Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.

Context: This study was conducted to quantify the effect of multidisciplinary care (MDC) on amputation-free survival (AFS) and wound healing within a chronic critical limb ischemia (CLI) population.', 'We performed a retrospective, single-center cohort study of consecutive CLI patients presenting to the Vascular Surgery Service. Patients who received initial and follow-up wound care from the MDC were compared with patients who received standard wound care (SWC). The MDC team consisted of vascular, plastic, and podiatric surgeons who jointly managed wound care and directed any other consults or services as deemed necessary. SWC consisted of an inconsistent mix of providers without a defined manager, including nurses, wound care midlevel providers, general surgeons, internists, or the patients themselves. The referring physician determined the allocation of patients. The primary outcome variable was AFS, with a secondary evaluation of wound healing. The effects of baseline demographics, comorbid medical conditions, laboratory values, ischemic lesion severity and location, Rutherford classification, and participation in MDC were assessed. Significant univariate predictors (P < .10) of AFS were entered into a multivariate Cox regression model and assessed at an = .05.', 'Between August 2010 and June 2012, 146 CLI patients (91 male [63%]) were evaluated by the Vascular Surgery Service and were followed up for a median of 539 days (interquartile range 314-679 days). Ischemic tissue loss was present in 85 patients (38 at Rutherford category 5, and 47 at Rutherford category 6). Within this cohort, 51 (60%) had MDC, and 34 (40%) had SWC. Fifty-eight patients (68%) underwent revascularization (open in 17, endovascular in 35, and hybrid in 6), 14 (8%) were managed with primary major amputation, and 13 (15%) declined revascularization. AFS was superior for patients in the MDC arm vs the SWC arm (593.3 53.5 days vs 281.0 38.2 days; log-rank, P = .02). Wound-healing times favored the MDC arm over the SWC arm (444.5 33.2 days vs 625.2 126.5 days), although this was not statistically significant (log-rank, P = .74). Multivariate modelling revealed that independent predictors of major amputation or death, or both, were nonrevascularized patients (hazard ratio [HR], 3.76; 95% confidence interval [CI], 1.78-8.02; (2), P < .01), treatment by SWC (HR, 2.664; 95% CI, 1.23-5.77; (2), P = .012), and baseline nonambulatory status (HR, 1.89; 95% CI, 1.17-2.85; (2), P < .01).
Answer: MDC pathways for the management of a population of CLI patients improved AFS by greater than twofold and should be the standard of care for the CLI population. Baseline nonambulatory status and unrevascularized patients also predict worse AFS. Wound healing remains prolonged regardless of preoperative or postoperative wound care. Future study is required to evaluate the costs and functional outcomes for MDC in the management of CLI.
Does multidisciplinary care improve amputation-free survival in patients with chronic critical limb ischemia?

Context: To evaluate the impact of elevated serum 4A levels on the hormonal and metabolic features of the different phenotypes of PCOS.', '1276 women with PCOS according to the Rotterdam criteria were included, in whom serum hormonal levels were determined.', 'In PCOS women as a whole, as well as in patients presenting clinical and/or biochemical hyperandrogenemia (phenotypes I and II), 4A levels >3.8 ng/ml were positively related to LH, LH/FSH ratio, T, DHEAS, 17 OH progesterone and FAI and negatively related to T/4A ratio. In the milder phenotype III, a positive correlation between 4A levels >3.8 ng/ml and T, DHEAS, 17 OH progesterone and FAI and a negative one between increased 4A and T/4A ratio were reported. In the whole PCOS group with androstenedione >3.8 ng/ml, an increased ovarian volume was observed, while a greater mean follicular number was found only in phenotypes I and II.
Answer: Increased serum 4A levels, which are associated with more severe PCOS phenotypes, possibly contribute to the worsening of PCOS features and therefore could be a valuable marker of biochemical hyperandrogenemia.
Is elevated serum androstenedione associated with a more severe phenotype in women with polycystic ovary syndrome ( PCOS )?

Context: Epigenetic modifications play an important role in the regulation of gene transcription and cellular function. Here, we examined if pro-inflammatory factors present in the inflamed joint of patients with rheumatoid arthritis (RA) could regulate histone deacetylase (HDAC) expression and function in fibroblast-like synoviocytes (FLS).', 'Protein acetylation in synovial tissue was assessed by immunohistochemistry. The mRNA levels of HDAC family members and inflammatory mediators in the synovial tissue and the changes in HDAC expression in RA FLS were measured by quantitative (q) PCR. FLS were either transfected with HDAC5 siRNA or transduced with adenoviral vector encoding wild-type HDAC5 and the effects of HDAC5 manipulation were examined by qPCR arrays, ELISA and ELISA-based assays.', 'Synovial class I HDAC expression was associated with local expression of tumour necrosis factor (TNF) and matrix metalloproteinase-1, while class IIa HDAC5 expression was inversely associated with parameters of disease activity (erythrocyte sedimentation rate, C-reactive protein, Disease Activity Score in 28 Joints). Interleukin (IL)-1 or TNF stimulation selectively suppressed HDAC5 expression in RA FLS, which was sufficient and required for optimal IFNB, CXCL9, CXCL10 and CXCL11 induction by IL-1, associated with increased nuclear accumulation of the transcription factor, interferon regulatory factor 1(IRF1).
Answer: Inflammatory cytokines suppress RA FLS HDAC5 expression, promoting nuclear localisation of IRF1 and transcription of a subset of type I interferon response genes. Our results identify HDAC5 as a novel inflammatory mediator in RA, and suggest that strategies rescuing HDAC5 expression in vivo, or the development of HDAC inhibitors not affecting HDAC5 activity, may have therapeutic applications in RA treatment.
Do inflammatory cytokines epigenetically regulate rheumatoid arthritis fibroblast-like synoviocyte activation by suppressing HDAC5 expression?