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BACKGROUND: Malignant Hyperthermia (MH) is a pharmacogenetic disorder triggered by halogenated anesthesia agents/succinylcholine and characterized by hypermetabolism crisis during anesthesia, but also by day-to-day symptoms, such as exercise intolerance, that may alert the health professional. OBJECTIVE: The study aimed to analyze the incidence of fatigue in MH susceptible patients and the variables that can impact perception of fatigue, such as the level of routine physical activity and depression. METHODS: A cross-sectional observational study was carried out with three groups ... 22 patients susceptible to MH (positive in vitro muscle contracture test), 13 non-susceptible to MH (negative in vitro muscle contracture test) and 22 controls (no history of MH). Groups were assessed by a demographic/clinical questionnaire, a fatigue severity scale (intensity, specific situations, psychological consequences, rest/sleep response), and the Beck depression scale. Subgroups were re-assessed with the Baecke habitual physical exercise questionnaire (occupational physical activity, leisure physical exercise, leisure/locomotion physical activity). RESULTS: There were no significant differences among the three groups regarding fatigue intensity, fatigue related to specific situations, psychological consequences of fatigue, fatigue response to resting/sleeping, depression, number of active/sedentary participants, and the mean time and characteristics of habitual physical activity. Nevertheless, unlike the control sub-group, the physically active MH-susceptible subgroup had a higher fatigue response to resting/sleeping than the sedentary MH susceptible subgroup (respectively, 5.9.ß...ß1.9 vs. 3.9.ß...ß2, t-test unpaired, p.ß

Introduction During pregnancy, women are at an increased risk of developing iron-deficiency anemia. Objective The objective of this study was to assess the diagnostic performance of the reticulocyte hemoglobin equivalent (RET-He) in the early detection of iron-deficiency anemia in a group of pregnant women and to establish a reference range for this parameter in a group of control individuals. Method: A total of 60 patients and 130 control subjects were included in the study. Blood samples collected from the subjects were submitted to a complete blood count and a serum ferritin test and the data were analyzed by comparing the groups and ROC curves. Results The reference range found for the RET-He was between 29.75pg and 38.24pg, with a median of 35pg. The receiver operating characteristic (ROC) curve analysis for the ferritin parameter showed an area under the curve of 0.732 for the RET-He, 0.586 for hemoglobin, 0.551 for the mean corpuscular hemoglobin concentration and 0.482 for the mean corpuscular volume. Conclusion Early diagnosis of iron deficiency anemia in pregnancy is essential to prevent damage to both maternal and fetal health. The RET-He presents an excellent potential as an auxiliary tool for the diagnosis of iron deficiency in pregnant women.

Purpose To identify presurgical and surgical factors associated with the development of hypopituitarism and its recovery after endoscopic endonasal transsphenoidal (EET) resection of pituitary adenomas (PAs). Methods Retrospective study of patients with PAs operated by the same neurosurgeon through an EET approach in two Spanish tertiary hospitals in ten years. Results 242 pituitary surgeries performed in 231 patients were analyzed. In the 154 surgeries performed in 146 patients with non-functioning PAs (NFPAs), 46.8% (n = 72) presented presurgical hypopituitarism. After PAs resection, 41 of these (56.9%) normalized pituitary function and 11 of 82 patients with preoperative normal function (13.4%) developed new pituitary deficits. Patients with preoperative visual impairment (OR = 3.9, p = 0.046) and operated in the first four years of the neurosurgeon's learning curve (OR = 5.7, p = 0.016) presented a higher risk of developing postoperative hypopituitarism. Of the 88 surgeries in 85 patients with functioning PAs (FPAs), 23.9% presented presurgical hypopituitarism, and 47.6% of those recovered after surgery. 9% of the cases with preoperative normal function developed new pituitary deficit/s. Diabetic patients presented a higher risk of persistence of hypopituitarism (OR = 10.5, p = 0.024). Patients with presurgical visual impairment (OR = 30.0, p = 0.010) and PAs >3 cm (OR = 14.0, p = 0.027) had higher risk of developing new pituitary deficits. Conclusion Approximately 50% of patients with PAs and preoperative hypopituitarism recover pituitary function after EET surgery. 10% of patients with normal function develop new deficits. Patients with NFPAs with visual involvement and operated in the first four years of neurosurgeon's learning curve, and FPAs patients with presurgical visual impairment and tumor size >3 cm have a higher risk of postoperative hypopituitarism.

Systemic sclerosis is an autoimmune disease whose etiology remains unknown. Some patients prove refractory and require other therapies. Recently, the use of mesenchymal stem cells (MSC) for the treatment of disease refractory to conventional treatments has been considered. We present a case of refractory systemic sclerosis; Wharton's jelly mesenchymal stem cell was given in response. Decrease in perioral wrinkles, reduced telangiectasia and decrease in modified Rodnan skin score were observed two years later. A decrease in brain natriuretic peptide and improved pulmonary function were also found. And improvement of pulmonary fibrosis on high resolution tomography and capillaroscopy changes. In conclusion, MSC infusion seems to be effective and safe treatment of refractory scleroderma.

Context Neurourological patients often encounter bacteriuria without any symptoms or may experience symptoms suspicious of urinary tract infections (UTIs). However, there is a lack of guidelines that unequivocally state the definition of UTIs in this specific patient group. Objective To present all used definitions of UTIs in neurourological patients. Evidence acquisition This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Studies were identified by electronic search of Medline, Embase, Cochrane controlled trials databases, and clinicaltrial.gov without a time limitation (last search September 2020) and by screening of reference lists and reviews. The occurrences of the various UTI definitions were counted and the frequencies calculated. Evidence synthesis After screening 7164 abstracts, we included 32 studies enrolling a total of 8488 patients with a neurourological disorder who took part in an interventional clinical study. UTI definitions were heterogeneous. The concordance to predefined definitions was low. Conclusions Interventional clinical studies rarely report specific definitions for UTIs, and both clinical and laboratory criteria used are heterogeneous. A generally accepted UTI definition for neurourological patients is urgently needed. Patient summary Patients suffering from neurological disorders often experience symptoms in their lower urinary tract that resemble urinary tract infections. Furthermore, they can have positive urine cultures without symptoms (the so-called asymptomatic bacteriuria). However, clinical studies rarely report specific definitions for urinary tract infections, and when it is done, they are heterogeneous. A generally accepted urinary tract infection definition for neurourological patients is urgently needed. Take Home Message Interventional clinical studies on neurourological patients rarely report specific definitions for urinary tract infections (UTIs), and both clinical and laboratory criteria used are heterogeneous. A generally accepted UTI definition for neurourological patients is urgently needed.

Introduction The benefits of mechanical thrombectomy in the treatment of patients with acute stroke due to large vessel occlusions (LVOs) have been extensively demonstrated by randomized trials and registries in developed countries. However, data on thrombectomy outside controlled trials are scarce in developing countries. The aim of this study was to assess the safety and efficacy, and to investigate the predictors for good and poor outcomes of thrombectomy for treatment of AIS due to anterior circulation LVOs in Brazil. Materials and Methods This was a single center registry of thrombectomy in the treatment of stroke caused by anterior circulation LVOs. Between 2011 and 2019, a total of 565 patients were included. Results the mean baseline NIHSS score on admission was 17.2. The average baseline ASPECTS was 8, and 91.0% of patients scored ≥6. Half of the patients received intravenous thrombolysis. The mean time from symptom onset to arterial puncture was 296.4 minutes. The mean procedure time was 61.4 minutes. The rates of the main outcomes were recanalization (TICI 2b-3) 85.6%, symptomatic intracranial hemorrhage (sICH) 8,1%, good clinical outcome (mRS=0-2) 43,5%, and mortality 22.1% at three months. Conclusions This study demonstrates the efficacy and safety of mechanical thrombectomy for treatment of patients with AIS of the anterior circulation in real-life conditions under limited facilities and resources. The results of the present study were relatively similar to those of large trials and population registers of developed countries.

