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Background: Idiopathic intracranial hypertension (IIH) is a neurological disorder characterized by elevated intracranial pressure, predominantly affecting young women with obesity. This study evaluates the effectiveness of semaglutide as an adjunctive therapy to standard IIH management using real-world data., Methods: We conducted a retrospective cohort analysis comparing IIH patients receiving semaglutide plus standard therapy versus standard therapy alone. After propensity score matching, we analyzed 635 patients in each cohort. Primary outcomes included papilledema, headache manifestations, visual disturbances, and refractory disease status at 3-months, 6-months, 12-months, and 24-months. Secondary outcomes included BMI changes., Result: Semaglutide demonstrated significant improvements across all outcomes. At three months, the treatment group showed reduced risks of visual disturbances (RR 0.28, 95% CI 0.179-0.440, p=0.0001), papilledema (RR 0.366, 95% CI 0.260-0.515, p=0.0001), and headache (RR 0.578, 95% CI 0.502-0.665, p=0.0001). These benefits persisted through 24 months. Refractory disease risk was reduced by 40% at three months (RR 0.6, 95% CI 0.520-0.692, p=0.0001). The semaglutide group showed progressive BMI reduction, with a baseline-adjusted difference of -1.38 kg/m 2 (95% CI [-1.671, -1.089], p<0.0001) at 24 months., Conclusions: Semaglutide as an adjunctive therapy demonstrates significant and sustained improvements in IIH-related outcomes, including visual disturbances, papilledema, and headache symptoms. These findings suggest semaglutide may be a valuable addition to standard IIH management protocols, particularly for patients with refractory disease.

Introduction: Idiopathic intracranial hypertension (IIH) has been traditionally viewed as a neuro-ophthalmic disorder, yet emerging evidence suggests broader systemic implications. Our study investigates the cardiometabolic outcomes associated with IIH through a comprehensive matched-cohort analysis., Methods: We conducted a retrospective analysis of electronic health records from 2009 to 2024. We compared IIH patients with matched controls using propensity score matching based on age, sex, race, ethnicity, and baseline BMI. Cardiovascular and metabolic outcomes were assessed over a ten-year follow-up period, with additional stratified analyses comparing obese and non-obese subgroups., Results: IIH patients demonstrated significantly increased risks of ischemic stroke/TIA (RR 2.515, 95% CI 2.250-2.812) and non-traumatic hemorrhagic stroke (RR 7.744, 95% CI 6.118-9.801). Notable metabolic findings included elevated risks of insulin resistance (RR 1.470, 95% CI 1.258-1.717) and type 2 diabetes mellitus (RR 1.210, 95% CI 1.171-1.250). These associations persisted in non-obese IIH patients, suggesting pathogenic mechanisms independent of adiposity. Additionally, IIH patients showed increased prevalence of polycystic ovarian syndrome (RR 1.470, 95% CI 1.258-1.717) and metabolic syndrome (RR 1.125, 95% CI 1.045-1.205)., Conclusions: Our findings highlight IIH as a complex multisystem disorder with significant cardiometabolic implications beyond its traditional neuro-ophthalmic presentation. The findings suggest the need for comprehensive cardiovascular and metabolic screening in IIH patients, regardless of BMI status, and indicate potential novel therapeutic targets for investigation.

Introduction: Idiopathic intracranial hypertension (IIH) remains a challenging condition to manage, with limited therapeutic options. This study investigated the potential of metformin as a novel treatment for IIH, exploring its effects on disease outcomes and safety profile., Methods: We conducted a retrospective cohort study using the TriNetX database, analyzing data from 2009 to August 2024. Patients diagnosed with IIH were included, with exclusions for other causes of elevated intracranial pressure and pre-existing diabetes. Propensity score matching was employed to balance cohorts according to age, sex, race, ethnicity, Hemoglobin A1C, and baseline body mass index (BMI) at the time of metformin initiation. Outcomes were assessed at various follow-up points up to 24 months., Results: Our study initially comprised 1,268 patients in the metformin group and 49,262 in the control group, with notable disparities in several parameters. Post-matching, both cohorts were refined to 1,267 patients each after matching with metformin group. Metformin-treated patients showed significantly lower risks of papilledema, headache, and refractory IIH status at all follow-up points (p<0.0001). The metformin group also had reduced rates of therapeutic spinal punctures and acetazolamide continuation. BMI reductions were more pronounced in the metformin group, with significant differences observed from 6 months onward (p<0.0001). Notably, metformin's beneficial effects persisted independently of BMI changes. The safety profile of metformin was favorable, with no significant differences in adverse events compared to the control group which did not receive metformin during the study timeframe., Conclusions: Our study provides evidence for metformin's potential as a disease-modifying therapeutic approach in IIH, demonstrating improvements across multiple outcomes. The benefits appear to extend beyond weight loss, suggesting complex mechanisms of action. These findings warrant further investigation through prospective clinical trials to establish metformin's role in IIH management and explore its underlying therapeutic mechanisms.

