Correlations between serum kidney injury molecule-1, cystatin C and immunosuppressants: A cross-sectional study of renal transplant patients in Bahrain.

Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for treatment. Serum creatinine is the standard for monitoring kidney function; however, cystatin C (Cys C) and kidney injury molecule-1 (KIM-1) have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney function. Here, we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil, tacrolimus, sirolimus, everolimus, or cyclosporine to evaluate kidney function. We used both the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation, which is based on creatinine and combined creatinine with Cys C, and the CKD-EPI 2012 equation, which is based on Cys C alone, to estimate glomerular filtration rate (GFR). Then, we assessed the association between serum KIM-1 and GFR < 90 mL/(min·1.73 m 2). We observed significantly higher serum Cys C levels in patients with the elevated serum creatinine, compared with those with normal serum creatinine. The estimated GFRs based on creatinine were significantly higher than those based on the other equations, while a significant positive correlation was observed among all equations. Serum KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations. A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR < 90 mL/(min·1.73 m 2). We observed a significant correlation between serum creatinine and Cys C in our renal transplant patients. Therefore, serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants.

Penetrating Ocular Fish-Hook Injury.

Penetrating ocular injuries caused by fish hooks, although rare, present unique challenges and significant risks to ocular structures and vision. We report a case of a 36-year-old male who presented with a fish hook embedded in his right eye. Clinical examination revealed a fish hook perforating the cornea, entering at the nasal cornea at 3 o'clock and exiting at the temporal cornea at 7 o'clock. Despite initial attempts to employ the advance-and-cut technique, the unsuccessful utilization of a wire cutter led to a shift in the removal approach. The modified backout method was successfully employed, allowing the safe extraction of the fish hook while minimizing iatrogenic damage. Follow-up appointments showed a gradual improvement in visual acuity despite early cataract formation and significant central scarring. To optimize the patient's visual outcome, a triple procedure involving penetrating keratoplasty (PKP), extra-capsular cataract extraction (ECCE), and intraocular lens (IOL) implantation has been scheduled. This case highlights the importance of prompt and adaptable management in ocular fish-hook injuries, emphasizing the need for comprehensive follow-up care. It also underscores the value of preventive measures, including the use of protective eyewear, to reduce the incidence of such injuries, given that the majority of ocular traumas are preventable.

A drug utilization and drug interaction study in renal transplant patients: Implications for an urgent need for drug deprescribing.

BACKGROUND: Renal transplant patients receive several drugs concomitantly. OBJECTIVE: Limited literature exists evaluating the drug use in this population that is at high risk for drug-induced acute kidney injury and complications due to under-or over-dosage of immunosuppressant drugs due to drug-drug interactions. METHODS: A retrospective observational study was carried out in 269 renal transplant patients in whom either oral or parenteral drugs were evaluated. World Health Organization (WHO) indicators of drug utilization such as the average number of drugs prescribed, daily defined dose, and proportion of drugs listed as WHO essential drugs were evaluated. Details on the drugs with nephrotoxic potential were obtained. Drug-drug interactions were assessed concerning the severity (major, moderate, and minor) as well as type (pharmacokinetic, pharmacodynamic, and toxicity). RESULTS: One-hundred and ninety-eight drugs were administered to the study participants. The median (range) total number of drugs received by the study participants was 23 (6-55). The proportion of drugs listed in the WHO essential drug database was 57.1 (16.7-100)%. Forty-six drugs with potential nephrotoxicity and seven drugs that were contra-indicated in patients with chronic renal disease/end-stage renal disease were administered to the study participants. The mean (SD) numbers of drug interactions observed amongst the study participants were 18.4 (10.1). Age (ß: 0.2, 95% CI: 0.1, 0.3) and duration of renal transplantation (ß: -0.3, 95% CI: -0.5, -0.1) were the significant predictors of drug burden. A total of 645 drug interactions were identified amongst the study participants (major - 240; moderate - 270; and minor - 135) of which the majority were pharmacokinetic followed by toxicity risk. Age was significantly associated with the risk of potential drug interaction (OR: 2.6, 95% CI: 1.8, 12.4; p = 0.001). CONCLUSION: Drug treatment in renal transplant patients poses a significant burden in terms of nephrotoxicity potential and drug-drug interactions. A dedicated ambulatory clinical pharmacy service monitoring the drug use coupled with drug deprescribing strategies are the need of the hour in this population.

Evaluation of the Association between Single Nucleotide Polymorphisms of Metabolizing Enzymes with the Serum Concentration of Paracetamol and Its Metabolites.

