Optimal cut-off value of preprocedural geriatric nutritional risk index for predicting the clinical outcomes of patients undergoing endovascular revascularization for peripheral artery disease

BackgroundMalnutrition measured by the geriatric nutritional risk index (GNRI) was reported to be associated with poor prognosis for patients with peripheral artery disease (PAD). However, the optimal cut-off value of preprocedural GNRI for critical limb ischemia (CLI) and intermittent claudication (IC) is unknown. We aimed to determine its optimal cut-off value for CLI or IC patients requiring endovascular revascularization.MethodsWe explored data of 2246 patients (CLI: n = 1061, IC: n = 1185) registered in the Tokyo-taMA peripheral vascular intervention research COmraDE (TOMA-CODE) registry, which prospectively enrolled consecutive PAD patients who underwent endovascular revascularization in 34 hospitals in Japan from August 2014 to August 2016. The optimal cut-off values of GNRI were assessed by the survival classification and regression tree (CART) analyses, and the survival curve analyses for major adverse cardiovascular and limb events (MACLEs) were performed for these cut-off values.ResultsIn addition to the first cut-off value of 96.2 in CLI and 85.6 in IC, the survival CART provided an additional cut-off value of 78.2 in CLI and 106.0 in IC for further risk stratification. The survival curve was significantly stratified by the GNRI-based malnutrition status in both CLI [high risk: 47.7% (51/107), moderate: 30.1% (118/392), and low: 10.2% (53/520), log–rank p < 0.001] and IC [high risk: 14.3% (7/49), moderate: 4.5% (29/646), and low: 0.5% (2/407), log–rank p < 0.001]. The multivariate Cox-proportional hazard analysis showed that a higher GNRI was significantly associated with a better outcome in both CLI [hazard ratio (HR) per 1-point increase: 0.97, 95% CI: 0.96–0.98, p < 0.001] and IC (HR: 0.94, 95% CI: 0.91–0.97, p < 0.001).ConclusionsPreprocedural nutritional status significantly stratified future events in patients with PAD. Given that the optimal cut-off value of GNRI in CLI was almost 10-points lower than that of IC, using a disease-specific cut-off value is important for risk stratification.     

J‐curve association between alcohol intake and varicose veins in Japan: The Shimane CoHRE Study

The effect of alcohol intake on varicose veins (VV) has not been determined by its consumption level. The aim of this study was to investigate the association between alcohol intake and VV in an elderly general population. Using a cross‐sectional approach, the Shimane CoHRE Study data, comprising a total of 1060 participants, were analyzed. By multivariate regression analysis adjusted with basic characteristics, past work history, lifestyle‐related factors and medical history, compared with non‐drinkers, mild drinkers (<20.0 g/day) showed a significantly lower adjusted odds ratio (aOR) of VV (aOR = 0.64, P = 0.036). In a similar way, regular drinkers (1–5 days/week) showed a significantly lower aOR of VV when compared with occasional drinkers (aOR = 0.57, P = 0.032). VV and alcohol intake showed J‐curve relationships. In a stratified analysis by alcohol consumption levels, the association of smoking and VV were also observed in moderate to heavy drinkers and habitual drinkers. These findings can provide better understanding of pathophysiological mechanism and be used for evidence‐based patient education.     

Parallel enlargement of Marinesco bodies and nuclei and progressive deposition of p62 in pigmented neurons of the substantia nigra

Marinesco bodies (MBs) are spherical nuclear inclusions found in pigmented neurons of the substantia nigra. Although MBs are abundant in senescent brains, how they are related to aging processes remains unclear. Here, we performed a morphometric analysis of midbrain pigmented neurons to identify the possible influence of MBs on nuclear size. The transected area of the nucleus (nuclear area) was larger in the presence of MBs and was correlated with the area of MB (MB area) in all tested brains. The MB-associated nuclear enlargement was significant even after MB areas were subtracted from nuclear areas. Moreover, higher MB immunoreactivity of p62 was detected in the nucleoplasm of the enlarged MB-associated nuclei. This study on human brains is the first quantitative approach demonstrating MB-associated nuclear enlargement and progressive accumulation of small nucleoplasmic materials. Although cellular hypertrophy is usually considered to be an indication of the upregulation of cellular function, this might not always be the case. These findings suggest that an age-related decline of ubiquitin-proteasome and autophagy system activity and stagnation of undegradable materials are one of the candidate mechanisms to explain the age-related decline of neural activity in the substantia nigra.     

