Effectiveness and safety of noninvasive positive pressure ventilation in the treatment of COVID-19-associated acute hypoxemic respiratory failure: a single center, non-ICU setting experience.

The role of noninvasive positive pressure ventilation (NIPPV) in COVID-19 patients with acute hypoxemic respiratory failure (AHRF) is uncertain, as no direct evidence exists to support NIPPV use in such patients. We retrospectively assessed the effectiveness and safety of NIPPV in a cohort of COVID-19 patients consecutively admitted to the COVID-19 general wards of a medium-size Italian hospital, from March 6 to May 7, 2020. Healthcare workers (HCWs) caring for COVID-19 patients were monitored, undergoing nasopharyngeal swab for SARS-CoV-2 in case of onset of COVID-19 symptoms, and periodic SARS-CoV-2 screening serology. Overall, 50 patients (mean age 74.6 years) received NIPPV, of which 22 (44%) were successfully weaned, avoiding endotracheal intubation (ETI) and AHRF-related death. Due to limited life expectancy, 25 (50%) of 50 NIPPV-treated patients received a "do not intubate" (DNI) order. Among these, only 6 (24%) were weaned from NIPPV. Of the remaining 25 NIPPV-treated patients without treatment limitations, 16 (64%) were successfully weaned, 9 (36%) underwent delayed ETI and, of these, 3 (33.3%) died. NIPPV success was predicted by the use of corticosteroids (OR 15.4, CI 1.79-132.57, p 0.013) and the increase in the PaO2/FiO2 ratio measured 24-48 h after NIPPV initiation (OR 1.02, CI 1-1.03, p 0.015), while it was inversely correlated with the presence of a DNI order (OR 0.03, CI 0.001-0.57, p 0.020). During the study period, 2 of 124 (1.6%) HCWs caring for COVID-19 patients were diagnosed with SARS-CoV-2 infection. Apart from patients with limited life expectancy, NIPPV was effective in a substantially high percentage of patients with COVID-19-associated AHRF. The risk of SARS-CoV-2 infection among HCWs was low.

Thromboembolic burden, prognostic assessment and outcomes of females compared to males in acute pulmonary embolism.

BACKGROUND: Literature lacks on sex differences in acute pulmonary embolism (PE). Therefore, the aim of our study was to provide information about sex difference in thromboembolic burden, prognostic assessment and outcomes of PE. MATERIALS AND METHODS: We analyzed and compared differences between females and males retrieving data of a multicenter, observational, retrospective, cohort study aimed to analyze characteristics of PE patients admitted in Internal Medicine wards of Tuscany, Italy. RESULTS: 272 (60.1%) of 452 patients enrolled in the study were females. Females were older than males (76.6 ± 12.0 vs. 73.5 ± 13.4 years, p = 0.0005). Mean length of hospital stay was longer in females (11.3 vs. 9.5 days, p = 0053). Reduced mobility was more frequent in females (46.3% vs. 35.5%, p = 0.0322), whereas COPD and active cancer were in males (20% vs. 9.9%, p = 0.0034, and 39.4% vs. 23.8%, p = 0.0004, respectively). Incidental diagnosis of PE was performed more often in males compared to females (19.3% vs. 11.4%, p = 0.0289). No sex difference was found in diagnostic approach, despite females underwent more often to legs ultrasonography compared to males (90.7% vs. 79.4%, p = 0.0008). Both all cause and PE-related mortality were higher in males (12.2 and 8.3% vs. 7.7 and 5.1%, respectively), despite difference was not significant. Females were found to have more likely central PE and distal deep vein thrombosis compared to males (57.7% vs. 43.8%, p = 0.0039, and 22.9% vs. 13.9%, p = 0.0206, respectively). None difference was found in shock index and median simplified PESI score between females and males, whereas according to 2008 ESC prognostic model females were more likely to be categorized at high or intermediate risk than in males (81.5% vs. 71.5%, p = 0.0159). Echocardiographic right heart dysfunction was found more often in females than in males (56.5% vs. 44%, p = 0.0124). No sex difference was found neither on acute treatment nor in prescription of vitamin K antagonists at hospital discharge. Bleeding events were significantly higher in females compared to males (4.7% vs. 0.5%, p = 0.0189). CONCLUSION: Understanding the difference between females and males is of utmost importance for physicians who manage acute PE in clinical practice. Females present major pulmonary thromboembolic burden, more frequently right heart dysfunction and treatment-related bleedings but lower in-hospital mortality than males. Our study could implicate that management of acute PE should be tailored according to sex. Prospective studies are warranted to better clarify this topic.

The role of osteoprotegerin (OPG) and estrogen receptor (ER-α) gene polymorphisms in rheumatoid arthritis.

