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The etiology of systemic sclerosis (SSc) remains unknown; however, several occupational and environmental factors have been implicated. Our objective was to perform a meta-analysis of all studies published on SSc associated with occupational and environmental exposure. The review was undertaken by means of MEDLINE and SCOPUS from 1960 to 2014 and using the terms: “systemic,” “scleroderma,” or “systemic sclerosis/chemically induced” [MesH]. The Newcastle-Ottawa Scale was used for the qualifying assessment. The inverse variance-weighted method was performed. The meta-analysis of silica exposure included 15 case-control studies [overall OR 2.81 (95%CI 1.86–4.23; p  < 0.001)] and 4 cohort studies [overall RR 17.52 (95%CI 5.98–51.37; p  < 0.001)]; the meta-analysis of solvents exposure included 13 case-control studies (overall OR 2.00 [95%CI 1.32–3.02; p  = 0.001); the meta-analysis of breast implants exposure included 4 case-control studies (overall OR 1.68 (95%CI 1.65–1.71; p  < 0.001)) and 6 cohort studies (overall RR 2.13 (95%CI 0.86–5.27; p  = 0.10)); the meta-analysis of epoxy resins exposure included 4 case-control studies (overall OR 2.97 (95%CI 2.31–3.83; p  < 0.001)), the meta-analysis of pesticides exposure included 3 case-control studies (overall OR 1.02 (95%CI 0.78–1.32; p  = 0.90)) and, finally, the meta-analysis of welding fumes exposure included 4 studies (overall OR 1.29 (95%CI 0.44–3.74; p  = 0.64)). Not enough studies citing risks related to hair dyes have been published to perform an accurate meta-analysis. Silica and solvents were the two most likely substances related to the pathogenesis of SSc. While silica is involved in particular jobs, solvents are widespread and more people are at risk of having incidental contact with them.

Abstract BackgroundIt is important to predict which patients infected by SARS-CoV-2 are at higher risk of life-threatening COVID-19. Several studies suggest that neutralizing auto-antibodies (auto-Abs) against type I interferons (IFNs) are predictive of critical COVID-19 pneumonia.ObjectivesWe aimed to test for auto-Abs to type I IFN and describe the main characteristics of COVID-19 patients admitted to intensive care depending on whether or not these auto-Abs are present.MethodsRetrospective analysis of all COVID-19 patients admitted to an intensive care unit (ICU) in whom samples were available, from March 2020 to March 2021, in Barcelona, Spain.ResultsA total of 275 (70.5%) out of 390 patients admitted to ICU were tested for type I IFNs auto-antibodies (α2 and/or ω) by ELISA, being positive in 49 (17.8%) of them. Blocking activity of plasma diluted 1/10 for high concentrations (10 ng/mL) of IFNs was proven in 26 (9.5%) patients. Almost all the patients with neutralizing auto-Abs were men (92.3%). ICU patients with positive results for neutralizing IFNs auto-Abs did not show relevant differences in demographic, comorbidities, clinical features, and mortality, when compared with those with negative results. Nevertheless, some laboratory tests (leukocytosis, neutrophilia, thrombocytosis) related with COVID-19 severity, as well as acute kidney injury (17 [65.4%] vs. 100 [40.2%]; p = 0.013) were significantly higher in patients with auto-Abs.ConclusionAuto-Abs neutralizing high concentrations of type I IFNs were found in 9.5% of patients admitted to the ICU for COVID-19 pneumonia in a hospital in Barcelona. These auto-Abs should be tested early upon diagnosis of SARS-CoV-2 infection, as they account for a significant proportion of life-threatening cases.