Background: The association between heart rate (HR) and pulmonary embolism (PE) outcomes has not been well studied. Furthermore, optimal cutoffs to identify low-risk and intermediate- to high-risk patients are not well known. Research Question: Does an association exist between baseline HR and PE outcome across the continuum of HR values? Study Design and Methods: The current study included 44,331 consecutive nonhypotensive patients with symptomatic PE from the Registro Informatizado de la Enfermedad TromboEmbólica registry between 2001 and 2021. Outcomes included 30-day all-cause and PE-specific mortality. We used hierarchical logistic regression to assess the association between admission HR and outcomes. Results: A positive relationship was found between admission HR and 30-day all-cause and PE-related mortality. Considering an HR of 80 to 99 beats/min as a reference, patients in the higher HR strata showed higher rates of all-cause death (adjusted OR, 1.5 for HR of 100-109 beats/min; adjusted OR, 1.7 for HR of 110-119 beats/min; adjusted OR, 1.9 for HR of 120-139 beats/min; and adjusted OR, 2.4 for HR of ≥ 140 beats/min). Patients in the lower strata of HR showed significantly lower rates of 30-day all-cause mortality compared with the same reference group (adjusted OR, 0.6 for HR of 60-79 beats/min; and adjusted OR, 0.5 for HR of < 60 beats/min). The findings for 30-day PE-related mortality were similar. For identification of low-risk patients, a cutoff value of 80 beats/min (vs 110 beats/min) increased the sensitivity of the simplified Pulmonary Embolism Severity Index (sPESI) from 93.4% to 98.8%. For identification of intermediate- to high-risk patients, a cutoff value of 140 beats/min (vs 110 beats/min) increased the specificity of the Bova score from 93.2% to 98.0%. Interpretation: In nonhypotensive patients with acute symptomatic PE, a high HR portends an increased risk of all-cause and PE-related mortality. Modifying the HR cutoff in the sPESI and the Bova score improves prognostication of patients with PE.

Data on the prevalence and mortality of paediatric sepsis in resource-poor settings are scarce. We aimed to assess the prevalence and in-hospital mortality of severe sepsis and septic shock treated in paediatric intensive care units (PICUs) in Brazil, and risk factors for mortality.We performed a nationwide, 1-day, prospective point prevalence study with follow-up of patients with severe sepsis and septic shock, using a stratified random sample of all PICUs in Brazil. Patients were enrolled at each participating PICU on a single day between March 25 and 29, 2019. All patients occupying a bed at the PICU on the study day (either admitted previously or on that day) were included if they were aged 28 days to 18 years and met the criteria for severe sepsis or septic shock at any time during hospitalisation. Patients were followed up until hospital discharge or death, censored at 60 days. Risk factors for mortality were assessed using a Poisson regression model. We used prevalence to generate national estimates.Of 241 PICUs invited to participate, 144 PICUs (capacity of 1242 beds) included patients in the study. On the day of the study, 1122 children were admitted to the participating PICUs, of whom 280 met the criteria for severe sepsis or septic shock during hospitalisation, resulting in a prevalence of 25·0% (95% CI 21·6-28·8), with a mortality rate of 19·8% (15·4-25·2; 50 of 252 patients with complete clinical data). Increased risk of mortality was associated with higher Pediatric Sequential Organ Failure Assessment score (relative risk per point increase 1·21, 95% CI 1·14-1·29, p0·0001), unknown vaccination status (2·57, 1·26-5·24; p=0·011), incomplete vaccination status (2·16, 1·19-3·92; p=0·012), health care-associated infection (2·12, 1·23-3·64, p=0·0073), and compliance with antibiotics (2·38, 1·46-3·86, p=0·0007). The estimated incidence of PICU-treated sepsis was 74·6 cases per 100 000 paediatric population (95% CI 61·5-90·5), which translates to 42 374 cases per year (34 940-51 443) in Brazil, with an estimated mortality of 8305 (6848-10 083).In this representative sample of PICUs in a middle-income country, the prevalences of severe sepsis or septic shock and in-hospital mortality were high. Modifiable factors, such as incomplete vaccination and health care-associated infections, were associated with greater risk of in-hospital mortality.Fundação de Amparo à Pesquisa do Estado de São Paulo and Conselho Nacional de Desenvolvimento Científico e Tecnológico.For the Portuguese translation of the abstract see Supplementary Materials section.

Background: The impact of biologics on the risk of postoperative complications (PC) in inflammatory bowel disease (IBD) is still an ongoing debate. This lack of evidence is more relevant for ustekinumab and vedolizumab. Aims: To evaluate the impact of biologics on the risk of PC. Methods: A retrospective study was performed in 37 centres. Patients treated with biologics within 12 weeks before surgery were considered “exposed”. The impact of the exposure on the risk of 30-day PC and the risk of infections was assessed by logistic regression and propensity score-matched analysis. Results: A total of 1535 surgeries were performed on 1370 patients. Of them, 711 surgeries were conducted in the exposed cohort (584 anti-TNF, 58 vedolizumab and 69 ustekinumab). In the multivariate analysis, male gender (OR: 1.5, 95% CI: 1.2–2.0), urgent surgery (OR: 1.6, 95% CI: 1.2–2.2), laparotomy approach (OR: 1.5, 95% CI: 1.1–1.9) and severe anaemia (OR: 1.8, 95% CI: 1.3–2.6) had higher risk of PC, while academic hospitals had significantly lower risk. Exposure to biologics (either anti-TNF, vedolizumab or ustekinumab) did not increase the risk of PC (OR: 1.2, 95% CI: 0.97–1.58), although it could be a risk factor for postoperative infections (OR 1.5, 95% CI: 1.03–2.27). Conclusions: Preoperative administration of biologics does not seem to be a risk factor for overall PC, although it may be so for postoperative infections.

Background: Telemedicine was implemented in Brazil as a way to support primary health care (PHC). Orthopedic complaints are common in PHC, and, because musculoskeletal diseases are the most frequent causes of chronic pain, it is important to explore knowledge gaps of PHC as well as to understand the teleconsultations' impact on reducing referrals to secondary care. Materials and Methods: Observational, retrospective study that analyzed consecutive orthopedic asynchronous teleconsultations from the Telehealth Network of Minas Gerais, a large-scale public telehealth service, performed from September 17, 2013 to June 18, 2020. Teleconsultations were analyzed based on the type of query. Results: Throughout the study, 1,174 teleconsultations from 254 municipalities were analyzed. Most requests for teleconsultations were from nurses (37.8%) and physicians (48.7%). In 58.3%, challenges could be solved by a general practitioner, meanwhile 38.4% needed referral to an orthopedic specialist. Most queries related to a specific case (assistencial teleconsultation, 66.0%), and the others were classified as educational (34%). With regard to the motivation for the assistencial teleconsultations, 72% approached treatment options, 49.5% surrounded possible diagnosis, and 20.1% discussed patient's rehabilitation. In addition, 95.5% of requests could be solved by teleconsultation, without the need for referral to in-person consultation with the specialist. Conclusions: Teleconsultations can help investigate the most frequent queries in PHC. Most of them were solved without the need for referral, showing the potential of teleconsultations in daily practice as a way to manage patients and guarantee better access to first-rate health care. As for the public health system, teleconsultations represent a way to overcome the distance barrier to health care access.

Adenoid ameloblastoma with dentinoid is an uncommon benign odontogenic neoplasm, and its unicystic variant seems to be even rarer. A 34-year-old man was referred for evaluation of an asymptomatic swelling in the posterior maxilla. Intraoral examination showed an expansive lesion, soft to palpation, covered by a normal color mucosa. Cone-beam tomography revealed a well-defined unilocular hypodense tumor involving the left maxillary sinus. Histopathological examination of the surgically excised specimen showed a cystic tumor lined by an ameloblastic-like epithelium containing columnar basal cells with hyperchromatic and polarized nuclei. In some areas of the capsule, the tumor showed mural infiltration by sheets of cells containing central whirling structures. Dentinoid material was also observed in association with ameloblastic-like cells. The tumor was BRAF and KRAS wild-type. Collectively, these findings were consistent with the diagnosis of a unicystic variant of adenoid ameloblastoma with dentinoid.

