Chlorfenapyr is a new contact and stomach insecticide derived from natural pyrroles secreted by Streptomyces spp. It is a pro-insecticide and acts after metabolic transformation to its active metabolite tralopyril. Tralopyril is an uncoupler of oxidative phosphorylation in the mitochondria of the target insects and of experiment animals, leading to the disruption of adenosine triphosphate synthesis and death. Several fatal human poisonings had been reported and no blood chlorfenapyr or tralopyril measurements were available. The treatment remains supportive. A 32-year-old healthy man ingested 200 mL of 10% chlorfenapyr as a suicide attempt. Unfortunately, he succumbed at 157 h post-ingestion, shortly after having fever and seizures. His serum level of chlorfenapyr at 4 h post-exposure was 77.4 ng/mL, and was undetectable at 113 and 156 h, respectively. The serum levels of tralopyril were 723.6, 14,179, and 9654.2 ng/mL at 4, 113, and 156 h post-ingestion, respectively. The delay in the rise of serum tralopyril levels was noticeable, which seems to correlate with the patient’s signs and symptoms. The information may have therapeutic implications in the management of this deadly poisoning.

Early detection of rapidly progressive kidney disease is key to improving the renal outcome and reducing complications in adult patients with type 2 diabetes mellitus (T2DM). We aimed to construct a 6-month machine learning (ML) predictive model for the risk of rapidly progressive kidney disease and the need for nephrology referral in adult patients with T2DM and an initial estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m². We extracted patients and medical features from the electronic medical records (EMR), and the cohort was divided into a training/validation and testing data set to develop and validate the models on the basis of three algorithms: logistic regression (LR), random forest (RF), and extreme gradient boosting (XGBoost). We also applied an ensemble approach using soft voting classifier to classify the referral group. We used the area under the receiver operating characteristic curve (AUROC), precision, recall, and accuracy as the metrics to evaluate the performance. Shapley additive explanations (SHAP) values were used to evaluate the feature importance. The XGB model had higher accuracy and relatively higher precision in the referral group as compared with the LR and RF models, but LR and RF models had higher recall in the referral group. In general, the ensemble voting classifier had relatively higher accuracy, higher AUROC, and higher recall in the referral group as compared with the other three models. In addition, we found a more specific definition of the target improved the model performance in our study. In conclusion, we built a 6-month ML predictive model for the risk of rapidly progressive kidney disease. Early detection and then nephrology referral may facilitate appropriate management.

Chronic allograft dysfunction (CAD) is a major condition affecting long-term kidney graft survival. Serum microRNA (miRNA) has been reported as a biomarker for various conditions of allograft injuries. The upregulation of miR-21 is the best-known miRNA change in graft tissue, urine and plasma. However, the correlation of plasma miR-21 with the severity of CAD remains unclear. In our study, 40 kidney transplantation recipients with late graft survival for more than 10 years were enrolled. The CAD group (n = 20) had either an eGFR between 15 to 60 mL/min or a biopsy-proved chronic allograft nephropathy or rejection. The control group (n = 20) had an eGFR ≥ 60 mL/min without proteinuria and hematuria for a consecutive 3 months before the study. We performed RNA sequencing to profile the miRNAs expression. There were six differentially expressed miRNAs in the CAD group. Among them, miR-21-5p and miR-101-3p were decreased, and miR-20a-5p was increased. We found that miR-21-5p, miR-20a-5p and miR-101-3p all participated in the TGF-beta pathway. We demonstrated that decreased miR-21-5p and miR-101-3p, and increased miR-20a-5p were the novel CAD-associated miRNAs in the TGF-beta pathway. These findings may pave the way for developing early prediction miRNAs biomarkers for CAD, and possibly developing therapeutic tools in the field of kidney transplantation.

In recent studies, much has been discussed about biomarkers used in the evaluation of the transplanted graft function. However, there remains a lack of research regarding the long-term effects of microRNAs (miRNAs) on the different genders for kidney transplant (KTx) patients. In this study, we aim to assess the functions of miRNAs on long term outcomes of KTx patients by extracting differently expressed miRNAs between patients of normal graft function and graft dysfunction, while further analyzing their impact on the different genders. We analyzed the data of 40 patients who had received KTx for a period of more than ten years and included data regarding renal function, immuno-related markers and plasma miRNAs. Data were classified by gender for further studies. Twelve out of 17 females and 8 out of 23 males had undergone graft dysfunction. Renal function analysis showed significantly worse outcomes in the female patients. There were five differently expressed miRNAs between the female control group and female dysfunction group: miR-128-3p, miR-21-5p, miR-150-5p, miR-92a-3p and miR-15a-5p, and five between the male control group and male dysfunction group: miR-23a-3p, miR-126-3p, miR-142-3p, miR-223-3p and miR-26a-5p. Gender differences exist in incidences of kidney graft dysfunction, with male patients displaying better preservation in graft functions. Overall, these differently expressed miRNAs either enhance or suppress host immune responses. They can be predictive markers for graft survival and can also be important factors that lead to worse long term kidney graft function in females when compared to males.

