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Given the increase in the aging population and thus in the prevalence of dementia, the identification of protective factors against cognitive decline is necessary. In a cohort of 1076 non-demented adults ≥ 65 years old (59.7% women) from the HELIAD study, we assessed whether changes in body mass index (BMI) were associated with changes in cognition over a 3-year follow-up period separately for those ≤ 75 and >75 years old. We identified six BMI trajectory groups based on participants' BMI status at baseline and at the first follow-up visit; normal to normal BMI was the reference group. Major cognitive domains were evaluated, and a composite index reflecting global cognition was calculated. In participants aged ≤75 years, weight loss-moving from obesity to overweight or normal BMI-was associated with less decline in the memory composite score over time (β = 0.141; p = 0.035), while 3-year maintenance of a BMI ≥ 25 kg/m 2 was related to greater reduction in the visuospatial composite score over time (β = -0.093; p = 0.020). Regarding participants aged >75 years, 3-year maintenance of a BMI ≥ 30 kg/m 2 contributed to a slower rate of decline in the memory composite score over time (β = 0.102; p = 0.042), whereas weight loss-from overweight to normal BMI-was associated with a decreased attention/processing speed composite score longitudinally (β = -0.275; p = 0.043). Our findings indicated that the association between changes in BMI and cognitive functioning was modified by age. Weight management may have the potential to delay cognitive decline in older adults.

Aims: Diagnosis of primary membranous nephropathy (PMN) is mainly based on immunofluorescence/immunohistochemistry findings. However, assessment of specific features on optical microscopy can help to estimate the severity of the disease, guide treatment and predict the response. The aim of this study was to identify, classify and grade the precise histological findings in PMN to predict renal function outcome and guide treatment., Methods and Results: Histological parameters, including focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH), were re-evaluated in 752 patients with PMN. Their predictive value was estimated separately, and also in a combination score (FSTIV) graded from 0 to 4. Finally, the impact of histology was assessed in the response to immunosuppressive treatment. Mean age of patients was 53.3 (15-85) years and most presented with nephrotic syndrome. FSGS was present in 32% and VH in 51% of the patients, while TA and IF were graded as stage ≥1 in 52% and 51.4%, respectively. The follow-up period was 122.3 (112-376) months. FSGS, TA and IF and VH were associated with impaired renal function at diagnosis (P = 0.02, P < 0.0001, P = 0.001 and P = 0.02, respectively) and at the end of follow-up (P = 0.004, P < 0.0001, P < 0.0001 and P = 0.04, respectively). In multiple regression and binary logistic analysis, the presence of FSGS and degree of TA were the most significant parameters predicting renal function outcome, defined either by eGFR (end), FSGS (r = 0.6, P < 0.0001) and TA (r = 0.6, P < 0.0001), or by the endpoint of >50% eGFR reduction, FSGS (P = 0.001) and TA (P = 0.02). Also, patients presented with FSGS, IF, VH and/or with FSTIV > 1 could benefit from immunosuppression, regardless of clinical presentation., Conclusions: The presence and degree of four histological indices, FSGS, VH, TA and IF, assessed separately or in combination, and FSTIV score not only predict renal function outcome after long-term follow-up, but can also help in the choice of appropriate treatment. Decisions concerning immunosuppressive treatment can be guided by pathology regardless of clinical findings., (© 2019 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Abstract Renal impairment (RI) is a common presenting complication of multiple myeloma associated with significant morbidity and early mortality, while it has been associated with inferior survival in patients treated with conventional regimens. We assessed the impact of RI in 203 unselected consecutive patients treated upfront with novel agents (thalidomide, lenalidomide, bortezomib). RI was assessed by the estimated glomerular filtration rate (eGFR). RI (eGFR <60 mL/min) was present in 93 (45.8%) of patients at diagnosis and was associated with advanced age, advanced International Staging System (ISS) stage, poorer performance status, hypercalcemia, urine Bence-Jones proteinuria, anemia and thrombocytopenia. Myeloma response rates were similar for patients with or without RI. In univariate analysis RI was associated with shorter survival and a higher rate of early death (7% vs. 3.5%); however, when adjusted for other prognostic factors, RI was not independently associated with survival. In conclusion, in unselected newly diagnosed patients treated with novel agent-based therapies, RI is not independently associated with inferior survival, probably due to the significant activity of novel agents even in the context of RI.

A 67-year-old male patient with diabetes mellitus and nephritic syndrome under cortisone treatment was admitted to our hospital with fever and severe perianal pain. Upon physical examination, a perianal abscess was identified. Furthermore, the scrotum was gangrenous with extensive cellulitis of the perineum and left lower abdominal wall. Crepitations between the skin and fascia were palpable. A diagnosis of Fournier's gangrene was made. He was treated with immediate extensive surgical debridement under general anesthesia. The patient received broad-spectrum antibiotics, and repeated extensive debridements were performed until healthy granulation was present in the wound. Due to the fact that his left testicle was severely exposed, it was transpositioned into a subcutaneous pocket in the inner side of the left thigh. He was finally discharged on the 57th postoperative day. Fournier's gangrene is characterized by high mortality rates, ranging from 15% to 50% and is an acute surgical emergency. The mainstay of treatment should be open drainage and early aggressive surgical debridement of all necrotic tissue, followed by broad-spectrum antibiotics therapy.