Objective: The co-occurrence of substance use disorders (SUD) and trauma-exposure is a risk factor for suicidal thoughts and behaviors (STB). However, traditional methods of measurement for suicidal thoughts and behaviors are limited by an overreliance on dichotomous (i.e., yes or no) and averaged/summed scale score measurements. Further, among trauma-exposed individuals with SUD, it remains unclear which specific demographic factors, types of SUDs, and trauma sequelae (e.g., posttraumatic stress disorder [PTSD] symptom clusters) may be associated with elevated STB. The present study utilized item response theory to (a) generate empirically derived STB severity scores and, (b) examine which demographic factors, SUD diagnoses, and DSM-IV PTSD symptom clusters are associated with suicidality in a trauma-exposed sample with SUDs. Method: Female trauma-exposed participants with SUDs (N = 544) were recruited from community substance use treatment facilities in the National Drug Abuse Treatment Clinical Trials Network (CTN). Clinician-administered interviews assessed STB, SUDs, and PTSD symptoms. Results: Results indicated that the unidimensional item response theory (IRT) model used to estimate latent STB severity scores fit well, with strong local reliability at higher levels of latent STB severity. Regression predictors of elevated STB severity included younger age, opioid dependence, and higher PTSD reexperiencing symptoms. Conclusions: Clinicians are advised to screen for and target opioid use disorders and reexperiencing symptoms when addressing suicidal thoughts and behavior in trauma-exposed individuals with SUDs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Introduction and objectives Hereditary transthyretin amyloidosis (hATTR) is a disease caused by mutations in the transthyretin gene that frequently shows cardiac involvement due to amyloid deposition in the myocardium. Our objective was to identify cardiac involvement in a Spanish cohort. Methods Retrospective multicenter study of patients diagnosed with hATTR with cardiac involvement from Spanish centers. We collected demographic, clinical, and genetic data. Results A total of 181 patients from 26 centers were included (65.2% men, with a median age at diagnosis of 62 years). The most frequent mutations were Val50Met (67.7%) and Val142Ile (12.4%). The main reason for consultation was extracardiac symptoms (69%), mainly neurological. The mean N-terminal pro-B-type natriuretic peptide level was 2145±3586 pg/mL. The most characteristic electrocardiogram findings were a pseudoinfarct pattern (25.9%) and atrioventricular block (25.3%). Mean ventricular thickness was 15.4±4.1mm. Longitudinal strain was reduced in basal segments by 29.4%. Late diffuse subendocardial enhancement was observed in 58.8%. Perugini grade 2 or 3 uptake was observed in 75% of scintigraphy scans. During follow-up, 24.9% of the patients were admitted for heart failure, 34.3% required a pacemaker, and 31.6% required a liver transplant. One third (32.5%) died during follow-up, mainly due to heart failure (28.8%). The presence of non-Val50Met mutations was associated with a worse prognosis. Conclusions HATTR cardiac amyloidosis in Spain shows heterogeneous genetic and clinical involvement. The prognosis is poor, mainly due to cardiac complications. Consequently early diagnosis and treatment are vital.

The most effective treatment for lung cancer is complete lung resection, although recurrences reach up to 10% and the appearance of second neoplasms, up to 6%. Therefore, the follow-up of these patients will be essential for the early detection and treatment of these events; however, there is no definition of the form, time and cadence of these follow-ups. In this consensus document, we try to define them based on the available scientific evidence. A critical review of the literature is carried out (meta-analysis, systematic reviews, reviews, consensus recommendations of scientific societies, randomized controlled studies, non-randomized controlled studies, observational studies and case series studies) and communications to the main congresses on oncology and thoracic surgery in Spanish, English and French. The evidences found are classified following the GRADE system. It is defined according to the existing evidence that the patient resected for lung cancer should be followed up, as well as that this follow-up should be close during the first years and with CT (not being necessary to follow up with PET-CT, biomarkers or bronchoscopy). Cessation of smoking is also recommended in this follow-up.

Introduction and aims: The primary aim was to explore the epidemiologic trend of pediatric inflammatory bowel disease in Latin America, and the secondary aims were to obtain an overview of the diagnostic/therapeutic focus of the members of the LASPGHAN and examine the relation of case frequency to year, during the study period. Materials and methods: Latin American pediatric gastroenterologists participated in an online survey, conducted through the SurveyMonkey platform, that investigated the yearly frequency of new inflammatory bowel disease patients within the time frame of 2005–2016, their disease variety, the gastrointestinal segments affected, and the diagnostic and treatment methods utilized. The correlation of new case frequency with each study year was evaluated. Results: A total of 607 patients were studied. The diagnoses were ulcerative colitis in 475 (78.3%) cases, Crohn’s disease in 104 (17.1%), and inflammatory bowel disease D unclassified in 28 (4.6%). The trend in ulcerative colitis was a lineal increase in the frequency of new cases related to each study year, with a significant correlation coefficient. Pancolitis was found in 67.6% of the patients. The diagnostic methods included clinical data, endoscopy, and biopsies in more than 99% of the cases, and imaging studies were indicated selectively. Drug regimens were limited to 5-aminosalicylic acid derivatives, azathioprine, 6-mercaptopurine, infliximab, and adalimumab. Conclusions: Pediatric inflammatory bowel disease in Latin America appears to have increased during the years included in the study period, with a predominance of moderate or severe ulcerative colitis. That lineal trend suggests the predictive likelihood of a gradual increase in the coming years, with possible epidemiologic and clinical implications. Resumen: Introducción y objetivos: El objetivo primario fue explorar la tendencia epidemiológica de la enfermedad intestinal inflamatoria pediátrica en América Latina; los secundarios, obtener una visión general del enfoque diagnóstico/terapéutico de miembros de la SLAGHNP y explorar la relación entre la frecuencia de casos y los años del período evaluado. Material y métodos: Se realizó una encuesta en línea a pediatras gastroenterólogos de América Latina con la plataforma SurveyMonkey. Se preguntó la frecuencia anual de pacientes nuevos de 2005 a 2016, su variedad, los segmentos del tubo digestivo afectados, los métodos de diagnóstico y el tratamiento utilizado. Se evaluó la correlación entre la frecuencia anual y los años de estudio. Resultados: Se estudió a 607 pacientes; el diagnóstico de colitis ulcerativa se realizó en 475 (78.3%), de enfermedad de Crohn en 104 (17.1%) y de enfermedad intestinal inflamatoria no clasificable en 28 (4.6%). La tendencia de colitis ulcerativa tuvo un incremento lineal con coeficiente de correlación significativo entre la frecuencia de casos nuevos y el año de estudio; 67.6% tuvieron pancolitis. Los métodos de diagnóstico incluyeron datos clínicos, endoscopia y biopsias en más del 99% de los casos; los estudios de imagen se indicaron de manera selectiva. Los esquemas farmacológicos se circunscribieron a derivados del ácido 5-aminosalicílico, azatioprina, 6-mercaptopurina, infliximab y adalimumab. Conclusiones: La enfermedad intestinal inflamatoria pediátrica en América Latina parece incrementarse en el período estudiado con predominio de formas moderadas o graves de colitis ulcerativa; esta tendencia lineal puede indicar la posibilidad predictiva de incremento gradual en la próxima década, lo que es probable que tenga implicaciones epidemiológicas y clínicas.

Amyotrophic lateral sclerosis (ALS) is now recognized as a multisystem neurodegenerative disorder, comprising autonomic dysfunction. We aimed to assess sudomotor function in ALS by measuring the electrochemical skin conductance (ESC).Thirty-one ALS patients [median age of 62 years (1st-3rd interquartile range - IQR, 56-72), male 71%] were prospectively compared with 29 healthy controls, matched for age and sex. We analysed ESC results from hands and feet, bilaterally.A total of 120 ESC recordings were obtained. Hands and feet ESC measurements were significantly lower in patients compared with controls [64 μS (1st-3rd IQR, 57-58) versus 78 μS (1st-3rd IQR, 70.5-84), p 0.001 and 76 μS (1st-3rd IQR, 68-83) versus 81 μS (1st-3rd IQR, 78-86), p = 0.008, respectively]. In ALS group, no differences were observed between spinal and bulbar-onset forms for hands and feet results (p 0.05). Hands and feet ESC measurements did not correlate also with disease duration, total ALSFRS-R scale, or ALSFRS-R progression rate (all p 0.05).ESC is a non-invasive, fast and quantitative method suitable for assessing sudomotor function. ALS patients revealed a decreased function in upper and lower extremities.Sudomotor dysfunction is part of the ALS manifestations.

