Search

Introduction Cisplatin is currently the key drug in the chemotherapy regimen for metastatic penile cancer. There are few reports of alternative medicines for patients who cannot tolerate cisplatin. This report describes a case in which carboplatin was used instead. Case presentation The patient presented with a chief complaint of edema in the groin area. On close examination, penile cancer (cT2‐3N3M0 stage IV) with pelvic lymph node metastasis was diagnosed. He was started on chemotherapy with cisplatin (50 mg/m2 on days 1 and 2), paclitaxel (120 mg/m2 on day 1), and 5‐fluorouracil (1000 mg/m2 on days 2–5), but he developed acute kidney failure on the 12th day, thought to be caused by cisplatin. Cisplatin was changed to carboplatin, and chemotherapy was continued. He has received nine courses of chemotherapy and is doing well. Conclusion A case of penile cancer safely and effectively treated with chemotherapy using carboplatin was reported.

Abstract Background Low birthrates and an aging society during population decline have brought about labor shortages and increased medical care needs. Medical resources should be distributed appropriately, particularly in rural areas. High‐quality primary care can make the medical system more effective and contribute to rural residents' health. However, there are no reports on the impact of primary care on health in the rural areas of Japan. This study examined the effect of primary care quality on self‐rated health in a rural Japanese area. Methods We conducted a cross‐sectional study using a questionnaire survey of residents of a rural area in northern Shiga Prefecture in 2021. Self‐rated health (SRH) was used as the health outcome (1–5 points), and the Japanese Primary Care Assessment Tool Short Form (JPCAT‐SF) was used to measure the patients' experience of primary care (0–100 points). We conducted a multivariate analysis using logistic regression analysis and examined the association between good SRH (4 points or more) and high JPCAT‐SF scores (above average score), adjusted for sociodemographic confounding factors. Results A total of 1108 men and 1412 women responded to the survey. The mean patient age was 69.8 years. The mean JPCAT‐SF score was 51.8 points. Among the 1172 patients with chronic diseases, good SRH was associated with high JPCAT‐SF scores (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.009–1.73). Conclusions Good SRH among rural residents with chronic disease was associated with high primary care quality.

Abstract Objectives Opioid availability for the palliative care of patients with advanced cancer is increasing globally. However, opioid availability remains extremely low in Japan. We investigated whether pain is appropriately controlled by low‐dose opioid prescriptions in patients with advanced cancer in Japan. Methods A web‐based nationwide survey for caregivers from 2000 community comprehensive support care centers was performed in Japan to assess details about pain in the 30 days before patients died of end‐stage cancer. Separately, the data for opioid prescription doses and medical services in the 90 days before the death of patients with cancer were extracted from a health insurance claim database. Results Responses from 1034 responders were retrieved and 665 patients were included. In total, 254 patients (38.2%) complained of severe‐to‐intolerable cancer‐related pain. The median cumulative prescription dose of opioids in the 90 days before patient death was 311.0 mg by oral morphine equivalent doses. Multiple regression analyses across prefectures revealed that the proportion of patients with severe‐to‐intolerable cancer‐related pain was negatively associated with the cumulative opioid consumption expressed as morphine‐equivalent doses within 90 days before death. Conclusions The very low availability of opioids for patients with end‐stage cancer could result in high rate of severe‐to‐intolerable cancer‐related pain patients. There were several limitations in this study, and the interpretations of the findings should be carefully. However, the increase in the absolute dose of opioids could improve the palliative care framework to the pain control levels of the global standard.

Abstract Immune checkpoint inhibitors (ICI) have shown a change in the prognosis of multiple malignancies, but a wide range of immune‐related adverse events (irAE) can occur. We present a case of a 72‐year‐old Caucasian male treated with Durvalumab for epidermic lung cancer, who developed a sclerosis‐like syndrome and myositis. The patient was admitted to our hospital with respiratory failure due to muscular weakness and pulmonary hypertension. Differential diagnoses pointed to scleroderma secondary to ICI. We report a rare case of ICI‐induced axonal polyneuropathy, myopathy and RNA polymerase III positive scleroderma. As this therapy is widely recommended, adverse effects may become more frequent. Early identification and treatment are warranted.