Background: Prostate cancer patients undergoing long-term (Androgen deprivation therapy) ADT will tend to have metabolic changes. Metabolic syndrome represents the accumulation of several medical conditions that significantly increase the risk of developing severe diseases like cardiovascular disorders, insulin resistance, and hyperglycemia. We are conducting this systematic review and meta-analysis to fill up the gap and to resolve the debate regarding the effectiveness of metformin in reducing metabolic syndrome associated with ADT in prostate cancer patients., Methods: We conducted the systematic review and meta-analysis according to the Handbook of Cochrane Systematic Review of Intervention and the PRISMA guidelines. We conducted the search process using the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Scopus, and Web of Science. We selected the articles that fit within the following criteria, Randomized Controlled Trials (RCTs) and Cohort studies which evaluate the efficacy of metformin in reducing metabolic syndromes for prostate cancer patients undergoing androgen deprivation therapy (ADT). The efficacy of metformin in metabolic syndrome that resulted from using androgen deprivation therapy for prostate cancer patients was evaluated by the changes from baseline in Body Mass Index (BMI), waist circumference by cm, glycated hemoglobin (HbA1c), and blood pressure both systolic and diastolic. Revman software Version 5.4.1 was used to perform all statistical analyses., Results: Our search retrieved 781 records. Seven records were included in our study: 5 published randomized control clinical trials and 2 cohort studies and only 6 studies were included in the meta-analysis. For BMI the pooled effect estimates of 3 studies favored Metformin over placebo, but this is not a significant difference (MD = -0.9, P = 0.05), for systolic pressure the pooled effect estimates of 3 studies favored Metformin over placebo, but this is not a significantly different placebo (MD = -3.18, P = 0.22), for HBA1c the pooled effect estimates of 3 studies showed that no significant difference between placebo and metformin (MD = -0.01, P = 0.86)002E CONCLUSION: Despite the promising direction in some parameters, our findings underscore the need for further research to establish a clearer understanding of metformin's role in mitigating metabolic changes in prostate cancer patients undergoing ADT., Competing Interests: Declaration of competing interest Dr. Abdelshafi has nothing to disclose. All the authors also declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Limited data exists on the safety and efficacy with the concomitant use of 4 factor prothrombic complex concentrate (4F-PCC) and andexanet alfa (AA). This case series describes 7 patients at our institution who received both 4F-PCC and AA for the management of life-threatening bleeding associated with apixaban or rivaroxaban. Four patients received AA due to worsening bleeding after 4F-PCC. Of the 7 patients in this case series, 1 had a documented thrombotic event which was an acute ischemic stroke. The thrombotic event rate in our case series was similar to the incidence of thrombotic events reported with the use of AA alone. In-hospital mortality occurred in 2 of 7 patients with 1 additional patient discharged to hospice care., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Objective: To evaluate the accuracy of abbreviated urine collection (≤12 hours) compared with 24-hour urine collection for measuring creatinine clearance (CrCl) in critically ill adult patients., Data Sources: We searched PubMed, Embase, Web of Science, Google Scholar, and ProQuest Dissertations and Thesis Global; screened reference lists of included studies; and contacted the authors when needed. English studies only were considered with no restriction on dates., Study Selection and Data Extraction: After duplicate removal, 2 reviewers screened titles/abstracts, reviewed full-text articles, and extracted data independently. Studies that compared abbreviated versus 24-hour urine collection for measuring CrCl were included. We assessed the risk of bias using the QUADAS-2 tool. We extracted correlation coefficients, mean prediction errors (ME)-as a measure of bias, and root mean squared prediction errors (RMSE)-as a measure of precision., Data Synthesis: Five studies were included, comprising 528 adult critically ill adults from surgical, medical, and trauma intensive care units (ICUs). Three studies had high risk of bias, and 2 had low risk. The studies evaluated different durations of urine collection, including 30-minute, 2-hour, 4-hour, 6-hour, and 12-hour. Mean 24-hour CrCl ranged from 57 mL/min/1.73 m 2 to 103 mL/min. Abbreviated urine collection led to CrCl that correlated well with the 24-hour measured CrCl (correlation coefficient ranged from 0.8 to 0.95). Mean prediction error ranged from 5 mL/min/1.73 m 2 to 16 mL/min (from 8% to 25% of the 24-hour CrCl). Root mean squared prediction error calculated from 1 study was 30.5 mL/min/1.73 m 2 ., Relevance to Patient Care and Clinical Practice: Abbreviated urine collection is used to measure CrCl for renal drug dosing in critically ill patients, but its accuracy is not well-established., Conclusions: Abbreviated urine collection may overestimate CrCl compared with 24-hour urine collection. Larger, well-conducted studies are needed to evaluate the accuracy of CrCl measured using different durations of urine collection in critically ill patients., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: A mainstay in the acute management of diabetic ketoacidosis (DKA) is fluid resuscitation. Normal saline is recommended by the American Diabetes Association; however, it has been associated with hyperchloremic metabolic acidosis and acute kidney injury. Limited literature is available to determine the most appropriate crystalloid fluid to treat patients with DKA., Objective: The purpose of this study was to compare lactated Ringer's (LR) to normal saline (NS) in the acute management of DKA., Methods: This was a retrospective, multicenter single health system cohort study. The primary outcome was to evaluate the time to high anion gap metabolic acidosis (HAGMA) resolution using LR compared to NS. Secondary outcomes included the incidence of nongap metabolic acidosis, hyperchloremia, acute kidney injury, and new renal replacement therapy. Other secondary outcomes included insulin infusion duration and hospital and intensive care unit length of stay. The Cox proportional hazards model was used for the primary outcome., Results: A total of 771 patient encounters were included. Lactated Ringer's was associated with faster time to HAGMA resolution compared to NS (adjusted hazard ratio 1.325; 95% confidence interval 1.121-1.566; p < 0.001). No difference was found in complications such as incidence of nongap metabolic acidosis, hyperchloremia, acute kidney injury, and new renal replacement therapy between the LR and NS groups. Additionally, there was no difference in insulin infusion duration and hospital or intensive care unit length of stay., Conclusion: Treatment with LR as the primary crystalloid for acute DKA management was associated with faster HAGMA resolution compared with NS. Similar incidence in complications and length of stay was observed between the two groups. The findings of this study add to the accumulating literature suggesting that balanced crystalloids may offer an advantage over NS for the treatment of patients with DKA., (© 2024 Pharmacotherapy Publications, Inc.)