Objective. Osteoclast activation at the cartilage pannus junction is an essential step in the destruction of bone matrix in patients affected by rheumatoid arthritis (RA). Receptor activator of NFkappaB ligand (RANK-L) is responsible for osteoclast differentiation and activation. Osteoprotegerin (OPG) is an alternative, high-affinity soluble receptor for RANK-L which significantly inhibits osteoclastogenesis. Estrogens and the specific receptors α and ß (ER-α and ER-α) are known to play an important role in the pathophysiology of osteoarthritis (OA). Scope of the present study is to investigate the role of ER-α and OPG gene polymorphisms in a group of women affected by RA.Materials and Methods. 139 consecutive RA patients (115 females and 34 males; median age 65.8 years) were selected. Bone mineral density (BMD) was measured by dual energy x-ray absorptinometry at the lumbar spine (LS-BMD) and femoral neck (FN-BMD) and the presence of bone erosions was evaluated by conventional X-ray. ER-α gene polymorphisms were determined by PvuII and XbaI restriction endonuclease digestion of polymerase chain reaction (PCR) products. By convention, the presence of the endonuclease restriction site was indicated with lowercase (p and x) letters while the absence of the restriction site was indicated with uppercase letters (P and X). OPG gene polymorphism was determined by RsaI restriction endonuclease digestion of PCR products and the presence and absence of restriction fragment was identified as TT and CC respectively.Results. Pearson's χ(2)analysis for the ER-α gene polymorphism showed a prevalence of Pp genotype (58%) (p=0.04) and Xx (54%) (p=0.04) in the total population, without differences between males and females. We did not observed any significant differences between ER-α genotypes and LS-BMD. However subjects with xx or pp genotype had a lower LS-BMD in comparison with the opposite genotype.For OPG gene polymorphism, non significant differences in the distribution of the genotypes were observed between males and females. In addition, we did not observed significant differences on LS-BMD between the genotypes.Finally, we observed that patients with ER-α pp genotype was significant more represented in patients with hand erosions (p = 0.05). No significant correlation was observed for ER-α XbaI genotype, however a trend characterized by a correlation between xx and hand erosions was observed (p = 0.13). For OPG gene polymorphism, we found a statistical correlation between C allele of OPG and hands bone erosions (p = 0.02).Conclusion. We found a significant association between ER-α and OPG gene polymorphisms and the presence of bone erosions in RA patients. These preliminary data suggest a role of ER-α and OPG gene polymorphisms in bone turnover and disease progression.

Arthritis and skin disease.

Skin lesions are frequently a harbinger of an underlying rheumatic disease or may be of great help in achieving the diagnosis of an underlying joint or connective tissue disease. For this reason, the evaluation of the skin is mandatory for the rheumatologist. In fact, the skin is the most accessible organ and often provides valuable diagnostic clues. Pattern recognition of skin lesions is based upon the type, configuration, distribution, and evolution of the lesions; selective laboratory techniques may further assist the diagnosis. This article focuses on the most relevant cutaneous disease in patients with rheumatic disease and emphasizes those characteristic features that will allow the clinician to identify cutaneous lesions that are commonly associated with musculoskeletal syndromes.

Immunology of cutaneous lupus erythematosus.

The cause and effect between ultraviolet light and cutaneous lupus erythematosus (CLE) is clear. In LE patients indeed, photosensitivity is one of the major diagnostic criteria of the systemic form of lupus erythematosus. This strong clinical association has led to the postulate that abnormal photosensitivity participates in the pathogenesis of cutaneous lesions in LE. What is not clear is how the ultraviolet radiation (UVR) induces cutaneous lesions in susceptible individuals despite the fact that profound effects of UVR on the cellular components of the skin have been extensively studied. The whole scenario is complicated by the relationship between sunlight and the cutaneous immune system. Pronounced effects of UVR on the cutaneous immune response further complicate the understanding of photosensitivity in LE. In addition, the network of cutaneous cytokines, chemokines, and adhesion molecules has become increasingly intricate, thus contributing to the genetic substrate of each individual, and to the tremendous complexity of the pathogenesis of CLE.

High prevalence of polymorphisms of angiotensin-converting enzyme (I/D) and endothelial nitric oxide synthase (Glu298Asp) in patients with systemic sclerosis.

PURPOSE: Systemic sclerosis is characterized by progressive microvascular occlusion and fibrosis and by an imbalance in the fibrinolytic system. In vivo and in vitro studies suggest that the renin-angiotensin system partly regulates vascular fibrinolytic balance. Angiotensin II increases the production and secretion of plasminogen activator inhibitor-1, while angiotensin-converting enzyme (ACE) contributes to reduced production of tissue plasminogen activator and endothelial nitric oxide synthesis by bradykinin degradation. The aim of our study was to investigate the effects of ACE insertion/deletion (I/D) and endothelial nitric oxide synthase (eNOS) Glu298Asp (G894-->T) and T-786-->C polymorphisms in patients with systemic sclerosis. SUBJECTS AND METHODS: We studied 73 consecutive patients (47 with limited and 26 with diffuse cutaneous systemic sclerosis) and 112 control subjects. ACE I/D and eNOS polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The ACE I/D and the eNOS G894-->T polymorphisms were more common in patients than in controls (for the ACE D allele: odds ratio [OR] = 3.4; 95% confidence interval [CI]: 1.5 to 7.9; P = 0.003; for the eNOS T allele: OR = 1.9; 95% CI: 1.0 to 3.4; P = 0.04). There was no association between the eNOS T-786-->C polymorphism and systemic sclerosis. CONCLUSIONS: Our findings of an increased risk of systemic sclerosis in ACE D and eNOS 894T allele carriers suggest that these polymorphisms may contribute to the pathogenesis of the disease.