Risk factors indicating immune-related adverse events with combination chemotherapy with immune checkpoint inhibitors and platinum agents in patients with non-small cell lung cancer: a multicenter retrospective study.

PURPOSE: Immune checkpoint inhibitors (ICI) ushered in a new era for the treatment of non-small cell lung cancer (NSCLC). However, they carry the risk of immune-related adverse events (irAEs). Recently, various studies have been conducted on the predictive factors for irAEs, but there are no reports focusing only on ICI plus platinum agents. The present study aimed to identify the risk factors for irAEs due to ICI combined with platinum-based induction immunochemotherapy in NSCLC patients, focusing only on the period of combined therapy and excluding the period of ICI maintenance therapy. METHODS: This retrospective study included 315 NSCLC patients who started ICI combined with platinum-based chemotherapy treatment at 14 hospitals between December 2018 and March 2021. A logistic regression analysis was used to explore the predictive factors. RESULTS: Fifty patients (15.9%) experienced irAEs. A multivariate analysis revealed that squamous cell carcinoma (P = 0.021; odds ratio [OR]: 2.30; 95% confidence interval [Cl]: 1.14-4.65), anti-programmed death 1 antibody (anti-PD-1) plus anti-cytotoxic T-lymphocyte antigen-4 antibody (anti-CTLA-4) regimens (P < 0.01; OR: 22.10; 95% Cl: 5.60-87.20), and neutrophil-to-lymphocyte rate (NLR) < 3 (P < 0.01; OR: 2.91; 95% Cl: 1.35-6.27) were independent predictive factors for irAEs occurrence. CONCLUSION: Squamous cell carcinoma, anti-PD-1 plus anti-CTLA-4 regimens, and NLR < 3 may be predictive factors for the occurrence of irAEs due to induction immunochemotherapy in patients with NSCLC. By focusing on the potential risk of irAEs in patients with these factors, irAEs can be appropriately managed from an early stage.

[A case of myasthenia-like symptoms induced by cibenzoline overdosage].

The present patient was an 87-year-old man who had been taking cibenzoline for tachyarrhythmia. Five years after initiation of administration, he was referred to our hospital for ptosis that worsened from midday, as well as weakness of the facial and limb muscles. He tested negative for anti-acetylcholine receptor antibody but positive in the edrophonium test, suggesting that he had myasthenia gravis. He was admitted to our hospital 3 years later due to worsening symptoms of ptosis and muscle weakness. He had hypoglycemia, cardiac conduction defect, and renal dysfunction. In addition, blood concentration of cibenzoline was markedly high (1,850 ng/ml). We terminated the administration of cibenzoline, after which the patient's neurologic symptoms improved. Our findings suggest that cibenzoline toxicity must be considered in differentiating myasthenia gravis when a patient also presents with renal dysfunction.

Investigation of the Efficacy of an Administration Plan for Tazobactam/Piperacillin (TAZ/PIPC) and the Incidence of Kidney and Hepatic Disorders.

Tazobactam/piperacillin (TAZ/PIPC) is widely used in the treatment of infectious disease. In this study, three hundred and sixty-three patients who were treated with the recommended dose of TAZ/PIPC were investigated for the proportion of time above the minimum inhibitory concentration (%TAM) and the frequency of renal and liver dysfunction. Of the whole patient population, 5.23%, exhibited increased creatinine levels, 9.37% and 8.82% exhibited increased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, respectively. The patients who exhibited high serum creatinine (SCr) levels before administration, exhibited significant increases of AST (p=0.0121). The patients who exhibited low albumin levels before administration, exhibited significant decreases in renal function (p=0.0041). In the case of a breakpoint (BP) of 64 µg/mL, the arrival probabilities of %TAM of 30% and 50% were 99.4% and 76.9%, respectively. We suggested that the dose of TAZ/PIPC should be adjusted according to the interview form finding and a %TAM>50% (maximal bactericidal action).

Pharmacokinetics of linezolid during continuous hemodiafiltration: A case report.

The pharmacokinetics of linezolid clearance (CLLZD) during continuous hemodiafiltration (CHDF) has not been comprehensively analyzed. Here, we examined CLLZD by CHDF in a patient with septic shock and disseminated intravascular coagulation due to methicillin-resistant Staphylococcus aureus. The extraction ratio of LZD by CHDF was 22.6%, and the protein-binding rate was 17.9% ± 7.7%. In addition, it was determined that the calculated total body clearance of LZD was 30.2 mL/min, plasma elimination half-life was 8.66 h, and the CLLZD by the dialyzer used for CHDF was 23.0 mL/min. From the obtained pharmacokinetics, the CLLZD of patients continuing CHDF was estimated to be approximately half of the reported CLLZD for healthy subjects. In addition, the LZD concentration of the sepsis patient who underwent CHDF remained higher than the minimum inhibitory concentration and was similar to the LZD concentrations reported in normal renal function patients. Although further studies are warranted, when LZD is administered to patients treated with CHDF, the present findings suggest that dose regulation is not required.

