Hospitalization Rates, Prevalence of Cardiovascular Manifestations, and Outcomes Associated With Sarcoidosis in the United States

Background: Recent trends of hospitalizations and in‐hospital mortality are not well defined in sarcoidosis. We examined aforementioned trends and prevalence of cardiovascular manifestations and explored rates of implantable cardioverter‐defibrillator implantation in hospitalizations with sarcoidosis. Methods and Results: Using data from the National Inpatient Sample, a retrospective population cohort from 2005 to 2014 was studied. To identify sarcoidosis, an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD‐9‐CM) diagnosis code was used. We excluded hospitalizations with myocardial infarction, coronary artery disease, and ischemic cardiomyopathy. Cardiovascular manifestations were defined by the presence of diagnosis codes for conduction disorders, arrhythmias, heart failure, nonischemic cardiomyopathy, and pulmonary hypertension. A total of 609 051 sarcoidosis hospitalizations were identified, with an age of 55±14 years, 67% women, and 50% black. The number of sarcoidosis hospitalizations increased from 2005 through 2014 (138 versus 175 per 100 000, P trend<0.001). We observed declining trends of unadjusted in‐hospital mortality (6.5 to 4.9 per 100 sarcoidosis hospitalizations, P trend<0.001). Overall ≈31% (n=188 438) of sarcoidosis hospitalizations had coexistent cardiovascular manifestations of one or more type. Heart failure (≈16%) and arrhythmias (≈15%) were the most prevalent cardiovascular manifestations. Rates of implantable cardioverter‐defibrillator placement were ≈7.5 per 1000 sarcoidosis hospitalizations (P trend=0.95) during the study period. Black race was associated with 21% increased risk of in‐hospital mortality (odds ratio, 1.21; 95% confidence interval, 1.16–1.27 [P<0.001]). Conclusions: Sarcoidosis hospitalizations have increased over the past decade with a myriad of coexistent cardiovascular manifestations. Black race is a significant predictor of in‐hospital mortality, which is declining. Further efforts are needed to improve care in view of low implantable cardioverter‐defibrillator rates in sarcoidosis

Imaging Electronic Correlations in Twisted Bilayer Graphene near the Magic Angle

Twisted bilayer graphene with a twist angle of around 1.1{\deg} features a pair of isolated flat electronic bands and forms a strongly correlated electronic platform. Here, we use scanning tunneling microscopy to probe local properties of highly tunable twisted bilayer graphene devices and show that the flat bands strongly deform when aligned with the Fermi level. At half filling of the bands, we observe the development of gaps originating from correlated insulating states. Near charge neutrality, we find a previously unidentified correlated regime featuring a substantially enhanced flat band splitting that we describe within a microscopic model predicting a strong tendency towards nematic ordering. Our results provide insights into symmetry breaking correlation effects and highlight the importance of electronic interactions for all filling factors in twisted bilayer graphene.Comment: Main text 9 pages, 4 figures; Supplementary Information 25 page

Second-line FOLFOX chemotherapy versus active symptom control for advanced biliary tract cancer (ABC-06): a phase 3, open-label, randomised, controlled trial