Background: Measurements of C-reactive protein (CRP) concentration and erythrocyte sedimentation rate (ESR) are frequently ordered jointly in clinical practice. Aim: To investigate the factors associated with discordances between CRP concentration and ESR in adults. Methods: We conducted a cross-sectional study of 1472 adults with no known inflammatory disorders (44.5% male; median age, 52 years; range, 18–91 years), randomly selected from a municipality in Spain. The participants underwent simultaneous measurements of ESR, serum CRP, and interleukin-6 concentrations. Alcohol consumption, smoking, and physical activity were evaluated by questionnaire. Body mass index (BMI) measurement and metabolic syndrome criteria were available for all participants. Results: Most (n = 1123, 74.9%) of the participants showed normal CRP and ESR values. Sixty-nine (4.6%) participants showed high CRP and ESR values. Seventy-two (4.8%) participants showed a discordant pattern of high ESR and normal CRP values, which was associated with age after adjusting for sex, alcohol consumption, physical activity, BMI, and the presence of metabolic syndrome (odds ratio [OR], 1.052; 95% CI, 1.034–1.071; P Conclusion: In this general adult population with no overt inflammatory disease, the discordant pattern of high ESR and normal CRP was associated with greater age, whereas the pattern of high CRP and normal ESR was associated with higher BMI.

A syndemic is the convergence of two or more diseases in the same space and time. In Mexico, the dengue epidemic is active and predominates in areas of the Pacific and the Gulf of Mexico; in turn, the COVID-19 epidemic severely affects the same areas as dengue fever. Given that both these diseases share many clinical manifestations, in areas where tropical diseases are endemic, it is important to make careful evaluations of the patient who consults for fever in order to establish a timely diagnosis. Laboratory diagnostic tests are necessary to take the pertinent measures for each patient. In Mexico, the risk of a syndemic between COVID-19 and dengue fever is high, and thus it that can collapse health systems. The states of southeastern Mexico and the Pacific region require special attention, since they have geographic, environmental and climatic conditions that favor the rapid spread of dengue and COVID-19. Simultaneous infection will worsen the epidemiological situation, and complicate the diagnosis, control and treatment of both diseases.Una sindemia es la convergencia de dos o más enfermedades en un mismo espacio y tiempo. En México, la epidemia de dengue está activa y predomina en zonas del Pacífico y Golfo de México; por su parte, la epidemia de COVID-19 afecta severamente las mismas zonas que el dengue. Dado que estas enfermedades comparten numerosas manifestaciones clínicas, en zonas endémicas de enfermedades tropicales es importante la evaluación minuciosa del paciente que consulta por fiebre, para establecer oportunamente un diagnóstico correcto. Las pruebas de laboratorio son necesarias para llevar a cabo las medidas pertinentes en cada paciente. En México, el riesgo de sindemia de COVID-19 y dengue es alto, por lo que puede colapsar los sistemas de salud. Los estados del sureste y los colindantes con el Pacífico requieren especial atención ya que presentan condiciones geográficas, ambientales y climáticas que favorecen la rápida propagación del dengue y COVID-19. La infección simultánea empeorará la situación epidemiológica, complicará el diagnóstico, control y tratamiento de ambas enfermedades.

SARS-CoV-2 infection (COVID-19) has become a pandemic with a high case fatality rate that mainly affects adults. Most severely ill adult patients develop a coagulopathy that was not described until recently, and which is currently considered a main cause of death. Everything indicates that a similar phenomenon also occurs in children with COVID-19. Anticoagulant treatment has become one of the therapeutic foundations for this infection; however, its implementation in children can be difficult since, until recently, it was not considered in the pediatric population. Evidence regarding the use of anticoagulants in COVID-19 is rapidly generated, changes constantly, it is often difficult to interpret, and can be contradictory. After an extensive review of the published literature, a proposal was generated that offers suggestions for anticoagulant treatment, considering available resources in Mexico.La infección por SARS-CoV-2 (COVID-19) se ha constituido en una pandemia con alto índice de letalidad que afecta principalmente a los adultos. La mayor parte de los pacientes adultos graves desarrolla una coagulopatía que no estaba descrita, la cual actualmente se considera la principal causa de muerte. Todo indica que un fenómeno parecido ocurre también en el niño con COVID-19. El tratamiento anticoagulante se ha convertido en uno de los fundamentos terapéuticos de esta infección; sin embargo, su establecimiento en el niño puede ser difícil ya que, hasta hace poco, no estaba considerado en la población pediátrica. La evidencia respecto al uso de anticoagulantes en COVID-19 se genera con rapidez, cambia constantemente, con frecuencia es difícil de interpretar y puede ser contradictoria. Después de una extensa revisión de la literatura publicada, se generó una propuesta que ofrece sugerencias para el tratamiento anticoagulante en la que se consideran los recursos disponibles en México.

A better assessment of prostate cancer (PrCa) risk is needed to improve screening. The PROFILE pilot study explored the feasibility of single nucleotide polymorphism profiling in men with a family history (FH) of PrCa to investigate the probability of detecting PrCa at prostate biopsy (PB). The results of the present pilot study have demonstrated that PB is a feasible and safe method of PrCa screening in men with a FH., Background. A better assessment of individualized prostate cancer (PrCa) risk is needed to improve screening. The use of the prostate-specific antigen (PSA) level for screening in the general population has limitations and is not currently advocated. Approximately 100 common single nucleotide polymorphisms (SNPs) have been identified that are associated with the risk of developing PrCa. The PROFILE pilot study explored the feasibility of using SNP profiling in men with a family history (FH) of PrCa to investigate the probability of detecting PrCa at prostate biopsy (PB). The primary aim of this pilot study was to determine the safety and feasibility of PrCa screening using transrectal ultrasound-guided PB with or without diffusion-weighted magnetic resonance imaging (DW-MRI) in men with a FH. A secondary aim was to evaluate the potential use of SNP profiling as a screening tool in this population. Patients and Methods. A total of 100 men aged 40–69 years with a FH of PrCa underwent PB, regardless of their baseline PSA level. Polygenic risk scores (PRSs) were calculated for each participant using 71 common PrCa susceptibility alleles. We treated the disease outcome at PB as the outcome variable and evaluated its associations with the PRS, PSA level, and DW-MRI findings using univariate logistic regression. Results. Of the 100 men, 25 were diagnosed with PrCa, of whom 12 (48%) had clinically significant disease. Four adverse events occurred and no deaths. The PSA level and age at study entry were associated with PrCa at PB (p = .00037 and p = .00004, respectively). Conclusion. The results of the present pilot study have demonstrated that PB is a feasible and safe method of PrCa screening in men with a FH, with a high proportion of PrCa identified requiring radical treatment. It is feasible to collect data on PrCa-risk SNPs to evaluate their combined effect as a potential screening tool. A larger prospective study powered to detect statistical associations is in progress. Implications for Practice: Prostate biopsy is a feasible and safe approach to prostate cancer screening in men with a family history and detects a high proportion of prostate cancer that needs radical treatment. Calculating a polygenic risk score using prostate cancer risk single nucleotide polymorphisms could be a potential future screening tool for prostate cancer.

Background The syndemics theory seeks to understand the effect of multiple synergic problems in promoting poor health outcomes. To disentangle which and how syndemic conditions affect quality of life (QoL) may be important to improve well-being of people living with HIV/AIDS (PLWHA). This study evaluates the association between syndemic conditions and quality of life among people living with HIV/AIDS. METHODS This was a secondary analysis from data obtained between 2014 and 2017 among PLWHA under care in Rio de Janeiro, Brazil. The outcomes were the six QoL domains (physical, psychological, level of independence, social relationships, environmental, and spirituality) measured through the World Health Organization Quality of Life in HIV infection scale, abbreviated version (WHOQOL-HIV-BREF). The independent variables were demographic and clinical characteristics, syndemic conditions (binge drinking, compulsive sexual behavior, polysubstance use, intimate partner violence, and depression), and syndemics (two or more syndemic conditions simultaneously). Bivariate analysis (t-test and ANOVA) and linear regressions were performed for each quality-of-life domain. RESULTS The analytical sample comprised 1530 participants, mostly male at birth (64%) and with median age of 43 years. The syndemic conditions most frequently observed were binge drinking (56%), IPV (13%), and depression (9%). Both individual syndemic conditions and syndemics were associated with worse QoL. In the multivariate analysis, positive screening for depression was associated with worse QoL in all domains. Polysubstance users presented worse QoL at social and environmental domains. Intimate partner violence was associated with worse QoL at environment domain while binge drinking was associated with worse scores in the physical domain. The presence of syndemics increased the likelihood of worse scores in the psychological, social, and environment domains. CONCLUSIONS Our study expands the understanding of QoL in PLWHA, as it considers a holistic/integral, multifactorial, and synergistic approach to the determinants of QoL. Seeking strategies that target syndemics may be important to improve patient-centered outcomes in health.

