Among patients undergoing resection of stage IIIB, IIIC, or IV melanoma, adjuvant therapy with nivolumab resulted in significantly longer recurrence-free survival and a lower rate of grade 3 or 4 adverse events than adjuvant therapy with ipilimumab. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 238 ClinicalTrials.gov number, NCT02388906 ; Eudra-CT number, 2014-002351-26 .).

The prompt and correct recognition of MG following treatment with immune checkpoint inhibitors in patients with cancer is important.

Multicentric Castleman disease (MCD) describes a heterogeneous group of disorders involving systemic inflammation, characteristic lymph node histopathology, and multi-organ dysfunction because of pathologic hypercytokinemia. Whereas Human Herpes Virus-8 (HHV-8) drives the hypercytokinemia in a cohort of immunocompromised patients, the etiology of HHV-8-negative MCD is idiopathic (iMCD). Recently, a limited series of iMCD cases in Japan sharing a constellation of clinical features, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been described as TAFRO syndrome. Herein, we report clinicopathological findings on 25 patients (14 males and 11 females; 23 Japanese-born and two US-born), the largest TAFRO syndrome case series, including the first report of cases from the USA. The median age of onset was 50 years old (range: 23-72). The frequency of each feature was as follows: thrombocytopenia (21/25), anasarca (24/25), fever (21/25), organomegaly (25/25), and reticulin fibrosis (13/16). These patients frequently demonstrated abdominal pain, elevated serum alkaline phosphatase levels, and acute kidney failure. Surprisingly, none of the cases demonstrated marked hypergammoglobulinemia, which is frequently reported in iMCD. Lymph node biopsies revealed atrophic germinal centers with enlarged nuclei of endothelial cells and proliferation of endothelial venules in interfollicular zone. 23 of 25 cases were treated initially with corticosteroids; 12 patients responded poorly and required further therapy. Three patients died during the observation period (median: 9 months) because of disease progression or infections. TAFRO syndrome is a unique subtype of iMCD that demonstrates characteristic clinicopathological findings. Further study to clarify prognosis, pathophysiology, and appropriate treatment is needed.

H. pylori eradication may reduce their risk of developing gastric cancer in patients with gastric ulcer. Large-scale studies in additional populations of this important international public-health issue are warranted.

A chloroform-methanol-extracted lipid of Helicobacter pylori was studied. Three kinds of glycolipids, accounting for about 25% (wt/wt) of the total lipid, were detected and identified to be cholesteryl glucosides. The structures of two of them were determined to be cholesteryl-␣-D-glucopyranoside and cholesteryl-6-O-tetradecanoyl-␣-D-glucopyranoside, and the plausible structure of the third one was identified as cholesteryl-6-Ophosphatidyl-␣-D-glucopyranoside. Cholesteryl glucosides are very rare in animals and bacteria. Furthermore, those in H. pylori had an ␣-glycosidic linkage, which is rather unusual for natural glycosides, and a phosphatelinked cholesteryl glycoside like the cholesteryl-6-O-phosphatidyl-␣-D-glucopyranoside has not been reported previously. As the cholesterol glucosides were detected in strains obtained from diverse geographical locations, the presence of cholesteryl glucosides in H. pylori is a very unique and a characteristic feature of the species. These findings add a new facet to the physiology and biochemistry, especially the cholesterol and glucose metabolism, of H. pylori. Furthermore, the cholesteryl glucosides of H. pylori showed hemolytic activities.Helicobacter pylori is a curved gram-negative bacterium which was first reported in 1983 (21, 35). The organism is now recognized as a primary cause of active chronic gastritis and is reported to be associated with peptic ulcer disease, gastric adenocarcinoma, and low-grade B-cell gastric lymphoma of mucosa-associated lymphoid tissue (4,14,36).The organism can colonize in and under the mucus layer of the human gastric mucosa without the copresence of other bacterial species. It, living in the unique gastric environment, is likely to have features distinct from other bacteria. Furthermore, it has been found to possess a unique urease having a very low K m value, which hydrolyzes urea efficiently even at the low urea concentration found in the gastric mucosa (13,24).On the other hand, the lipid composition of microorganisms can adapt in response to alterations of environmental conditions (15, 25), and those living in unique environments may have special lipids (5). It is likely that H. pylori living in the gastric niche may have a distinct lipid composition or structure. The fatty acid composition of H. pylori has been studied extensively (9, 10, 19), and it has been shown that the cellular fatty acids 3-OH C 16:0 and 3-OH C 18:0 are unique to this organism. However, little is known about the polar lipid composition of H. pylori.Therefore, we studied the lipid composition of H. pylori and detected three kinds of glycolipids, which were identified as cholesteryl glucosides (CGs). Additionally, the molecular structures of these CGs have been determined. MATERIALS AND METHODSBacterial strains and growth conditions. H. pylori NCTC 11638 was mainly used in this study. H. pylori ATCC 43504 and two clinical isolates of H. pylori obtained from Japan and Bangladesh were used for comparison. These were grown in brain heart infusion broth (Difco, D...

The grade of gastric atrophy was closely related to the development of gastric cancer after receiving H. pylori eradication therapy. Thus, eradication of H. pylori before the significant expansion of atrophy is most beneficial to prevent gastric cancer.

No abstract

ContextImmune checkpoint inhibitors, including anti–programmed cell death-1 (PD-1) antibodies, have become promising treatments for a variety of advanced malignancies. However, these medicines can cause immune-related adverse events (irAEs), including endocrinopathies.ObjectiveThis study examined the incidence of endocrine irAEs induced by nivolumab.Patients and Main Outcome MeasuredSixty-six patients treated with nivolumab at Nagoya University Hospital were prospectively evaluated for pituitary hormones, thyroid function, antithyroid antibodies (Abs), and glucose levels every 6 weeks after the initiation of nivolumab for 24 weeks.ResultsFour out of 66 patients developed destructive thyroiditis, and three patients developed hypothyroidism requiring levothyroxine replacement. The prevalence of positive anti-thyroglobulin Abs (TgAbs) and/or anti–thyroid peroxidase Abs (TPOAbs) at baseline was significantly higher in the group that developed destructive thyroiditis (3/4) compared with the group that did not develop thyroiditis (3/62; P = 0.002). There were no significant differences in other clinical variables between the groups. There were no endocrine irAEs other than destructive thyroiditis during the 24 weeks. The prevalence of TgAbs and/or TPOAbs at baseline was not associated with the development of other irAEs, including pneumonitis, colitis, or skin reactions.ConclusionsOur real-world data showed that destructive thyroiditis was an endocrine irAE that was frequently induced by nivolumab and was significantly associated with positive TgAbs and/or TPOAbs before treatment. Our findings indicate that evaluating these Abs before treatment may help identify patients with a high risk of thyroidal irAEs and may have important clinical benefit.