Female reproductive factors, exogenous hormone use, and incident chronic kidney disease and end-stage renal disease.

CONTEXT: Younger women have a slower progressive loss of kidney function than age-matched men and the sex advantage diminishes after menopause, suggesting a role for female hormones in the development of kidney diseases. OBJECTIVE: To examine the relationships of numerous reproductive factors and exogenous hormone use with long-term risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in women. METHODS: A total of 260,108 women without prevalent CKD and ESRD were included. The relationships of various reproductive factors and exogenous hormone use with incident CKD and ESRD were assessed, with multivariable adjustment for potential confounders. RESULTS: During a median of ∼12.5 years of follow-up, 8,766 CKD and 554 ESRD cases were identified. Younger age at first live birth, hysterectomy or bilateral oophorectomy before 50 years old, menopausal before 45 years old, and menopausal hormone therapy (MHT) initiated before 50 years old was associated with a higher risk of CKD. The relationships of these factors with ESRD were generally consistent with those for CKD. Each 5-year increment in menopausal age was associated with an 11% lower risk of CKD (HR = 0.89; 95% CI: 0.87, 0.91) and a 13% lower risk of ESRD (HR = 0.87; 95% CI: 0.79, 0.95). Each 5-year delay in starting MHT was associated with a 13% lower risk of CKD (HR = 0.87; 95% CI: 0.84, 0.90) and a 15% lower risk of ESRD (HR = 0.85; 95% CI: 0.73, 0.99). CONCLUSION: Several reproductive characteristics reflecting shorter cumulative exposure to endogenous estrogen or premature exposure to exogenous hormones are associated with a greater risk of CKD and ESRD in women, supporting a potential role of female hormones in renal pathophysiology.

Effects of intensive glycemic control on microvascular outcomes in type 2 diabetes mellitus are modified by long-term HbA1c variability: A post hoc analysis of the ACCORD trial.

AIMS: To assess the impact of long-term visit-to-visit variability in HbA1c on microvascular outcomes in type 2 diabetes mellitus (T2DM), and its influence on the effects of intensive glycemic control. METHODS: Included were participants with T2DM enrolled in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) who had at least three measurements of HbA1c prior to new-onset microvascular outcomes, namely nephropathy, retinopathy and neuropathy. Variability in HbA1c was defined as the coefficient of variation (CV) across HbA1c measurements obtained from enrollment to the transition from intensive to standard glycemic therapy. RESULTS: During a median of 22,005, 23,121, and 13,080 person-years of follow-up, 2,905 nephropathy, 2,655 retinopathy, and 1,974 neuropathy cases were recorded, respectively. Median CV (IQR) was 7.91 % (5.66 %-10.76 %) in the standard treatment group and 9.79 % (7.32 %-13.35 %) in the intensive treatment group. In the standard treatment group, lower HbA1c-CV (the first versus the second quartile) was associated with a higher risk of all microvascular outcomes, while higher HbA1c-CV (the fourth quartile) was associated with a higher risk of nephropathy only. In the intensive treatment group, only higher HbA1c-CV was associated with a higher risk of developing the microvascular outcomes. Intensive therapy reduced all microvascular outcomes among individuals with lower HbA1c-CV, but increased the risk among those with the highest HbA1c-CV (all P values for interaction < 0.0001). For example, hazard ratios (95 % CI) of retinopathy comparing intensive with standard treatments were 0.65 (0.56-0.75), 0.84 (0.71-0.98), 0.97 (0.82-1.14) and 1.28 (1.08-1.53) across the lowest to the highest quartiles of HbA1c variability. CONCLUSIONS: The effects of intensive glycemic control on microvascular outcomes in T2DM appear to be modified by the variability of HbA1c during the treatment process, suggesting the significance of dynamic monitoring of HbA1c levels and timely adjustments to the therapeutic strategy among individuals with a high HbA1c variability.

Coffee Consumption and Incidence of Cardiovascular and Microvascular Diseases in Never-Smoking Adults with Type 2 Diabetes Mellitus.

