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BackgroundHuman papillomavirus vaccination is not widespread in Japan, and the low screening rates result in many cases of locally advanced cervical cancer. We investigated the prognostic significance of sarcopenia in patients with cervical cancer to guide healthcare policies to improve treatment outcomes.MethodsThis retrospective study included 83 patients with cervical cancer without distant metastasis who underwent primary concurrent chemoradiotherapy between 2013 and 2018. We analyzed the indicators of physical condition and muscle quantity using the SYNAPSE VINCENT software. Muscle mass and the relationship between treatment toxicity and prognosis were evaluated.ResultsThe patients’ median age was 60 (range 33‒80) years. Cancer stage distribution was as follows: cT2b or higher, 84.3%; N1, 65.1%; and MA, 27.7%. The overall sarcopenia (skeletal muscle index [SMI] < 38.5) rate was 30.1%, and the rate was 33.9 and 22.2% in patients aged < 64 and ≥ 65 years, respectively. No correlation was observed between clinical stage and musculoskeletal indices. Treatment resulted in decreased body weight and SMI; after treatment, the sarcopenia rate increased to 37.3%. A higher intramuscular adipose tissue content (IMAC) reduced the number of chemotherapy cycles needed. Treatment-associated SMI decreases of ≥ 7% indicated poor prognosis, with significant differences in progression-free survival and overall survival (p = 0.013 and p = 0.012, respectively). Patients who were very lean (body mass index < 18.5 kg/m2) before treatment had a poor prognosis (p = 0.016 and p < 0.001).ConclusionsOur findings emphasize the importance of assessing original nutritional status and maintaining muscle mass and quality during the treatment of patients with cervical cancer.

Tenapanor is a minimally absorbed, small-molecule inhibitor of sodium/hydrogen exchanger 3 and thus suppresses sodium absorption in the gastrointestinal tract. It is approved by the FDA for the treatment of hyperphosphatemia in dialysis patients. This randomized controlled trial evaluated its efficacy in the treatment of hyperphosphatemia and constipation in hemodialysis patients. Ninety hemodialysis patients were randomized 1:1 to receive either tenapanor or standard care. Randomization was performed using a computer-generated sequence stratified by baseline serum phosphorus levels. The tenapanor group began treatment with a dosage of 10 mg/day, which was adjusted based on serum phosphorus levels. Primary outcomes were changes in serum phosphorus levels in the tenapanor and control groups and changes in stool consistency, assessed weekly using the Bristol Stool Form Scale (BSFS) in the tenapanor group. Secondary outcomes included laxative use and phosphate binder prescription patterns. Serum phosphorus levels, serum calcium, albumin, and related biochemical parameters were monitored every two weeks. Data were analyzed using intention-to-treat principles. This study was not blinded. Of the 90 randomized participants, 69 completed the 23-week study. Tenapanor significantly improved stool consistency and resolved constipation (BSFS types 1-2) by week 5. A transient increase in loose stools (BSFS types 6-7) occurred early, with 10 participants discontinuing due to diarrhea. Laxative use decreased significantly in the tenapanor group, from 58.2% at baseline to 35.6% at week 23 (p < 0.01). Serum phosphorus levels were decreased in both groups, with comparable control. Lanthanum carbonate prescriptions decreased significantly in the tenapanor group and were largely replaced by low-dose tenapanor. Tenapanor improves stool consistency, reduces laxative use, and provides effective phosphorus control in hemodialysis patients and represents a promising alternative to conventional phosphate binders.

Background Vascular access (VA) monitoring is critical for hemodialysis patients. While vascular ultrasound (US) provides high diagnostic accuracy for VA stenosis, its reliance on equipment and trained operators can limit routine implementation. The Hemodialysis Vascular Sound Index (HVSI), derived from vascular murmur analysis, may provide a simple, objective adjunct for triaging patients who require confirmatory US and/or vascular access interventional treatment (VAIVT). Objectives This study evaluated the diagnostic performance of HVSI for detecting VA stenosis and reduced brachial artery flow volume (FV), and examined its association with US-based parameters including resistance index (RI). Methods This prospective matched observational study included 202 hemodialysis patients: 101 with clinically significant stenosis requiring VAIVT (study group) and 101 ultrasound-confirmed stable controls (control group). Participants were matched by age, sex, dialysis duration, diabetes status, Kt/V, and blood data using propensity score matching. HVSI was measured using an electronic stethoscope placed over the anastomosis before dialysis. FV and RI were assessed using Doppler US. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analyses, including sensitivity, specificity, and area under the curve (AUC). A small verification cohort ( n  = 20) was also analyzed to explore the reproducibility of predefined HVSI cutoffs. Results HVSI showed significant correlation with FV (R 2  = 0.58, p  < 0.001) and inverse correlation with RI (R 2  = 0.32, p  < 0.001). For FV thresholds ≤500, ≤400, and ≤350 mL/min, HVSI showed sensitivities of 86.3–94.4%, specificities of 78.7–82.9%, and AUCs of 0.90–0.94. Diagnostic accuracy tended to be higher in non-bifurcated vessels. In the verification cohort, predefined HVSI cutoffs showed high specificity for FV < 400 mL/min and strong concordance for identifying VAIVT necessity. Conclusion HVSI demonstrated clinically meaningful diagnostic accuracy for reduced FV and VA stenosis in this matched observational cohort. However, because this design compared clinically evident stenosis cases with ultrasound-confirmed stable controls, diagnostic performance may be overestimated relative to consecutive real-world screening populations. Therefore, HVSI should be interpreted not as a replacement for vascular ultrasound, but as a simple screening adjunct to triage patients who require confirmatory ultrasound and/or VAIVT. Further studies in consecutively enrolled cohorts are warranted to validate generalizability and optimize implementation.

