Objective: To evaluate the nephroprotective effect of lycopene (LPN) in acute kidney injury (AKI) regarding the oxidative stress (OS). Materials and Methods: Thirty Sprague Dawley male rats were divided into three groups – control group: rats treated with distilled water (orally) for 10 days (n = 10); AKI group: rats treated with distilled water and diclofenac (intraperitoneal) for 10 days (n = 10); treated group: rats treated with LPN (orally) and diclofenac for 10 days (n = 10). Body mass index (BMI) and estimated glomerular filtration rate (eGFR) were measured. Blood urea, serum creatinine (CreSerum), serum malondialdehyde (MDA), superoxide dismutase (SOD), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecules (KIM-1) were measured in the all groups on the 11^th day of the experiment. Results: Diclofenac-induced AKI led to significant elevations of BMI, CreSerum, and blood urea compared with control (P < 0.05). In AKI model, eGFR was reduced to 11.69 ± 2.64 ml/min/1.73 compared with control group (15.88 ± 3.75 ml/min/1.73, P = 0.03). NGAL, MDA, and KIM-1 were elevated in AKI compared with control (P < 0.001). Pretreatment with LPN led to the reduction of blood urea and CreSerum as compared with AKI (P < 0.001). Similarly, eGFR was increased significantly to 14.81 ± 3.21 ml/min/1.73 compared with 11.69 ± 2.64 ml/min/1.73 in AKI (P = 0.02). Serum levels of NGAL, KIM-1, and MDA were reduced significantly in the LPN group as compared with AKI (P = 0.001), while the SOD serum level was increased to 33. 86 ± 8.61 pg/ml as compared to 22.78 ± 7.56 pg/ml in AKI (P = 0.006). As well, LPN reduced MDA/SOD ratio as compared with AKI (P = 0.00001). Conclusion: The finding of this study illustrated that LPN is an effective natural antioxidant that attenuates and prevents AKI through modulation of OS and lipid peroxidation. As well, LPN might be of great value in the prevention of nephrotoxicity that induced by nephrotoxic agents like diclofenac.

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Background: Sepsis is one of the most common triggering factors for acute kidney injury (AKI). The aim of the study is to evaluate the outcome in sepsis with AKI and determine the prognostic value of urinary neutrophil gelatinase-associated lipocalin (NGAL) in septicemic AKI. Materials and Methods: This prospective follow-up study was carried out over a period of 1 year after ethical clearance from the Institutional Ethics committee, a total 165 cases of septicemia were recruited, of which 15 patients were dropped out, 150 patients were identified suffering from septicemia defined as per the organ dysfunction criteria (according to third international consensus 2016) and patients of AKI defined as per the Kidney Disease Improving Global Outcomes 2012 criteria). Results: Out of 150 patients of septicemia enrolled in the study, only 38 (25.33%) suffering from AKI were classified as Group I and rest 112 (74.67%) patients of septicemia not suffering from AKI were classified as Group II. In total, 60.0% (90) patients were discharged from the hospital, rest of the patients (40%) expired. Mean duration of survival was higher in Group II (21.29 ± 1.89 days) as compared to Group I (13.67 ± 1.06 days). Cases with ≥121.90 urine NGAL, rate of mortality (41.7%), were higher as compared to alive patients discharged (34.4%). Conclusion: Sequential organ failure assessment score, hospital stay, and mortality were high in septicemic patients with AKI as compared to sepsis without AKI. Survival of patients also not good with septic AKI, those patients who had high NGAL value had poor prognosis.

