Sex hormones and the total testosterone:estradiol ratio as predictors of severe acute respiratory syndrome coronavirus 2 infection in hospitalized men.

BACKGROUND: The predictive ability of the early determination of sex steroids and the total testosterone:estradiol ratio for the risk of severe coronavirus disease 2019 or the potential existence of a biological gradient in this relationship has not been evaluated. OBJECTIVES: To assess the relationship of sex steroid levels and the total testosterone:estradiol ratio with the risk of severe acute respiratory syndrome coronavirus 2 infection in men, defined as the need for intensive care unit admission or death, and the predictive ability of each biomarker. MATERIALS AND METHODS: This was a prospective observational study. We included all consecutive adult men with severe acute respiratory syndrome coronavirus 2 infections in a single center admitted to a general hospital ward or to the intensive care unit. Sex steroids were evaluated at the centralized laboratory of our hospital. RESULTS: We recruited 98 patients, 54 (55.1%) of whom developed severe coronavirus disease in 2019. Compared to patients with nonsevere coronavirus disease 2019, patients with severe coronavirus disease 2019 had significantly lower serum levels of total testosterone (111 ± 89 vs. 191 ± 143 ng/dL; p < 0.001), dehydroepiandrosterone (1.69 ± 1.26 vs. 2.96 ± 2.64 ng/mL; p < 0.001), and dehydroepiandrosterone sulfate (91.72 ± 76.20 vs. 134.28 ± 98.261 µg/dL; p = 0.009), significantly higher levels of estradiol (64.61 ± 59.35 vs. 33.78 ± 13.78 pg/mL; p = 0.001), and significantly lower total testosterone:estradiol ratio (0.28 ± 0.31 vs. 0.70 ± 0.75; p < 0.001). The lower the serum level of androgen and the lower the total testosterone:estradiol ratio values, the higher the likelihood of developing severe coronavirus disease 2019, with the linear trend in the adjusted analyses being statistically significant for all parameters except for androstenedione (p = 0.064). In the receiver operating characteristic analysis, better predictive performance was shown by the total testosterone:estradiol ratio, with an area under the curve of 0.77 (95% confidence interval 0.68-0.87; p < 0.001). DISCUSSION AND CONCLUSION: Our results suggest that men with severe acute respiratory syndrome coronavirus 2 infection, decreased androgen levels and increased estradiol levels have a higher likelihood of developing an unfavorable outcome. The total testosterone:estradiol ratio showed the best predictive ability.

Individuals with psychosis present a reduced lung diffusion capacity and early spirometry alterations: Results from a cross-sectional study.

OBJECTIVE: Individuals with psychosis present a greater prevalence of chronic lung diseases, including Chronic Obstructive Pulmonary Disease (COPD). These chronic respiratory diseases are preceded by early lung function alterations; such as preserved ratio impaired spirometry (PRISm) or normal spirometry but low diffusion capacity of the lung for carbon monoxide (DLCO). However, there is no previous evidence on these lung function alterations in psychosis. The aim of this study is to evaluate the risk of having spirometry and DLCO alterations in subjects with psychosis compared with a control group. METHODS: Cross-sectional study on a cohort of 170 individuals including 96 subjects with psychosis and 74 sex-age-and smoking habit matched healthy controls. All subjects were under 60 years-old, and without COPD or asthma. Respiratory function was evaluated through spirometry. Clinical characteristics and DLCO values were recorded. RESULTS: Patients with psychosis showed lower spirometry results, both in terms of absolute and percentage of Forced Vital Capacity (FVC) and Forced Expiratory Volume in one second (FEV1). Absolute and percentage levels of diffusion were also lower in patients with psychosis. The percentage of individuals with DLCO<80% was higher among patients with psychosis (75% vs. 40%, p < 0.001). And the prevalence of PRISm was higher among patients with psychosis (10.4% vs. 1.4%, p < 0.001). Multivariate logistic regression analysis indicated that psychosis was an independent predictor of DLCO<80% (OR 5.67, CI95% 1.86-17.27). CONCLUSION: Patients with psychosis and females had early alterations in lung function. These results suggest that early screening for lung disease should be encouraged in psychosis.

Increased risk of early lung function alterations in people with psychosis: A cross-sectional case-control study.

