The emotional impact of the COVID-19 pandemic on individuals with progressive multiple sclerosis

Journal of Neurology - Individuals with pre-existing chronic illness have shown increased anxiety and depression due to COVID-19. Here, we examine the impact of the COVID-19 pandemic on emotional...     

Long-term outcome in diabetic heart failure patients treated with cardiac resynchronization therapy

BACKGROUND: Diabetes mellitus is an independent risk factor for increased morbidity and mortality in heart failure (HF) patients. AIMS: To compare functional and structural improvement, as well as long-term outcome, between diabetic and non-diabetic HF patients treated with cardiac resynchronization therapy (CRT). METHODS: We compared response to CRT in 141 diabetic and 214 non-diabetic consecutive patients. Major events were; death from any cause, urgent heart transplantation and implantation of a left ventricular (LV) assist device. Frequencies of hospitalisation and defibrillator (CRT-D) discharges were also analyzed. RESULTS: CRT was able to significantly improve functional capacity, ventricular geometry and neurohumoral imbalance in both diabetic and non-diabetic patients over a median follow-up time of 34 months. Overall event-free survival was similar in diabetic and non-diabetic patients (HR 1.23, p=0.363), as was survival free from CRT-D interventions (HR 1.72; p=0.115) and hospitalisations (HR 1.12; p=0.500). On multivariable analysis, NYHA class IV (p=0.002), low LV ejection fraction (p=0.002), absence of beta-blocker therapy (p<0.001), impaired renal function (p=0.003), presence of an epicardial lead (p=0.025), but not diabetes (p=0.821) were associated with a poor outcome after CRT. CONCLUSIONS: Diabetic HF patients treated with CRT had a very favourable functional and survival outcome, which was comparable to non-diabetic patients.     

New perspectives on the long-term outcome of segmental colectomy for Crohn’s colitis: an observational study on 200 patients

Background and aims

Surgical management of Crohn’s colitis represents one of the most complex situations in colorectal surgery. Segmental colectomy (SC) and total abdominal colectomy with ileorectal anastomosis (TAC-IRA) are the most common procedures, but there are few available data on their long-term outcome. The aim of the present study was to analyze the long-term outcome of patients who underwent segmental colectomy for Crohn’s colitis, with regard to the risk for total abdominal colectomy.

Methods

In this observational, monocentric, retrospective analysis, we analyzed patients who received a segmental colectomy for Crohn’s colitis at our institution. The database was updated by asking patients to complete a questionnaire by telephone or at the outpatient clinic. Only patients followed up at our Hospital were included. Patients were followed up by a specialized multidisciplinary team (IBD Unit). The primary endpoint was the interval between segmental colectomy and, when performed, total abdominal colectomy.

Results

Between 1973 and 2014, 200 patients underwent segmental colectomy for Crohn’s colitis. The median follow-up was 13.5 years (interquartile range [IQR] 7.8–21.5). Overall, 62 patients (31%) had a surgical recurrence, of these, 42 (21%) received total abdominal colectomy. At multivariate analysis, the presence of ≥?3 sites (HR =?2.47; 95% CI 1.22–5.00; p?=?0.018) and perianal disease (HR =?3.23; 95% CI 1.29–8.07; p?=?0.006) proved to be risk factors for total abdominal colectomy.

Conclusions

The risk for surgical recurrence after SC for Crohn’s colitis is acceptable. We recommend a bowel-sparing policy for the treatment of Crohn’s colitis in any case in which the extent of the disease at the moment of surgery makes the conservative approach achievable.

     

Testicular vasculitis: findings differentiating isolated disease from systemic disease in 72 patients

