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Dermatomyositis is a rare, autoimmune systemic disorder of unknown aetiology that presents as a constellation of clinical symptoms and signs primarily affecting skin and muscles. Patients with dermatomyositis can present with rare "non-canonical" manifestations. Focal or generalised oedema is an infrequent and often overlooked symptom of the disease, while spontaneous intramuscular haemorrhage is an even rarer and under-recognised, life-threatening complication that constitutes a medical emergency for clinical physicians. There are no known predisposing factors able to predict which patients will develop this complication and specific instructions considering treatment approach are currently lacking. Herein, we present a case of a patient with dermatomyositis complicated by both anasarca and spontaneous intramuscular haemorrhage. In order to raise awareness and timely diagnosis of such patients, we provide a review of the relevant literature and of the cases reported this far. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to determine whether the introduction of anti-SARS-CoV-2 vaccines and the dominance of the omicron variant had a significant impact on the outcome of COVID-19 in patients with systemic autoimmune rheumatic diseases (SAIRDs). Methods: Using data entered to the Greek Rheumatology Society COVID-19 registry, we investigated the incidence of hospitalization and death due to COVID-19, during the successive periods of the pandemic according to the prevalent strain (wild-type, Alpha, Delta, Omicron) in vaccinated and unvaccinated patients. Variables independently associated with hospitalization and death were explored using multivariate regression analyses, while Kaplan–Meier curves were used to depict survival data. Results: From August 2020 until June 30, 2022, 456 cases (70.2% females) of COVID-19 with a mean age (± SD) of 51.4 ± 14.0 years were reported. In unvaccinated patients, the proportions of hospitalization and death were 24.5% and 4%, compared to 12.5% and 0.8% in the vaccinated group (p < 0.001 for both comparisons). The rates of hospitalization for the wild-type, Alpha, Delta, and Omicron periods were 24.7%, 31.3%, 25.9%, and 8.1% respectively (p < 0.0001), while the case fatality rates were 2.7%, 4%, 7%, and 0%, respectively (p = 0.001). Using multivariable regression analysis, factors independently associated with hospitalization were infection by a non-Omicron variant, being non-vaccinated, exposure to rituximab, older age, and respiratory and cardiovascular disease. Independent predictors for death were contracting COVID-19 during the Alpha or Delta period, pulmonary disease, and older age, while being vaccinated was protective. Conclusions: In this 2-year analysis, the rates of hospitalization and death among patients with SAIRDs have declined significantly. Vaccination and the dominance of the Omicron variant appear to be the major determinants for this shift. Key points • During the late phase of the pandemic, the proportion of severe COVID-19 cases, defined as requiring hospitalization or resulting in death, in patients with systemic autoimmune rheumatic diseases has declined. • Anti-SARS-CoV-2 vaccination and the dominance of the Omicron strain are the key factors that have independently contributed to this shift. [ABSTRACT FROM AUTHOR]

Patients with familial mediterranean fever (FMF) often present with musculoskeletal involvement typical of spondyloarthropathy (SpA) or ankylosing spondylitis (AS), posing a diagnostic challenge for medical practitioners and leading to the description of the FMF-related SpA/AS clinical spectrum. Currently, the available data focuses on SpA diagnosis in patients with known FMF, while the contrary is rarely reported in the medical literature. We describe an unusual case of concomitant FMF diagnosis in a patient with an eight-year long history of typical, human leukocyte antigen-B27 positive AS on adalimumab treatment, who presented with recurrent febrile attacks and abdominal pain. The laboratory work-up revealed high titres of serum amyloid A while genetic testing was positive for the pathogenic M694V heterozygous variant in the MEFV gene. The patient was promptly treated with colchicine, showing complete remission of clinical symptoms and normalisation of inflammatory markers to date. We also performed a review of the available literature elaborating on the interrelationship of AS and FMF in terms of pathogenesis and clinical characteristics. Our case highlights the need for reporting of similar cases and further explores the association of AS and FMF as distinct clinical entities or as constituents of the same disease continuum model. [ABSTRACT FROM AUTHOR]