BACKGROUND: Tobacco smoking has been described as the main cause of chronic obstructive pulmonary disease (COPD) and this habit is clearly more frequent among individuals with psychosis than in the general population, with rates reaching up to 60%. However, little attention has been focused on the association of COPD and psychosis. We aimed to explore the risk of presenting early lung function alterations in a group of individuals with psychosis. METHODS: Following an observational cross-sectional design we studied a cohort of individuals with established psychosis (N=128), and compared them with a sex, age, and smoking habit matched control group (N=79). We evaluated respiratory symptoms by means of mMRC, CAT and Dyspnea-12 scales. And lung function through spirometry tests. RESULTS: Individuals with psychosis presented more respiratory symptoms than controls. Similarly, we observed significant differences in the lung function tests between these two groups, where individuals with psychosis presented worse results in most of the spirometry mean values (FEV1 or forced expiratory volume in the first one second: 3.29L vs. 3.75L, p<0.001; forced vital capacity or FVC: 4.25L vs. 4.72L, p=0.002; and FEV1/FVC ratio: 0.78 vs. 0.80, p=0.052). Patients also presented worse values of lung diffusion, with lower diffusing capacity for carbon monoxide (DLCO) than controls (6.95 vs. 8.54mmol/min/kPa, p<0.001). CONCLUSIONS: The individuals with psychosis in our study presented greater respiratory symptoms and poorer lung function measured through spirometry. These signs have been described as early signs of COPD.

Metallomic Signatures of Lung Cancer and Chronic Obstructive Pulmonary Disease.

Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC.

Adherence and quality of life in patients with chronic lymphocytic leukemia treated with oral antineoplastic drugs. / Adherencia y calidad de vida en los pacientes con leucemia linfocítica crónica tratados con antineoplásicos orales.

OBJECTIVE: To evaluate adherence and quality of life to oral antineoplastic treatment in patients with chronic lymphocytic leukemia. To compare adherence and QoL according to treatment subgroups and treatment-line subgroups. METHODS: We conducted a descriptive prospective study from June to November 2021 in a tertiary care hospital. Patients treated at the Oncology Pharmacy with a diagnosis of chronic lymphocytic leukemia and treatment with oral antineoplastics for at least 6 months before inclusion in the study were included. Adherence was assessed using Morisky's 8 item Medication Adherence Scale and leftover pills counts, considering adherents if their adherence rate was ≥ 90%. Quality of life was assessed with Euro-Qol EQ-5D-3L questionnaire, Functional Assessment of Chronic Illness Therapy - Fatigue scale and QLQ-C30 questionnaire from European Organization for Research and Treatment of Cancer. Two interviews were scheduled: at the time of inclusion and at 3 months. Variable collected: demographic data, clinical data (disease and treatment); and response (scores obtained from questionnaires and adherence rate). The data statistical analysis was carried out with SPSS® 25.0 software. RESULTS: Twenty three patients were included, all of them showed an adherence rate higher than 90%; 20 patients were considered high adherent, and 3 patients medium adherent to treatment according to Morisky's 8 item Medication Adherence Scale. The results of the EQ-5D-3L questionnaire showed that the patients were all of them autonomous in their personal care and daily activities, 69.6% did not have any mobility problems and 78.3% did not have anxiety/depression; 56.5% had some type of pain. Eighteen patients had no fatigue, and 5 had mild/moderate fatigue according to Functional Assessment of Chronic Illness Therapy - Fatigue scale. The results of the EORTC QLQ-C30 questionnaire showed that patients had a high /healthy functional level, a good quality of life and a low level of symptoms. Analysis by treatment subgroups and by treatment-line subgroups did not show statistically significant differences in adherence or quality of life. CONCLUSIONS: Patients diagnosed with chronic lymphocytic leukemia and treated with oral antineoplastic therapies showed a high adherence rate and referred a good quality of life.

[Translated article] Adherence and quality of life in patients with chronic lymphocytic leukemia treated with oral antineoplastic drugs.