Hereditary cancer risk syndromes are caused by germline variants. Most studies on hereditary cancer have been conducted in white populations. We report the largest study in Brazilian individuals with multiple ethnicities. We genotyped 1682 individuals from all regions of the country with Next-generation sequencing (NGS) panels. Most were women with personal/family history of cancer, mostly breast and ovarian. We identified 321 pathogenic/likely pathogenic (P/LP) variants in 305 people (18.1%) distributed among 32 genes. Most were on BRCA1 and BRCA2 (129 patients, 26.2% and 14.3% of all P/LP, respectively), MUTYH (42 monoallelic patients, 13.1%), PALB2 (25, 7.8%), Lynch syndrome genes (17, 5.3%), and TP53 (17, 5.3%). Transheterozygosity prevalence in our sample was 0.89% (15/1682). BRCA1/BRCA2 double heterozygosity rate was 0.78% (1/129) for BRCA variants carriers and 0.06% (1/1682) overall. We evaluated the performance of the genetic testing criteria by NCCN and Brazilian National Health Agency (ANS). We observed false negative rates of 17.3% and 44.2%, meaning that both failed to detect a substantial part of P/LP positive patients. Our results add knowledge on the Brazilian spectrum of cancer risk germline variants, demonstrate that large multigene panels have high rates of positivity, and indicate that Brazilian testing guidelines should be improved.

International audience; Thymic epithelial tumors are rare neoplastic proliferations of thymic epithelial cells. The aggressiveness of these malignancies increases as higher is the histologic subtype, being thymic carcinoma the most aggressive subtype, with a greater tendency to metastatic spread. In metastatic setting, there is no standard treatment after progression on platinum-based chemotherapy. In this scenario, monotherapy treatment either with lenvatinib, a multi-tyrosine kinase inhibitor with antiangiogenic properties, or pembrolizumab, an immune-checkpoint inhibitor, has reported clinical activity. Potential combination of both agents may have synergistic activity as reported in other cancer types. PECATI trial is a single-arm, investigator-initiated phase II study aiming to assess the activity and safety of the combination of lenvatinib and pembrolizumab in 43 patients with advanced B3-thymoma or thymic carcinoma who progressed on or after at least one previous line of platinum-based chemotherapy. The primary endpoint of the trial is 5-month progression-free survival rate and the secondary endpoints include overall response rate, duration of response, and overall survival.

Background Component resolved diagnosis can be very valuable for the diagnosis and treatment of honeybee venom allergy (HVA) patients. Our aim is to study whether any of the allergens not included in the usual diagnostic platforms are relevant in our population. Methods The allergenic sensitization profile of Spanish patients who suffered a systemic reaction after a honeybee sting and were diagnosed with HVA was studied by immunoblotting using raw autochthonous Apis mellifera venom obtained and characterized by SDS-PAGE and mass spectrometry and with a commercial assay (ImmunoCAP). Results Allergens described in the International Union of Immunological Societies (IUIS) database were detected in the A. mellifera raw venom extract used, except Api m 12. Sera from 51 patients with a median age of 46.2 years (interquartile range 35.6-54.6) were analyzed. Api m 1 and Api m 10 were detected as major allergens (88.2% and 74.5% respectively) using ImmunoCAP. Moreover, Api m 6 (85.4%) was found by immunoblotting. Conclusion Api m 1, Api m 6 and Api m 10 are major A. mellifera venom allergens recognized in our population.

Purpose: Prostate cancer (PCa) is the second most common oncologic disease among men. Radical treatment with curative intent provides good oncological results for PCa survivors, although definitive therapy is associated with significant number of serious side-effects. In modern-era of medicine tissue-sparing techniques, such as focal HIFU, have been proposed for PCa patients in order to provide cancer control equivalent to the standard-of-care procedures while reducing morbidities and complications. The aim of this systematic review was to summarise the available evidence about focal HIFU therapy as a primary treatment for localized PCa. Material and methods: We conducted a comprehensive literature review of focal HIFU therapy in the MEDLINE database (PROSPERO: CRD42021235581). Articles published in the English language between 2010 and 2020 with more than 50 patients were included. Results: Clinically significant in-field recurrence and out-of-field progression were detected to 22% and 29% PCa patients, respectively. Higher ISUP grade group, more positive cores at biopsy and bilateral disease were identified as the main risk factors for disease recurrence. The most common strategy for recurrence management was definitive therapy. Six months after focal HIFU therapy 98% of patients were totally continent and 80% of patients retained sufficient erections for sexual intercourse. The majority of complications presented in the early postoperative period and were classified as low-grade. Conclusions: This review highlights that focal HIFU therapy appears to be a safe procedure, while short-term cancer control rate is encouraging. Though, second-line treatment or active surveillance seems to be necessary in a significant number of patients.

Background: The coronavirus disease 2019 (COVID-19) pandemic led to the suspension or postponement of care for non-urgent conditions worldwide. Regula Mais Brasil is an initiative of the Unified Health System (SUS) in Brazil to optimize the management of referrals to specialized care by using telehealth. Objectives: To report the expansion of telehealth activities of Regula Mais Brasil in response to COVID-19 and to assess qualification of referrals in primary health care (PHC) units as well as the added value of teleconsultation in qualifying referral cases. Methods: Descriptive study of the teleconsultations carried out as an additional strategy to the remotely operated referral management system, responsible for navigating cases from PHC units to specialized care in Recife, Brazil, between May 6, 2020 and September 30, 2020. Teleconsultation was implemented as a tool for reducing delays in the access to health care due to COVID-19 and ultimately allowed for reclassification of the referral adequacy and priority. Changes in referral priority ratings and referral decisions after teleconsultation were analyzed. Results: A total of 622 referral cases were analyzed. Approved referrals represented 51.9% of cases. The main reason for approved referrals was the need for diagnostic resources. There was a reduction in priority ratings in 449 cases (72.2%) after teleconsultation. There was a statistically significant association between the change of priority ratings and the decision on referral (Pearson's χ2, p-value

No studies evaluating the rapidity of response to biological therapies are available for Crohn's disease (CD). The aim of this study was to evaluate rapidity of onset of clinical response and impact on quality of life (QoL) of adalimumab therapy in adult anti-TNF-naïve patients with moderately-to-severely active CD.RAPIDA was an open-label, single-arm, prospective, multicenter clinical trial. Adult patients with moderately-to-severely active luminal CD, anti-TNF-naïve, and unresponsive to conventional therapy were treated with adalimumab. Clinical disease activity, QoL and inflammatory biomarkers were measured at day 4, and weeks 1, 2, 4, and 12 after treatment initiation.Eighty-six patients were included in the intention-to-treat (ITT) analyses. Clinical disease activity was reduced from a median of 9.0 points to 6.0 points at day 4. Clinical response (≥ 3-point reduction in the Harvey-Bradshaw Index, HBI) was achieved by 61.6% (d4) and 75.6% (w1) of patients in the ITT population (median 2.5 days) and with non-responder imputation (NRI), by 55.8% and 53.4%, respectively. The proportion of patients in clinical remission (HBI5) at weeks 2 and 4 in the ITT population was 54.7% and 62.8%, respectively (median 7.0 days), and 38.4% and 45.3% in the NRI population. All QoL scores significantly improved and inflammatory biomarkers significantly decreased from day 4 onwards (p0.0001).Rapid clinical response and remission, improvement in QoL and fatigue, and a reduction of inflammatory biomarkers were achieved with adalimumab as early as day 4 in adult anti-TNF-naïve patients with moderately-to-severely active CD.