Objective: To describe the rate and type of adverse effects (AEs) and the frequency of disease flares after COVID-19 vaccination and to assess the reasons for vaccination hesitancy (non-vaccination) in SRD patients. Methods: Telephone interviews were conducted of SRD patients consecutively enrolled (15/06/2021–1/7/2021). Participants were asked about the type of AEs and disease flare after vaccination. Reasons for vaccination hesitancy were recorded. Univariate and mutivariable analyses examined associations of demographic, clinical and other features, with occurrence of AEs, disease flare and non-vaccination. For the latter, association with negative vaccination behaviour (not influenza vaccinated for the last 2 years) and nocebo-prone behaviour (denoting AEs attributed to negative expectations [Q-No questionnaire]) was also tested. Results: 561 out of 580 contacted patients were included in the study. 441/561 (78.6%) patients were vaccinated [90% (Pfizer, Moderna), 10% (Astra-Zeneca)]. AEs were reported by 148/441 (33.6%), with rates being comparable between the three vaccines. AEs were more common in females and those with chronic obstructive pulmonary disease [OR, 95% CI; females: 2.23 (1.30–3.83); COPD: 3.31 (1.24–8.83)]. Disease flare was reported in 9/441 (2%) patients. For those unvaccinated, fear that the vaccine would be harmful (53.3%), could cause disease flare (24.2%) and/or could cause thrombosis (21.7%) were the main reasons to do so. Multivariable analysis identified as independent variables for non-vaccination: nocebo-prone behaviour (OR; 95% CI, 3.88; 1.76–8.55), negative vaccination behaviour (6.56; 3.21–13.42) and previous COVID-19 infection (2.83; 1.13–7.05). Higher educational status was protective (0.49; 0.26–0.92). Conclusion: No new safety signals for COVID-19 vaccination were observed. Vaccination campaign should target SRD patients with nocebo-prone and negative influenza vaccination behaviour. [ABSTRACT FROM AUTHOR]

To assess non-compliance and potential changes in seasonal flu vaccination coverage before and during the Covid-19 pandemic in patients with autoimmune rheumatic diseases (ARDs). Consecutive patients with ARDs followed-up in 2 tertiary hospitals were telephone-interviewed (December 12–30, 2020) regarding seasonal flu vaccination during the 2019/20 and 2020/21 time periods. Self-reported disease flares that occurred after flu vaccination, as well as reasons for non-vaccination were recorded. One thousand fifteen patients were included. The rate of flu vaccination increased from 76% before to 83% during the COVID-19 pandemic (p = 0.0001). The rate of self-reported disease flares was < 1% among vaccinated patients. Reasons for not vaccination in both periods, respectively, included: 'was not recommended by their rheumatologists' (35.0vs.12.2%, p < 0.0001), 'did not feel that they would have any benefit' (36.9 vs. 32.6%), felt unsafe to do so (27.5 vs. 30.2%), or other reasons (18.9 vs. 23.8%). By multivariate analysis, age [OR = 1.03 (95% CI 1.02–1.04)] vs. [1.04 (95% CI 1.02–1.05)] and treatment with biologics [OR = 1.66 (95% CI 1.22–2.24) vs. [1.68 (95% CI 1.19–2.38)] were independent factors associated with vaccination in both periods. These findings, although are temporally encouraging, emphasize the need for continuous campaigns aiming at increasing patients' and physicians' awareness about the benefits of vaccination. [ABSTRACT FROM AUTHOR]

Background: Acute cholecystitis is a life-threatening emergency in elderly patients. This population-based cohort study aimed to evaluate the commonly used management strategies for elderly patients with acute cholecystitis as well as resulting mortality and re-admission rates.Methods: Data from all consecutive elderly patients (≥ 80 years) admitted with acute cholecystitis in England from 1997 to 2012 were captured from the Hospital Episode Statistics database. Influence of management strategies upon mortality was analyzed with adjustment for patient demographics and treatment year.Results: 47,500 elderly patients were admitted as an emergency with acute cholecystitis. On the index emergency admission the majority of patients (n = 42,620, 89.7%) received conservative treatment, 3539 (7.5%) had cholecystectomy, and 1341 (2.8%) underwent cholecystostomy. In the short term, 30-day mortality was increased in the emergency cholecystectomy group (11.6%) compared to those managed conservatively (9.9%) (p < 0.001). This was offset by the long-term benefits of cholecystectomy with a reduced 1-year mortality [20.8 vs. 27.1% for those managed conservatively (p < 0.001)]. Management with percutaneous cholecystostomy had increased 30-day and 1-year mortality (13.4 and 35.0%, respectively). The annual proportion of cholecystectomies performed laparoscopically increased from 27% in 2006 to 59% in 2012. Within the cholecystectomy group, laparoscopic approach was an independent predictor of reduced 30-day mortality (OR 0.16, 95% CI 0.10-0.25). Following conservative management, there were 16,088 admissions with further cholecystitis. Only 11% of patients initially managed conservatively or with cholecystostomy received subsequent cholecystectomy.Conclusion: Acute cholecystitis is associated with significant mortality in elderly patients. Potential benefits of emergency cholecystectomy in selected elderly patients include reduced rate of readmissions and 1-year mortality. Laparoscopic approach for emergency cholecystectomy was associated with an 84% relative risk reduction in 30-day mortality compared to open surgery. [ABSTRACT FROM AUTHOR]

