Background: Arterial hypertension (AH) is associated with heart and chronic kidney disease (CKD). However, the precise mechanisms of myocardial remodeling (MR) in the settings of CKD remain elusive. We hypothesized that TRPC6, calcineurin/NFAT, and Wnt/β-catenin signaling pathways are involved in the development of MR in the background of CKD and AH. Methods: Early CKD was induced by performing a 5/6 nephrectomy (5/6NE) in spontaneously hypertensive rats (SHR-NE). Sham-operated (SO) SHR (SHR-SO) and Wistar Kyoto (WKY-SO) rats served as controls. Systolic blood pressure (SBP), heart rate, myocardial mass index (MMI), serum creatinine, cardiomyocyte diameter (dCM), myocardial fibrosis (MF), serum and kidney α-Klotho levels, myocardial expression of calcineurin (CaN), TRPC6, and β-catenin were measured two months after 5/6NE or SO. Results: NE-induced kidney dysfunction corresponded to mild-to-moderate human CKD and was associated with an increase in FGF23 and a decrease in renal α-Klotho. The levels of SBP, MMI, dCM, and MF were higher in SHRs compared to WKY-SO as well as in SHR-NE vs. SHR-SO. The MR was associated with increased cardiomyocyte expression of CaN/NFAT and β-catenin along with its intracellular re-distribution. TRPC6 protein levels were substantially elevated in both SHR groups with higher Trpc6 mRNA expression in SHR-NE. Conclusions: The Wnt/β-catenin and TRPC6/CaN/NFAT hypertrophic signaling pathways seem to be involved in myocardial remodeling in the settings of AH and CKD and might be mediated by FGF23 and α-Klotho axis.
In recent years, the definitions and classifications of congenital tubulo-interstitial kidney diseases have been significantly revised. This is primarily due to the achievements in the molecular biology and genetics, which made it possible to significantly clarify the role of a number of genes encoding certain proteins that are closely involved in kidney functions. In 2015, KDIGO proposed to unify the terminology, diagnostic criteria and approaches to monitoring conditions associated with mutations of the MUC1, UMOD, HNF1B and REN genes, which led to the development of ideas about the new nosology - autosomal dominant tubulointerstitial kidney disease (ADTKD). A brief description of the basic information about the ADTKD compiled the content of this message.
Background We hypothesized that increasing body mass index is a risk factor for surgical complications in surgery for diverticulitis. We assessed the relationship of body mass index and surgical complications following surgery for diverticular disease. Methods We used National Surgical Quality Improvement Program database from 2005 to 2015. Patients undergoing surgery for diverticular disease during that period were included and stratified into 9 groups based on their body mass index (< 18.5, 18.6–24.9, 25.0–29.9, 30.0–34.9, 35.0–39.9, 40.0–44.9, 45.0–49.9, 50.0–54.9, > 55). Outcomes of interest were complications of superficial surgical site infection, deep incisional surgical site infection, organ space surgical site infection, wound disruption complications, pneumonia, ventilator dependence > 48 hours, acute renal failure, myocardial infarction, return to operating room, and 30-day mortality. Results Morbidly obese patients had higher rates of diabetes, hypertension, and steroid use. They had higher American Society of Anesthesiologists classification and were more likely to have emergency and open cases. Interestingly, increased body mass index was inversely associated with age. Increasing body mass index was associated with worse outcomes including superficial surgical site infection, deep incisional surgical site infection, organ space surgical site infection, wound disruption complications, ventilator dependence > 48 hours, acute renal failure, and return to operating room. Risk of developing pneumonia didn't have similar correlation with body mass index. Overweight status had protective effect on mortality. No statistically significant differences in increased rates of myocardial infarction were noted. Underweight patients also developed worse outcomes. Conclusion Obesity is associated with a number of complications following surgery for diverticulitis. Elevated body mass index adds significant risk to procedures for diverticulitis and should be accounted for in risk stratification models. Patients should be counseled on weight reduction before undergoing elective surgery for diverticular disease.