Intravenous paracetamol is a commonly administered analgesic and antipyretic in inpatient settings. Paracetamol is metabolized by cytochrome P450 (CYP) enzymes followed by conjugating enzymes to mainly glucuronide but to a lesser extent, sulphate metabolites, and oxidative metabolites. Single nucleotide polymorphisms (SNPs) in the CYP enzymes result in modified enzymatic activity. The present study was carried out to evaluate the prevalence of SNPs related to paracetamol metabolism and principal metabolites in critically ill patients, and those with chronic kidney disease. The present study is a cross-sectional study carried out in adults (>21 years) requiring intravenous paracetamol as part of their standard of care. Details regarding their demographics, and renal and liver function tests were collected. Blood was withdrawn for the analysis of paracetamol and their metabolites, and the SNPs of key CYP enzymes. Paracetamol/paracetamol glucuronide (P/PG), paracetamol/paracetamol sulphate (P/PS) and PG/PS were estimated. Acute liver injury (ALI) and renal dysfunction were defined using standard definitions. We observed a significant prevalence of SNPs in CYP1A2*1C, CYP3A4*3, CYP1A2*1K, CYP1A2*6, CYP2D6*10, and CYP2E1*2 amongst the 150 study participants. Those with CYP1A2*6 (CC genotype) were observed with significantly lower PG and PS concentrations, and a higher P/PS ratio; CYP2D6*10 (1/1 genotype) with a significantly lower PG concentration and a higher P/PG ratio; and CYP1A2*1K (CC genotype) was observed with a significantly higher PG/PS ratio. Good predictive accuracies were observed for determining the SNPs with the cut-off concentration of 0.29 µM for PS in determining CYP1A2*1K, 0.39 µM for PG and 0.32 µM for PS in determining CYP1A2*6 genotype, and 0.29 µM for PG in determining the CYP2D6*10 genotype. Patients with renal dysfunction were observed with significantly greater concentrations of paracetamol, PG and P/PS, and PG/PS ratios, with a lower concentration of PS. No significant differences were observed in any of the metabolites or metabolite ratios in patients with ALI. We have elucidated the prevalence of key CYP enzymes involved in acetaminophen metabolism in our population. Alterations in the metabolite concentrations and metabolic ratios were observed with SNPs, and in patients with renal dysfunction. Population toxicokinetic studies elucidating the dose-response relationship are essential to understand the optimized dose in this sub-population.

A Case Report of Lifesaving Intravenous Bolus Epinephrine Administration in a Case of Severe Refractory Anaphylactic Shock.

Anaphylaxis is a life-threatening response to various types of allergens. Early recognition and management are crucial for reducing mortality. This case report highlights a 31-year-old male with a background of hypertension who presented to the emergency department with nausea, vomiting, right flank pain, headache, and elevated blood pressure (BP) of 212/134 mmHg. The patient was started on stat captopril 12.5 mg tablet and stat amlodipine 5 mg tablet for his high BP and stat diclofenac 75 mg (1 mg/kg) intramuscular (IM) for his flank pain. Two minutes later the patient started developing swelling of his mucosal membranes with no urticaria or rashes and his BP suddenly dropped and was unrecordable. First-line management was immediately initiated including the administration of two standard adult doses of IM epinephrine of 500 mcg each with a 5-minute interval. The BP remained undetectable; accordingly, a third IM epinephrine dose of 500 mcg was administered along with an intravenous (IV) epinephrine drip initiated at a rate of 4 mcg/min. The BP became 60/40 mmHg but kept dropping, thus an IV epinephrine bolus of 300 mcg (4 mcg/kg) was given along with the ongoing IV epinephrine drip. BP increased to 126/75 mmHg. While on the IV epinephrine drip the BP dropped again to 88/59 mmHg, a second IV epinephrine bolus of 200 mcg (2.6 mcg/kg) was given and the BP became 140/90 mmHg and recovery was achieved. Emergency cases require immediate recognition and intervention. Currently, IM epinephrine is the primary treatment for anaphylaxis. We hope our case report contributes to the database on severe refractory anaphylaxis by discussing a successful case where IV bolus epinephrine was used to prevent imminent cardiovascular collapse. Highlighting the need for appropriate escalation of management given the availability of physicians with expertise.

Anxiety is associated with extraneous cognitive load during teaching using high-fidelity clinical simulation.

High-fidelity clinical simulation is currently a well-established teaching tool. However, high-fidelity representations of patients in critical conditions have the potential to elicit emotions among learners and impact their cognitive load (CL). Teaching with clinical simulation may induce both emotional and cognitive overloads. The relationship between anxiety and CL during clinical simulation was studied. Forty-one undergraduate medical students participated in this study; 19 males and 22 females. The state-anxiety component of State-Trait Anxiety Inventory was administered during clinical simulation teaching sessions at time points: pre-scenario, post-scenario and post-debriefing. The Cognitive Load Scale (Leppink et al.) questionnaire was also completed post-scenario. This assessed the three components of CL: intrinsic cognitive load (ICL), extraneous cognitive load (ECL) and self-perceived learning (SPL). Median CL scores for ICL, ECL and SPL were compared between groups of low-anxiety and high-anxiety participants using a Mann-Whitney U test. State-anxiety scores were high for both the pre-scenario and post-scenario time points with a significant reduction following post-debriefing. The median (interquartile range) state-anxiety scores were 41.0 (33.0-50.0), 46.0 (33.0-52.0) and 31.0 (23.0-39.0) for the pre-scenario, post-scenario and post-debriefing time points respectively. Students with high state-anxiety had higher ECL scores (median = 2.0) than students with low state-anxiety (median = 0.9) at the post scenario time point (U = 220, p = 0.043). No statistical relation was seen with state-anxiety for either ICL or SPL. State-anxiety immediately after the simulation scenario is associated with ECL but not ICL or SPL.

Concentric-needle single-fiber electromyography for the diagnosis of myasthenia gravis.

The goal of this study was to estimate the accuracy of concentric-needle single-fiber electromyography (CN-SFEMG) for the diagnosis of myasthenia gravis (MG). A consecutive series of patients referred for CN-SFEMG was evaluated by an investigator blinded to the results of CN-SFEMG in order to determine the presence or absence of MG using an independent reference standard. Sensitivity, specificity, predictive values, and likelihood ratios were calculated. The study population included 51 patients (21 with MG). CN-SFEMG was normal in 34 patients (67%) and abnormal in 17 (33%). The sensitivity of CN-SFEMG for the diagnosis of MG was 0.67 and the specificity was 0.96. The positive likelihood ratio was 16.8 and the negative likelihood ratio was 0.34. The positive and negative predictive values were 0.93 and 0.76, respectively. These results indicate that CN-SFEMG showing abnormal jiggle is extremely useful for confirming the diagnosis of MG, but that CN-SFEMG showing normal jiggle has limited utility in excluding the diagnosis.