Background: Over the past 14 years, we have used different malabsorptive bariatric operations to treat super-obesity. We compared the efficacy and safety of our preferred procedure for the last 8 years with previous methods used in super-obese. Methods: Our first procedure was distal Roux-en-Y gastric bypass (distal RYGBP) (gastric pouch 15 ± 5 mL, 80 cm biliopancreatic limb, 100 cm common limb [CL]). The second was distal RYGBP with short alimentary limb (distal RYGBP-sAL) (gastric pouch 15 ± 10 mL, alimentary limb [AL] 250 cm, CL 100 cm). Our preferred procedure for the past 8 years has been biliopancreatic diversion with RYGB and long limbs (BPD-RYGB-LL) (gastric pouch 40 ± 10 mL, AL 400 cm, CL 100 cm). Results: Seventy-five patients underwent distal RYGBP, 44 distal RYGBP-sAL, and 841 BPD-RYGB-LL. Eight years postoperatively, the mean BMIs were 39.0, 29.4, and 29.2, respectively. The greatest reduction of 47.6% was achieved with BPD-RYGB-LL (distal RYGBP 30.6%; distal RYGBP-sAL 43.1%). Mean excess weight loss was 51.3% for distal RYGBP, 76.5% for distal RYGBP-sAL, and 80.9% for BPD-RYGB-LL. Six patients died at the early postoperative period. Sixteen patients died during the first eight postoperative years, of whom significantly more were after distal RYGBP-sAL ( P = 0.0003). Complications were significantly more frequent after distal RYGBP-sAL ( P = 0.001). All procedures led to rapid and sustained resolution of major comorbidities in almost all patients affected. Metabolic and nutritional deficiencies were similar and manageable. Conclusions: Our variant of biliopancreatic diversion (BPD-RYGB-LL) results in substantial and sustained weight loss in super-obese, without compromising safety. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is currently the gold standard bariatric procedure for the treatment of morbid obesity. Laparoscopic sleeve gastrectomy (LSG) is a relatively innovative procedure which has been increasingly applied lately as a sole bariatric procedure. A randomized trial was conducted in a Greek population to evaluate perioperative safety and 3-years results. Methods: Sixty patients with body mass index (BMI) ≤ 50 Kg/m were randomized to LRYGB or LSG. Patients were monitored for 3 years postoperatively and throughout the study period weight loss, in terms of percent excess weight loss (%EWL), early and late complications, improvement of obesity related comorbidities and nutritional deficiencies were compared between groups. Results: There was no death in either group and there was no significant difference in early (10% after LRYGB and 13% after LSG, P > 0.05) and late morbidity (10% in each group). Weight loss was significantly better after LSG in the first years of the study and at 3 years %EWL reached 62% after LRYGB and 68% after LSG ( p = 0.13). There was no significant difference in the overall improvement of comorbidities. Nutritional deficiencies occurred at the same rate in the two groups except to vitamin B deficiency which was more common after LRYGB ( P = 0.05). Conclusion: LSG and LRYGB are equally safe and effective in the amelioration of comorbidities, while LSG is associated with fewer postoperative metabolic deficiencies, without the need of supplementation. Furthermore, LSG is a promising bariatric procedure, equally effective to LRYGB at 3 years follow up on weight reduction. [ABSTRACT FROM AUTHOR]