Testicular vasculitis (TV) may be part of systemic (testicular) vasculitis (STV) or may exist as single-organ/isolated (testicular) vasculitis (ITV). In the current study we sought to identify clinical and histologic features that distinguish STV from ITV. The distinction was deemed important because it is already well established that in other forms of single organ vasculitis, surgical therapy alone may be curative. We identified patients with biopsy-proven TV from pathology databases from our institution and from an English-language PubMed search. Patients were included if data were available to determine TV extent confidently. Data recorded included clinical, laboratory, and histologic features; treatment; and clinical follow-up. The study included 72 patients with TV (mean age, 42 yr; range, 4-78 yr) (7 from our institution). About 74% of patients presented with painful testicular swelling/mass, 10% with a painless testicular swelling/mass, and 4% with epididymal swelling/mass. Eleven percent had no testicular complaints and vasculitis was discovered at autopsy or in other surgical interventions. Vasculitis involved the testicle in 80.3% of cases, the epididymis in 44.6%, and the spermatic cord in 30.6%. Thirty-seven (51%) patients had ITV and 35 (49%) had STV. No differences between ITV and STV patients were found in regards to age, presenting testicular features, duration of testicular symptoms, and time of follow-up. Compared to ITV patients, STV patients presented more often with constitutional/musculoskeletal symptoms (74.3% vs. 8.3%, respectively; p = 0.0001), elevated erythrocyte sedimentation rate (94.7% vs. 16%; p = 0.0001), and anemia (50% vs. 0%; p = 0.0001). Neoplasm was more frequently suspected in ITV than in STV (74.2% vs. 31.6%; p = 0.001), but only occurred in 2 ITV patients. Long-term glucocorticoid therapy was given only to STV patients, and 59.1% of them also received cytotoxic agents. ITV was diagnosed more often by orchiectomy (81.1% vs. 42.9%; p = 0.001) and less frequently by testicular biopsy (2.7% vs. 28.6%; p = 0.003) than STV. Nongranulomatous inflammation affecting medium-sized vessels occurred in most patients with both ITV and STV. Among STV, polyarteritis nodosa was the most frequently diagnosed (63%), followed by Wegener granulomatosis (17%).In summary, TV occurs as ITV in men usually presenting with a testicular mass in the absence of systemic symptoms and normal laboratory results. In most ITV patients, a testicular neoplasm is initially suspected, and TV is an unexpected finding. After surgical removal, ITV does not require systemic therapy. Polyarteritis nodosa is the systemic vasculitis most frequently associated with testicular involvement.     

The role of macrophage colony-stimulating factor in patients with acute myocardial infarction: a pilot study

We assessed whether macrophage colony-stimulating factor (M-CSF) levels are associated with left ventricular systolic dysfunction (LVSD) in patients with acute myocardial infarction (AMI). We studied 56 patients with AMI (mean age: 67 ± 12 years) and identified those with clinical (Killip class >II) or echocardiographic signs (ejection fraction ≤45%) of LVSD. We evaluated the established cardiovascular risk factors and measured several cardiovascular biomarkers, including M-CSF. Serum M-CSF concentrations (pg/mL) were significantly increased in patients with both clinical and echocardiographic signs of LVSD (460 ± 265 vs 290 ± 210, P = .0103 and 493 ± 299 vs 287 ± 174, P = .0028, respectively). We found a significant inverse association between M-CSF and ejection fraction (r = -.351, P = .0079). Logistic regression analysis revealed that, among all evaluated clinical and biochemical parameters, the stronger predictor of LVSD was M-CSF (odds ratios 2.1, 95% confidence interval 1.1-2.9, P = .0168). This is the first study reporting plasma M-CSF levels as independent determinants of low LV ejection fraction and clinical LV dysfunction in patients with AMI.     

Cytotoxic effects of bortezomib in myelodysplastic syndrome/acute myeloid leukemia depend on autophagy-mediated lysosomal degradation of TRAF6 and repression of PSMA1

Bortezomib (Velcade) is used widely for the treatment of various human cancers; however, its mechanisms of action are not fully understood, particularly in myeloid malignancies. Bortezomib is a selective and reversible inhibitor of the proteasome. Paradoxically, we find that bortezomib induces proteasome-independent degradation of the TRAF6 protein, but not mRNA, in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) cell lines and primary cells. The reduction in TRAF6 protein coincides with bortezomib-induced autophagy, and subsequently with apoptosis in MDS/AML cells. RNAi-mediated knockdown of TRAF6 sensitized bortezomib-sensitive and -resistant cell lines, underscoring the importance of TRAF6 in bortezomib-induced cytotoxicity. Bortezomib-resistant cells expressing an shRNA targeting TRAF6 were resensitized to the cytotoxic effects of bortezomib due to down-regulation of the proteasomal subunit α-1 (PSMA1). To determine the molecular consequences of loss of TRAF6 in MDS/AML cells, in the present study, we applied gene-expression profiling and identified an apoptosis gene signature. Knockdown of TRAF6 in MDS/AML cell lines or patient samples resulted in rapid apoptosis and impaired malignant hematopoietic stem/progenitor function. In summary, we describe herein novel mechanisms by which TRAF6 is regulated through bortezomib/autophagy-mediated degradation and by which it alters MDS/AML sensitivity to bortezomib by controlling PSMA1 expression.