Purpose To assess the prevalence of urgent hospitalization due to adverse drug reactions (ADRs) in patients aged ≥65 years, to compare the in-hospital mortality rates between patients admitted for ADRs and those admitted for other causes, and to describe the ADRs, the used and suspected drugs, and the drug-reaction associations. Methods A cross-sectional study was conducted by using the institutional database of the Pharmacovigilance Programme of Bellvitge University Hospital, a 750-bed tertiary care hospital, with information corresponding to a 7-year period. ADR-related admissions of patients aged ≥65 years prospectively identified through a systematic daily review of all admission diagnosis were reviewed. Results ADRs were suspected to be the main reason for urgent admission in 1976 out of 60,263 patients aged ≥65 years (prevalence of ADR-related hospitalization 3.3 % [95 % CI 3.1–3.4 %]). The crude in-hospital mortality rate was 10.2 % in patients with ADR-related admission and 9 % in patients admitted for other causes ( p  = 0.077). Most patients (86 %) were exposed to polypharmacy, and a drug-drug interaction was suspected in 49 % of cases. The most frequent drug-reaction associations were acute renal failure related to renin-angiotensin system inhibitors, gastrointestinal bleeding caused by antithrombotics and/or non-steroidal anti-inflammatories, and intracranial bleeding induced by vitamin K antagonists. Conclusions One out of every 30 urgent admissions of patients aged ≥65 years is ADR-related. These ADRs can be as serious and life-threatening as any other acute pathology that merits urgent hospital admission. Most cases involve patients exposed to polypharmacy and result from well-known reactions of a few commonly used drugs.

IntroductionLoss-of-function TLR7 variants have been recently reported in a small number of males to underlie strong predisposition to severe COVID-19. We aimed to determine the presence of these rare variants in young men with severe COVID-19.MethodsWe prospectively studied males between 18 and 50 years-old without predisposing comorbidities that required at least high-flow nasal oxygen to treat COVID-19. The coding region of TLR7 was sequenced to assess the presence of potentially deleterious variants.ResultsTLR7 missense variants were identified in two out of 14 patients (14.3%). Overall, the median age was 38 (IQR 30-45) years. Both variants were not previously reported in population control databases and were predicted to be damaging by in silico predictors. In a 30-year-old patient a maternally inherited variant [c.644A>G; p.(Asn215Ser)] was identified, co-segregating in his 27-year-old brother who also contracted severe COVID-19. A second variant [c.2797T>C; p.(Trp933Arg)] was found in a 28-year-old patient, co-segregating in his 24-year-old brother who developed mild COVID-19. Functional testing of this variant revealed decreased type I and II interferon responses in peripheral mononuclear blood cells upon stimulation with the TLR7 agonist imiquimod, confirming a loss-of-function effect.ConclusionsThis study supports a rationale for the genetic screening for TLR7 variants in young men with severe COVID-19 in the absence of other relevant risk factors. A diagnosis of TLR7 deficiency could not only inform on treatment options for the patient, but also enables pre-symptomatic testing of at-risk male relatives with the possibility of instituting early preventive and therapeutic interventions.

Background Comorbidity is related to poor health results in chronic heart failure (HF). Aims The purpose of the study was to assess whether a high Charlson Comorbidity Index score (CCI) relates to 1 year mortality after a first hospitalization for acute HF (AHF). Methods We reviewed the medical records of 897 patients > 65 years of age admitted within a two-year period because of a first episode of AHF. We analyzed two groups: low (CCI ≤ 2) and high (CCI > 2) comorbidity. Results Patients’ mean CCI was 2.2 ± 1.7; 344 patients (38.35%) had a CCI > 2. 1-year all-cause mortality rate in the high comorbidity group was 32.6%, worse than that among low comorbidity group patients (23.7%, p  = 0.002). Cox multivariate analysis identified a CCI > 2 as an independent risk factor for 1-year mortality ( p  = 0.002; HR: 1.525; CI 95% 1.161–2.003), along with older age, history of arterial hypertension, and higher admission heart rate and serum potassium values. Analyzing CCI as a continuous variable, the association remained is also significant ( p  = 0.0001; HR 1.145; CI 95% 1.069–1.854). Conclusions Higher global comorbidity (CCI > 2) at the time of a first hospitalization because of AHF is an independent predictor of mid-term post-discharge mortality among elderly HF patients.