Background: The International Subarachnoid Aneurysm Trial (ISAT) concluded that “there is currently no reason to doubt that the reduction of dependent survival or death after endovascular coiling seen in all patients in the ISAT cohort should not be valid in the elderly”. We feel that this generalization requires further investigation to assess its validity. Methods: We studied the impact of treatment era and independent risk factors for outcome in 179 consecutive elderly (≥70 years) aneurysmal subarachnoid hemorrhage (aSAH) patients admitted to Kuopio University Hospital either between 1983 and 1992 (Era I, n = 56), prior to the introduction of endovascular management, or between 1995 and 2004 (Era II, n = 123) when the endovascular treatment was established at our institute. Altogether 150 patients underwent occlusive aneurysm treatment, 47 clipping in the Era I as against 49 clipping, 49 endovascular therapy, and five combination therapy in the Era II. Results: The 12-month survival ( n = 179) did not improve from the Era I to the Era II. The proportion of good outcome (GOS IV–V) after occlusive therapy ( n = 150) was equal in the Era I and Era II ( n = 27/47; 57% vs. n = 56/103; 54%). In multivariate logistic regression analysis, independent predictors of poor outcome were age, poor grade (Hunt&Hess IV–V), hydrocephalus, hypertension, and intraventricular hemorrhage, but not the mode of occlusive therapy (microsurgical vs. endovascular) Conclusion: Clinical severity of the SAH was the most significant predictor of outcome. Integration of coil treatment in clinical practice has not improved the overall outcome of aSAH in the elderly at our institute. [ABSTRACT FROM AUTHOR]

Increased activity of CYP2E1 has been associated with increased risk of chemically-mediated cancers, through enhanced activation of a variety of procarcinogens. In this context, inhibition of CYP2E1 is potentially of significance in xenobiotic toxicity. The aim of the present study was to test the hypothesis that quinacrine inhibits hepatic CYP2E1. For this purpose, disulfiram (75 mg/kg i.p) as an inhibitor and isoniazid (100 mg/kg i.p) as an inducer of CYP2E1, as well as quinacrine (50 mg/kg i.p) were administered to Wistar rats and the hepatic activity of CYP2E1 was measured. The expression of CYP2E1 was further assessed by Western blot analysis. As expected, disulfiram inhibited, while isoniazid induced the activity and expression of the enzyme. Interestingly, treatment with quinacrine resulted in a significant decrease of CYP2E1 activity and expression. To investigate any similarities in the inhibition of CYP2E1 by quinacrine and disulfiram, molecular modeling techniques were adopted and revealed that quinacrine molecule anchors inside the same binding pocket of the protein where disulfiram is also attached. Finally, as assessed by the sister chromatid exchanges (SCE) assay, quinacrine was demonstrated to reduce the mutagenic effects of the tobacco-specific N-nitrosamine 4-(methyl nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which is known to be converted to active mutagen in the liver principally through CYP2E1. We suggest that these antimutagenic effects of quinacrine could be possibly attributed, at least in part, to its ability to block the bioactivation of NNK, mainly by the inhibition of CYP2E1. Our results, even preliminary, indicate that quinacrine as an inhibitor of CYP2E1 might be protective against chemically-induced toxicities such as NNK-induced mutagenicity. [ABSTRACT FROM AUTHOR]

The sensitivity of breast neoplasms to hormonal control provides the basis of novel investigational treatments with steroidal alkylators. An androsterone D-lactam steroidal ester, the 3β-hydroxy-13α-amino-13,17-seco- 5α-androstan-17-oic-13,17-lactam, p-bis(2-chloroethyl)amino phenyl acetate (lactandrate) was synthesized and tested for antitumor activity against six human breast cancer cell lines in vitro and against two murine and one xenograft mammary tumors in vivo. A docking study on the binding interactions of lactandrate with the ligand-binding domain (LBD) of estrogen receptor-alpha (ERα) was inquired. In vitro testing of lactandrate cytostatic and cytotoxic activity was performed on T47D, MCF7, MDA-MB-231, BT-549, Hs578T, MDA-MB-435 breast adenocarcinoma human cell lines. In vivo testing was performed on two murine mammary tumors, the MXT tumor and CD8F1 adenocarcinoma, as well as on human mammary carcinoma MX-1 xenograft. Molecular modeling techniques were adopted to predict a possible location and interaction mode of the molecule into LBD. Lactandrate induced significantly high antitumor effect against all tested in vitro and in vivo models. The cell lines with positive ER expression found to be significantly more sensitive to lactandrate. Moreover, lactandrate found to be positioned inside the binding cavity with its steroidal moiety, whilst the alkylating moiety protrudes out of receptor’s pocket. Lactandrate produced important anticancer activity on breast cancer in vitro and in vivo. Some correlation between ER and lactandrate effect was demonstrated. Docking studies provide the basis for the structure-based design of improved steroidal alkylating esters for the treatment of estrogen-related cancers. [ABSTRACT FROM AUTHOR]