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Context: Coagulation abnormalities have been observed among leptospirosis patients. However, coagulopathy in severe leptospirosis has not been further characterized. Aims: The aim of this study was to evaluate conventional coagulation and rotational thromboelastometry (ROTEM^®) parameters in leptospirosis patients. Settings and Design: This prospective cross-sectional comparative study included patients presenting to a tertiary hospital in Sri Lanka with clinically and serologically confirmed leptospirosis (14 severe and 6 mild), dengue (6), sepsis (5), and 6 healthy individuals. Subjects and Methods: Blood samples were collected between the 3^rd and 10^th days of illness for prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), fibrinogen, lupus anticoagulant, factors VII and VIII, D-dimer, platelet count, and ROTEM. Statistical Analysis Used: ANOVA post hoc comparison using Bonferroni was applied to compare groups. Results: PT and aPTT were prolonged in leptospirosis patients and were corrected with normal plasma. TT was not significantly prolonged in leptospirosis. Fibrinogen was significantly elevated in severe leptospirosis (P = 0.001) and sepsis (P = 0.001) compared with healthy controls and dengue. Thirty percent of leptospirosis patients had thrombocytopenia (17% in mild and 36% in severe). No significant differences were seen in inTEM clotting time (CT) and exTEM CT in leptospirosis when compared to the other three groups. inTEM clot formation time (CFT) and exTEM CFT in dengue were significantly higher compared to severe (P = 0.001) and mild (P = 0.005) leptospirosis. inTEM maximum clot firmness (MCF) (P = 0.001) and exTEM MCF (P = 0.001) were significantly lower in dengue than in leptospirosis. Only one patient with leptospirosis had bleeding manifestations. Conclusions: Abnormalities in conventional coagulation parameters occur in leptospirosis. However, ROTEM parameters in leptospirosis are not significantly altered.

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Background: Assessment of kidney function is fundamental to optimize drug dosing. The Cockcroft–Gault (CG) equation is widely used but has questionable validity for females, changing renal function, and the critical ill. Eight-hour urine collections (U_8h) offer direct measurement of creatinine clearance (CrCl) but lack the data for drug dosing. The primary objective of this study was to determine if there was a difference in renal drug dosing based on the estimation of CG CrCl (CrCl_CG) versus 8-h CrCl (CrCl_8h). Methods: This was an observational, retrospective cohort study of adult patients admitted between March 2018 and September 2018 with a collection U_8hduring hospitalization. The primary outcome was discordance of renal drug dosing defined as the percentage of U_8hfor which at least one different active medication CrCl dosing cutoff would result using the CrCl_CGversus CrCl_8h. The secondary outcomes were correlation between CrCl_CGand CrCl_8hand percentage of CrCl_CGvalues outside ± 20% of the CrCl_8h. Results: One hundred collections drawn from 85 unique patients (50.6% male, median age 55 [41–70] years, intensive care unit 88%) were included in the analysis. Median serum creatinine was 0.76 (0.52–1.06) mg/dL and blood urea nitrogen was 20 (14–28) mg/dL at time of collection_8h. Median CrCl_8hwas 86.2 (43.5–140.3) mL/min versus 99.7 (56.5–166.9) mL/min CrCl_CG(P < 0.001) and discordance was 25%. The correlation between CrCl_8hand CrCl_CGwas 0.76 (P < 0.001). Only 31% of CrCl_CGvalues were within ± 20% of the CrCl_8hvalue. Conclusion: We found 25% discordance for drug dosing between CrCl_8hand CrCl_CG.Further studies are needed to determine the impact on clinical outcomes.

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Objective: To evaluate the effects of thioctic acid (TA) add-on metformin therapy on glycemic indices and associated inflammatory reactions induced-endothelial dysfunction (ED) in patients with type 2 diabetes mellitus (T2DM). Methods: In this case–control clinical study, a total number of 70 patients with T2DM compared with 30 healthy controls were divided into three groups: Group A (n = 30), healthy controls; Group B (n = 36), T2DM patients on metformin and Group C (n = 34), T2DM patients on metformin plus TA 600 mg/day. Anthropometric measurements, lipid profile, and routine biochemical variables were estimated. Serum human vascular cell adhesion molecule-1 (VCAM-1) and E-selectin were measured before and after 10 consecutive week's therapy with metformin and/or TA. Results: Metformin therapy led to significant reduction of fasting insulin and insulin resistance (IR) with an increment in the insulin sensitivity (P < 0.01). Metformin therapy improved lipid profile compared to the baseline (P < 0.01) with significant reduction of atherogenic index. Metformin plus TA therapy reduced fasting blood glucose, glycated hemoglobin, and IR and showed increment in the insulin sensitivity (P < 0.01) with insignificant effect on fasting insulin (P = 0.09) compared with metformin monotherapy. sVCAM-1 level was high in patients with T2DM (3.74 ± 1.34 ng/ml) at baseline, which decreased by metformin monotherapy to 2.32 ± 0.67 ng/ml or metformin plus TA to 1.98 ± 0.31 ng/ml (P < 0.01), but metformin plus TA illustrated insignificant difference compared to metformin alone (P = 0.29). Conclusion: TA add on metformin therapy improves glycemic indices and associated inflammatory mediators in patients with T2DM through modulation of IR , IS , and direct direct anti-inflammatory effect.