A higher incidence of thrombotic events, mainly pulmonary embolism (PE), has been reported in hospitalized patients with COVID-19. The main objective was to assess clinical and laboratory differences in hospitalized COVID-19 patients according to occurrence of PE. This retrospective study included all consecutive patients hospitalized with COVID-19 who underwent a computed tomography (CT) angiography for PE clinical suspicion. Clinical data and median blood test results distributed into weekly periods from COVID-19 symptoms onset, were compared between PE and non-PE patients. Ninety-two patients were included, 29 (32%) had PE. PE patients were younger (63.9 (SD 13.7) vs 69.9 (SD 12.5) years). Clinical symptoms and COVID-19 CT features were similar in both groups. PE was diagnosed after a mean of 20.0 (SD 8.6) days from the onset of COVID-19 symptoms. Corticosteroid boluses were more frequently used in PE patients (62% vs. 43%). No patients met ISTH DIC criteria. Any parameter was statistically significant or clinically relevant except for D-Dimer when comparing both groups. Median values [IQR] of D-dimer in PE vs non-PE patients were: week 2 (2010.7 [770.1-11208.9] vs 626.0 [374.0-2382.2]; p = 0.004); week 3 (3893.1 [1388.2-6694.0] vs 1184.4 [461.8-2447.8]; p = 0.003); and week 4 (2736.3 [1202.1-8514.1] vs 1129.1 [542.5-2834.6]; p = 0.01). Median fold-increase of D-dimer between week 1 and 2 differed between groups (6.64 [3.02-23.05] vs 1.57 [0.64-2.71], p = 0.003); ROC curve AUC was 0.879 (p = 0.003) with a sensitivity and specificity for PE of 86% and 80%, respectively. Among hospitalized COVID-19 patients, D-dimer levels are higher at weeks 2, 3 and 4 after COVID-19 symptom onset in patients who develop PE. This difference is more pronounced when the fold increase between weeks 1 and 2 is compared.

Background Lymphopenia is a common finding in elderly patients and its relevance is unknown. Aims To evaluate the clinical prognostic value of lymphopenia on the admission of elderly hospitalized patients. Methods From 2012 to 2013, all consecutive patients >75 hospitalized because of medical conditions were prospectively included in the study. Sociodemographic, clinical and laboratory data were collected. Lymphopenia was considered by a plasmatic lymphocyte count of <1100 × 10 9 /l. Hospital length of stay, in-hospital mortality and mortality after a 1-year follow-up were assessed. Results The total sample consisted of 180 patients, 90 of whom were females (50 %). Mean age was 83.8 years (SD 5.4). Lymphopenia was present in 45 patients (25 %) upon admission. When compared, those patients with lymphopenia showed a longer hospital stay (19.9 vs. 15.7 days; p 0.002) and higher in-hospital mortality (26.7 vs 7.7 %; p 0.001). The odds ratio for in-hospital mortality in patients with lymphopenia was 3.9 ( p 0.03) and the hazard ratio for 1-year mortality 1.9 ( p 0.038). Both groups of elderly patients, with and without lymphopenia on admission, showed no differences related to sociodemographic, clinical, or other laboratory data. The study showed no difference in rate of infections between the groups. Conclusion A quarter of our elderly hospitalized patients had lymphopenia on admission. Furthermore, lymphopenia seemed to constitute as a predictor for bad outcome in terms of a longer hospital stay, in-hospital mortality and 1-year mortality after discharge.