A juvenile case of epilepsy-associated,isocitrate dehydrogenase wild-type/histone 3 wild-type diffuse glioma with a rare BRAF A598T mutation

Here, we report a juvenile (18-year-old male) case of epilepsy-associated, isocitrate dehydrogenase wild-type/histone 3 wild-type diffuse glioma with a rare BRAF mutation and a focal atypical feature resembling diffuse astrocytoma. The patient presented with refractory temporal lobe epilepsy. Subsequently, magnetic resonance imaging revealed a hyperintense lesion in the right temporal lobe on fluid attenuated inversion recovery images. The patient underwent right lateral temporal lobectomy and amygdalohippocampectomy. Histopathologically, the tumor showed isomorphic, diffuse, infiltrative proliferation of glial tumor cells and intense CD34 immunoreactivity. The tumor cells were immunonegative for isocitrate dehydrogenase 1 (IDH1) R132H and BRAF V600E. Notably, the tumor cells showed the lack of nuclear staining for α-thalassemia/mental retardation syndrome, X-linked (ATRX). In addition, the Ki-67 labeling index, using a monoclonal antibody MIB-1, was elevated focally at tumor cells with p53 immunoreactivity. Molecular analyses identified a BRAF^A598T mutation, the first case reported in a glioma. BRAF^A598T is predicted to result in loss of kinase action; however, inactive mutants can stimulate mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling through CRAF activation. Thus, according to the recent update of the consortium to inform molecular and practical approaches to central nervous system tumor taxonomy (cIMPACT-NOW update 4), our case is also compatible with diffuse glioma with the mitogen-activated protein kinase (MAPK) pathway alteration. Thorough immunohistochemical and molecular studies are necessary for diagnosis of epilepsy-associated, diffuse gliomas. Partial resemblance in histopathological and molecular genetic features to diffuse astrocytoma also calls for attention.     

Clinical characteristic of esophageal cancer without lugol-voiding lesions in the background esophagus

Lugol chromoendoscopy is useful for the detection of early esophageal squamous cell cancer (ESCC). Multiple lugol-voiding lesions (LVLs) on lugol chromoendoscopy are associated with a very high risk of multiple cancers arising in the esophagus. Due to the widespread use of narrow band image technology in many institutions, esophageal cancer without LVLs in the background esophagus is sometimes detected. This retrospective study aims to clarify the clinical characteristic of esophageal cancer without LVLs in the background esophagus. A total of 191 consecutive patients with 204 ESCCs had undergone endoscopic submucosal dissection (ESD) from 2011 and 2014. Amongst these lesions, the number of LVLs in the background esophagus per endoscopic view was counted excluding main lesion, and the grading was divided into no LVLs ESCC (nL-ESCC) group and LVLs ESCC (L-ESCC) group. This study evaluated the clinical characteristics and the cumulative incidence of metachronous ESCC after ESD in both groups. Thirty-six patients with 36 lesions and 155 patients with 168 lesions were separated into the nL-ESCC group and L-ESCC group, respectively. On multivariate analysis, the nL-ESCC group was found to be more common in females, who were non-drinkers, or with erosive esophagitis. During follow-up periods, the cumulative incidence of metachronous ESCC at 3-years was 14.4% and 0.00% in the L-ESCC and nL-ESCC groups, respectively (P < 0.01). Our study showed that esophageal cancer without LVLs in the background esophagus was mostly occurred in females, who were non-drinkers, or with erosive esophagitis, which are uncommon features of ESCC.     