RATIONALE: Whether biomarkers can be used to predict response to inhaled corticosteroids (ICS) or long-acting muscarinic antagonists (LAMA) in mild persistent asthma is unclear. OBJECTIVES: In a prespecified exploratory analysis of a randomized clinical trial of 295 participants 12 years of age or older with uncontrolled mild persistent asthma, we sought to identify biomarkers of treatment response after 12 weeks of ICS (mometasone, 200 μg or 220 μg twice/d), LAMA (tiotropium, 5 μg/d), or placebo in adults (⩾18 yr) and adolescents (12–17 yr) separately. METHODS: The primary outcome was a composite outcome of asthma control (treatment failure, asthma control days, and forced expiratory volume in 1 second [FEV(1)]). Analyses examined type 2 inflammatory biomarkers and physiologic biomarkers. We assessed the area under the receiver operating characteristic curve (AUC) for response to ICS and LAMA (each versus placebo). An AUC of 0.5 suggests no discrimination, 0.7–0.8 is considered acceptable, more than 0.8–0.9 is considered excellent, and more than 0.9 is considered outstanding. RESULTS: In 237 adults, sputum and blood eosinophil levels and fractional exhaled nitric oxide (Fe(NO)) each predicted ICS response (AUCs: 0.61 [95% confidence interval (CI), 0.53–0.69], 0.64 [95% CI, 0.56–0.72], and 0.62 [95% CI, 0.54–0.70], respectively; all P

Aim: At presentation, 15–20% of patients with rectal cancer already have synchronous liver metastases. The aim of this study was to determine the surgical and survival outcomes in patients with advanced rectal cancer who underwent combined pelvic exenteration and liver (oligometastatic) resection. Method: Data from 20 international institutions that performed simultaneous pelvic exenteration and liver resection between 2007 and 2017 were accumulated. Primarily, we examined perioperative outcomes, morbidity and mortality. We also assessed the impact that margin status had on survival. Results: Of 128 patients, 72 (56.2%) were men with a median age of 60 years [interquartile range (IQR) 15 years]. The median size of the liver oligometastatic deposits was 2 cm (IQR 1.8 cm). The median duration of surgery was 406 min (IQR 240 min), with a median blood loss of 1090 ml (IQR 2010 ml). A negative resection margin (R0 resection) was achieved in 73.5% of pelvic exenterations and 66.4% of liver resections. The 30-day mortality rate was 1.6%, and 32% of patients had a major postoperative complication. The 5-year overall survival for patients in whom an R0 resection of both primary and metastatic disease was achieved was 54.6% compared with 20% for those with an R1/R2 resection (P = 0.006). Conclusion: Simultaneous pelvic exenteration and liver resection is feasible, with acceptable morbidity and mortality. Simultaneous resection should only be performed where an R0 resection of both pelvic and hepatic disease is anticipated.

Background: Plasma AR status has been identified as a potential biomarker of response in metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel or AR-targeted therapies. However, the relevance of plasma AR in the overall management of CRPC patients receiving different docetaxel doses is unknown. Patients and methods: This was a multi-institution study of associations between baseline plasma AR copy number status, assessed by droplet digital PCR, and outcome in 325 mCRPC patients receiving docetaxel at standard or adapted regimen at the discretion of the treating physician. Upon analysis, patients were assigned randomly to either a training (n = 217) or validation (n = 108) cohort. Results: In the training cohort, AR-gained patients treated with adapted docetaxel regimen had a significantly worse median progression-free survival (PFS) (3.8 vs 6.3 months, hazard ratio [HR] 2.58, 95% confidence interval [CI] 1.34–4.95, p < 0.0001), median overall survival (10.8 vs 20.6 months, HR 1.98, 95% CI 1.09–3.62, p = 0.0064) and PSA response (PSA > −50%: odds ratio 4.88 95%CI 1.55–14.32, p = 0.013) as compared to plasma AR normal patients. These findings were all confirmed in the validation cohort. However, in patients treated with standard docetaxel regimen, these differences were not seen. The interaction between AR CN status and dose reduction of docetaxel was considered as independent factor for PFS in both the training and validation cohort (HR 2.84, 95% CI 1.41–5.73, p = 0.003, and HR 4.79, 95% CI 1.79–12.82, p = 0.002). Conclusion: Despite the retrospective non-randomised design of this study, our hypothesis-generating findings could suggest plasma AR as a potential biomarker for optimal docetaxel timing and dose in mCRPC patients. Prospective trials are warranted.

Introducción. El reciente interés del uso de la dieta cetógenica como alternativa al tratamiento de obesidad, ha despertado la necesidad en los profesionales de la salud de volver a examinar los posibles beneficios de este estilo de alimentación. Objetivo. Resumir los antecedentes y sintetizar las diferentes aplicaciones de dietas cetogénicas en el tratamiento de la obesidad. Métodos. Se usaron tres bases de datos (PubMed, Google Scholar y Clinical Trials). Los términos usados en la búsqueda fueron dieta cetogénica, obesidad, cuerpos cetónicos, entre otros. Se combinaron con operadores lógicos como cetólisis, oxidación de ácidos grasos, regulación hormonal, saciedad, ejercicio, entre otros. Resultados. Se consideraron para la revisión un total de 23 artículos de reciente publicación con ensayos clínicos y aplicados en modelos animales. Los artículos excluidos no cumplieron con criterios de los niveles de evidencia y de la guía PRISMA. Conclusiones. Aunque se han demostrado los numerosos beneficios de las dietas cetogénicas, la utilización debe ir acompañada de un asesoramiento dietético y no abusar de su uso. El modelo de evolución de la nutrición es integrar e individualizar los diversos factores dietéticos que puedan contribuir a mejorar el estilo de vida a largo plazo.

Background: Anxiety and depression symptoms are known to increase cancer symptom burden, yet little is known about the longitudinal integrations of these among Hispanic/Latinx patients. The goal of this study was to explore the trajectory and longitudinal interactions among anxiety and depression, cancer symptom burden, and health-related quality of life in Hispanic/Latinx cancer patients undergoing chemotherapy. Methods: Baseline behavioral assessments were performed before starting chemotherapy. Follow-up behavioral assessments were performed at 3, 6, and 9 months after starting chemotherapy. Descriptive statistics, chi-square tests, Fisher’s exact tests, and Mann–Whitney tests explored associations among outcome variables. Adjusted multilevel mixed-effects linear regression models were also used to evaluate the association between HADS scores, follow-up visits, FACT—G scale, MDASI scale, and sociodemographic variables. Results: Increased cancer symptom burden was significantly related to changes in anxiety symptoms’ scores (adjusted β^ = 0.11 [95% CI: 0.02, 0.19]. Increased quality of life was significantly associated with decreased depression and anxiety symptoms (adjusted β^ = −0.33; 95% CI: −0.47, −0.18, and 0.38 adjusted β^= −0.38; 95% CI: −0.55, −0.20, respectively). Conclusions: Findings highlight the need to conduct periodic mental health screenings among cancer patients initiating cancer treatment.

BACKGROUND: In patients co-infected with HIV and tuberculosis, antiretroviral therapy options are limited due to drug—drug interactions with rifampicin. A previous phase 2 trial indicated that raltegravir 400 mg twice a day or efavirenz 600 mg once a day might have similar virological efficacy in patients given rifampicin. In this phase 3 trial, we assessed the non-inferiority of raltegravir to efavirenz. METHODS: We did a multicentre, open-label, non-inferiority, randomised, phase 3 trial at six sites in Côte d'Ivoire, Brazil, France, Mozambique, and Vietnam. We included antiretroviral therapy (ART)-naive adults (aged ≥18 years) with confirmed HIV-1 infection and bacteriologically confirmed or clinically diagnosed tuberculosis who had initiated rifampicin-containing tuberculosis treatment within the past 8 weeks. Using computerised random numbers, we randomly assigned participants (1:1; stratified by country) to receive raltegravir 400 mg twice daily or efavirenz 600 mg once daily, both in combination with tenofovir and lamivudine. The primary outcome was the proportion of patients with virological suppression at week 48 (defined as plasma HIV RNA concentration

Background & aims. Fragility fractures are those caused by low-energy trauma or falls from standing height. The mortality after the first year of suffering a hip fracture ranges from 15 to 30%. This problem has been addressed through the creation of interdisciplinary programs for fragility fracture early diagnosis and prevention. Describing the clinical characteristics of a cohort of patients diagnosed with fragility fractures in 10 fracture liaison services in Colombia. Methods. Led by the Asociaci n Colombiana de Osteoporosis y Metabolismo Mineral, this is a cross-sectional descriptive study, in patients with a diagnosis of fragility fracture in 10 fracture liaison services. Demographic and clinical variables were described for one year from the diagnosis of the fracture. Results. were analyzed 1699 records of patient fractures between 50 and 101 years of age, 1334 were women (76.5%), 581/1484 (39.1%) had previous fragility fractures, 570/1599 (35.7%) had a previous diagnosis of osteoporosis. Of these, 70/1051 (7%) received anti-osteoporosis medication, and 311/733 (42.4%) received it post-fracture. Of the total records with information, 65/707 (9.2%) died the following year of the fracture. Conclusions. Fracture prevention programs in institutions allow for de16 A. Medina et al. tecting patients with fragility fractures, clinical characteristics of these, in addition to strengthening the conditions of a centralized national registry, based on the parameters of the International Osteoporosis Foundation - Capture the Fracture program, through strategies with multidisciplinary personnel.