The association between salt intake and clinical outcomes in hemodialysis patients has been controversial. This study aimed to clarify the association between salt intake and mortality in hemodialysis patients. The present study included patients who underwent hemodialysis from June 1st 2016 to May 31st 2020. Corrected salt intake by ideal body weight was the main predictor of outcomes. Ideal body weight was calculated assuming that the ideal body mass index is 22 kg/m2 for the Japanese population. The multivariate Cox proportional hazards model was used to determine the association between corrected salt intake and mortality, adjusting for potential confounders. The outcomes considered were all-cause mortality and cumulative incidence of cardiovascular events at year 4. A total of 492 adult patients were enrolled in the study. The mean daily salt intake and corrected salt intake at baseline were 9.5 g/day and 0.17 g/kg/day, respectively. The low corrected salt intake group (< 0.13 g/kg/day) demonstrated the highest 4-year all-cause mortality. No association was observed between corrected salt intake and the cumulative incidence of cardiovascular events. In multivariate Cox proportional hazards analysis, only the group with corrected salt intake of 0.16-0.20 g/kg/day was associated with a decreased hazard risk for all-cause death compared with the low corrected salt intake group. The present study found that a low salt intake was associated with high all-cause mortality in hemodialysis patients. Reduced long-term survival may be attributed to malnutrition resulting from excessive salt restriction.

Resveratrol, a natural product and peroxisome proliferator-activated receptor (PPAR) agonist, has been reported to exert anti-cancer effects in several tumor models. A previous study by our group reported that prostaglandin J2, a PPARγ ligand, inhibited cell proliferation in a uterine sarcoma cell line. The aim of the present study was to investigate the role of the Wnt signaling pathway in resveratrol-induced apoptosis and inhibition of cell proliferation in the MES-SA human uterine sarcoma cell line. A WST-1 assay demonstrated that resveratrol inhibited cell proliferation in the MES-SA cell line, and flow cytometry revealed that the number of apoptotic cells increased in a resveratrol dose-dependent manner. The mechanisms underlying these effects of resveratrol were speculated to involve the expression of β-catenin and its target gene, c-myc, which were examined using western blot analysis. The results revealed a dose-dependent downregulation of this β-catenin and c-myc. This effect was blunted by a pharmacological inhibitor of glycogen synthase kinase 3β. Therefore, it is likely that resveratrol inhibited the cell proliferation and increased the number of apoptotic cells, at least partially, via the Wnt signaling pathway. The present results suggest that resveratrol is a potential candidate for the treatment of uterine sarcoma.

Secreted frizzled-related proteins (SFRPs) are involved in the development of various types of cancer and function by suppressing the Wnt signaling pathway. To elucidate the clinical implications of SFRPs in uterine sarcoma, SFRP expression levels and their effects on uterine leiomyosarcoma cells were examined. Immunostaining for SFRP4 was performed on uterine smooth muscle, uterine fibroid and uterine leiomyosarcoma tissues. Additionally, the effects of SFRP4 administration on cell viability, migration and adhesion were evaluated in uterine leiomyosarcoma SKN cells using the WST-1 assay (Roche Diagnostics) and the CytoSelect™ 24-well Cell Migration Assay Kit and the CytoSelect™ 48-well Cell Adhesion Assay Kit. The expression levels of SFRP4 in uterine leiomyosarcoma tissues were lower than those in normal smooth muscle and uterine fibroid tissues. In addition, SFRP4 suppressed the viability and migration, and increased the adhesion ability of uterine leiomyosarcoma cells compared with in the control group. In conclusion, SFRP4 may suppress the viability and migration, and enhance the adhesion of sarcoma cells. These results suggested that SFRP4 could be considered as a novel therapeutic target for uterine sarcoma.