The relationship between coffee consumption and diabetes-related vascular complications remains unclear. To eliminate confounding by smoking, this study assessed the relationships of coffee consumption with major cardiovascular disease (CVD) and microvascular disease (MVD) in never-smokers with type 2 diabetes mellitus (T2DM). Included were 9964 never-smokers with T2DM from the UK Biobank without known CVD or cancer at baseline (7781 were free of MVD). Participants were categorized into four groups according to daily coffee consumption (0, 0.5-1, 2-4, ≥5 cups/day). CVD included coronary heart disease (CHD), myocardial infarction (MI), stroke, and heart failure (HF). MVD included retinopathy, peripheral neuropathy, and chronic kidney disease (CKD). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidential intervals (CIs) of total CVD and MVD and the component outcomes associated with coffee consumption. During a median of 12.7 years of follow-up, 1860 cases of CVD and 1403 cases of MVD were identified. Coffee intake was nonlinearly and inversely associated with CVD (P-nonlinearity = 0.023) and the component outcomes. Compared with no coffee intake, HRs (95% CIs) associated with a coffee intake of 2 to 4 cups/day were 0.82 (0.73, 0.93) for CVD, 0.84 (0.73, 0.97) for CHD, 0.73 (0.57, 0.92) for MI, 0.76 (0.57, 1.02) for stroke, and 0.68 (0.55, 0.85) for HF. Higher coffee intake (≥5 cups/day) was not significantly associated with CVD outcomes. Coffee intake was linearly and inversely associated with risk of CKD (HR for ≥5 vs. 0 cups/day = 0.64; 95% CI: 0.45, 0.91; P-trend = 0.0029) but was not associated with retinopathy or peripheral neuropathy. Among never-smoking individuals with T2DM, moderate coffee consumption (2-4 cups/day) was associated with a lower risk of various CVD outcomes and CKD, with no adverse associations for higher consumption.

Methylprednisolone for idiopathic granulomatous mastitis: a prospective observational cohort study.

Background: Idiopathic granulomatous mastitis (IGM) is a rare, benign, but locally aggressive breast disease. Steroids are widely used as a breast-conserving option, however, the response rate of steroids varies in reported studies, as well as its different reported usage. This prospective observational cohort study aimed to report the outcomes of methylprednisolone for IGM treatment. Methods: From Aug 2019 to Dec 2021, the clinicopathological information of 156 IGM patients who sought treatment at West China Hospital was prospectively collected. A total of 88 patients treated with methylprednisolone were included in the study. The clinical features, treatment response, and follow-up data were analyzed. Results: The median age at diagnosis was 32 years, and 90.9% of patients were multipara. The predominant symptom at presentation was painful breast mass, with a median size of 4.7 cm. For steroid usage, an initial 20 mg methylprednisolone daily was given until disease stable. The median duration of 20 mg methylprednisolone treatment was 45 (range, 14-376) days. The median duration of whole steroid therapy was 105 (range, 28-381) days. A total of 80.7% of patients (71/88) responded well to steroid treatment. In 63 patients, steroid treatment was successfully withdrawn, and treatment was completed. With an average of 283 days follow-up (range, 0-770 days), relapse was observed in 21 (33.33%) patients. Compared with patients with residual disease as shown by physical examination (PE), those with complete clinical remission (CCR) at the end of treatment had longer relapse-free intervals. Conclusions: Steroids are the preferable breast-conserving option for IGM. Treatment with 20 mg methylprednisolone for an average of 1.5 months is usually required, and full steroid treatment might last for 3 months.

Preoperative high-frequency color Doppler ultrasound assessment of the blood vessels of the fibular myocutaneous flap.

OBJECTIVE: The fibular myocutaneous flap is a classic flap used to reconstruct oral and maxillofacial defects. This study aimed to evaluate the effectiveness of high-frequency color Doppler ultrasound in detecting the blood vessels in the fibular myocutaneous flap, analyze the influence of variations in the peroneal vessels and perforating peroneal arteries on the surgical design, and explore the value of this technology in preoperatively assessing the blood vessels of the fibular myocutaneous flap. METHODS: Twenty-five patients with mandibular disease or defect underwent preoperative evaluation of the blood vessels of the calf by high-frequency color Doppler ultrasound. The inner diameter and peak systolic velocity (PSV) of the peroneal arteries and veins and the perforating peroneal arteries were compared between different groups. The consistency between the perforating peroneal arteries marked by ultrasonography and the intraoperative findings was analyzed. RESULTS: The initial segment of the peroneal artery had a larger inner diameter (p<0.001) and lower PSV (p<0.05) than the middle segment. The perforating peroneal arteries were mainly distributed in the middle of the fibula. The inner diameter of the perforating peroneal artery was larger in men than in women (p<0.05). In comparison with surgical exploration as the gold standard, high-frequency color Doppler ultrasound results showed good consistency (Kappa=0.684, 95% CI: 0.512-0.856, p<0.001), with a sensitivity of 89.36%, specificity of 78.57%, and accuracy of 85.33%. CONCLUSION: High-frequency color Doppler ultrasound can detect, quantitatively evaluate, and accurately mark the peroneal artery and vein and perforating peroneal artery before fibular myocutaneous flap transplantation.