Objective: Our study aimed to compare the outcomes of COVID-19 patients who met a low-risk inclusion criteria for veno-venous extra corporeal membrane oxygenation (VV ECMO) with those who did not meet criteria due to higher risk but were subsequently cannulated., Methods: This was a retrospective observational cohort study that included adult patients who were placed on VV ECMO for COVID-19 related acute respiratory distress syndrome (ARDS) at a tertiary care academic medical center. The primary outcome was the association between the low-risk criteria and mortality. The patients met the criteria if they met EOLIA severe ARDS criteria, no absolute contraindications (age > 60 years, BMI > 55 kg/m 2 , mechanical ventilation (MV) duration >7 days, irreversible neurologic damage, chronic lung disease, active malignancy, or advanced multiorgan dysfunction), and had three or less relative contraindications (age > 50 years, BMI > 45 kg/m 2 , comorbidities, MV duration > 4 days, acute kidney injury, receiving vasopressors, hospital LOS > 14 days, or COVID-19 diagnosis > 4 weeks)., Results: Sixty-five patients were included from March 2020 through March 2022. Patients were stratified into low-risk or high-risk categories. The median Sequential Organ Failure Assessment score was 7 and the median PaO2/FiO2 ratio was 44 at the time of ECMO cannulation. The in-hospital mortality was 47.8% in the low-risk group and 69.0% in the high-risk group ( p  = 0.096)., Conclusion: There was not a statistically significant difference in survival between low-risk patients and high-risk patients; however, there was a trend toward higher survival in the lower-risk group., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Chemotherapy is still the mainstay of treatment for triple-negative breast cancer (TNBC) patients. Yet only 20% of TNBC patients show a pathologic complete response (pCR) after neoadjuvant chemotherapy. 5-Fluorouracil (5-FU) is a stable cornerstone in all recommended chemotherapeutic protocols for TNBC patients. However, TNBC patients' innate or acquired chemoresistance rate for 5-FU is steeply escalating. This study aims to unravel the mechanism behind the chemoresistance of 5-FU in the aggressive TNBC cell line, MDA-MB-231 cells, to explore further the role of the tumor suppressor microRNAs (miRNAs), miR-1275, miR-615-5p, and Let-7i, in relieving the 5-FU chemoresistance in TNBC, and to finally provide a translational therapeutic approach to co-deliver 5-FU and the respective miRNA oligonucleotides using chitosan-based nanoparticles (CsNPs). In this regard, cellular viability and proliferation were investigated using MTT and BrdU assays, respectively. 5-FU was found to induce JAK/STAT and PI3K/Akt/mTOR pathways in MDA-MB-231 cells with contaminant repression of their upstream regulators miR-1275, miR-615-5p, and Let-7i. Moreover, CsNPs prepared using the ionic gelation method were chosen and studied as nanovectors of 5-FU and a combination of miRNA oligonucleotides targeting TNBC. The average particle sizes, surface charges, and morphologies of the different CsNPs were characterized using dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. In addition, the encapsulation efficiency (EE%), drug loading capacity (DLC%), and release manner at two different pH values were assessed. In conclusion, the novel CsNPs co-loaded with 5-FU and the combination of the three miRNA oligonucleotides demonstrated synergistic activity and remarkable repression in cellular viability and proliferation of TNBC cells through alleviating the chemoresistance to 5-FU.