Purpose We investigated whether impaired patterns of myocardial fatty acid imaging were associated with cardiac death in dialysis patients without coronary lesions. Methods We prospectively enrolled 155 hemodialysis patients without obstructive coronary artery disease, who had been examined by single-photon emission computed tomography (SPECT) using the iodinated fatty acid analogue BMIPP. Uptake of BMIPP on SPECT was graded in 17 segments on a five-point scale (0, normal; 4, absent) and assessed as BMIPP summed scores. Of the enrolled 155 participants, we analyzed 95 who had BMIPP summed scores ≥ 6 (52 men and 43 women, 65 ± 11 years). BMIPP scores ≥ 2 in ≥ 2 consecutive segments in SPECT were defined as focal, and the others as non-focal pattern. Results Of 95 participants analyzed, 42 (44.2 %) showed focal and 53 (55.8 %) non-focal type. During follow-up for 5.1 ± 2.0 years, 42 died of cardiac events. The occurrence of cardiac death was higher in the focal than in the non-focal group (30/42 [71.4 %] versus 12/53 [22.6 %], p  = 0.001). In stepwise Cox hazard analysis, focal pattern was associated with cardiac death (hazard ratio 2.266), independent of impairment of BMIPP SPECT (BMIPP summed scores ≥ 12). The predictive potential of BMIPP SPECT for cardiac death was higher ( p  < 0.001) in the left anterior descending artery area compared with other coronary territories. Conclusions Focal impairment in myocardial fatty acid imaging in the left anterior descending area may strongly predict cardiac death in this population.

Background Treatment-related infertility is an important issue for cancer survivors of reproductive age. We aimed to determine the understanding and management of fertility issues in cancer survivors by health care providers. Methods We studied 112 patients aged 15–40 years who underwent chemotherapy in Tokushima University Hospital. The gynecologists and oncologists who treated these patients were surveyed regarding their concerns about infertility issues in young cancer survivors. Results Of the 112 women studied, 57 had iatrogenic amenorrhea. Five were referred to reproductive specialists before or during treatment. Three patients with breast cancer were referred after treatment; they could not undergo fertility treatment due to ovarian failure after chemotherapy. Forty-five medical doctors answered the survey: 21 gynecologists (including 9 fertility specialists), 13 oncologists, and 11 surgeons. Of the oncologists and surgeons, 37.5 % (9/24) referred their patients to fertility experts. They listed certain issues regarding the patients: (1) anxiety that the intervention will alter the prognosis by delaying cancer treatment, and (2) a lack of communication between the oncologist and the fertility specialist. Almost all physicians agreed that fertility counseling was needed before chemotherapy. Conclusion This report showed the importance of oncofertility counseling and cooperation between oncologists and fertility specialists. Fertility in cancer survivors depends on type of cancer treatment applied, chemotherapy regimen, and age at treatment. Our institute is now equipped for oncofertility counseling and refers patients for fertility preservation prior to cancer treatment.

Although endometrial cancer is extremely rare during pregnancy, the placental metastasis of endometrial cancer is even rarer. The current study presents a case of endometrial carcinoma that was diagnosed through the pathological examination of the placenta. A 35-year-old primipara woman who underwent frozen-thawed embryo transfer at the Keiai Ladies Clinic in Tokushima prefecture (Japan) received regular prenatal check-ups. She was transferred to Tokushima University Hospital for perinatal management due to the preterm premature rupture of membranes at 21 weeks and 6 days gestation. The administration of antibiotics and tocolytic agents was continued; however, labor pain occurred at 23 weeks and 3 days gestation, and a female fetus weighing 524 g was delivered vaginally. The placenta weighed 262 g and had no macroscopic abnormalities. It was submitted for pathological examination, which revealed metastatic adenocarcinoma (clear cell carcinoma suspected). The patient was subsequently diagnosed with endometrial cancer (stage I suspected), and underwent abdominal total hysterectomy, bilateral salpingo-oophorectomy, partial omentectomy and pelvic lymph node dissection. The final diagnosis was stage IA endometrial cancer (endometrioid carcinoma, G2). At 1 year after surgery, there was no evidence of disease. The present case highlights the importance of considering the emergence of endometrial cancer during pregnancy.

Aims This study aimed to investigate the association between the time to achieve walkability after cardiac surgery and the risk of cardiovascular disease after hospital discharge. Methods We conducted a prospective cohort study involving 553 ambulatory patients aged 71.5 (range, 64.0–77.0) years who underwent cardiac surgery. All patients were divided into five groups based on the time to achieve walkability ≥100 m within 1, 2, 3, 4 or 5 days after cardiac surgery. We examined the risk of post‐cardiovascular disease outcomes, including readmission due to heart failure, ischaemic heart disease and other cardiovascular disease, according to the time to achieve walkability with reference to 5 days using the Fine and Gray regression model, considering competing risks. Results In the survival curve analysis, we examined the time to experience post‐cardiovascular disease incidence after hospital discharge. During a median of 3.3 years of follow‐up, 118 patients developed cardiovascular disease. We observed a positive association between the time to achieve walkability and cardiovascular disease risk, particularly heart failure. The multivariate hazard ratios (95% confidence intervals) for heart failure readmission were N/A (not assessed due to the sample size being too small) for 1 day, 0.31 (0.10–0.99) for 2 days, 0.60 (0.21–1.79) for 3 days and 0.76 (0.22–2.72) for 4 days (P for trend = 0.032). Conclusions The shorter walkability achievement time was associated with a lower risk of cardiovascular diseases, more specifically heart failure readmission, among patients who underwent cardiac surgery. The time required to achieve walkability is a useful predictor for cardiovascular diseases after hospital discharge.