function in mouse retinal astrocytes by modulating PTP1B activity.

ßA3/A1-crystallin, a lens protein that is also expressed in astrocytes, is produced as ßA3 and ßA1-crystallin isoforms by leaky ribosomal scanning. In a previous human proteome high-throughput array, we found that ßA3/A1-crystallin interacts with protein tyrosine phosphatase 1B (PTP1B), a key regulator of glucose metabolism. This prompted us to explore possible roles of ßA3/A1-crystallin in metabolism of retinal astrocytes. We found that ßA1-crystallin acts as an uncompetitive inhibitor of PTP1B, but ßA3-crystallin does not. Loss of ßA1-crystallin in astrocytes triggers metabolic abnormalities and inflammation. In CRISPR/cas9 gene-edited ßA1-knockdown (KD) mice, but not in ßA3-knockout (KO) mice, the streptozotocin (STZ)-induced diabetic retinopathy (DR)-like phenotype is exacerbated. Here, we have identified ßA1-crystallin as a regulator of PTP1B; loss of this regulation may be a new mechanism by which astrocytes contribute to DR. Interestingly, proliferative diabetic retinopathy (PDR) patients showed reduced ßA1-crystallin and higher levels of PTP1B in the vitreous humor.