The purpose of this analysis was to assess the effect of novel agent-based regimens on the improvement of renal impairment (RI) in newly diagnosed patients with multiple myeloma. Ninety-six consecutive patients with RI received conventional chemotherapy (CC)-based regimens (n=32), IMiDs-based regimens (n=47) or bortezomib-based regimens (n=17) as frontline therapy. Improvement of RI was more frequent in patients treated with novel agents (79% in IMiD- and 94% in bortezomib-treated groups versus 59% in CC-treated group; p=0.02). Bortezomib-based regimens and CrCl>30 ml/min at baseline independently correlated with a higher probability of at least renal partial response (PRrenal) and with a shorter time to PRrenal or better. Thus bortezomib-based regimens may be the preferred treatment for newly diagnosed myeloma patients with RI., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Objectives: Lenalidomide and dexamethasone (LenDex) is an active regimen for relapsed/refractory multiple myeloma (MM). However, there is limited data for the effect of LenDex on renal impairment (RI) and on renal reversibility., Patients & Methods: Fifty consecutive patients with relapsed/refractory MM received LenDex in 28-d cycles. Median lines of previous therapies were 2 (range: 1-6). Lenalidomide was administered on days 1-21 according to creatinine clearance (CrCl), while dexamethasone was given at a dose of 40 mg on days 1-4 and 15-18 for the first four cycles and only on days 1-4 thereafter., Results: Twelve patients (24%) had RI at baseline, defined as CrCl < 50 mL/min. Most patients were pretreated with either thalidomide or bortezomib and > 50% of them were refractory to both drugs. At least partial response was documented in 60.5% and 58% of patients with and without RI. Median progression-free survival (PFS) and overall survival (OS) for all patients was 9 and 16 months, respectively. RI was not associated with an inferior PFS or OS. There were no differences in the incidence of adverse events among patients with and without RI. Three of 12 patients with RI (25%) achieved complete renal response and two (16%) achieved minor renal response with LenDex., Conclusions: We conclude that LenDex is an active treatment even in heavily pretreated MM. With dosing of lenalidomide according to renal function, LenDex can be administered to patients with RI (who may not have other treatment options) without excessive toxicity. Furthermore, LenDex may improve the renal function in approximately 40% of patients with RI.

Purpose: Renal impairment is a frequent complication of multiple myeloma (MM) and is associated with significant morbidity and increased early death rate. Bortezomib is active and well tolerated in patients with MM who present or develop renal impairment., Patients and Methods: We analyzed 46 consecutive patients who presented with renal impairment in order to evaluate the impact of bortezomib on the improvement of renal function and to identify predictive factors associated with renal response. All patients received bortezomib with dexamethasone with or without other agents., Results: Renal response was documented in 59% of patients within a median of 11 days (range, 8-41 days). Two of 9 patients who required dialysis became dialysis independent. A complete renal response (CRrenal) was documented in 30% of patients. Toxicities were similar to those seen in myeloma patients without renal failure who were treated with bortezomib-based regimens. Patients with light chain-only myeloma had a higher probability of achieving a renal response, and previously untreated patients had a higher probability for complete resolution of renal impairment, while light chain-only myeloma was independently associated with a shorter time to renal response. The degree of renal impairment was not predictive of the probability for renal response or CRrenal; however, in a subset of patients for whom cystatin C was available, a baseline cystatin C > 2 mg/L or cystatin C calculated estimated glomerular filtration rate < 30 mL/min were associated with a lower probability of CRrenal., Conclusion: We conclude that bortezomib-based regimens may improve renal function in the majority of myeloma patients with renal impairment.

Unlabelled: Renal failure is a common feature of multiple myeloma and a major management problem. However there is limited data regarding the reversibility of renal failure, the kinetics of serum creatinine and the safety of novel agents such as bortezomib when administered to newly diagnosed or relapsed/refractory patients with renal failure., Patients and Methods: We evaluated 20 consecutive patients with newly diagnosed or relapsed/refractory multiple myeloma and renal failure, defined as a serum creatinine >or= 2 mg/dl. All patients received bortezomib with dexamethasone or in combination with other agents (thalidomide, doxorubicin or melphalan)., Results: Reversal of renal failure was documented in 40% of all patients and the median time to reversal was 17 days. Moreover 10 patients (50%) had 50% decrease in serum creatinine and the median time to decrease was 35 days. Some decrease of creatinine was documented in 85% of patients. The objective response rate was 65%. Toxicities were similar to those seen in myeloma patients without renal failure., Conclusions: Bortezomib based regimens can be administered to myeloma patients with renal impairment and their toxicity and efficacy are similar to those observed in patients without renal impairment. Moreover, bortezomib-based regimens induce improvement of serum creatinine in most patients and reversal of renal failure in approximately one-third.