A longitudinal study for the prediction of the mature acetabular morphology using childhood magnetic resonance imaging

BackgroundAlthough acetabular dysplasia is a common etiology of osteoarthritis of the hip regardless of the history of developmental dysplasia of the hip (DDH), whether or not corrective surgeries are beneficial for the childhood asymptomatic acetabular dysplasia remains controversial due to a lack of evidence. We conducted a longitudinal study to compare the cartilaginous morphology on childhood magnetic resonance imaging (MRI) and the mature hip morphology of the same patient and to assess the predictive indicators for future acetabular dysplasia.MethodsA total of 92 unaffected hips (47 unilateral DDH and 45 unilateral Legg-Calvé-Perthes disease) were reviewed for X-ray and MRI findings on childhood (mean age: 6.0 years) and X-ray findings from a skeletally mature age with a mean follow-up period of 15.1 years. The following parameters were measured and compared: the immature-acetabular index (AI) and center edge angle (CE) on immature X-ray; the cartilage- and bone- AI, CE, Sharp and acetabular head index (AHI) on childhood MRI; and the mature-acetabular roof obliquity (ARO), CE, Sharp and AHI on skeletally mature X-ray. The prognostic factors on childhood MRI for acetabular dysplasia, defined by a CE of <20° on skeletally mature X-ray were also assessed.ResultsPositive correlations were shown between the cartilage-AI and mature-ARO (7.6°/6.3°; r = 0.44), the cartilage-CE and mature-CE (27.8°/28.0°; r = 0.62), the cartilage-Sharp and mature-Sharp (44.4°/41.8°; r = 0.52) and the cartilage-AHI and mature-AHI (78.7%/80.3%; r = 0.46). A multivariate analysis indicated cartilage-CE to be an independent predictor for acetabular dysplasia with a cut-off value of 22°. Children with a cartilage-CE <22° developed more frequently acetabular dysplasia compared to the others (52.4% vs. 1.4%).ConclusionsChildhood MRI findings are useful for the prediction of acetabular dysplasia without a DDH history. Children with a cartilage-CE ≥23° are likely to achieve a non-dysplastic hip without the need for surgical intervention.     

Pharmacokinetic study of the oral fluorouracil antitumor agent S‐1 in patients with impaired renal function

Although dose reduction of S‐1 is recommended for patients with impaired renal function, dose modification for such patients has not been prospectively evaluated. The aim of the present study was to investigate the pharmacokinetic parameters of 5‐fluorouracil, 5‐chloro‐2,4 dihydroxypyridine and oteracil potassium, and to review the recommended dose modification of S‐1 in patients with renal impairment. We classified patients receiving S‐1 into 4 groups according to their renal function, as measured using the Japanese estimated glomerular filtration rate (eGFR) equation. The daily S‐1 dose was adjusted based on the patient's eGFR and body surface area. Blood samples were collected for pharmacokinetic analysis. A total of 33 patients were enrolled and classified into 4 groups as follows: 10 patients in cohort 1 (eGFR ≥ 80 mL/min/1.73 m²), 10 patients in cohort 2 (eGFR = 50‐79 mL/min/1.73 m²), 10 patients in cohort 3 (eGFR = 30‐49 mL/min/1.73 m²), and 3 patients in cohort 4 (eGFR < 30 mL/min/1.73 m²). Those in cohorts 3 and 4 treated with an adjusted dose of S‐1 showed a similar area under the curve for 5‐fluorouracil (941.9 ± 275.6 and 1043.5 ± 224.8 ng/mL, respectively) compared with cohort 2 (1034.9 ± 414.3 ng/mL). Notably, while there was a statistically significant difference between cohort 1 (689.6 ± 208.8 ng/mL) and 2 (P = 0.0474) treated with an equal dose of S‐1, there was no significant difference observed in the toxicity profiles of the cohorts. In conclusion, dose adjustment of S‐1 in patients with impaired renal function using eGFR is appropriate and safe.