Risk Factors Associated with Cisplatin-Induced Nephrotoxicity in Patients with Advanced Lung Cancer.

Cisplatin (CDDP) combination chemotherapy is widely administered to patients with advanced lung cancer. The dose depends on multiple factors, including whether the tumor is non-small-cell lung cancer (NSCLC) or small-cell lung cancer (SCLC). Although efficacy is limited by cisplatin-induced nephrotoxicity (CIN), little is known about the risk factors for this complication. The aim of this study was to identify the risk factors for CIN in patients with advanced lung cancer, both NSCLC and SCLC. We retrospectively reviewed clinical data for 148 patients who underwent initial chemotherapy including CDDP ≥50 mg/m2 per patient per day for the first course at Kyushu Medical Center between October 2010 and September 2013. All data were collected from the electronic medical record system. Nephrotoxicity was defined as an increase in serum creatinine concentration of at least grade 2 during the first course of CDDP chemotherapy, as described by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. CIN was observed in nine patients. Univariate analysis revealed that cardiac disease and lower baseline serum albumin (Alb) values conferred a higher risk of nephrotoxicity (p<0.05). The cut-off value of Alb was 3.8 g/dL, calculated by receiver operating characteristics (ROC) curves. Multivariable logistic regression analysis revealed that cardiac disease (odds ratio=11.7; p=0.002) and hypoalbuminemia (odds ratio=6.99 p=0.025 significantly correlated with nephrotoxicity. In conclusion, cardiac disease and low baseline Alb values are possible risk factors for CIN.

Relationship of Prescribed Drugs with the Risk of Fall in Inpatients.

Falls are common in elderly patients and are often serious. Several drugs have been associated with an increased risk of fall. Older adults often take multiple drugs for chronic diseases, and thus may be at increased risk from drugs associated with fall. We investigated the association between drug use and falling in hospitalized older people, with the goal of identifying medications that may increase the risk of a fall. A retrospective case control study was performed at the National Hospital Organization Kumamoto Saishunso Hospital in Japan. Medications taken by patients who fell (n=57) were compared with those taken by patients who did not fall (n=63). The median age (interquartile range; IQR) of the fall and non-fall groups were 75.0 (67.0-83.0) and 80.0 (70.3-84.5) years, respectively. The characteristics of the two groups were similar, with no significant differences in age, sex, or body weight. The probability of falling increased when the patients used zolpidem [odds ratio (OR)=2.47; 95%CI: 1.09-5.63; p<0.05] and calcium channel antagonists (OR=0.299; 95%CI: 0.13-0.68; p<0.01), and was also related to physical factors (OR=2.27; 95%CI: 1.01-5.09; p<0.05). Elderly patients taking zolpidem may fall due to sleepiness, and blood pressure control may be important to prevent orthostatic high blood pressure. In the treatment of elderly people, medical staff should try to choose drugs that prevent fall or are not associated with falling.

Comparison of predictive accuracy of teicoplanin concentration using creatinine clearance and glomerular filtration rate estimated by serum creatinine or cystatin C.

We compared the predictive accuracy of TEIC concentrations (TEIC_conc) calculated using either serum cystatin C (CysC) or serum creatinine (SCr) and the population mean method using the mean population parameter of TEIC_conc for Japan. We also compared the predicted TEIC_conc to measured TEIC_conc. Creatinine clearance (CLCr) predicted using the Cockcroft-Gault (C&G) equation with SCr was 45.23 mL/min (interquartile range [IQR]: 32.12-58.28), and the glomerular filtration rate (GFR) predicted using the Hoek equation with CysC was 45.23 mL/min (IQR: 35.40-53.79). The root mean-squared prediction error (IQR) based on CLCr predicted using the C&G equation with SCr was 6.88 (3.80-9.96) µg/mL, and that based on GFR predicted using the Hoek equation with CysC was 6.72 (3.77-9.68) µg/mL. Predicted TEIC_conc did not differ significantly between the two methods. The predictive accuracy of the TEIC_conc using the Hoek equation with CysC was similar to that of CLCr using the C&G equation with SCr. These findings suggest that the predictive accuracy of the TEIC_conc using CLCr based on the G&G equation and SCr might be sufficient for the initial dose adjustment of TEIC. Given that we were unable to confirm that CysC is the optimal method for predicting TEIC_conc, the expensive measurement of CysC might not be necessary.