Introduction: Right ventricular function is a determinant of prognosis and survival in patients with pulmonary hypertension. The pulmonary hypertensive right ventricle has a complex shape. Transthoracic two-dimensional echocardiography is the primary examination for demonstrating right ventricular impairment. Nowadays, many indices have been linked with pulmonary hypertension. The myocardial performance index (MPI), which may be determined by both conventional Doppler and tissue Doppler imaging (TDI), is one of these., Methods: Ninety-three patients with pulmonary hypertension were examined retrospectively over 3 years' treatment. The relationship between MPI and right ventricular impairment was studied, as well as the correlation with various echocardiographic determinants. In addition, we examined the correlation between conventional echocardiography and tissue Doppler imaging with reference to the MPI., Results: MPI had a statistically significant relationship with the visual estimation of right ventricular impairment (r = 0.714, p = 0.001), the degree of pulmonary regurgitation (r = 0.155, p = 0.048), left ventricular eccentricity index (r = 0.299, p = 0.001 in systole) and the presence of pericardial effusion (r = 0.199, p = 0.008), while it was inversely correlated with left ventricular fractional shortening (r = -0.284, p = 0.001). However, the index had no correlation with tricuspid regurgitant velocity, right ventricular acceleration time or right atrial volume. There was significant agreement between the MPI measured by conventional Doppler echocardiography and by TDI (r = 0.83, p < 0.001; mean value -0.10, SD 0.2). Finally, some patients showed a significant decrease in tricuspid regurgitant velocity and MPI during their treatment., Conclusion: Right ventricular MPI has a good correlation with several parameters and can be a good prognostic factor for right ventricular impairment in patients with pulmonary hypertension.

The impact of high dose dexamethasone containing regimens with or without the novel agents thalidomide and bortezomib on the reversal of renal failure (RF) was evaluated in 41 consecutive newly diagnosed patients with multiple myeloma (MM) treated in a single institution. RF was reversed in 73% of all patients within a median of 1.9 months. In patients treated with dexamethasone and novel agents (thalidomide and/or bortezomib) the reversibility rate was 80% within a median of 0.8 months. Severe RF and significant Bence Jones proteinuria were associated with a lower probability of RF reversal. Patients who responded to treatment achieved RF reversal more often than in those who did not (85% versus 56%, p=0.046). In conclusion, RF is reversible in the majority of newly diagnosed MM patients treated with high-dose dexamethasone containing regimens. The addition of novel agents induces a more rapid RF reversal.

The liberalization of acceptance criteria for dialysis and the progressive increase of the elderly population overall have increased the number of elderly dialysis patients worldwide. The main underlying diseases leading to end stage renal disease (ESRD) in the elderly patients are hypertension and diabetes, but in many patients, the cause of renal disease is unknown. The principal form of renal replacement therapy (RRT) in the elderly is hospital hemodialysis. The 1995 annual report of the US Renal Data System (USRDS) indicated that from 1986 to 1990 for patients who were older than 65 years, the two major types of vascular access were arteriovenous fistula and synthetic polytetrafluoroethylene (PTFE) graft (more than 80% of the total). The elderly on hemodialysis have a higher rate of access morbidity, and, in them, the most common hemodialysis-related complications in the elderly are hypotension, arrthythmias, and gastrointestinal bleeding. Peritoneal dialysis is the only method that permits home treatment for most elderly people, the frequency of peritonitis and catheter-related complications are similar between young and elderly patients. Incidence of malnutrition increases significantly with age; the quality of life of these patients varies according to different investigators, who described results that are lower, similar, or better than those in younger patients. Not unexpectedly, mortality is higher among the elderly dialysis patients in whom cardiovascular diseases and infections are the most common causes of death. In elderly patients, an adequate social support system, of which the family unit is the crucial component, is an important element in any form of chronic dialysis. ESRD treatment in the elderly raises many ethical issues and dilemmas. Nephrologists, citizens, politicians, and bureaucrats are concerned about the high cost of long-term therapy. Conflicts over treatment futility and rationing are inevitable. The financial restrictions on dialysis resources have had a powerful impact on patient selection; when the health care resources become limited, the elderly are the first group to be considered expendable. The most common dilemma faced by the nephrologist is the withholding and/or withdrawing of treatment from older patients.

Procollagen-I carboxylterminal extension peptide (PICP) was determined in the serum and dialysate of 26 continuous ambulatory peritoneal dialysis (CAPD) patients and in the serum of 11 healthy controls. PICP serum levels were significantly higher in CAPD patients than in healthy controls (p < 0.001). There was no correlation between serum PICP levels and those of calcium, phosphorus, magnesium, alkaline phosphatase, osteocalcin, and intact parathyroid hormone (iPTH). Serum and dialysate levels of osteocalcin and iPTH showed a significant correlation (p < 0.001). The dialysate-to-serum PICP ratio in 21 patients was lower than 1.0. In the remaining 5 patients, however, the above ratio was higher than 1.0. We conclude that in CAPD patients serum PICP levels do not correlate with biochemical parameters of renal osteodystrophy. A dialysate-to-serum PICP ratio above 1.0 could implicate an increased local peritoneal fibroblastic activity and could be a useful marker of peritoneal fibrosis in CAPD.