Objectives: To describe cangrelor use in patients on concurrent mechanical circulatory support who underwent postpercutaneous coronary intervention., Design: A single-center, retrospective, cohort study., Setting: At a quaternary teaching hospital., Participants: Included patients were ≥18 years old, admitted to the intensive care unit, underwent percutaneous coronary intervention with stent placement, initiated on mechanical circulatory support, and received cangrelor in the postpercutaneous coronary intervention period., Interventions: Retrospectively analyzed cangrelor use in patients on mechanical circulatory support., Measurements and Main Results: The primary outcome was the incidence of thrombosis and bleeding events during cangrelor administration. Additional outcomes included initial cangrelor dose, number of cangrelor dose adjustments per patient, survival from mechanical circulatory support, and mortality within 30 days. Overall, 19 patients were included in this study. In total, 14 patients (74%) experienced a bleeding event; however, 93% were classified as a minor bleed. There was 1 major bleeding event. There were no thrombotic events observed during cangrelor administration. The median initial cangrelor dose was 0.5 µg/kg/min. There were 10 patients who underwent dose adjustment, with the majority being dose reductions based on antiplatelet monitoring (VerifyNow assay). Survival from mechanical circulatory support occurred in 17 patients (89%), and 30-day mortality occurred in 8 patients (42%)., Conclusions: For patients receiving cangrelor as a bridge to oral P2Y12 inhibitor therapy on mechanical circulatory support, the authors observed a low rate of major bleeding and no episodes of thrombosis. Lower starting doses appear feasible with no observed increased risk of thrombotic complications. Future studies are needed to confirm these observations., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Severe COVID-19 is associated with a dysregulated immune response that usually leads to cytokine release syndrome. This study aimed to compare the use of extracorporeal blood purification therapy (Oxiris ® ) versus standard continuous renal replacement therapy (CRRT) in critically-ill patients with severe COVID-19., Methods: This was a national, multicenter, retrospective study of patients with COVID-19 admitted to the intensive care unit (ICU) between March and October 2020 who required CRRT. Patients were categorized into two groups: Oxiris ® CRRT and standard CRRT. The primary outcome was the number of patients alive and ventilator-free at 30-days post-CRRT treatment. Key secondary endpoints included change in inflammatory markers, Sequential Organ Failure Assessment (SOFA) scores, and PaO 2 /FiO 2 ratio at 24- and 72-h post Oxiris ® initiation., Results: Thirty-five patients received Oxiris ® CRRT and 23 patients received standard CRRT. The primary outcome was 31.4% in the Oxiris ® group versus 4.3% in the standard CRRT group (adjusted odds ratio 5.97, 95% confidence interval [CI], 0.64-55.6; p  = 0.117). In the Oxiris ® group, interleukin-6 (IL-6) concentrations significantly decreased at 24 and 72-h ( p  = 0.033) and PaO 2 /FiO 2 ratio significantly increased at 24 and 72 h after Oxiris ® initiation ( p  = 0.001). There was no significant change in SOFA scores at 24- and 72-h after Oxiris ® initiation., Conclusion: The number of patients alive and ventilator-free at 30-days was higher in the Oxiris ® group than that in the standard CRRT group; however, the difference did not reach statistical significance after adjusting for the baseline severity of illness. There was a significant reduction in IL-6 and significant improvement in PaO 2 /FiO 2 ratio after Oxiris ® CRRT initiation., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

To provide precise medical regimens, photonics technologies have been involved in the field of nanomedicine. Phototriggered liposomes have been cast as promising nanosystems that achieve controlled release of payloads in several pathological conditions such as cancer, autoimmune, and infectious diseases. In contrast to the conventional liposomes, this photoresponsive element greatly improves therapeutic efficacy and reduces the adverse effects of gene/drug therapy during treatment. Recently, cancer immunotherpay has been one of the hot topics in the field of oncology due to the great success and therapeutic benefits that were well-recognized by the patients. However, several side effects have been encountered due to the unmonitored augmentation of the immune system. This Review highlights the most recent advancements in the development of photoresponsive liposome nanosystems in the field of oncology, with a specific emphasis on challenges and opportunities in the field of cancer immunotherapy., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Immune surveillance by natural killer (NK) cells and their recruitment to sites of inflammation renders them susceptible to viral infection, potentially modulating their effector function. Here, we analyzed innate RNA receptor signaling in NK cells downstream of direct Influenza A virus (IAV) infection and its impact on NK cell effector function. Infection of NK cells with IAV resulted in the activation of TBK1, NF-ϰB and subsequent type-I IFN secretion. CRISPR-generated knockouts in primary human NK cells revealed that this effect depended on the antiviral cytosolic RNA receptor RIG-I. Transfection of NK cells with synthetic 3p-dsRNA, a strong RIG-I agonist that mimics viral RNA, resulted in a similar phenotype and rendered NK cells resistant to subsequent IAV infection. Strikingly, both IAV infection and 3p-dsRNA transfection enhanced degranulation and cytokine production by NK cells when exposed to target cells. Thus, RIG-I activation in NK cells both supports their cell intrinsic viral defense and enhances their cytotoxic effector function against target cells.