ABSTRACT Background This study aimed to determine the factors associated with feeling ashamed of disclosing HIV‐positive status among females who self‐reported to health facilities for HIV testing in Kenya. Method This study used the Kenya Demographic Health Survey data set for 2022. A total of 18,506 women aged 15–49 years were selected from the sample clusters; 13,815 had ever tested for HIV and 332 had positive results for HIV. The chi‐squared test was applied to determine the association between the selected variables of interest and the outcome variable. Furthermore, to identify the explanatory variables that were associated with the outcome variable of interest, logistic binary regression was performed. A p > 0.05 and all statistical analyses were conducted using Microsoft Excel (xlsx) and STATA15. Results The analysis included 332 women who had tested positive during the survey out of which 125(38%) women agreed to have felt ashamed to disclose their HIV+ status. Agreed to stigma (AOR = 1.92, 95% CI: 1.15, 3.22; p

Introduction Redo pyeloplasty can be difficult due to scar tissue or fibrosis. Ureteral reconstruction with a buccal mucosal graft is performed safely and successfully, but most reports of ureteral reconstruction using a buccal mucosal graft are of robot‐assisted surgery, with few reports of laparoscopic‐assisted surgery. A case of laparoscopic‐assisted redo pyeloplasty using a buccal mucosal graft is presented. Case presentation A 53‐year‐old woman was diagnosed with ureteropelvic junction obstruction, and a double‐J stent was placed to relieve backache. She visited our hospital 6 months after double‐J stent placement. Three months later, laparoscopic pyeloplasty was performed. At 2 months postoperatively, anatomic stenosis occurred. Holmium laser endoureterotomy and balloon dilation were performed; however, the anatomic stenosis recurred, and laparoscopic redo pyeloplasty with a buccal mucosal graft was performed. After redo pyeloplasty, obstruction was improved, and her symptoms disappeared. Conclusion This is the first case of using a buccal mucosal graft for laparoscopic pyeloplasty in Japan.

Abstract Variation in pollinator foraging behavior can influence pollination effectiveness, community diversity, and plant–pollinator network structure. Although effects of interspecific variation have been widely documented, studies of intraspecific variation in pollinator foraging are relatively rare. Sex‐specific differences in resource use are a strong potential source of intraspecific variation, especially in species where the phenology of males and females differ. Differences may arise from encountering different flowering communities, sex‐specific traits, nutritional requirements, or a combination of these factors. We evaluated sex‐specific foraging patterns in the eastern regal fritillary butterfly (Argynnis idalia idalia), leveraging a 21‐year floral visitation dataset. Because A. i. idalia is protandrous, we determined whether foraging differences were due to divergent phenology by comparing visitation patterns between the entire season with restricted periods of male–female overlap. We quantified nectar carbohydrate and amino acid contents of the most visited plant species and compared those visited more frequently by males versus females. We demonstrate significant differences in visitation patterns between male and female A. i. idalia over two decades. Females visit a greater diversity of species, while dissimilarity in foraging patterns between sexes is persistent and comparable to differences between species. While differences are diminished or absent in some years during periods of male–female overlap, remaining signatures of foraging dissimilarity during implicate mechanisms other than phenology. Nectar of plants visited more by females had greater concentrations of total carbohydrates, glucose, and fructose and individual amino acids than male‐associated plants. Further work can test whether nutritional differences are a cause of visitation patterns or consequence, reflecting seasonal shifts in the nutritional landscape encountered by male and female A. i. idalia. We highlight the importance of considering sex‐specific foraging patterns when studying interaction networks, and in making conservation management decisions for this at‐risk butterfly and other species exhibiting strong intraspecific variation.

Extranodal NK/T-cell lymphoma (ENKTL) is a highly aggressive and heterogeneous disease with poor clinical outcome. Our previous work had demonstrated that circulating tumor DNA (ctDNA) analyses were feasible in ENKTL, and dynamic tracing of ctDNA could be used to monitor the disease status. However, the prognostic value of ctDNA in ENKTL has not been fully investigated. Patients with newly diagnosed ENKTL from February 2017 to December 2021 (n = 70) were enrolled. The pretreatment ctDNA concentration (hGE/mL) was measured. The prognostic value of ctDNA, international prognostic index (IPI), Korean prognostic index (KPI), PINK-E, and the combination of PINK-E and ctDNA (PINK-EC) were investigated in our cohort. The IPI and PINK-E risk categories had a significant difference in progression-free survival (PFS) and overall survival (OS) between the low-risk and intermediate-risk groups. The KPI risk category had a difference in PFS and OS between the intermediate-risk and high-risk groups. Furthermore, integrating ctDNA into the PINK-E model could overcome the shortcomings of other prognostic models, which could significantly distinguish the different-risk groups. Overall, our results demonstrated that PINK-EC showed a superior prognostic prediction value and stability compared with IPI, KPI, and PINK-E. The integration of molecular features of the tumor into classic risk categories might better characterize a high-risk group where novel treatment approaches are most needed.