Anemia is a risk factor related to morbidity and mortality in patients with chronic heart failure (HF). Less is known about its influence in patients in an early stage of HF. Our aim is to investigate the prognostic role of anemia in patients initially hospitalized for acute HF. We reviewed all consecutive patients admitted within a 18-month period with a main diagnosis of acute HF. We collected demographic, clinical and treatment data. Anemia is defined as Hemoglobin <12/13 g/dL upon admission in female/male patients, respectively. 719 patients were included (55.5% female), with a mean age of 78.7 ± 9 years. Anemia was present in 59.6% of patients upon admission, with a mean Hb of 10.4 ± 1.4 g/dL. Multivariate analysis confirms the relationship between the presence of anemia and older age, a previous diagnostic history of diabetes, and the presence of chronic kidney disease. In-hospital mortality is similar for anemic and non-anemic patients (6.8 vs 3.8%, p  = n.s.) However, the difference is significant when one-year mortality is evaluated (31% in anemic patients vs 19% in non-anemic patients, p  < 0.001). Cox regression analysis confirms the association between anemia and higher risk of one-year mortality, as well as with older age and a higher Charlson comorbidity index. Our study confirms that the presence of anemia is an independent factor for mid-term (1-year) mortality even in patients experiencing a first admission due to acute HF.

BackgroundSystolic blood pressure (SBP) and heart rate (HR) are well-known prognostic factors in heart failure (HF).AimsOur objective was to assess the value of the combination of admission SBP and HR to estimate 1-year mortality risks in elderly patients admitted due to a first episode of acute HF (AHF).MethodsDuring a 36-month period, we retrospectively reviewed 901 consecutive patients aged ≥ 75 admitted because of a first episode of AHF. According to admission SBP–HR combinations, three groups were defined: “low-risk” (HR < 70 bpm and SBP ≥ 140 mmHg), “moderate-risk” (HR < 70 bpm and SBP < 140 mmHg or HR ≥ 70 bmp and SBP ≥ 120 mmHg), and “high-risk” (HR ≥ 70 bpm and SBP < 120 mmHg). We analyzed all-cause mortality using Cox mortality analysis.ResultsOne-year mortality ranged from 16.5% for patients in the low-risk group to 50% for those in the high-risk group (p < 0.0001). Multivariate Cox regression for 1-year mortality showed hazard risk (HzR) ratios, compared to that (HzR 1) of the low-risk reference group, of 1.759 (95% CI 1.035–2.988, p = 0.037) for moderate-risk, and 3.171 (95% CI 1.799–5.589, p = 0.0001) for high-risk group. Prior use of a high number of chronic therapies (HzR 1.045), lower admission diastolic BP (HzR 0.986) and higher admission serum potassium values (HzR 1.534) were also significantly associated with mortality.ConclusionIn elderly population firstly hospitalized due to AHF, the simple combined admission measurement of SBP and HR predicts higher risk for 1-year all-cause mortality.

Background The aim of this study was to evaluate how hospital capacity was managed focusing on standardizing the admission and discharge processes. Methods This study was set in a 900-bed university affiliated hospital of the National Health Service, near Barcelona (Spain). This is a cross-sectional study of a set of interventions which were gradually implemented between April and December 2008. Mainly, they were focused on standardizing the admission and discharge processes to improve patient flow. Primary administrative data was obtained from the 2007 and 2009 Hospital Database. Main outcome measures were median length of stay, percentage of planned discharges, number of surgery cancellations and median number of delayed emergency admissions at 8:00 am. For statistical bivariate analysis, we used a Chi-squared for linear trend for qualitative variables and a Wilcoxon signed ranks test and a Mann–Whitney test for non-normal continuous variables. Results The median patients’ global length of stay was 8.56 days in 2007 and 7.93 days in 2009 (p < 0.051). The percentage of patients admitted the same day as surgery increased from 64.87% in 2007 to 86.01% in 2009 (p < 0.05). The number of cancelled interventions due to lack of beds was 216 patients in 2007 and 42 patients in 2009. The median number of planned discharges went from 43.05% in 2007 to 86.01% in 2009 (p < 0.01). The median number of emergency patients waiting for an in-hospital bed at 8:00 am was 5 patients in 2007 and 3 patients in 2009 (p < 0.01). Conclusions In conclusion, standardization of admission and discharge processes are largely in our control. There is a significant opportunity to create important benefits for increasing bed capacity and hospital throughput.