Síndrome de fatiga crònica; Diferències de gènere; Variabilitat de la freqüència cardíaca Síndrome de fatiga crónica; Diferencias de género; Variabilidad del ritmo cardíaco Chronic fatigue syndrome; Gender differences; Heart rate variability In a previous study using mobile-health technology (mHealth), we reported a robust association between chronic fatigue symptoms and heart rate variability (HRV) in female patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This study explores HRV analysis as an objective, non-invasive and easy-to-apply marker of ME/CFS using mHealth technology, and evaluates differential gender effects on HRV and ME/CFS core symptoms. In our methodology, participants included 77 ME/CFS patients (32 men and 45 women) and 44 age-matched healthy controls (19 men and 25 women), all self-reporting subjective scores for fatigue, sleep quality, anxiety, and depression, and neurovegetative symptoms of autonomic dysfunction. The inter-beat cardiac intervals are continuously monitored/recorded over three 5-min periods, and HRV is analyzed using a custom-made application (iOS) on a mobile device connected via Bluetooth to a wearable cardiac chest band. Male ME/CFS patients show increased scores compared with control men in all symptoms and scores of fatigue, and autonomic dysfunction, as with women in the first study. No differences in any HRV parameter appear between male ME/CFS patients and controls, in contrast to our findings in women. However, we have found negative correlations of ME/CFS symptomatology with cardiac variability (SDNN, RMSSD, pNN50, LF) in men. We have also found a significant relationship between fatigue symptomatology and HRV parameters in ME/CFS patients, but not in healthy control men. Gender effects appear in HF, LF/HF, and HFnu HRV parameters. A MANOVA analysis shows differential gender effects depending on the experimental condition in autonomic dysfunction symptoms and HF and HFnu HRV parameters. A decreased HRV pattern in ME/CFS women compared to ME/CFS men may reflect a sex-related cardiac autonomic dysfunction in ME/CFS illness that could be used as a predictive marker of disease progression. In conclusion, we show that HRV analysis using mHealth technology is an objective, non-invasive tool that can be useful for clinical prediction of fatigue severity, especially in women with ME/CFS. This research was funded by “Ministerio de Ciencia e Innovación” of the Spanish Government, grant number PID2019-107473RB-C2.

Las fracturas de diáfisis tibiales cerradas son las fracturas de huesos largos más comunes, siendo a su vez las fracturas de espina tibial (FET) que conllevan a inestabilidad y artrosis en la rodilla si no es tratada adecuada y oportunamente. El estudio fue observacional descriptivo con una población de 33 pacientes con fractura de espina tibial. De acuerdo con la clasificación de Meyers y Mc-Keever, el tipo I donde no existe desplazamiento y sólo el labio anterior de la espina están ligeramente elevado, sin exposición, fue el tipo de fractura más frecuente. Se obtuvo que el hueso tibial izquierdo fue ligeramente más frecuente (51,5 %) respecto al del lado derecho; el mecanismo de lesión más frecuente fue la hiperextensión de la rodilla (60,6 %), las causas más frecuentes de la lesión fueron accidente tránsito y la lesión deportiva (ambas representaron el 27,3 %). El 78,8 % de las fracturas no fueron expuestas y de acuerdo con la clasificación de Meyers y McKeever, el tipo I fue el tipo de fractura más frecuente (57,6 %). Dentro de las afecciones que suelen acompañar a la fractura de espina tibial, sólo un 15 % presentó afección meniscal y; sólo un 12 % presentó afección al platillo tibial.

Assessment of asthma comorbidities, conditions that adversely affect the pathobiology of asthma or impair its response to therapies, is a fundamental step in the evaluation and management of patients with difficult-to-treat asthma. Identifying and effectively treating asthma comorbidities, such as obesity, obstructive sleep apnea, and chronic sinusitis with nasal polyps may improve asthma control and reduce exacerbations. Additionally, identifying comorbid T2 inflammatory conditions may help guide optimal selection of biologic therapies. Here, we describe common comorbid conditions found in adult and pediatric difficult-to-control asthma, discuss evidence for the association with asthma morbidity and treatment benefit, and provide information on how and when to assess comorbidities.

To investigate a potential association between beta-blocker exposure and survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM).In this real-world prospective registry of 128 consecutive patients with ATTR-CM recruited in 7 institutions in Galicia (Spain), survival of 65 patients who received beta blockers on registry enrollment was compared with that of 63 untreated controls by means of both unweighted Cox regression and Cox regression with inverse probability of treatment weighting. Tolerance to and adverse effects of beta blockers were recorded. Median study follow-up was 520 days.Patients with ATTR-CM who received beta blockers showed statistically significant lower all-cause mortality than untreated controls as evaluated by either unweighted Cox regression (hazard ratio, 0.31; 95% CI, 0.12 to 0.79) or Cox regression with inverse probability of treatment weighting (hazard ratio, 0.18; 95% CI, 0.08 to 0.41; P.001). Several sensitivity analyses confirmed the internal validity of these results. The overall frequency of beta-blocker suspension due to adverse effects was 25% (95% CI, 15.5% to 34.5%).In this real-world, prospective, multi-institutional registry, patients with ATTR-CM who received beta blockers had lower all-cause mortality than untreated controls.

Pulmonary alveolar proteinosis is a rare disease characterized by progressive accumulation of lipoprotein material in the alveoli as a result of a dysfunction in surfactant clearance. The whole-lung lavage procedure is considered the current standard of care and consists of the sequential lavage of both lungs for mechanical removal of residual material in the alveoli. However, a lack of standardization has resulted in different procedural techniques among institutions. Even though whole-lung lavage is considered to be a safe procedure, unforeseen complications might occur, and proper knowledge of physiologic implications may allow clinicians to establish the appropriate therapy. This review provides an insight into the underlying physiology of the disease, the technical details of the procedure from an anesthesiologist's perspective, and discussion of potential intraoperative complications.

Exudative retinal detachment (ERD) is a rare complication that occurring in 1% of patients with preeclampsia, its incidence is increased when it is associated with HELLP syndrome. Preeclampsia is defined by the development of arterial hypertension and proteinuira occurs after 20 weeks of gestation until postpartum. HELLP syndrome (low platelets, hemolysis and elevated liver enzymes) is a severe form of preeclampsia. ERD in preeclampsia is related to choroidal ischaemia, in the vast majority of the cases associated with hypertensive retinopathy. However, it has been proposed that the combination of hypertension with a microangiopathic hemolysis, hipercoagulability and hypoalbuminemia are the main factors contributing to the development of ERD. Its treatment includes a rapid resolution of labor to reverse ocular manifestations and prevent visual sequels. We describe the case of a pregnant woman with atypical preeclampsia who, in the postpartum of a cesarean, presented an ERD concomitantly with a HELLP syndrome.

Despite a series of advances in the establishment of specialized services for women in all regions of the country, many still face great difficulties in accessing abortion services. Even in relation to anencephaly, there are still challenges for the proper structuring of legal abortion services, as it is difficult to identify health professionals available for abortion care permitted by law. This article discusses the issues involved in these cases. It was concluded that, due to the moral and religious stigma, there is a refusal of doctors related to the practice of abortion, despite the existence of Brazilian technical norms that regulate this practice. However, the right to conscientious objection is not necessarily recognized in the absence of another medical professional to assist women when there is a risk of death. Keywords: Anencephaly, Abortion, Women's Rights.