BACKGROUND:Little is known about the long-term functional outcomes of restorative proctocolectomy. OBJECTIVE:The aim of this study was to examine ileoanal pouch outcomes 20 and 30 years postoperatively.DESIGN: This is a retrospective case series. SETTING:This study was conducted at a tertiary care referral center. PATIENTS:Patients who underwent restorative proctocolectomy between 1980 and 1994 were identified.Those with ≥20 years of in-person follow-up were included. MAIN OUTCOMES MEASURES:Pouch function, pouchitis, anal stricture, and pouch failure rates were analyzed.RESULTS: A total of 203 patients had ≥20 years of follow-up. Of those, 71 had ≥30 years of follow-up. Initial diagnoses included ulcerative colitis (83%), indeterminate colitis (9%), familial adenomatous polyposis (4%), and Crohn's disease (3%). Twenty-one percent of those with ulcerative or indeterminate colitis later transitioned to Crohn's disease. Mean daily stool frequency was 7 (IQR 6-8), 38% experienced seepage, 31% had anal stenosis, 47% experienced pouchitis, and 18% had pouch failure. Over time, stool frequency increased in 41% of patients, stayed the same in 43%, and decreased in 16%.Patients older than 50 years at the time of construction had more daily bowel movements (median 8 vs 6; p = 0.02) and more seepage (77% vs 35%; p = 0.005) than those younger than 50 years. Patients with Crohn's disease had higher stool frequency (median 8 vs 6; p < 0.001) and higher rates of anal stenosis (44% vs 26%; p = 0.02), pouchitis (70% vs 40%; p < 0.001), and pouch failure (38% vs 12%; p < 0.001) compared to non-Crohn's patients. Patients with ≥30 years of follow-up had similar function as those with 20-30 years of follow-up.LIMITATIONS: This was a retrospective, single-institution study. Only 35% of pouches created during the study period had >20 years of follow-up. CONCLUSIONS:Most patients maintain reasonably good function and retain their pouches after 20 years. Over time, stool frequency and seepage increase. Older age and Crohn's disease are associated with worse outcomes. See Video Abstract at http://links.lww.com/DCR/B801. ¿QUÉ NOS DICE UN RESERVORIO A LARGO PLAZO? RESULTADOS DE LOS RESERVORIOS ILEOANALES MAYORES DE 20 AÑOSANTECEDENTES: se sabe poco sobre los resultados funcionales a largo plazo de la proctocolectomía restauradora.OBJETIVO: El objetivo de este estudio fue examinar los resultados del reservorio ileoanal 20 y 30 años después de la operación.DISEÑO: Serie de casos retrospectiva.ENTORNO CLÍNICO: Centro de referencia de atención terciaria PACIENTES: Se identificaron pacientes que se sometieron a proctocolectomía restauradora entre 1980 y 1994. Se incluyeron aquellos con ≥20 años de seguimiento en persona.
INTRODUCTION.It is suggested that fibroblast growth factor 23 (FGF23) and its co-receptor Klotho are probably associatedwith changes in calcium metabolism in chronic kidney disease (CKD) due to ability to regulate intracellular Ca transport bymodulating the cationic channels TRPV5 and TRPV6.THE AIMis to investigate the association between Klotho, FGF23 and renal excretion of Ca in the initial stages of experimental CKD.MATERIAL AND METHODS.The experimental models of chronic kidney injury were resection of the renal tissue in spontaneously hypertensive rats (SHR). Serum concentrations of intact FGF23 and PTH were determined by ELISA, renal Klotho protein expression by IHC. The indices of Ca excretion were calculated.RESULTS.Serum creatinine concentration, creatinine clearance and the severity of interstitial fibrosis in experimental models corresponded to the initial stages of chronic kidney disease. UCa24 and FECa were higher, Klotho protein expression was lower in groups with more severe renal dysfunction, without significant differences in FGF23 and PTH levels. Multiple regression analysis showed that FECa and UCa24 were not associated with FGF23, Klotho, and PTH.CONCLUSION.Renal excretion of Ca in initial stages of experimental kidney damage is not associated with Klotho and FGF23 levels.
CASE SUMMARY: A 48-year-old healthy man presented to the office reporting a long-standing history of anal pruritus. He had tried various over-the-counter creams without much success. Besides an anal fissure in the past, which responded to nitroglycerin ointment, his medical history was unremarkable. On physical examination, he was found to have grade I hemorrhoids and mild fecal smearing on perianal skin. Recent colonoscopy and laboratory work ordered by the primary care provider were normal. He was counseled on common inciting agents and local irritants and was advised on hygiene, diet modification, and stool-bulking agents. The colorectal surgeon recommended that the patient keep a journal about his symptoms, foods, and household chemicals used. He was seen twice more over the course of 6 months to pinpoint the cause of his pruritus. A short-course trial of topical steroid, barrier cream, and topical tacrolimus was not helpful. A biopsy of perianal skin was performed and was unrevealing. Eventually, given the persistence of symptoms, it was decided that he would undergo methylene blue injection to address his pruritus (Fig. 1). The procedure consisted of several intradermal and subcutaneous injections of 10 mL of 1% methylene blue combined with 7.5 mL of 0.25% bupivacaine with adrenaline (1/100,000) and 7.5 mL 0.5% lidocaine. After the methylene blue injection, the severity of his symptoms improved, but pruritus still persisted. A methylene blue injection of the same concentration was repeated in 3 months with complete resolution of symptoms.
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