Abstract Aim Previously, we reported on the efficacy and safety of guanfacine extended‐release (GXR) in Japanese adults with attention‐deficit/hyperactivity disorder (ADHD) from a phase 3, double‐blind, placebo‐controlled, randomized trial. In this exploratory post hoc analysis, we assessed the efficacy and/or safety of GXR in the following subgroups: ADHD‐combined (ADHD‐C) and ADHD‐predominantly inattentive (ADHD‐I) subtypes, age (≥31,

Abstract Background The etiology of many genetic diseases is challenging. This is especially true for developmental disorders of the central nervous system, since several genes can be involved. Many of such pathologies are considered rare diseases, since they affect less than 1 in 2000 people. Due to their low frequency, they present several difficulties for patients, from the delay in the diagnosis to the lack of treatments. Next‐generation sequencing techniques have improved the search for diagnosis in several pathologies. Many studies have shown that the use of whole‐exome/genome sequencing in rare Mendelian diseases has a diagnostic yield between 30% and 50% depending on the disease. Methods Here, we present the case of an undiagnosed 6‐year‐old boy with severe encephalopathy of unclear cause, whose etiological diagnosis was achieved by whole‐genome sequencing. Results We found a novel variant that has not been previously reported in patients nor it has been described in GnomAD. Segregation analysis supports a de novo mutation, since it is not present in healthy parents. The change is predicted to be harmful to protein function, since it falls in the first quarter of the protein producing an altered reading frame and generating a premature stop codon. Additionally, the variant is classified as pathogenic according to ACMG criteria (PVS1, PM2, and PP3). Furthermore, there are several reported frameshift mutations in nearby codons as well as nonsense mutations that are predicted as pathogenic in other studies. Conclusion We found a novel de novo frameshift mutation in the PURA gene (MIM number 600473), c.151_161del, with sufficient evidence of its pathogenicity.

Background We previously showed that levels of prebeta‐1 high‐density lipoprotein (HDL), the principal acceptor of cholesterol effluxed from cells, including artery wall macrophages, are positively associated with coronary heart disease (CHD) and myocardial infarction (MI) risk. Methods and Results In a multiethnic follow‐up cohort of 1249 individuals from University of California–San Francisco clinics, we determined the degree to which prebeta‐1 HDL levels, both absolute and percentage of apolipoprotein AI, are associated with CHD and history of MI. Independent, strong, positive associations were found. Meta‐analysis revealed for the absolute prebeta‐1 HDL for the top tertile versus the lowest, unadjusted odds ratios of 1.90 (95% CI, 1.40–2.58) for CHD and 1.79 (95% CI, 1.35–2.36) for MI. For CHD, adjusting for established risk factors, the top versus bottom tertiles, quintiles, and deciles yielded sizable odds ratios of 2.37 (95% CI, 1.74–3.25, P

Aim Patients with gangrenous appendicitis usually require emergency surgery. Preoperative diagnosis of gangrenous appendicitis is clinically important but not always straightforward. We undertook this study to identify preoperative predictors of gangrenous appendicitis. Methods This was a single‐center case–control study. We identified 162 patients who underwent appendectomy between September 2011 and August 2014 after the diagnosis of acute appendicitis was established. We identified laboratory parameters and computed tomography (CT) scan findings predictive of histologically or surgically diagnosed gangrenous appendicitis by univariable and multivariable analyses. Results Of 146 study patients, gangrenous appendicitis was confirmed in 102. Univariable analysis showed that two laboratory factors (C‐reactive protein []and total bilirubin [T‐Bil]) and three CT scan findings were significant predictors for gangrenous appendicitis. Multivariable analysis showed that T‐Bil and two CT scan findings (appendicolith and fat stranding around the appendix) were independent predictors. The combination of “T‐Bil ≥ 1.0 mg/dL or appendicolith” was able to predict gangrenous appendicitis with a sensitivity of 90.5%, positive predictive value of 80.4%, and accuracy of 77.8%. The combination of “T‐Bil ≥ 1.0 mg/dL or fat stranding around the appendix” was able to predict gangrenous appendicitis with a sensitivity of 98.9%, positive predictive value of 76.4%, and accuracy of 71.9%. Conclusion These combinations of laboratory and CT scan findings could be valuable as predictors of gangrenous appendicitis.

