The HeartWare Ventricular Assist Device (HVAD) was widely used for mechanical circulatory support in patients with end-stage heart failure. However, there have been reports of a critical issue with HVAD pumps failing to restart, or experiencing delays in restarting, after being stopped. This case report describes 2 instances of HVAD failure-to-restart during heart transplantation surgery and routine outpatient care. Despite multiple attempts to restart the pump using various controllers and extensions, the HVAD failed to restart, triggering a hazard alarm for pump stoppage. In one case, the patient survived after receiving a heart transplantation, while in the other, the patient died immediately following the controller exchange. These cases highlight the rare but life-threatening complication of HVAD failure-to-restart, underscoring the importance of awareness among clinicians, patients, and caregivers, and adherence to the manufacturer’s guidelines and recommendations for HVAD management.

Purpose: NUT carcinoma (NC) is a solid tumor caused by the rearrangement of NUTM1 that usually develops in midline structures, such as the thorax. No standard treatment has been established despite high lethality. Thus, we investigated whether targeting the junction region of NUTM1 fusion breakpoints could serve as a potential treatment option for NC. Materials and Methods: We designed and evaluated a series of small interfering RNAs (siRNAs) targeting the junction region of BRD4-NUTM1 fusion (B4N), the most common form of NUTM1 fusion. Droplet digital polymerase chain reaction using the blood of patients was also tested to evaluate the treatment responses by the junction sequence of the B4N fusion transcripts. Results: As expected, the majority of NC fusion types were B4N (12 of 18, 67%). B4N fusion-specific siRNA treatment on NC cells showed specific inhibitory effects on the B4N fusion transcript and fusion protein without affecting the endogenous expression of the parent genes, resulting in decreased relative cell growth and attenuation of tumor size. In addition, the fusion transcript levels in platelet-rich-plasma samples of the NC patients with systemic metastasis showed a negative correlation with therapeutic effect, suggesting its potential as a measure of treatment responsiveness. Conclusion This study suggests that tumor-specific sequences could be used to treat patients with fusion genes as part of precision medicine for a rare but deadly disease.

We analyzed 1,079 forensic autopsies conducted in 2021 by the National Forensic Service Daejeon Institute from the Jungbu province in the central part of South Korea, for their manner and cause of death. Among the manner of death (n=1,079), 45.3% (n=489) were categorised as unnatural, 39.5% (n=426) as natural, and 15.2% (n=164) were unknown. Among the unnatural deaths (n=489), 40.7% (n=199) were accidents, 36.8% (n=180) were suicides, 14.1% (n=69) were undetermined, and 8.4% (n=41) were homicides. The major causes of unnatural deaths (n=489) were by trauma, causing 34.4% (n=168), poisoning causing 26.8% (n=131), and asphyxia causing 17.2% (n=84). The major cause of death by trauma (n=168) was falling at 46.4% (n=78), and by asphyxia (n=84) was strangulation at 76.2% (n=64). Among natural deaths (n=426), heart disease was the major cause at 49.8% (n=212) followed by vascular disease at 16.7% (n=71). In future, a time-series statistical analysis on the manner and causes of death in Jungbu province may provide insight and allow for more advanced interpretations about both healthcare and public safety.

With the increasing number of medications demonstrating mortality benefits in heart failure with reduced ejection fraction (HFrEF), the pharmacological treatment of HFrEF is entering a new phase. To enhance outcomes in heart failure patients through medical treatment, the choice of appropriate medications and simultaneous and rapid uptitration are critical. However, there are several challenges encountered during this medication uptitration, including issues like hypotension, fatigue, worsening renal function, and hyperkalemia. This paper addresses strategies for effectively managing these challenges to successfully reach the maximum tolerated dose in patients. Additionally, it will discuss the management of comorbidities often associated with heart failure, the importance of exercise and rehabilitation, and the significance of proper nutrition intake, in addition to guideline-directed medical therapy.

The 2009 Chronic Kidney Disease Epidemiology Collaboration creatinine-based estimated glomerular filtration rate (eGFRcr) equation contains a race component that is not based on biology and may cause a bias in results. Therefore, the 2021 eGFRcr and creatinine-cystatin C–based eGFR (eGFRcr-cysC) equations were developed with no consideration of race. This study compared the cardiovascular event (CVE) and all-cause mortality and CVE combined predictability among the three eGFR equations in Korean chronic kidney disease (CKD) patients. Methods: This study included 2,207 patients from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease. Receiver operating characteristic (ROC) and net reclassification improvement (NRI) index were used to compare the predictability of the study outcomes according to the 2009 eGFRcr, 2021 eGFRcr, and 2021 eGFRcr-cysC equations. Results: The overall prevalence of CVE and all-cause mortality were 9% and 7%, respectively. There was no difference in area under the curve of ROC for CVE and mortality and CVE combined among all three equations. Compared to the 2009 eGFRcr, both the 2021 eGFRcr (NRI, 0.013; 95% confidence interval [CI], – 0.002 to 0.028) and the eGFRcr-cysC (NRI, –0.001; 95% CI, –0.031 to 0.029) equations did not show improved CVE predictability. Similar findings were observed for mortality and CVE combined predictability with both the 2021 eGFRcr (NRI, –0.019; 95% CI, –0.039–0.000) and the eGFRcr-cysC (NRI, –0.002; 95% CI, –0.023 to 0.018). Conclusion: The 2009 eGFRcr equation was not inferior to either the 2021 eGFRcr or eGFRcr-cysC equation in predicting CVE and the composite of mortality and CVE in Korean CKD patients.