OBJECTIVE: To evaluate adherence and quality of life to oral antineoplastic treatment in patients with chronic lymphocytic leukemia. To compare adherence and quality of life according to treatment subgroups and treatment-line subgroups. METHODS: We conducted a descriptive prospective study from June to November 2021 in a tertiary care hospital.  Patients with chronic lymphocytic leukaemia, seen at the Oncology Pharmacy and treated with oral antineoplastic drugs for at least 6 months prior to inclusion in the study were included. Adherence was assessed using Morisky's 8 item Medication Adherence Scale and leftover pills counts, considering adherents if their adherence rate was ≥90%. Quality of life was assessed with Euro-Qol EQ-5D-3L questionnaire, Functional Assessment of Chronic Illness Therapy - Fatigue scale and QLQ-C30 questionnaire from European Organization for Research and Treatment of Cancer. Two interviews were scheduled: at the time of inclusion and at 3 months. The clinical history was reviewed and demographic and clinical variables were collected. The data statistical analysis was carried out with SPSS® 25.0 software. RESULTS: Twenty three patients were included, all of them showed an adherence rate higher than 90%; 20 patients were considered high adherent, and 3 patients médium adherent to treatment according to Morisky's 8 item Medication Adherence Scale. The results of the EQ-5D-3L questionnaire showed that the patients were all of them autonomous in their personal care and daily activities, 69.6% did not have any mobility problems and 78.3% did not have anxiety/depression; 56.5% had some type of pain. Eighteen patients had no fatigue, and 5 had mild/moderate fatigue according to Functional Assessment of Chronic Illness Therapy - Fatigue scale. The results of the EORTC QLQ-C30 questionnaire showed that patients had a high /healthy functional level, a good quality of life and a low level of symptoms. Analysis by treatment subgroups and by treatment-line subgroups did not show statistically significant differences in adherence or quality of life. CONCLUSIONS: Patients diagnosed with chronic lymphocytic leukemia and treated with oral antineoplastic therapies showed a high adherence rate and referred a good quality of life.

Trajectories of Severe Exacerbations of Chronic Obstructive Pulmonary Disease and Their Relationship with Mortality Risk.

PURPOSE: Acute exacerbations of COPD (AECOPD) are important factors contributing to mortality risk. The rate of exacerbations varies overtime. An inconsistent pattern of exacerbation occurrence is a common finding. The mortality risk associated with such a pattern is not entirely clear. Our objective was to assess the risk of mortality associated with various possible patterns of AECOPD trajectories. METHODS: This is a multicenter historical cohort study. Four different exacerbation trajectories were defined according to the incidence of severe AECOPD requiring hospital admission 2 years before and after the date of the first visit to the respiratory clinic-Consistent non-exacerbators (NEx): no AECOPD before or after the index date; consistent exacerbators (Ex): at least one AECOPD both before and after the index date; converters to exacerbators (CONV-Ex): no exacerbations before and at least one AECOPD after the index date; converters to non-exacerbators (CONV-NEx): at least one AECOPD before the index date, and no exacerbations after said date. All-cause mortality risk for these trajectories was assessed. RESULTS: A total of 1713 subjects were included in the study: NEx: 1219 (71.2%), CONV-NEx: 225 (13.1%), CONV-Ex: 148 (8.6%), Ex: 121 (7.1%). After correcting for confounding variables, the group with the highest mortality risk was Ex. The CONV-Ex and CONV-Nex groups had a mortality risk between Ex and NEx, with no significant differences between them. CONCLUSION: Different possible trajectories of severe AECOPD before and after a first specialized consultation are associated with different mortality risks. An inconsistent pattern of exacerbations has a mortality risk between Ex and NEx, with no clear differences between CONV-Ex and CONV-NEx.

Assessing the Usefulness of the Prevexair Smartphone Application in the Follow-Up High-Risk Patients with COPD.

INTRODUCTION: This manuscript analyzes the exacerbations recorded by the Prevexair application through the daily analysis of symptoms in high-risk patients with COPD and explores its usefulness in assessing clinical stability with respect to that reported in visits. PATIENTS AND METHODS: This study is a multi-centre cohort of COPD patients with the exacerbator phenotype who were monitored over 6 months. The Prevexair application was installed on the patients' smartphones. Patients used the app to record symptom changes, use of medication and use of healthcare resources. It is not established a recommended action plan when worsening of symptoms. At their clinical visit during the follow-up period, patients were asked about exacerbations suffered during these 6 months of monitoring. The investigators who conducted the visit were blinded about the Prevexair app records. RESULTS: The patients experienced a total of 185 exacerbations according to daily records in the app whereas only 64 exacerbations were recalled during medical visits. Perception became more accurate for severe exacerbations (kappa 0.6577), although we found no factors that predicted poor recall. The proportion of 72.5% patients were classified as unstable if the exacerbations captured by Prevexair were used to define stability, versus 47.8% if the exacerbations recall in visit was used. Two-thirds of the exacerbations recorded in the Prevexair application were not reported to doctors during their clinical visits. Almost half were treated with oral corticosteroids and/or antibiotics and more than one-quarter of the exacerbations treated did not seek medical attention. CONCLUSION: The findings of this cohort study confirm that patients do not always remember the exacerbations suffered during their medical visit. The prevexair application is useful in monitoring COPD patients at high risk, in order to a better assessment of exacerbations of COPD during medical visits. Further research must be carried out to evaluate this strategy in clinical practice.