Abstract: Purpose: The aim of the study is to evaluate the effect of combined hydrocortisone, vitamin C, and thiamine (triple therapy) on the mortality of patients with septic shock. Methods : This multicenter, open-label, two-arm parallel-group, randomized controlled trial was conducted in four intensive care units in Qatar. Adult patients diagnosed with septic shock requiring norepinephrine at a rate of ≥0.1 μg/kg/min for ≥6 h were randomized to a triple therapy group or a control group. The primary outcome was in-hospital mortality at 60 days or at discharge, whichever occurred first. Secondary outcomes included time to death, change in Sequential Organ Failure Assessment (SOFA) score at 72 h of randomization, intensive care unit length of stay, hospital length of stay, and vasopressor duration. Results: A total of 106 patients (53 in each group) were enrolled in this study. The study was terminated early because of a lack of funding. The median baseline SOFA score was 10 (interquartile range, 8-12). The primary outcomes were similar between the two groups (triple therapy, 28.3% vs. control, 35.8%; P = 0.41). Vasopressor duration among the survivors was similar between the two groups (triple therapy, 50 h vs. control, 58 h; P = 0.44). Other secondary and safety endpoints were similar between the two groups. Conclusion: Triple therapy did not improve in-hospital mortality at 60 days in critically ill patients with septic shock or reduce the vasopressor duration or SOFA score at 72 h. Trial Registration:ClinicalTrials.gov identifier: NCT03380507. Registered on December 21, 2017., Competing Interests: The authors report no conflict of interests., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Shock Society.)

Background: Acute respiratory distress syndrome (ARDS) management is primarily supportive. Pulmonary vasodilators, such as inhaled epoprostenol (iEPO), have been shown to improve PaO 2 :FiO 2 (PF) and are used as adjunctive therapy., Objective: To identify the positive response rate and variables associated with response to iEPO in adults with ARDS. A positive response to iEPO was defined as a 10% improvement in PF within 6 hours., Methods: This retrospective study included adults with ARDS treated with iEPO. The primary endpoint was the variables associated with a positive response to iEPO. Secondary endpoints were positive response rate and the change in PF and SpO 2 :FiO 2 within 6 hours. Statistical analysis included multivariable regression., Results: Three hundred thirty-one patients were included. As baseline PF increased, the odds of responding to iEPO decreased (odds ratio [OR], 0.752, 95% CI, 0.69-0.819, p  < 0.001). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related ARDS (OR 0.478, 95% CI, 0.281-0.814, p  = 0.007) was associated with decreased odds of a positive response to iEPO. The total population had a 68.3% positive response rate to iEPO. SARS-CoV-2-related ARDS and non-SARS-CoV-2-related ARDS had a 59.5% and 72.7% positive response rate, respectively. iEPO significantly improved PF (71 vs 95, P  < 0.001) in the whole population., Conclusion and Relevance: iEPO was associated with a positive effect in a majority of moderate-to-severe ARDS patients, including patients with SARS-CoV-2-related ARDS. Lower baseline PF and non-SARS-CoV-2-related ARDS were significantly associated with a positive response to iEPO. The ability to predict which patients will respond to iEPO can facilitate better utilization.

Few studies have evaluated the use of ceftriaxone (CRO) in the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) infections. The purpose of this study was to compare the safety and efficacy of CRO versus cefazolin (CZO) for patients with MSSA bacteraemia. This was a multicentre, single health-system, retrospective study. Adult inpatients were included if they had a primary episode of MSSA bacteraemia and received CRO or CZO as definitive therapy. The primary endpoint was clinical cure at 28 days or at discharge, whichever came first. Secondary endpoints included treatment failure at 90 days, time to treatment failure, re-admission due to recurrent MSSA bacteraemia, duration of bacteraemia, discontinuation of treatment due to adverse drug events, and Clostridioides difficile infection. A total of 248 patients were included, of which 87 (35.1%) received CRO and 161 (64.9%) received CZO. There was no difference in the primary outcome of clinical cure at 28 days or at discharge between the CRO and CZO groups [75 (86.2%) vs. 145 (90.1%); P = 0.359], even after adjusting for Charlson comorbidity index and Pitt bacteremia score (adjusted OR = 1.35, 95% CI 0.58-3.12; P = 0.49). There were no differences in time to clinical cure, treatment failure at 90 days or safety events between the two groups. In conclusion, our findings suggest no clinical difference between CRO and CZO for the definitive treatment of MSSA bacteraemia. Further prospective studies are needed to confirm these findings., (Copyright © 2022. Published by Elsevier Ltd.)