The incidence of hypocalcemia is high in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) undergoing denosumab treatment. Since 2018, we have carried out a “multidisciplinary integrated care program for osteoporosis among patients with CKD and ESRD” in our hospital. The aim of this study was to compare the incidence of denosumab-associated hypocalcemia among patients with advanced CKD and ESRD before and after the integrated care program. We retrospectively reviewed the records of patients on their first dose of denosumab treatment from January 2012 to December 2021. A total of 3208 patients were included in our study. Among the 3208 patients, there were 101 dialysis patients, 150 patients with advanced CKD (stage 4 and 5), and 2957 patients with an estimated glomerular filtration rate (eGFR) higher than or equal to 30. The incidence of post-treatment severe hypocalcemia (corrected calcium level less than 7.0 mg/dl) within 30 days was significantly higher in the dialysis and advanced CKD group than in patients with an eGFR higher than or equal to 30 (6.9% vs. 2.0% vs. 0.1%, respectively, p < 0.001). Based on the results of the multivariate regression model, poor renal function (p < 0.05) and lower baseline corrected calcium level (p < 0.05) were associated with severe hypocalcemia within 30 days following the first dose of denosumab treatment. The incidence of post-treatment severe hypocalcemia within 30 days in advanced CKD and dialysis patients was significantly lower after the integrated care program (6.8% vs. 0.8%, p < 0.05). Our study shows that multidisciplinary integrated care may reduce the incidence rate of denosumab-associated severe hypocalcemia among patients with advanced CKD and ESRD.

Osteoporosis is a common condition that increases the risk of fracture and mortality. In Taiwan, clinical guidelines recommend pharmaceutical therapy for patients with a T-score of ≤ − 2.5; however, Taiwan’s National Health Insurance (NHI) only covers these medications for those with a history of fragility fractures. This gap in coverage necessitates a discussion of out-of-pocket treatment options. To address this, we provided an integrated care program with patient education and shared decision-making by nurse case managers specializing in osteoporosis. We evaluated whether education by nurse case managers influences patients with a T-score ≤ − 2.5, who are not covered by the NHI, to choose out-of-pocket pharmaceutical therapy. We retrospectively reviewed medical records of patients who underwent bone density scanning at our hospital between January 2014 and December 2021. We identified 4,462 patients with a T-score of ≤ − 2.5 who were ineligible for NHI-covered anti-osteoporotic therapy and analyzed trends in out-of-pocket medication use. Since the integrated care program began in 2018, we evaluated whether education by nurse case managers between 2018 and 2021 influenced patients’ decisions to pay out-of-pocket for therapy. After the implementation of the integrated care program, we identified 2,910 patients with a T-score ≤ -2.5 who were ineligible for NHI-covered anti-osteoporotic therapy. Of these, 640 opted for out-of-pocket treatment, while 2,270 chose conservative care. After a 1:1 propensity score match based on age and sex, logistic regression was used to analyze the impact of nurse case manager education on these decisions. Between 2014 and 2021, 888 of the 4,462 patients chose out-of-pocket pharmaceutical therapy. Before the implementation of the integrated care program and patient education by nurse case managers (2014–2017), 16% of the patients opted to pay out-of-pocket for anti-osteoporotic therapy. After the program was implemented (2018–2021), the rate increased significantly to 22% (P < 0.001). A multivariate logistic regression model showed that a history of osteoarthritis (adjusted odds ratio = 1.576; P = 0.009) and education provided by the nurse case managers (adjusted odds ratio = 5.044; P < 0.001) were significantly associated with choosing out-of-pocket therapy. Education from nurse case managers significantly increased the likelihood of patients choosing out-of-pocket anti-osteoporotic therapy in our hospital, thereby bridging the gap between clinical guidelines and NHI reimbursement criteria.