The Efficacy of vitamin C, thiamine, and corticosteroid therapy in adult sepsis patients: a systematic review and meta-analysis

Manoj Kumar Reddy Somagutta,Maria Kezia Lourdes Pormento,Muhammad Adnan Khan,Alaa Hamdan,Namrata Hange,Manish KC,Sukrut Pagad,Molly Sanjay Jain,Sivasthikka Lingarajah,Vishal Sharma,Jaspreet Kaur,Berna 대한중환자의학회 2021 Acute and Critical Care Vol.36 No.3

Background: Previous studies have suggested favorable outcomes of hydrocortisone, ascorbic acid (vitamin C), and thiamine (HAT) therapy in patients with sepsis. However, similar results have not been duplicated in sequential studies. This meta-analysis aimed to reevaluate the value of HAT treatment in patients with sepsis. Methods: Electronic databases were searched up until October 2020 for any studies that compared the effect of HAT versus non-HAT use in patients with sepsis. Results: Data from 15 studies (eight randomized controlled trials [RCTs] and seven cohort studies) involving 67,349 patients were included. The results from the RCTs show no significant benefit of triple therapy on hospital mortality (risk ratio [RR], 0.99; P=0.92; I2=0%); intensive care unit (ICU) mortality (RR, 0.77; P=0.20; I2=58%); ICU length of stay (weighted mean difference [WMD], 0.11; P=0.86; I2=37%) or hospital length of stay (WMD: 0.57; P=0.49; I2=17%), and renal replacement therapy (RR, 0.64; P=0.44; I2=39%). The delta Sequential Organ Failure Assessment (SOFA) score favored treatment after a sensitivity analysis (WMD, –0.72; P=0.01; I2=32%). However, a significant effect was noted for the duration of vasopressor use (WMD, –25.49; P<0.001; I2=46%). The results from cohort studies have also shown no significant benefit of HAT therapy on hospital mortality, ICU mortality, ICU length of stay, length of hospital stay, the delta SOFA score, the use of renal replacement therapy, or vasopressor duration. Conclusions: HAT therapy significantly reduced the duration of vasopressor use and improved the SOFA score but appeared not to have significant benefits in other outcomes for patients with sepsis. Further RCTs can help understand its benefit exclusively.

The Safety and Efficacy of Anakinra, an Interleukin-1 Antagonist in Severe Cases of COVID-19: A Systematic Review and Meta-Analysis

Manoj Kumar Reddy Somagutta,Lourdes Pormento Maria Kezia,Pousette Hamid,Alaa Hamdan,Muhammad Adnan Khan,Rockeven Desir,Rupalakshmi Vijayan,Saloni Shirke,Rishan Jeyakumar,Zeryab Dogar,Sarabjot Singh Ma 대한감염학회 2021 Infection and Chemotherapy Vol.53 No.2

This study aims to assess anakinra's safety and efficacy for treating severe coronavirus disease 2019 (COVID-19). Numerous electronic databases were searched and finally 15 studies with a total of 3,530 patients, 757 in the anakinra arm, 1,685 in the control arm were included. The pooled adjusted odds ratio (OR) for mortality in the treatment arm was 0.34 (95% confidence interval [CI], 0.21 - 0.54, I2 = 48%), indicating a significant association between anakinra and mortality. A significant association was found regarding mechanical ventilation requirements in anakinra group compared to the control group OR, 0.68 (95% CI, 0.49 - 0.95, I2 = 50%). For the safety of anakinra, we evaluated thromboembolism risk and liver transaminases elevation. Thromboembolism risk was OR, 1.59 (95% CI, 0.65 - 3.91, I2 = 0%) and elevation in liver transaminases with OR was 1.35 (95% CI, 0.61 - 3.03, I2 = 76%). Both were not statistically significant over the control group. Anakinra is beneficial in lowering mortality in COVID-19 patients. However, these non-significant differences in the safety profile between the anakinra and control groups may have been the result of baseline characteristics of the intervention group, and further studies are essential in evaluating anakinra's safety profile.

Dietary Changes Leading to Euglycemic Diabetic Ketoacidosis in Sodium-Glucose Cotransporter-2 Inhibitor Users: A Challenge for Primary Care Physicians?