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Severe fever with thrombocytopenia syndrome (SFTS) is associated with a high mortality caused by rapidly progressive multiple organ failure. SFTS virus induces immunosuppression, mediated by interleukin-10 production, reduction of CD3⁺ and CD4⁺ T cells, and cytokine storms, and this may lead to various complications in critical SFTS patients. Recently, there have been reports of cases of invasive pulmonary Aspergillosis (IPA) in patients with SFTS in the absence of predisposing factors of IPA. However, there is no known relationship between SFTS and mycosis. Here, we report a SFTS patient with a low CD4⁺ T-cell count and a high viral load, who developed possible IPA in the absence of common risk factors for mycosis. This case adds to the evidence that IPA may occur as a complication of SFTS.

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Cannabis, popularly known as marijuana, is a recreational drug derived from the plant Cannabis Sativa. It has been recognized as the most widely used mood-altering substance in the world and is falsely perceived as a safe substance by the public at large. This is mostly due to lack of awareness of its adverse effects as well as successful attempts for legalization of its use in many states. We present a unique case of a 56-year-old man who presented with neurological deficits concerning for stroke. Soon after presentation, he required endotracheal intubation for airway protection due to worsening mental status changes and pulmonary edema. Echocardiogram revealed severe hypokinesis of the basal and mid-left ventricular (LV) walls with hyperdynamic motion of the apex (reverse takotsubo). Coronary angiography revealed no obstructive disease. Urine toxicology screen was positive for Δ-9-tetrahydrocannabinol. The patient then stated to have used excess marijuana before the symptom onset, while denying any recent emotional stressors. The findings were consistent with stress cardiomyopathy (SC) triggered by marijuana use. Myocardial infarction, stroke, and peripheral arteriopathy have been increasingly reported in younger individuals using marijuana. SC appears to be another unique complication of marijuana use triggered through its effects on the autonomic nervous and endocannabinoid systems.

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Background: Catecholamines play a central role in pathogenesis of stress cardiomyopathy (SC). We aimed to review the clinical characteristics, procedural details and outcomes of patients with SC during dobutamine stress echocardiography (DSE). Methods/Results: A total of 20 adults [age 64±15 years, 80% women, 67% hypertension, 20% diabetes, 33% hypercholesterolemia, 19% chronic kidney disease, 13% known anxiety disorder] with SC during DSE were identified from local digital archives of our laboratory (n=3) or reports in English literature (n=17). Indication for DSE was suspected coronary artery disease (CAD) in all patients. Left ventricular (LV) ejection fraction was normal at baseline. SC developed at a blood pressure of 154±47/86±24 mmHg, heart rate of 130±17 bpm (88±10% predicted maximum) and peak rate-pressure product of 20559±3898 mmHg*bpm. ST segment elevation was seen in 65%. SC occurred at peak dobutamine infusion rate of 38±6 μg/kg/min in 85% and during recovery in 15%. Atropine [0.7±0.6 (0.25-2) mg] was given to 7 patients. LV ejection fraction dropped to 30±6% with apical (40%), apical and mid (45%) or basal and mid (10%) circumferential LV ballooning. One patient (5%) had a mixed pattern of wall motion abnormality. LV outflow tract obstruction developed in 15%. Major adverse cardiac events occurred in 7 (35%) and included death (n=1), congestive heart failure (n=2), hypotension (n=3) and atrial fibrillation with heart failure (n=1). At a mean follow up duration of 19±19 days, complete or partial recovery of LV wall motion abnormality was seen in 18 and 1 patient, respectively. Conclusion: SC uncommonly occurs during DSE. However, death and other adverse events (hypotension, heart failure and atrial fibrillation) may occur and require urgent attention. Once managed, complete recovery is expected in most patients.