Objectives: To describe angiotensin II (ANGII) use in patients on mechanical circulatory support (MCS). To evaluate the efficacy and safety of ANGII in patients with shock on MCS., Design: Retrospective cohort study., Setting: A single-center, quaternary care academic medical center., Participants: The study comprised critically ill patients on MCS., Interventions: None., Measurements and Main Results: Fourteen patients were included in this retrospective analysis. The median age was 54 years (44.8, 68.3) and 78.6% were men. Six patients were receiving venoarterial extracorporeal membrane oxygenation support, 4 patients were receiving venovenous extracorporeal membrane oxygenation support, and 4 patients were on left ventricular assist devices. Five patients (36%) achieved hemodynamic response to ANGII at 3 hours, defined as a mean arterial pressure (MAP) of ≥65 mmHg or a 10-mmHg increase in MAP with a decrease or no change in total vasopressor dose. Overall, the median MAP increased from 61 mmHg (51, 73) at baseline to 66 mmHg (58, 71) at 3 hours, and the median norepinephrine dose decreased from 0.45 µg/kg/min (0.28, 0.6) at baseline to 0.2 µg/kg/min (0.18, 0.32) at 3 hours. The in-hospital mortality rate was 78.6%. Two patients experienced severe adverse drug events and 1 patient had a sentinel thrombotic event., Conclusions: This study suggested that ANGII may provide a salvage treatment option in patients on MCS with refractory vasodilatory shock. There are several safety considerations with the use of ANGII in these patients. Prospective randomized controlled trials are needed to evaluate the safety and efficacy of ANGII in patients on MCS., Competing Interests: Conflict of Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To compare Anti-Xa directed thromboprophylaxis using low molecular weight heparin (LMWH) (anti-Xa peak goal 0.2-0.5 IU/mL) to alternative anticoagulation strategies in critically ill COVID-19 patients. Methods: This was a retrospective, multicenter, single health-system study. Primary outcomes were thromboembolic events and clinically important bleeding events. Secondary outcomes included dosing comparisons between LMWH cohorts. Main Results: A total of 695 patients were included. No differences were found in the incidence of thrombotic events with any of the dosing strategies. The incidence of major bleeding was significantly higher in the standard dose thromboprophylaxis, intermediate dose subcutaneous heparin (SQH), and therapeutic anticoagulation cohorts. Forty-nine percent of patients within the anti-Xa directed group had their first anti-Xa peak at goal, while 43% were above goal. Patients who had levels above goal had dose modifications made, therefore anti-Xa directed LMWH resulted in significantly lower total daily doses compared to intermediate dose LMWH. Conclusions: Anti-Xa directed LMWH dosing provided comparable thromboprophylaxis with lower total daily doses of LMWH in critically ill COVID-19 patients. Further randomized controlled trials are needed to confirm our findings.

Background: Few studies have evaluated the early use of insulin glargine in the management of diabetic ketoacidosis (DKA) patients. Early insulin glargine use in DKA was safe and associated with a trend towards faster DKA resolution., Objectives: To evaluate the efficacy and safety of early insulin glargine administration for acute management of DKA in critically ill patients., Methods: This single-center retrospective cohort study included patients, who were >18 years of age with DKA, admitted to the intensive care unit (ICU) for at least 12 h, and received intravenous insulin infusion for at least 6 h. The primary endpoint was the association between the time to insulin glargine administration and time to DKA resolution. Linear and logistic regression analyses were performed., Results: Of the 913 patients evaluated, 380 were included in the study. The overall mean age was 45±17 years, 196 (51.6%) were female, and 262 (70%) patients had type 1 diabetes mellitus. The mean blood glucose level was 584.9±210 mg/dL, pH was 7.16±0.17, anion gap was 28.17±6.9 mEq/L, and serum bicarbonate level was 11.19±5.72 mEq/L. Every 6-h delay in insulin glargine administration was associated with a 26-min increase in time to DKA resolution (95% confidence interval [CI], 14.76-37.44; p<0.0001), 3.2-h increase in insulin infusion duration (95% CI, 28.8-36; p<0.0001), and 6.5-h increase in ICU LOS (95% CI, 5.04-7.92; p<0.0001)., Conclusion: Early administration of insulin glargine is potentially safe and may be associated with a reduction in time to DKA resolution and a shorter duration of insulin infusion., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Hydrocortisone showed to be effective in reducing the time until reversal of shock when added to standard therapy in managing septic shock. Hyperglycemia is one of the common adverse effects associated with corticosteroid treatment. However, the difference in hyperglycemia risk with different methods of hydrocortisone administration is not clear. The objective of this study was to evaluate the risk of hyperglycemia of intermittent hydrocortisone boluses vs continuous infusion in septic shock patients., Materials and Methods: This was a retrospective observational study. Data were collected from the electronic medical records of eligible patients admitted to intensive care units. All patients admitted with septic shock who received noradrenaline and hydrocortisone were included. Only patients who exceeded 200 mg/day of hydrocortisone were excluded. The primary outcome was mean blood glucose., Results: A total of 108 patients (with 3,021 blood glucose readings) were included in the final analysis. Seventy-six patients received hydrocortisone as intermittent boluses (70.3%), and 32 patients (29.7%) received continuous infusion. For the primary outcome, no statistically or clinically significant difference was found in the blood glucose estimated marginal mean: 8.58 mmol/L (95% confidence interval [CI]; 8.01-9.16) in the bolus group and 8.9 mmol/L (95% CI; 7.99-9.82) in the infusion group with a mean difference of 0.32 mmol/L (95% CI; -0.77 to 1.41). For secondary outcomes, no difference was found between the two groups in mortality, length of stay, reversal of shock, or hypoglycemic events., Conclusion: Intermittent boluses of hydrocortisone were not associated with a higher risk of hyperglycemia than continuous infusion in septic shock patients., How to Cite This Article: Mitwally H, Saad MO, Mahmoud S, Mohamed A. Hyperglycemia Risk Evaluation of Hydrocortisone Intermittent Boluses vs Continuous Infusion in Septic Shock: A Retrospective Study. Indian J Crit Care Med 2021;25(1):29-33., Competing Interests: Source of support: Medical Research Center, Hamad Medical Corporation, Qatar (Internal funding). Conflict of interest: None, (Copyright © 2021; Jaypee Brothers Medical Publishers (P) Ltd.)