Resumen Introduccion El gen ATXN2 presenta un VNTR (CAG)n con locus en el exon 1, los alelos largos dentro del rango normal (22-29 repeticiones) se asocian con obesidad severa en sujetos del Reino Unido, Indonesia y el Caribe. Objetivo Analizar la influencia del VNTR (CAG)n del gen ATXN2 en el perfil metabolico en adultos con obesidad y preobesidad asi como analizar su asociacion con parametros metabolicos y ambientales de riesgo cardiovascular. Metodos y materiales Se incluyeron 255 adultos de origen etnico amerindio chinanteca a quienes se les realizo evaluacion antropometrica y bioquimica. El VNTR fue amplificado por PCR punto final y electroforesis PAGE al 8%. Resultados Se encontraron diferencias en la circunferencia indice cintura/cadera e indice de masa corporal en los portadores de genotipos diferentes al homocigoto de 22 repeticiones con un valor para la prueba t de Student de 0,0041 y 0,0334 respectivamente. Tambien encontramos asociacion con la historia familiar de enfermedad cronica. Conclusion El VNTR de ATXN2 se asocia al grado de obesidad en adultos mexicanos con ancestria chinanteca.

The onset and mechanisms underlying neurodegenerative diseases remain uncertain. The main features of neurodegenerative diseases have been related with cellular and molecular events like neuronal loss, mitochondrial dysfunction and aberrant accumulation of misfolded proteins or peptides in specific areas of the brain. The most prevalent neurodegenerative diseases belonging to age-related pathologies are Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis. Interestingly, mitochondrial dysfunction has been observed to occur during the early onset of several neuropathological events associated to neurodegenerative diseases. The master regulator of mitochondrial quality control and energetic metabolism is the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Additionally, it has been observed that PGC-1α appears to be a key factor in maintaining neuronal survival and synaptic transmission. In fact, PGC-1α downregulation in different brain areas (hippocampus, substantia nigra, cortex, striatum and spinal cord) that occurs in function of neurological damage including oxidative stress, neuronal loss, and motor disorders has been seen in several animal and cellular models of neurodegenerative diseases. Current evidence indicates that PGC-1α upregulation may serve as a potent therapeutic approach against development and progression of neuronal damage. Remarkably, increasing evidence shows that PGC-1α deficient mice have neurodegenerative diseases-like features, as well as neurological abnormalities. Finally, we discuss recent studies showing novel specific PGC-1α isoforms in the central nervous system that appear to exert a key role in the age of onset of neurodegenerative diseases and have a neuroprotective function in the central nervous system, thus opening a new molecular strategy for treatment of neurodegenerative diseases. The purpose of this review is to provide an up-to-date overview of the PGC-1α role in the physiopathology of neurodegenerative diseases, as well as establish the importance of PGC-1α function in synaptic transmission and neuronal survival.

Background: It is well known that the family environment is associated with child health behavior and outcomes. However, there is a lack of available instruments to measure family health behaviors, even more so in languages other than English. The aim of the present study was to adapt and validate the Family Health Behavior Scale (FHBS) for Brazilian families.Methods: The FHBS was translated and culturally adapted for the Brazilian families. Psychometric properties (content validity, construct validity, and concurrent validity) and reliability (internal consistency, ceiling-floor effect, and test-retest) were evaluated in a sample of healthy community-dwelling children who were between 5 to 12 years old, of both sexes. Caregivers responded to the FHBS. Concurrent validity was assessed by comparing the FHBS scale with Body Mass Index (BMI) percentile, percent body fat, and physical activity level.Results: 272 children (54% girls) with a mean age of 7.9 years (SD = 2.0) and their caregivers were tested. Confirmatory analysis of the initial 4-factor structure (as proposed in the original English version of the questionnaire) suggested its performance was below acceptable. Exploratory factor analysis showed however an acceptable fit (Kaiser-Meyer-Olkin index = 0.79), and the factor loadings suggested a 7-factor model. Children who were considered obese (BMI percentile ≥ 97) had lower mean total FHBS scores than children who had a healthy weight or were overweight. Children who were classified as having a healthy fat percentage had higher FHBS scores than children classified as having an excessively high fat percentage. Children who were physically active had significantly higher total FHBS scores than children who were physically inactive. Cronbach's alpha was 0.81 and we noted acceptable values of the ceiling-floor effect. Test-retest analyses showed lower agreement and intraclass correlation coefficients ​​than expected 0.63 (95% CI 0.41 to 0.78).Conclusion: The adapted Family Health Behavior Scale for the Brazilian population showed adequate psychometric properties.

Background and Aims Obesity affects metabolism, increasing the risk of developing non-communicable diseases in adolescence, due to excess adipose tissue and low cardiorespiratory fitness (CRF). The metabolomics approach allows the elucidation of metabolites, which may have the concentrations altered by several factors, such as body composition (BC). We aimed to analyze the metabolomic profile of adolescents with normal and overweight and associate the metabolites with clinical markers related to BC, insulin resistance (IR), and CRF. Methods and Results The sample was composed of 57 adolescents, divided into normal-weight (NWG, n = 24) and overweight (OWG, n = 33) groups. They underwent blood collection, anthropometric, BC, and CRF assessment. Blood serum samples were analyzed by 1H-NMR spectroscopy (600 MHz). The OWG presented higher values of body weight (BW), body mass index (BMI), waist circumference (WC), fasting glucose, insulin, IR, cholesterol, percentage of fat mass (% FM), and lower levels of V O2peak compared to NWG. The OWG presented lower concentrations of 3-hydroxyisovalerate, glutamate, and methionine, as well as higher concentrations of aspartate, asparagine, creatine, glycerol, myo-inositol, proline, pyruvate, tyrosine, and valerate compared to NWG. The concentrations of glutamate, myo-inositol, creatine, methionine, and valerate correlated with % FM, pyruvate, and valerate positively correlated with IR, while glutamate, tyrosine, and valerate negatively correlated with CRF. Conclusion Body composition changes the metabolomic profile of adolescents, and the altered metabolites are associated with increased IR and low CRF. These results suggest new targets for health monitoring, prevention of cardiovascular and metabolic diseases in adolescents.

Resumen: Antecedentes y objetivos: Comparar la morbimortalidad, el tiempo de estancia hospitalaria y el gasto económico de la fractura por fragilidad de cadera en 2 años no consecutivos gracias a la atención ortogeriátrica integrada. Material y método: Estudio observacional retrospectivo de cohorte con 633 pacientes con fractura por fragilidad de cadera, con una media de edad de 85,5 años, tratados en un mismo servicio de cirugía ortopédica y traumatología en 2 años diferentes (2012 y 2017). Se midieron la estancia media, la demora quirúrgica, la mortalidad perioperatoria, al mes y al año, y las complicaciones perioperatorias como la retención aguda de orina, las úlceras por presión y la necesidad de transfusión. Resultados: La mortalidad durante el ingreso disminuyó del 10% en 2012 al 3,6% en 2017 (p = 0,004), a la vez que la mortalidad a los 30 días (10,5% frente a 7%) (p = 0,123) y al año (28,9% frente a 24,9%) (p = 0,277). También disminuyeron los tiempos de estancia hospitalaria, la demora quirúrgica y el tiempo de ingreso postoperatorio. El ahorro económico total anual estimado gracias a la atención ortogeriátrica integrada supuso 1.017.084,94 €. Conclusiones: La atención ortogeriátrica integrada del paciente con fractura por fragilidad de la cadera resulta en un modelo de atención más efectivo y eficiente. Se mejora tanto la calidad asistencial como la situación clínica de los pacientes en el periodo perioperatorio, se disminuyen significativamente tanto la estancia hospitalaria como la mortalidad durante el ingreso, y todo ello con un importante ahorro económico asociado. Abstract: Background and objectives: Compare the morbidity and mortality, the length of hospital stay and the economic cost of the fragility fracture of the hip, in two nonconsecutive years thanks to the integrated orthogeriatric care. Material and method: Retrospective observational cohort study with 633 patients with hip fragility fracture with a mean age of 85.5 years, treated in the same Trauma and Orthopaedic Surgery service in two different years (2012 and 2017). Mean stay, surgical delay, perioperative mortality, one month and one year, and perioperative complications such as acute urine retention, pressure ulcers, and need for transfusion were measured. Results: Mortality during admission decreased from 10% in 2012 to 3.6% in 2017 (P = .004 *), while mortality at thirty days (10.5% vs 7%) (P = .123) and one year (28.9% versus 24.9%) (P = .277). Hospital stay times, surgical delay, and postoperative admission time also decreased. The estimated total annual economic savings thanks to integrated orthogeriatric care amounted to € 1,017,084.94. Conclusions: Integrated orthogeriatric care of the patient with fragility fracture of the hip, results in a more effective and efficient care model. Both the care and the clinical situation of patients are improved in the perioperative period, both hospital stay and mortality during admission are significantly reduced, and all this with significant associated economic savings.