Sweet Syndrome, Not so Sweet during an Ulcerative Colitis Flare Especially When You Cannot Eat

Sweet syndrome is a rare skin condition characterized by painful papules, nodules, or plaques with dense neutrophilic infiltrate in the upper dermis. It has been observed as idiopathic (classical), malignancy-associated, and drug-induced. The pathogenesis is not completely understood, but it is thought to involve hypersensitivity reactions to specific triggers. In some cases the etiology is unclear or may be multifactorial. We present a case of Sweet syndrome secondary to ulcerative colitis flare versus adalimumab re-induction

Influence of Polymorphism in the Genes for the Interleukin (IL)-1 Receptor Antagonist and IL-1β on Tuberculosis

Several lines of evidence suggest that host genetic factors controlling the immune response influence infection by Mycobacterium tuberculosis. The proinflammatory cytokine interleukin (IL)-1β and its antagonist, IL-1Ra (IL-1 receptor agonist), are strongly induced by M. tuberculosis and are encoded by polymorphic genes. The induction of both IL-1Ra mRNA and secreted protein by M. tuberculosis in IL-1Ra allele A2–positive (IL-1Ra A2+) healthy subjects was 1.9-fold higher than in IL-1Ra A2− subjects. The M. tuberculosis–induced expression of mRNA for IL-1β was higher in subjects of the IL-1β (+3953) A1+ haplotype (P = 0.04). The molar ratio of IL-1Ra/IL-1β induced by M. tuberculosis was markedly higher in IL-1Ra A2+ individuals (P < 0.05), with minor overlap between the groups, reflecting linkage between the IL-1Ra A2 and IL-1β (+3953) A2 alleles. In M. tuberculosis–stimulated peripheral blood mononuclear cells, the addition of IL-4 increased IL-1Ra secretion, whereas interferon γ increased and IL-10 decreased IL-1β production, indicative of a differential influence on the IL-1Ra/IL-1β ratio by cytokines. In a study of 114 healthy purified protein derivative–reactive subjects and 89 patients with tuberculosis, the frequency of allelic variants at two positions (−511 and +3953) in the IL-1β and IL-1Ra genes did not differ between the groups. However, the proinflammatory IL-1Ra A2−/IL-1β (+3953) A1+ haplotype was unevenly distributed, being more common in patients with tuberculous pleurisy (92%) in comparison with healthy M. tuberculosis–sensitized control subjects or patients with other disease forms (57%, P = 0.028 and 56%, P = 0.024, respectively). Furthermore, the IL-1Ra A2+ haplotype was associated with a reduced Mantoux response to purified protein derivative of M. tuberculosis: 60% of tuberculin-nonreactive patients were of this type. Thus, the polymorphism at the IL-1 locus influences the cytokine response and may be a determinant of  delayed-type hypersensitivity and disease expression in human tuberculosis

AIDS-related mycoses: the way forward.

The contribution of fungal infections to the morbidity and mortality of HIV-infected individuals is largely unrecognized. A recent meeting highlighted several priorities that need to be urgently addressed, including improved epidemiological surveillance, increased availability of existing diagnostics and drugs, more training in the field of medical mycology, and better funding for research and provision of treatment, particularly in developing countries

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p&lt;0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (&lt;1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (&lt;1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

The millennium library. : V. 135.: The man who loved children.

Londonxxxvii, 529 p.; 21c

The man who loved children

xxxvii, 529 tr. ; 22 cm