Objectives. To determine whether an alkaline phosphatase (ALP) flare after androgen deprivation therapy (ADT) is associated with the treatment response in castration-resistant prostate cancer (CRPC) and predicts the prognosis of metastatic prostate cancer (PCa) patients. Methods. One hundred and nineteen patients diagnosed with metastatic PCa between 2008 and 2017 were retrospectively studied. The ALP flare ratio was calculated as the ratio of ALP levels 1 month after beginning ADT to ALP levels at diagnosis. The association of the ALP flare ratio with the prostate-specific antigen (PSA) response to CRPC treatment (second-generation androgen receptor targeted therapy (ART) or docetaxel), time to CRPC, and overall survival (OS) were investigated. Results. The time to CRPC and OS was significantly longer in patients with an ALP flare ratio less than 1.33 compared to a ratio more than 1.33. No difference in PSA response was seen regarding the ALP flare ratio in both ART and docetaxel treatment. Second-generation ART-treated patients with a low ALP flare ratio showed longer OS than those with a higher ALP flare ratio (p=0.0367). However, no difference was seen between a high and low ALP flare ratio (p=0.8054) in docetaxel-treated patients. The ALP flare ratio was the most significant prognostic factor for OS (p

Beckwith–Wiedemann syndrome (BWS) is a rare congenital condition characterized by complex overgrowth of different body parts. Children with Beckwith–Wiedemann syndrome, particularly those with hemihypertrophy, experience an increased risk of developing benign and malignant tumors. This case report presents an 18-month-old girl with features suggestive of Beckwith–Wiedemann syndrome who developed pubic hair, high levels of testosterone, and DHEAS with normal cortisol and progesterone levels. Computed tomography revealed a left adrenal mass. Histopathological examination of the resected mass showed an adrenocortical tumor. Her postoperative evaluation showed normal testosterone and DHEAS levels. Early diagnosis and detection of intra-abdominal neoplasms in infants with Beckwith–Wiedemann syndrome are essential to avoid serious clinical complications.

Androgen deprivation therapy is frequently used to treat prostate cancer (PCa), but resistance can occur, a condition known as castration‐resistant prostate cancer (CRPC). Thus, novel approaches for identification of CRPC are important for designing effective PCa treatments. Analysis of microRNA (miRNA) expression signatures by RNA sequencing showed that both passenger and guide strands of the miR‐455‐duplex (miR‐455‐5p and miR‐455‐3p, respectively) acted as antitumor miRNAs in PCa cells. The involvement of miRNA passenger strands in cancer pathogenesis is a novel concept for miRNA functionality. Based on a large patient cohort in The Cancer Genome Atlas, expression of eight miR‐455‐5p/‐3p target genes (PIR: P = 0.0137, LRP8: P = 0.0495, IGFBP3: P = 0.0172, DMBX1: P = 0.0175, CCDC64: P = 0.0446, TUBB1: P = 0.0149, KIF21B: P = 0.0336, and NFAM1: P = 0.0013) was significantly associated with poor prognosis of PCa patients. Here, we focused on PIR (pirin), a highly conserved member of the cupin superfamily. PIR expression was directly regulated by miR‐455‐5p, and PIR overexpression was detected in hormone‐sensitive prostate cancer (HSPC) surgical specimens and CRPC autopsy specimens. Loss‐of‐function assays using siRNA or an inhibitor (bisamide) showed that downregulation of PIR expression blocked cancer cell migration and invasion. Moreover, the miR‐455‐5p/PIR axis contributed to cancer cell aggressiveness. These results suggest that PIR might be a promising diagnostic marker for HSPC and CRPC. Furthermore, CRPC treatment strategies targeting PIR may be possible in the future. Identification of antitumor miRNAs, including miRNA passenger strands, may contribute to the development of new diagnostic markers and therapeutic strategies for CRPC.

Abstract Effective treatments for patients with castration‐resistant prostate cancer (CRPC) have not yet been established. Novel approaches for identification of putative therapeutic targets for CRPC are needed. Analyses of RNA sequencing of microRNA (miRNA) expression revealed that miR‐99a‐3p (passenger strand) is significantly downregulated in several types of cancers. Here, we aimed to identify novel miR‐99a‐3p regulatory networks and therapeutic targets for CRPC. Ectopic expression of miR‐99a‐3p significantly inhibited cancer cell proliferation, migration, and invasion in PCa cells. Non‐SMC condensin I complex subunit G (NCAPG) was a direct target of miR‐99a‐3p in PCa cells. Overexpression of NCAPG was detected in CRPC clinical specimens and was significantly associated with shorter disease‐free survival and advanced clinical stage. Knockdown of NCAPG inhibited cancer cell aggressiveness. The passenger strand miR‐99a‐3p acted as an antitumor miRNA in naïve PCa and CRPC. NCAPG was regulated by miR‐99a‐3p, and its overexpression was involved in CRPC pathogenesis. Involvement of passenger strand of miRNA in cancer pathogenesis is novel concept, and identification of antitumor miRNA regulatory networks in CRPC might be provided novel prognostic markers and therapeutic targets for this disease.