Compliance and Utility of a Smartphone App for the Detection of Exacerbations in Patients With Chronic Obstructive Pulmonary Disease: Cohort Study.

BACKGROUND: In recent years, mobile health (mHealth)-related apps have been developed to help manage chronic diseases. Apps may allow patients with a chronic disease characterized by exacerbations, such as chronic obstructive pulmonary disease (COPD), to track and even suspect disease exacerbations, thereby facilitating self-management and prompt intervention. Nevertheless, there is insufficient evidence regarding patient compliance in the daily use of mHealth apps for chronic disease monitoring. OBJECTIVE: This study aimed to provide further evidence in support of prospectively recording daily symptoms as a useful strategy to detect COPD exacerbations through the smartphone app, Prevexair. It also aimed to analyze daily compliance and the frequency and characteristics of acute exacerbations of COPD recorded using Prevexair. METHODS: This is a multicenter cohort study with prospective case recruitment including 116 patients with COPD who had a documented history of frequent exacerbations and were monitored over the course of 6 months. At recruitment, the Prevexair app was installed on their smartphones, and patients were instructed on how to use the app. The information recorded in the app included symptom changes, use of medication, and use of health care resources. The patients received messages on healthy lifestyle behaviors and a record of their cumulative symptoms in the app. There was no regular contact with the research team and no mentoring process. An exacerbation was considered reported if medical attention was sought and considered unreported if it was not reported to a health care professional. RESULTS: Overall, compliance with daily records in the app was 66.6% (120/180), with a duration compliance of 78.8%, which was similar across disease severity, age, and comorbidity variables. However, patients who were active smokers, with greater dyspnea and a diagnosis of depression and obesity had lower compliance (P<.05). During the study, the patients experienced a total of 262 exacerbations according to daily records in the app, 99 (37.8%) of which were reported exacerbations and 163 (62.2%) were unreported exacerbations. None of the subject-related variables were found to be significantly associated with reporting. The duration of the event and number of symptoms present during the first day were strongly associated with reporting. Despite substantial variations in the COPD Assessment Test (CAT), there was improvement only among patients with no exacerbation and those with reported exacerbations. Nevertheless, CAT scores deteriorated among patients with unreported exacerbations. CONCLUSIONS: The daily use of the Prevexair app is feasible and acceptable for patients with COPD who are motivated in their self-care because of frequent exacerbations of their disease. Monitoring through the Prevexair app showed great potential for the implementation of self-care plans and offered a better diagnosis of their chronic condition.

Male precocious puberty described in literature of the Spanish Golden Age.

Aristotle was the first author who described the existence of abnormalities in the timing of human puberty. In the classic Greek-Roman period, Pliny the Elder and Phlegon of Tralles described the first individual cases of precocious puberty in children. During the Middle Ages, precocious puberty in the male (but not in the female) was ignored. We present what is, to our knowledge, the first full description in European literature of male precocious puberty and its consequences in an adult. This case is included in a book of the miscellaneous genre of Spanish Renaissance literature (Jardin de Flores Curiosas) written by Antonio de Torquemada in the sixteenth century.

[Assessment of the impact of pulmonary rehabilitation on sexual activity in patients with chronic obstructive pulmonary disease]. / Evaluación del impacto sobre la actividad sexual de un programa de rehabilitación pulmonar para pacientes con enfermedad pulmonar obstructiva crónica.