Purpose: Piperacillin/tazobactam (PT), when combined with vancomycin, is associated with an increased risk of acute kidney injury (AKI). It is not known whether PT alone is associated with a higher incidence of AKI compared to other β-lactams among critically ill patients. The objective of this study was to compare the incidence of AKI associated with the use of PT to other β-lactams among adult critically ill patients METHODS: This retrospective study was conducted in the surgical and the medical intensive care units at two hospitals within Hamad Medical Corporation (HMC) in Qatar and included adult critically ill patients who received at least one dose of anti-pseudomonal β-lactams. The primary outcome was acute kidney injury, defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multiple logistic regression with adjustment for pre-specified potential confounders was used for the primary outcome analysis., Results: A total of 669 patients were included in the analysis: 507 patients in the PT group and 162 patients in the control (meropenem/cefepime) group. AKI occurred in 136 (26.8%) members of the PT group and 38 (23.5%) members of the control group [odds ratio (OR) 1.2; 95% confidence interval (CI) 0.79-1.8]. The results were not significantly altered after adjusting for the pre-specified potential confounders (adjusted OR 1.38; 95% CI 0.88-2.15)., Conclusion: In this study, PT was not associated with a higher risk of AKI compared to cefepime or meropenem among adult critically ill patients.

[Purpose] Cervicogenic headache is a major problem in patients with upper cervical dysfunction. However, its physical therapy management is a topic of debate. This study aims to determine the effect of C1-C2 Mulligan sustained natural apophyseal glide mobilizations on cervicogenic headache and associated dizziness. [Participants and Methods] This study included 48 patients with cervicogenic headache, who were randomly assigned to three equal groups: Group A (Headache SNAG), group B (C1-C2 SNAG rotation), and group C (combined). Neck Disability Index was used to examine neck pain intensity and cervicogenic headache symptoms. The 6-item Headache Impact Test scale was used to examine headache severity and its adverse effects on social life and functions. Flexion-Rotation Test was used to assess rotation range of motion at the level of C1-C2 and confirmed by a cervical range of motion device. Dizziness Handicap Inventory scale was used to evaluate dizziness. The evaluation was done pre- and post-treatment and compared between the groups. [Results] Group C showed significant improvement in all variables compared with groups A and B. [Conclusion] Sustained natural apophyseal glide mobilizations used in the study were effective in reducing cervicogenic headache and dizziness in all groups with a greater improvement in the combined group. The use of cervical SNAG mobilizations is encouraged as a noninvasive intervention depending on the therapist's assessment, findings, and clinical reasoning., Competing Interests: None to declare.

One strategy to manage patients on warfarin starting an interacting drug is to increase the frequency of monitoring. Another strategy is to adjust warfarin dose around the time patient is started on an interacting medication, which is known as "preemptive warfarin dose adjustment." The main objective of this study is to compare preemptive to nonpreemptive strategy and their impact on the quality of anticoagulation management. This is a retrospective cohort study performed at the pharmacist-managed anticoagulation clinic in a tertiary hospital in the State of Qatar. Over a 4-year period, 340 patients were evaluated, and 58 warfarin-drug interaction encounters were identified. Mean age of the patients was (57.7 ± 13.7), and 50% of them were females. Preemptive dose adjustment was used in 17 (29.3%) cases. Incidence of out-of-target international normalized ratio (INR) was statistically lower in the preemptive arm compared to the control group (41.2% [7/17] vs 69.2% [27/39], P = .048). Incidence of extreme out-of-target INR was numerically lower in the preemptive arm compared to the control but did not reach statistical significance (11.8% [2/17] vs 29.3% [12/41], P = .139). Change in frequency of INR monitoring was not different between the 2 groups. However, overall frequency of INR monitoring after onset/discontinuation of interacting medication increased compared to baseline (7 [9] vs 21 [16] days, P < .001). Preemptive strategy was shown in our study to decrease incidence of the out-of-target INR visits, although patients remained in need for close monitoring.

