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High‐dose methylprednisolone plus rituximab (R‐HDMP) is a useful treatment in chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) patients unfit for chemo‐immunotherapy and has proven its utility on the treatment of CLL/SLL complicated by auto‐immune cytopenias. We performed a retrospective, single‐centre study, of CLL/SLL patients treated with R‐HDMP for 9 years. Thirty‐nine patients were included, median age at time of treatment was 77 years. Most patients had stage Rai III/IV and Binet C disease. Twenty‐eight patients had relapsed/refractory disease at time of treatment with a median of 1 previous line of therapy; 53.8% had prior exposure to fludarabine and 25% to rituximab. Grade 3–4 neutropenia and thrombocytopenia were recorded in 10.2% and 17.9% patients, respectively. While on treatment, 51.3% had documented infectious complications, but no other non‐haematological toxicities grades 3–4 were identified. Overall response rate was 64%. Median overall survival and progression‐free survival were 24 and 13 months, respectively. Twenty four patients relapsed and 16 received another line of treatment after R‐HDMP, with median time to next treatment of 13.5 months. Thirteen out of the 24 patients improved performance status and were subsequently considered fit for chemo‐immunotherapy. R‐HDMP is a valuable option for elderly and frail patients, with low risk of severe myelotoxicity and other severe adverse events. It was shown to work as a bridge to other lines of treatment, including chemo‐immunotherapy., High dose methylprednisolone plus rituximab (R‐HDMP) is a useful treatment in chronic lymphocytic leukaemia/small lymphocytic lymphoma patients unfit for chemo‐immunotherapy. We present a cohort of patients with median age of 77 years, most with stage Rai III/IV and Binet C disease. Overall response rate was 64% and median overall survival and progression‐free survival were 24 and 13 months, respectively, with an acceptable toxicity profile, highlighting R‐HDMP utility for elderly and frail patients.

Examining clinical features of depressive episodes may help elucidating the nature of association between depression and obesity, related to specific symptoms such as appetite and weight changes. This meta-analysis of observational studies evaluated whether subtypes of depression are associated with specific anthropometric profiles in adults. We searched MEDLINE, LILACS, PsycINFO, Scopus, Web of Science databases, and Grey Literature for articles published up to October 2016 that examined depressive subtypes and adiposity measures among adults. The pooled effect size was estimated with random effects models. The PRISMA guidelines were adopted to reporting results, and this review was registered in PROSPERO (CRD42016035685). A total of 22 articles were included in this systematic review, of which eight had data included in the meta-analysis, assessing 14 757 individuals with depression. Patients with atypical depression presented a 2.55 higher BMI score compared with those with melancholic depression. Subgroup analysis identified a differential distribution of anthropometric measures in studies conducted with Chinese populations. Among the remainder studies, only one reported discrepant results, possibly due to the exclusion of "weight change" in defining subtypes of depression. Atypical depression was significantly associated with elevated BMI compared with melancholic depression, deserving particular attention due to its clinical importance.

Lateral meningocele syndrome (LMS, OMIM%130720), also known as Lehman syndrome, is a very rare skeletal disorder with facial anomalies, hypotonia and meningocele-related neurologic dysfunction. The characteristic lateral meningoceles represent the severe end of the dural ectasia spectrum and are typically most severe in the lower spine. Facial features of LMS include hypertelorism and telecanthus, high arched eyebrows, ptosis, midfacial hypoplasia, micrognathia, high and narrow palate, low-set ears and a hypotonic appearance. Hyperextensibility, hernias and scoliosis reflect a connective tissue abnormality, and aortic dilation, a high-pitched nasal voice, wormian bones and osteolysis may be present. Lateral meningocele syndrome has phenotypic overlap with Hajdu–Cheney syndrome. We performed exome resequencing in five unrelated individuals with LMS and identified heterozygous truncating NOTCH3 mutations. In an additional unrelated individual Sanger sequencing revealed a deleterious variant in the same exon 33. In total, five novel de novo NOTCH3 mutations were identified in six unrelated patients. One had a 26 bp deletion (c.6461_6486del, p.G2154fsTer78), two carried the same single base pair insertion (c.6692_93insC, p.P2231fsTer11), and three individuals had a nonsense point mutation at c.6247A > T (pK2083*), c.6663C > G (p.Y2221*) or c.6732C > A, (p.Y2244*). All mutations cluster into the last coding exon, resulting in premature termination of the protein and truncation of the negative regulatory proline-glutamate-serine-threonine rich PEST domain. Our results suggest that mutant mRNA products escape nonsense mediated decay. The truncated NOTCH3 may cause gain-of-function through decreased clearance of the active intracellular product, resembling NOTCH2 mutations in the clinically related Hajdu–Cheney syndrome and contrasting the NOTCH3 missense mutations causing CADASIL. © 2014 Wiley Periodicals, Inc.

Lateral meningocele syndrome is a rare disorder of unknown etiology, first described in 1977 and subsequently reported in nine other patients. These patients present distinctive craniofacial features and skeletal abnormalities in addition to multiple lateral meningoceles, suggesting a connective tissue disorder. Autosomal dominant inheritance is clearly suggested in one family and could explain familiar aggregation in another. We describe a simplex case of lateral meningocele syndrome with bicuspid aortic valve, supporting the hypothesis of a connective tissue basis for this disorder and further expanding the phenotype.

Wine industry produces large quantities of by-products rich in bioactive compounds from grapes, which could be utilized for nutraceutical purposes. We aim to evaluate antioxidant activity (AC) and bioactivity of grape pomace extract from Brazilian wine industry in human hepatocarcinoma cells (HepG2). The content of bioactive compounds and AC of extracts were determined by ORAC, TEAC (ABTS•-) and TRAP assays. Bioactivity was assessed on HepG2 and on normal human fibroblasts (BEAS). Cellular viability was accessed by MTT reduction and cellular antioxidant capacity (CAC) by dichlorofluorescein oxidation, under short-, medium-, and long-term incubation periods. Total phenolics, flavonoids and anthocyanins of extracts where, respectively, (mean±SD) 473.8±52.4 mg GAE/100g, 147.5±2.77 mg CE/100g and 105.5±7.27 mg cyanidin3-glycoside/100g. Extract AC was (mean±SD; µmol TE/g) 27.1±0.33, 9.33±6.74, 122.2±2.40. HepG2 viability reduced in a time- and dose-dependent manner. Short-term incubation had no effect whereas ...

The purpose of this study was to investigate the prevalence of migraine in medical students, as well as its clinical aspects and impact. All 595 medical students of Santa Casa School of Medicine of São Paulo, Brazil were asked if they had experienced any kind of headache in the past year. Those who responded positively were further investigated by an appropriate questionnaire. Diagnosis of migraine was based on the International Headache Society criteria of 1988. Forty percent of students suffered from some kind of headache; 40.2% of these headaches were migraine. The prevalence of migraine was 54.4% in women and 28.3% in men. Migraine headaches were unilateral in 24.2%, had a gradual onset in 69%, and were of a throbbing type in 88.3%. Migraine was considered incapacitating by 53.9% of students. Migraine with aura caused more disability than migraine without aura. Women experienced more intense migraine than men, and migraine with aura was especially more severe than migraine without aura. Photophobia, phonophobia, and nausea were more commonly encountered in migraine with aura. Despite the high prevalence, the high rate of disability, and the need for analgesic medication, only 7.1% of students with migraine had sought medical treatment.