Background Advanced biliary tract cancer has a poor prognosis. Cisplatin and gemcitabine is the standard first-line chemotherapy regimen, but no robust evidence is available for second-line chemotherapy. The aim of this study was to determine the benefit derived from second-line FOLFOX (folinic acid, fluorouracil, and oxaliplatin) chemotherapy in advanced biliary tract cancer. Methods The ABC-06 clinical trial was a phase 3, open-label, randomised trial done in 20 sites with expertise in managing biliary tract cancer across the UK. Adult patients (aged ≥18 years) who had histologically or cytologically verified locally advanced or metastatic biliary tract cancer (including cholangiocarcinoma and gallbladder or ampullary carcinoma) with documented radiological disease progression to first-line cisplatin and gemcitabine chemotherapy and an Eastern Cooperative Oncology Group performance status of 0–1 were randomly assigned (1:1) centrally to active symptom control (ASC) and FOLFOX or ASC alone. FOLFOX chemotherapy was administered intravenously every 2 weeks for a maximum of 12 cycles (oxaliplatin 85 mg/m2, L-folinic acid 175 mg [or folinic acid 350 mg], fluorouracil 400 mg/m2 [bolus], and fluorouracil 2400 mg/m2 as a 46-h continuous intravenous infusion). Randomisation was done following a minimisation algorithm using platinum sensitivity, serum albumin concentration, and stage as stratification factors. The primary endpoint was overall survival, assessed in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. The study is complete and the final results are reported. This trial is registered with ClinicalTrials.gov, NCT01926236, and EudraCT, 2013-001812-30. Findings Between March 27, 2014, and Jan 4, 2018, 162 patients were enrolled and randomly assigned to ASC plus FOLFOX (n=81) or ASC alone (n=81). Median follow-up was 21·7 months (IQR 17·2–30·8). Overall survival was significantly longer in the ASC plus FOLFOX group than in the ASC alone group, with a median overall survival of 6·2 months (95% CI 5·4–7·6) in the ASC plus FOLFOX group versus 5·3 months (4·1–5·8) in the ASC alone group (adjusted hazard ratio 0·69 [95% CI 0·50–0·97]; p=0·031). The overall survival rate in the ASC alone group was 35·5% (95% CI 25·2–46·0) at 6 months and 11·4% (5·6–19·5) at 12 months, compared with 50·6% (39·3–60·9) at 6 months and 25·9% (17·0–35·8) at 12 months in the ASC plus FOLFOX group. Grade 3–5 adverse events were reported in 42 (52%) of 81 patients in the ASC alone group and 56 (69%) of 81 patients in the ASC plus FOLFOX group, including three chemotherapy-related deaths (one each due to infection, acute kidney injury, and febrile neutropenia). The most frequently reported grade 3–5 FOLFOX-related adverse events were neutropenia (ten [12%] patients), fatigue or lethargy (nine [11%] patients), and infection (eight [10%] patients). Interpretation The addition of FOLFOX to ASC improved median overall survival in patients with advanced biliary tract cancer after progression on cisplatin and gemcitabine, with a clinically meaningful increase in 6-month and 12-month overall survival rates. To our knowledge, this trial is the first prospective, randomised study providing reliable, high-quality evidence to allow an informed discussion with patients of the potential benefits and risks from second-line FOLFOX chemotherapy in advanced biliary tract cancer. Based on these findings, FOLFOX should become standard-of-care chemotherapy in second-line treatment for advanced biliary tract cancer and the reference regimen for further clinical trials. Funding Cancer Research UK, StandUpToCancer, AMMF (The UK Cholangiocarcinoma Charity), and The Christie Charity, with additional funding from The Cholangiocarcinoma Foundation and the Conquer Cancer Foundation Young Investigator Award for translational research

Rheumatoid Arthritis Disease Activity Index-5: an easy and effective way of monitoring patients with rheumatoid arthritis

Objective To study the utility of the Rheumatoid Arthritis Disease Activity Index-5 (RADAI-5) as a valid tool for daily rheumatoid arthritis (RA) monitoring and to compare its predictability to assess RA activity with respect to Disease Activity Score 28 (DAS28) and Clinical Disease Activity Index (CDAI). Patients and methods A total of 100 patients with RA (diagnosed as per American College of Rheumatology 1987 criteria) were enrolled in the study group. Each patient was assessed two times with 3-month interval for disease activity (DA) using DAS28, CDAI, and RADAI-5. Spearman’s correlation coefficient (ρ) for correlation and kappa for agreement between different activity measures were assessed. Results In our study group, 19% patients were men and 81% patients were women, with male to female ratio of 1 : 4.3. Their mean age was 44.4±11.8 years, and their mean disease duration was 67.5±59.8 months. On initial visit, that is, baseline, mean DA as per RADAI-5, DAS28, and CDAI were 5.14±2.17, 5.58±1.55, and 27.96±15.46, respectively, and on follow-up visit, the readings were 3.76±1.92, 4.54±1.41, and 17.67±12.46, respectively. The mean changes in DA at follow-up visit were −1.37±2.15 by RADAI-5, −1.04±1.58 by DAS28, and −10.29±15.75 by CDAI. Changes in DA indices correlated significantly with each other with ρ ranging from 0.8 to 0.9 (P<0.001). An average agreement was found among all three measures at different DA level. Conclusion RADAI-5 seems to be an effective tool with high tendency to assess the changes in RA DA in routine patient care in hospital settings as well as in home-based settings

Second-line FOLFOX chemotherapy for advanced biliary tract cancer - Authors' reply.

From PubMed via Jisc Publications RouterHistory: received 2021-06-07, accepted 2021-06-08Publication status: ppublis