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Introduction: Hypothermic machine perfusion (HMP) has been established as an efficacious method for preserving kidney allografts from deceased donors in clinical trials, but little data are available on the effectiveness of HMP in real-world settings. We examined factors associated with HMP use and clinical outcomes in a real-world organ procurement organization setting. Methods: We conducted a retrospective cohort study of the Lifecenter Northwest organ procurement database from 2010 to 2015, linked to the United Network of Organ Sharing outcomes database. We examined HMP utilization, and our primary outcomes were delayed graft function (DGF) and graft survival, using multivariable Poisson and Cox regression models. Results: Among 1729 deceased-donor kidneys, 797 (46%) were preserved with HMP. Higher donor age, region of procurement, and donation type were associated with HMP use. HMP was associated with a 37% decreased risk of DGF (adjusted relative risk 0.63, 95% confidence interval [CI]: 0.51–0.78), with no effect on 1-year graft survival (adjusted hazard ratio 0.83, 95% CI: 0.38–1.80). Conclusion: Variation exists in the utilization of HMP for deceased donor kidneys. HMP reduced the risk for DGF, but was not associated with improvements in long-term graft survival.

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Context: Epidemiologic studies in critical care routinely rely on the codes listed in International Classification of Diseases (ICD) manuals which are primarily intended for reimbursement of claims to payers. Standardized billing codes may minimize the measurement error when used in conjunction with ICD codes. Aims: The aim was to examine the impact of using charge codes in addition to ICD codes for ascertaining two common procedures in surgical intensive care unit (ICU) settings: hemodialysis (HD) and red blood cell (RBC) transfusions. Settings and Design: This was a retrospective cohort study of Premier Inc. Database. Subjects and Methods: Elective surgical patients aged >18 years treated in the ICU postoperatively were included in this study. This includes the ascertainment of HD and RBC transfusions in the population using a standard “ICD code” versus an “either ICD code or charge code” approach. Statistical Analysis Used: Descriptive analysis using t-tests, Chi-square tests as appropriate was used. Results: A total of 40,357 patients were identified as having undergone elective surgery, followed by admission to an ICU across 520 US hospitals. The use of “ICD codes only” uniformly underestimated rates of HD or RBC transfusions when compared to “Charge Codes only” and “ICD Codes or Charge Codes” (% increase of 15.4%–45.6% and 50.8%–93.1%, respectively). Differences varied with specific surgical populations studied. Patients identified using the “ICD code” approach had more comorbidities, were more likely to be female, and more likely to be Medicare beneficiaries. Conclusions: Epidemiologic studies in critical care should consider using multiple independent data sources to improve ascertainment of common critical care interventions.

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Introduction: The main goal of a critical care response team (CCRT) is to quickly assess and transfer, if required, rapidly deteriorating patients to an intensive care unit (ICU) to prevent cardiopulmonary arrest, stabilize patients' condition, and help in optimizing the care provided by the primary team. The objective of this study was to investigate the correlation between early intervention by CCRT and the outcome of oncology patients. Materials and Methods: This is a retrospective cohort study conducted at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. KAMC is a tertiary care facility with 1200-bed capacity. The study compared oncology patients to nononcology patients. Results: Over 4 years, a total number of 4941 patients were reviewed, of which 172 were oncology patients. The average age of patients in the oncology group was 48.8 ± 20.7, while the average age for nononcology was 52.8 ± 21.2 (P = 0.016). The average Acute Physiology and Chronic Health Evaluation II score on admission for oncology patients was higher than that for the nononcology group (27.8 ± 8.9 vs. 23.6 ± 9.3, respectively). Lower ICU mortality was seen after CCRT implementation (38.8% vs. 62.7%). The average duration of hospital stay and ICU stay increased after CCRT implementation (37.34 vs. 29.31 and 11.93 vs. 8.9, respectively). Conclusion: In this study, we identified that early intervention by implementing CCRT had a significant impact in reducing ICU mortality for oncology and nononcology patients.

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