BACKGROUND AND OBJECTIVE: Chronic obstructive pulmonary disease (COPD) affects life quality, and also sexual activity. Pulmonary rehabilitation (PR) is a helpful treatment in COPD patients. The aim of this study is to assess sexual activity on COPD patients, and the effect of PR over it. PATIENTS AND METHODS: Single cohort prospective study over male COPD candidates to PR. Clinical, respiratory and biochemical assessment (FSH, LH, T, and progesterone) was performed. Patients were asked to fill baseline International Index of Erectile Function (IIEF) questionnaire, and 6 months after PR. A descriptive initial analysis compared respiratory values between patients with and without sexual activity. Changes in IIEF results were assessed after PR, and satisfaction with treatment using Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS). RESULTS: Between 2014 and 2016, 62 male COPD patients enlisted. Mean age: 66.5 years (SD 7.2). 52 Ex-smokers. 10 declared being sexually active (16.1%). No hormonal levels alterations. No significant differences on respiratory parameters between sexually active and non-active patients (FEV1, 6-minutes walking test, number of exacerbations, CAT score). Baseline mean IIEF values: Erectile function 8, orgasmic function 4, sexual desire 5.6, intercourse satisfaction 5.3, and overall satisfaction 4.5. After PR, significant increase in mean IIEF value: 6.1 (CI95% 1.9-10.3). Improvement was found in all domains, with statistical significance on intercourse satisfaction 0.9 (CI95% 0.2-1.6). Moderate satisfaction with treatment was achieved according to EDITS. CONCLUSIONS: Only a low percentage of COPD males included in PR is sexually active. No pulmonary differences were found between sexually active and non-active patients. PR improves sexual function, particularly intercourse satisfaction domain.

Translation and Validation of the Multidimensional Dyspnea-12 Questionnaire. / Traducción y validación del cuestionario multidimensional Disnea-12.

INTRODUCTION: Dyspnea is a multidimensional symptom, but this multidimensionality is not considered in most dyspnea questionnaires. The Dyspnea-12 takes a multidimensional approach to the assessment of dyspnea, specifically the sensory and the affective response. The objective of this study was to translate into Spanish and validate the Dyspnea-12 questionnaire. METHODS: The original English version of the Dyspnea-12 questionnaire was translated into Spanish and backtranslated to analyze its equivalence. Comprehension of the text was verified by analyzing the responses of 10 patients. Reliability and validation of the questionnaire were studied in an independent group of COPD patients attending the pulmonology clinics of Hospital Universitario Marqués de Valdecilla, diagnosed and categorized according to GOLD guidelines. RESULTS: The mean age of the group (n=51) was 65 years and mean FEV1 was 50%. All patients understood all questions of the translated version of Dyspnea-12. Internal consistency of the questionnaire was α=0.937 and intraclass correlation coefficient was=.969; P<.001. Statistically significant correlations were found with HADS (anxiety r=.608 and depression r=.615), mMRC dyspnea (r=.592), 6MWT (r=-0.445), FEV1 (r=-0.312), all dimensions of CRQ-SAS (dyspnea r=-0.626; fatigue r=-0.718; emotional function r=-0.663; mastery r=-0.740), CAT (r=0.669), and baseline dyspnea index (r=-0.615). Dyspnea-12 scores were 10.32 points higher in symptomatic GOLD groups (B and D) (P<.001). CONCLUSION: The Spanish version of Dyspnea-12 is a valid and reliable instrument to study the multidimensional nature of dyspnea.

Mutilating Purpura Fulminans in an Adult with Meningococcal Sepsis.

We report a dramatic case of meningococcal sepsis manifesting as purpura fulminans in an elderly diabetic woman. Hemodynamic instability and severe bilateral cutaneous lesions involving her hands and feet developed rapidly. Specific antibiotic therapy and the administration of inotropic and vasopressor drugs were initiated. The severity and extension of the cutaneous lesions (attributed to purpura fulminans) worsened because of the need for vasoconstrictors for the treatment of septic shock. Bilateral transmetatarsal and metacarpal amputations were required to stabilize the patient.

Calcitriol-modulated human antibiotics: New pathophysiological aspects of vitamin D.

Traditionally, calcitriol has been considered a calcium and phosphate regulating hormone, but has recently been shown to play a pivotal role in innate immunity. Many barrier and immune cells have membrane and intracellular receptors that recognize different microbial antigens. Activation of these receptors induces synthesis of 1α-hydroxylase, which acts on 25 hydroxyvitamin D to generate intracellular calcitriol. Calcitriol activates its receptor and enhances the synthesis of important human antibiotics like cathelicidin and ß2-defensin while inhibiting hepcidin. These pluripotent peptides have an important role in innate immunity, and their regulation is abnormal in hypovitaminosis D. The literature on their secretion mechanisms, levels in different organic fluids, mechanism of action, and relationship with vitamin D is reviewed here.