Manoj Kumar Reddy Somagutta,Utkarsha Uday,Nishat Shama,Narayana Reddy Bathula,Siva Pendyala,Ashwini Mahadevaiah,Greta Mahmutaj,Ngaba Negumadji Ngardig 대한가정의학회 2022 Korean Journal of Family Medicine Vol.43 No.6

Background: The use of euglycemic diabetic ketoacidosis (EDKA) related to sodium-glucose cotransporter 2 in-hibitors (SGLT2i) use in people with diabetes has been increasingly reported. The causes are multifactorial, and di-etary changes in SGLT2i users were observed to trigger EDKA. A ketogenic diet or very low-carbohydrate diet (VLCD) enhances body ketosis by breaking down fats into energy sources, causing EDKA. This study aimed to un-derstand the patient specific risk factors and clinical characteristics of this cohort. Methods: Several databases were carefully analyzed to understand the patients’ symptoms, clinical profile, labora-tory results, and safety of dietary changes in SGLT2i’s. Thirteen case reports identifying 14 patients on a ketogenic diet and SGLT2i’s diagnosed with EDKA were reviewed. Results: Of the 14 patients, 12 (85%) presented with type-2 diabetes mellitus (DM) and 2 (15%) presented with type-1 DM. The duration of treatment with SGLT2i before the onset of EDKA varies from 1 to 365 days. The duration of consuming a ketogenic diet or VLCD before EDKA onset varies from 1 to 90 days, with over 90% of patients hospi-talized <4 weeks after starting the diet. At presentation, average blood glucose was 167.50±41.80 mg/dL, pH 7.10±0.10, HCO3 8.1±3.0 mmol/L, potassium 4.2±1.1 mEq/L, anion-gap 23.6±3.5 mmol/L, and the average hemo-globin A1c was 10%±2.4%. The length of hospital stay ranged from 1 to 15 days. None of the patients were reinitiated on SGLT2i’s, and 50% (2/4) of the patients reported were on the ketogenic diet or VLCD upon patient questioning.Conclusion: Despite the popularity of the ketogenic diet and VLCD for weight loss, their use in diabetics taking SGLT2i’s is associated with EDKA. Physicians should educate patients with diabetes taking SGLT2i’s about the risk of EDKA. In addition, patients should be encouraged to include their physicians in any decision related to signifi-cant changes in diet or exercise routines. Further research is needed to address if SGLT2i’s should be permanently discontinued in patients with diabetes on SGLT2i and whether the ketogenic diet developed EDKA.

Ruxolitinib and the Mitigation of Severe COVID-19: A Systematic Review and Meta-analysis

Jorge R. Quiros,Jennifer Ross-Comptis,Donald Hathaway,Azza Sarfraz,Zouina Sarfraz,Zhanna Grigoryan,Kimberly Anne Romero,Abubakar Gapizov,Fortunato S Príncipe-Meneses,Manoj Reddy Somagutta,Adrian Riva- 대한감염학회 2021 Infection and Chemotherapy Vol.53 No.3

Background: The cause of end-organ damage and acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) patients is postulated to be connected to the uncontrolled increase of pro-inflammatory cytokines. The upregulation of many cytokines is dependent on signaling through the Janus kinase 1 (JAK-1) and JAK-2 pathways. Ruxolitinib, a JAK-1 and JAK-2 inhibitor, is documented to have potent anti-inflammatory activity by targeting several cytokines and growth factors with proposed efficacy in the cytokine storm observed in severe COVID-19 patients; therefore, this study examines the efficacy and tolerability of ruxolitinib for adult COVID-19 patients. Materials and Methods: This review was conducted using preferred reporting items for aystematic reviews and meta-analyses (PRISMA) methodology. Six reviewers analyzed 1,120 results. Seven studies were selected and validated. A quantitative meta-analysis was further performed to evaluate clinical improvement at day 28, mortality at day 28, and oxygen requirements comparing treatment and standard of care groups. Results: 168 individuals were involved in the studies selected: 122 in cohort studies, 4 in case reports, and 41 in randomized controlled studies. The ruxolitinib group had a higher likelihood of clinical improvement by the 28th day of treatment when assessed with the standard of care (SOC) group (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 0.53 - 4.16; P = 0.45; I2 = 0%). The SOC group was at a higher risk of experiencing serious adverse events (OR: 0.17; 95% CI: 0.03 - 1.13; P = 0.07). Notably the SOC group had a higher likelihood of death (OR: 0.51; 95% CI: 0.11-2.29; P = 0.07; I2 = 0%). Conclusion: Prior studies on ruxolitinib have demonstrated it is able to decrease inflammatory markers. In recent studies on COVID-19, treatment with ruxolitinib decreased the time on mechanical ventilation, hospitalization time, and the need for vasopressor support. Additionally, ruxolitinib showed decreased mortality and demonstrated improvement in lung congestion as evidenced by computerized tomography imaging. These findings warrant further clinical investigation into Ruxolitinib as a potential treatment approach for severe COVID-19.