BACKGROUND Dexmedetomidine is a sedating agent approved for use in non-intubated patients and procedural sedation due to its efficacy in conscious sedation and minimal risks of respiratory depression. Previous reports proved the effectiveness of clonidine in treatment of withdrawal symptoms, but none have discussed cases with co-existing non-controlled psychiatric illness and prolonged duration of dexmedetomidine exposure. CASE REPORT We report a case of a 40-year-old woman diagnosed with viral meningitis. Due to her complicated psychiatric illness and viral meningitis, she developed severe agitation unresponsive to standard therapy. The patient had to be placed on dexmedetomidine, to which she developed dependence. There were several attempts to gradually withdraw dexmedetomidine but these were unsuccessful despite adding multiple antipsychotic medications. Withdrawal was manifested in multiple symptoms, including severe agitation, sweating, and tachycardia. Clonidine was used and was an effective treatment option to successfully withdraw the patient from dexmedetomidine. A smaller initial dose was used due to low baseline systolic blood pressure, which was successful. CONCLUSIONS This report proves that clonidine is an effective option for treatment of dexmedetomidine dependence compared to other antipsychotic agents. The present report is the first to discuss severe psychiatric illness and prolonged dexmedetomidine duration (>7 days) in a non-intubated patient. Dexmedetomidine withdrawal must be considered in the differential diagnosis of patients with psychiatric illness, which can be easily treated with clonidine.

Introduction: Hyperlipidemia is a risk factor for cardiovascular diseases such as acute infarction. Inflammation and platelet activation are critical phenomena in acute myocardial infarction (AMI)., Aim: The aim of the study was to assess potential protective effects of aspirin and/or clopidogrel on AMI in hypercholesterolemic rats., Methods: Forty adult male Wistar rats were divided into five groups (eight rats in each). Group I included normal healthy rats. The other 32 rats were subjected to induction of hypercholesterolemia by high-fat diet for 3 weeks, followed by induction of AMI by subcutaneous injections of isoproterenol (85 mg/kg/day, for 2 days). Rats were divided into the following groups: group II, rats with induced hypercholesterolemia and AMI; group III, hypercholesterolemic rats that received aspirin 30 mg/kg/day orally for 7 days before induction of AMI; group IV, hypercholesterolemic rats that received clopidogrel 10 mg/kg/day orally for 7 days before induction of AMI; and group V, hypercholesterolemic rats treated with both aspirin and clopidogrel in the same doses for 7 days before induction of AMI. Serum levels of pentraxin 3 (PTX3), transforming growth factor-β1 (TGF-β1), creatine kinase (CK), lactate dehydrogenase (LDH), total cholesterol and triglycerides were estimated in all rats., Results: Isoproterenol-induced AMI in hypercholesterolemic rats was associated with an increase in serum levels of PTX3, TGF-β1, CK and LDH. Aspirin and/or clopidogrel pretreatment for 1 week led to a reduction of their levels as compared with non-treated rats. However, the reduction caused by combination of aspirin and clopidogrel was more than that caused by each drug separately., Conclusion: Combination of aspirin and clopidogrel could be a therapeutic option for hypercholesterolemic patients to attenuate the complex vascular inflammatory process which is a key step in the setting of AMI.

Unlabelled: Orexin-A has been shown to modulate pain sensation and increase appetite. Rheumatoid arthritis (RA) is characterized by joint destruction, deformity, hyperalgesia, and weight reduction., Aim: Evaluate the possible effect of orexin-A on hyperalgesic and cachectic manifestations in an adjuvant-induced arthritis (AIA) rat model., Methods: Forty adult male Wistar rats were distributed among 4 groups; I, normal controls; II, rats with AIA induced by intradermal injection of Mycobacterium butyricum, but with no other treatment; III, AIA rats treated daily with an intravenous injection of orexin-A for 8 days; and IV, AIA rats treated orally with dexamethasone for 8 days. The parameters we assessed were pain-associated behavior, body mass, hind paw volume, serum levels of nerve growth factor (NGF) and neuropeptide Y (NPY)., Results: Orexin-A caused a significant reduction in pain sensation and NGF levels, and increased body mass and the levels of NPY, whereas treatment with dexamethasone led to significant reductions in paw swelling and pain sensation., Conclusion: Orexin-A has hypoalgesic properties and increases body mass, whereas dexamethasone has a potent anti-inflammatory effect. Therefore, the combination of orexin-A and dexamethasone should have a greater effect with respect to attenuating the manifestations and complications associated with RA.