Unusual foreign body spontaneously discharged from the submandibular gland: A case report.

Obstructive sialadenitis of the submandibular gland is most often caused by sialolithiasis and rarely by a foreign body. Here, we describe a patient with acute submandibular inflammation caused by a bamboo splinter. Transcutaneous and transoral ultrasound precisely located the splinter within Wharton's duct. Shortly thereafter, the bamboo splinter was spontaneously discharged while eating, which allowed complete remission of pain and swelling. Ultrasound confirmed the absence of the foreign body within Wharton's duct and relief of sialadenitis. Combined use of transcutaneous and transoral ultrasound can provide detailed information regarding the submandibular gland and foreign bodies, which enables proper treatment planning and adequate follow-up.

SPARC regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma.

BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) is implicated in cancer progression, but its role and associated molecular mechanism in the sorafenib sensitivity of hepatocellular carcinoma cells (HCC) remains elusive. METHODS: Human HCC cell lines Hep3B and HepG2 were treated with sorafenib alone or combined with activator or inhibitor of ferroptosis. Cell viability assay, reactive oxygen species (ROS) assay, lactate dehydrogenase (LDH) assay and western blot were used to study the regulatory mechanism of SPARC on HCC cells. RESULTS: Overexpression of SPARC enhanced the cytotoxic effect of sorafenib in Hep3B and HepG2 cells compared with parental cells. Depletion of SPARC decreased the cytotoxic effect of sorafenib in Hep3B and HepG2 cells compared with parental cells. Moreover, overexpression of SPARC significantly induced LDH release, whereas depletion of SPARC suppressed the release of LDH in Hep3B and HepG2 cells. Inhibition of ferroptosis exerted a clear inhibitory role against LDH release, whereas activation of ferroptosis promoted the release of LDH in HCC cells, as accompanied with deregulated expression of ferroptosis-related proteins. Furthermore, overexpression of SPARC induced oxidative stress, whereas depletion of SPARC suppressed the production of ROS. Deferoxamine (DFX)-induced inhibition of ferroptosis suppressed the production of ROS, while activation of ferroptosis promoted the contents of ROS in HCC cells exposed to sorafenib. CONCLUSION: Our findings give a better understanding of ferroptosis and its molecular mechanism in HCC cells that is regulated by SPARC in response to sorafenib.

MiR-4262 promotes cell apoptosis and inhibits proliferation of colon cancer cells: involvement of GALNT4.

A role of microRNA-4262 (miR-4262) in the carcinogenesis of colon cancer remains undetermined. In this study, we studied the effects and mechanisms of miR-4262 to the colon cancer cell proliferation and apoptosis. We found that the levels of miR-4262 significantly down-regulated in colon cancer tissue, compared to the paired adjacent non-tumor colon tissue. The miR-4262 levels in colon cancer cell lines were significantly lower than those in control normal colon tissues. Transfection with the miR-4262 mimic decreased the cell proliferation and increased cell apoptosis in colon cancer cells, while transfection with the antisense of miR-4262 (as-miR-4262) increased cell proliferation and suppressed cell apoptosis in colon cancer cells. Bioinformatics analyses showed that GALNT4 was a potential target gene of miR-4262. The luciferase activities assay and Western blot verified that miR-4262 targeted GALNT4 mRNA to modulate its protein levels. When we treated cells with miR-4262 and GALN4 siRNA, the cell viability was significantly decreased. Together, our study suggests that aberrantly expressed miR-4262 may affect cell apoptosis and proliferation of human colon cancer cells via GALNT4, which appears to be a promising therapeutic target for colon cancer.

Placement of a duodenal stents bridge the duodenal papilla may predispose to acute pancreatitis.