Background: It remains unclear whether coffee intake is associated with the risk of hypertension. This study aimed to investigate the association between coffee intake and the risk of hypertension by using a meta-analysis of cohort studies. Methods: PubMed and Embase were searched using keywords in September 2022 to identify studies on coffee intake and the risk of hypertension. Results: We included a total of 13 longitudinal cohort studies, which involved a total of 64,650 incident cases of hypertension among 314,827 participants. In a random effects model meta-analysis of all the studies, coffee intake was not significantly associated with the risk of hypertension (relative risk [RR], 0.97; 95% confidence interval [CI], 0.90–1.05; I2 = 58.0%; n = 13). In the subgroup meta-analysis, coffee intake was associated with a decreased risk of hypertension in studies conducted in America (RR, 0.93; 95% CI, 0.87–0.98; I 2 = 4.6%; n = 5) and in low-quality studies (RR, 0.92; 95% CI, 0.88–0.96; I2 = 0.0%; n = 7). In the remaining subgroup meta-analyses by amount of coffee intake, gender, type of coffee (decaffeinated vs. caffeinated), smoking, and years of follow-up, coffee intake was not significantly associated with the risk of hypertension. Conclusion The current meta-analysis showed that coffee intake is not associated with the risk of hypertension.

Purpose: To find biomarkers for disease, there have been constant attempts to investigate the genes that differ from those in the disease groups. However, the values that lie outside the overall pattern of a distribution, the outliers, are frequently excluded in traditional analytical methods as they are considered to be ‘some sort of problem.’ Such outliers may have a biologic role in the disease group. Thus, this study explored new biomarker using outlier analysis, and verified the suitability of therapeutic potential of two genes (TM4SF4 and LRRK2). Materials and Methods: Modified Tukey’s fences outlier analysis was carried out to identify new biomarkers using the public gene expression datasets. And we verified the presence of the selected biomarkers in other clinical samples via customized gene expression panels and tissue microarrays. Moreover, a siRNA-based knockdown test was performed to evaluate the impact of the biomarkers on oncogenic phenotypes. Results: TM4SF4 in lung cancer and LRRK2 in breast cancer were chosen as candidates among the genes derived from the analysis. TM4SF4 and LRRK2 were overexpressed in the small number of samples with lung cancer (4.20%) and breast cancer (2.42%), respectively. Knockdown of TM4SF4 and LRRK2 suppressed the growth of lung and breast cancer cell lines. The LRRK2 overexpressing cell lines were more sensitive to LRRK2-IN-1 than the LRRK2 under-expressing cell lines Conclusion Our modified outlier-based analysis method has proved to rescue biomarkers previously missed or unnoticed by traditional analysis showing TM4SF4 and LRRK2 are novel target candidates for lung and breast cancer, respectively.

Background: Peritoneal dialysis (PD) is improving as a renal replacement therapy for end-stage renal disease (ESRD) patients. We analyzed the main outcomes of PD over the last three decades at a single large-scale PD center with an established high-quality care system. Methods: As a retrospective cohort study, we included participants (n = 1,203) who began PD between 1990 and 2019. Major PD-related outcomes were compared among the three 10-year cohorts. Results: The 1,203 participants were 58.3% male with a mean age of 47.9 ± 13.8 years. The median PD treatment duration was 45 months (interquartile range, 19–77 months); 362 patients (30.1%) transferred to hemodialysis, 289 (24.0%) received kidney transplants, and 224 (18.6%) died. Overall, the 5- and 8-year adjust patient survival rates were 64% and 49%, respectively. Common causes of death included infection (n = 55), cardiac (n = 38), and cerebrovascular (n = 17) events. The 5- and 8-year technique survival rates were 77% and 62%, respectively, with common causes of technique failure being infection (42.3%) and solute/water clearance problems (22.7%). The 5-year patient survival significantly improved over time (64% for the 1990–1999 cohort vs. 93% for the 2010–2019 cohort). The peritonitis rate also substantially decreased over time, from 0.278 episodes/patient-year (2000–2004) to 0.162 episodes/patient-year (2015–2019). Conclusion PD is an effective treatment option for ESRD patients. There was a substantial improvement in the patient survival and peritonitis rates over time. Establishing adequate infrastructure and an effective system for high-quality PD therapy may be warranted to improve PD outcomes.