Aldose reductase inhibition ameliorates pupillary light reflex and F-wave latency in patients with mild diabetic neuropathy

WSTĘP. Zbadanie wpływu inhibitora reduktazy aldozy, epalrestatu, na wczesną fazę neuropatii autonomicznej i somatycznej u chorych na cukrzycę typu 2 przez ocenę odruchu źrenicznego na światło oraz minimalnej latencji fali F. MATERIAŁ I METODY. Badanie objęło 30 chorych na cukrzycę z podkliniczną lub łagodną neuropatią cukrzycową, których losowo przydzielono do grupy kontrolnej (n = 15) lub do grupy leczonej epalrestatem (150 mg/d., n = 15). Po 24 tygodniach przeprowadzono badanie odruchu źrenicznego na światło, testy włókien autonomicznych układu sercowo-naczyniowego oraz badanie przewodzenia nerwowego. WYNIKI. Korzystny wpływ epalrestatu na odruch źreniczny na światło zaobserwowano w odniesieniu do minimalnej średnicy po bodźcu świetlnym (p = 0,044), wskaźnika zwężenia (p = 0,014) oraz maksymalnej szybkości zwężania (p = 0,008). Spośród testów autonomicznych układu sercowo-naczyniowego leczenie epalrestatem spowodowało poprawę wskaźnika najdłuższego odstępu RR podczas wydechu do najkrótszego odstępu RR w czasie wdechu obserwowanego podczas testu głębokiego oddychania (p = 0,037). Minimalna latencja fali F nerwów pośrodkowego oraz piszczelowego uległa istotnemu skróceniu w grupie chorych leczonych epalrestatem (odpowiednio p = 0,002 oraz p = 0,001); nie stwierdzono jednak istotnego wpływu na prędkość przewodzenia nerwowego w nerwach czuciowych oraz ruchowych. WNIOSKI. Powyższe obserwacje sugerują, że epalrestat może korzystnie działać we wczesnej fazie neuropatii cukrzycowej oraz że odruch źreniczny na światło i minimalna latencja fali F mogą stanowić przydatne wskaźniki neuropatii cukrzycowej.INTRODUCTION. The present study was conducted to investigate the effect of an aldose reductase inhibitor, epalrestat, on autonomic and somatic neuropathy at an early stage in type 2 diabetic patients by assessing the pupillary light reflex and minimum latency of the F-wave. MATERIAL AND METHODS. A total of 30 diabetic patients with subclinical or mild diabetic neuropathy were randomly allocated to a control group (n = 15) and epalrestat (150 mg/day) group (n = 15). After 24 weeks, the pupillary light reflex test, cardiovascular autonomic function tests, and nerve conduction study were performed. RESULTS. The beneficial effect of epalrestat on the pupillary light reflex was observed in the minimum diameter after light stimuli (P = 0.044), constriction ratio (P = 0.014), and maximum velocity of constriction (P = 0.008). Among cardiovascular autonomic nerve functions, the ratio of the longest expiratory R-R interval to the shortest inspiratory R-R interval during deep breathing was significantly improved by epalrestat (P = 0.037). Minimum latencies of F-wave of median and tibial motor nerves were significantly shortened by epalrestat (P = 0.002 and P = 0.001, respectively); however, no significant effects were observed in motor or sensory nerve conduction velocity. CONCLUSIONS. These observations suggest that epalrestat may have therapeutic value at the early stage of diabetic neuropathy and that the pupillary light reflex and minimum latency of F-wave may be useful indicators of diabetic neuropathy

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

A Case of Perianal Mucinous Adenocarcinoma Arising from an Anorectal Fistula Successfully Resected after Preoperative Radiotherapy

A case of mucinous adenocarcinoma arising on a long-standing anorectal fistula is described. A 60-year-old man with a long history of mucinous discharge, pain and perianal induration underwent a biopsy of the external opening of the fistula that showed a mucinous infiltrating adenocarcinoma. Due to the large size of the tumor and the fact that it had extended into the surrounding tissue, preoperative radiotherapy was performed. Radiotherapy was given with 40 Gy in 25 fractions for 5 weeks through posterior and bilateral portals. After radiotherapy the tumor was markedly shrunk and the serum level of carcinoembryonic antigen was also improved. Abdominoperineal resection was performed 8 weeks after the termination of radiotherapy. Histological examination of the resected specimen revealed that the invasion of the tumor remained within the sphincter muscle and that no cancer cells were present on the surgical margin. The histological effect of radiotherapy was judged as grade 1b. This treatment can result in downstaging and R0 resection, which also has a possibility to prevent local recurrence. This case suggests that preoperative radiotherapy may play an important role in the definitive treatment of locally advanced perianal mucinous adenocarcinoma

Pediatric Patient and Parental Anxiety and Impressions Related to Initial Gastrointestinal Endoscopy: A Japanese Multicenter Questionnaire Study

Objective. To assess anxiety among pediatric patients and their parents related to initial gastrointestinal endoscopy. Methods. Patients aged <19 years undergoing initial gastrointestinal (GI) endoscopy and their parents were invited to complete a self-administered questionnaire related to endoscopy in 13 institutions in Japan. Results. The subjects were 128 children, aged 1 month to 17 years. Forty-eight patients (37.5%) underwent esophagogastroduodenoscopy (EGD), 32 (25%) underwent colonoscopy (CS), 39 (30.5%) underwent both EGD and CS, 3 (2.3%) underwent balloon enteroscopy (BE), 3 (2.3%) underwent capsule endoscopy (CE), and 3 (2.3%) underwent CE and other endoscopic procedures. In the preendoscopy questionnaire, the most common concerns of the patients and parents before undergoing the procedure were “Pain” (45% of the patients underwent EGD or BE via the oral approach, and 52% of the patients underwent CS or BE via the anal approach) and “Procedural accidents related to the endoscopy” (63% of parents). In the postendoscopy questionnaire, the most common difficulty that patients and parents actually experienced before and after undergoing the procedure was “Hunger.” Conclusion. A preparatory intervention including an explanation regarding specific concerns before initial GI endoscopy, which this study revealed, could reduce anxiety experienced by both pediatric patients and parents