BACKGROUND/AIMS: To retrospective evaluate the incidence, predictive factors, and management of acute pancreatitis after placement of duodenal stent in patients with malignant gastroduodenal obstruction. METHODOLOGY: Among 242 patients with symptomatic malignant gastroduodenal obstruction successfully treated with duodenal stent placement, acute pancreatitis occurred in 10 (4.1%) of the patients 1-7 days after stent placement. The variables were analyzed. Univariate and multivariate analysis was performed to evaluate factors predictive of acute pancreatitis. Management of acute pancreatitis also was evaluated. RESULTS: All patients with acute pancreatitis were presented with abdominal pain and distention with vomiting 1-7 days after stent placement, in which 7 patients developed acute janudice. Four patients were cured by fasting and intravenous nutrition, and the remaining 6 cases were managed with percutaneous cholangiography and drain placement (PTCD). Univariate analysis showed acute pancreatitis was associated with location in the descending duodenum (p = 0.001) and stent bridge the duodenal papilla (p < 0.001). Multivariate analysis exhibited that the presence of stent bridged the duodenal papilla (odds ratio (OR), 18.48; 95% CI, 2.298-148.48; p = 0.006) was independent predictors of acute pancreatitis. CONCLUSIONS: Acute pancreatitis is an uncommon early complication of placement of duodenal stents in patients with malignant gastroduodenal obstruction. Acute pancreatitis occurred most commonly in descending duodenum, and in patients with stent bridged the duodenal papilla. Stent bridged the duodenal papilla may be the most important predictors for acute pancreatitis. Acute pancreatitis can be managed conservatively or by PTCD when developed to acute jaundice.

Postoperative complications in patients with portal vein thrombosis after liver transplantation: evaluation with Doppler ultrasonography.

AIM: To study the postoperative complications in patients with preoperative portal vein thrombosis (PVT) undergoing liver transplantation (LT) and to evaluate the complications with Doppler ultrasonography. METHODS: Retrospective studies were performed on 284 patients undergoing LT (286 LT) with respect to pre- and postoperative clinical data and Doppler ultrasonography. According to the presence and grade of preoperative PVT, 286 LTs were divided into three groups: complete PVT (c-PVT), partial PVT (p-PVT) and non-PVT, with 22, 30 and 234 LTs, respectively. Analyses were carried out to compare the incidence of early postoperative complications. RESULTS: PVT, inferior vena cava (IVC) thrombosis, hepatic artery thrombosis (HAT) and biliary complications were found postoperatively. All complications were detected by routine Doppler ultrasonography and diagnoses made by ultrasound were confirmed by clinical data or/and other imaging studies. Nine out of 286 LTs had postoperative PVT. The incidence of the c-PVT group was 22.7%, which was higher than that of the p-PVT group (3.3%, P < 0.05) and non-PVT group (1.3%, P < 0.005). No difference was found between the p-PVT and non-PVT groups (P > 0.25). Of the 9 cases with postoperative PVT, recanalizations were achieved in 7 cases after anticoagulation under the guidance of ultrasound, 1 case received portal vein thrombectomy and 1 case died of acute injection. Ten LTs had postoperative IVC thrombosis. The c-PVT group had a higher incidence of IVC thrombosis than the non-PVT group (9.1% vs 2.6%, P < 0.05); no significant difference was found between either the c-PVT and p-PVT groups (9.1% vs 6.7%, P > 0.5) or between the p-PVT and non-PVT groups (P > 0.25). Nine cases with IVC thrombosis were cured by anticoagulation under the guidance of ultrasound, and 1 case gained natural cure without any medical treatment after 2 mo. HAT was found in 2 non-PVT cases, giving a rate of 0.7% among 286 LTs. Biliary complications were seen in 12 LTs. The incidence of biliary complications in the c-PVT, p-PVT and non-PVT groups was 9.1%, 3.3% and 4.3%, respectively (P > 0.25 for all), among which 2 stenosis led retransplantations and others were controlled by relative therapy. CONCLUSION: C-PVT patients tend to have a higher incidence of PVT and IVC thrombosis than non-PVT patients after LT. The incidence of postoperative complications in p-PVT patients does not differ from that of non-PVT patients. A relatively low incidence of HAT was seen in our study. Doppler ultrasonography is a convenient and efficient method for detecting posttransplant complications and plays an important role in guiding treatment.