Effect of intraspecific seed trait variation on the germination of eight tropical dry forest species.

Functional traits can have intraspecific and interspecific variations essential in the structure and dynamics of natural communities. These traits may have implications in the germination and seedling establishment phases in seeds. The objective of this study was to evaluate the effect of variations in mass, volume, and nutrient content (C, N, and P) on the germination of eight species representative of the tropical dry forest (TDF). Our results showed that seed size, both in terms of mass and volume, did not predict germination rates or percentages, nor were they related to nutrient content. In contrast, N content was the most important trait in the germination phase. Larger seeds did not germinate more or faster, but they could offer better resistance against desiccation, since they had higher C/N ratios in their tissues, a characteristic of orthodox seeds. The species A. guachapele, B. arborea, H. crepitans, and V. tortuosa presented a high biological potential in terms of their regeneration capacity, particularly, because the characteristics of their seeds, as well as the nutrient content, revealed consistent implications in their reproductive success, promoting high germination percentages in less time. In general, the results obtained in this study provide basic knowledge for future research, offering starting points for further exploration of species-specific adaptations and how they may be affected by the environment.

Corrigendum: Sex differences in the genetics of sarcoidosis across European and African ancestry populations.

[This corrects the article DOI: 10.3389/fmed.2023.1132799.].

Low-Flow, Low-Gradient Severe Aortic Stenosis in patients with preserved or reduced ejection fraction: a systematic literature review.

OBJECTIVES: A systematic review of the literature was conducted to analyze the current evidence on low-flow, low-gradient severe aortic stenosis. This analysis aimed to differentiate between subgroups of patients with reduced and preserved left ventricular ejection fraction (LVEF). METHODS: After conducting a systematic literature review, 35 observational studies were included. Out of these, 28 were prospective and 7 retrospective. The studies that included a mortality risk stratification of low-flow, low-gradient aortic stenosis (LF- LG AS) with both preserved and reduced LVEF were reviewed. RESULTS: The importance of considering multiple clinical and echocardiographic variables in diagnostic evaluation and therapeutic decision-making was highlighted. CONCLUSIONS: LF- LG AS, in any of its subgroups, is a common and challenging valve lesion. A careful assessment of severity and, in specific scenarios, a thorough reclassification is important. More high-quality studies are required to more precisely define the classification and prognosis of this entity.

Myxoma Mimic in a Patient With Acute Myeloid Leukemia.

Cardiac masses are rare conditions that, depending on their size and location, can cause several cardiac and systemic symptoms. We describe a case of a 21-year-old male with a history of syphilis, pulmonary tuberculosis, and acute myeloid leukemia (AML), in whom a transthoracic echocardiogram assessment was solicited before the initiation of induction chemotherapy. The study revealed a pedunculated, highly mobile mass in the right atrium that protruded to the right ventricle. Surgical resection was performed. During surgery, tricuspid valve perforation was noted and was associated with severe tricuspid valve regurgitation. Histopathological analysis of the resected mass determined that the lesion was a cardiac thrombus.

Peripheral blood lymphopenia in sarcoidosis associates with HLA-DRB1 alleles but not with lung immune cells and organ involvement.

Different human leukocyte antigen (HLA) alleles associate with disease phenotypes in sarcoidosis. Peripheral blood (PB) lymphopenia is reported as more common in sarcoidosis patients with worse prognosis. The mechanisms behind are unrecognized but a PB depletion due to lymphocytes migrating to lung and/or extra pulmonary organs has been suggested. Insights into associations between HLA alleles, lung immune cells, clinical phenotype including extra pulmonary manifestations (EPM), and PB lymphopenia may provide mechanistic clues and enable adequate intervention in this patient group. In this situdy,141 treatment naïve, newly diagnosed patients were retrospectively identified in a Swedish cohort of sarcoidosis patients. Data on HLA-DRB1 alleles, lung immune cells from bronchoalveolar lavage fluid (BALF), PB lymphocytes and clinical parameters including treatment and disease course (chronic vs. resolving) were collected. The patients were followed for 2 years. PB lymphopenia associated with male sex, development of non-resolving disease, a need for first- and second-line systemic immunosuppressant treatment and HLA- DRB1*07. No correlation between BALF and PB lymphocytes, and no difference in EPM was detected between patients with and without PB lymphopenia. In conclusion, PB lymphopenia is associated with a more severe disease phenotype and carriage of the HLA-DRB1*07 allele. The results do not lend support to the hypothesis about sarcoidosis PB lymphopenia being due to a migration of PB lymphocytes to other organs. Rather, they provide a basis for future studies on the connection between HLA-DRB1*07 and PB lymphopenia mechanisms.

From Karl Wurm and Guy Scadding's staging to 18F-FDG PET/CT scan phenotyping and far beyond: perspective in the evading history of phenotyping in sarcoidosis.

Sarcoidosis is an inflammatory granulomatous disease of unknown etiology involving any organ or tissue along with any combination of active sites, even the most silent ones clinically. The unpredictable nature of the sites involved in sarcoidosis dictates the highly variable natural history of the disease and the necessity to cluster cases at diagnosis based on clinical and/or imaging common characteristics in an attempt to classify patients based on their more homogeneous phenotypes, possibly with similar clinical behavior, prognosis, outcome, and therefore with therapeutic requirements. In the course of the disease's history, this attempt relates to the availability of a means of detection of the sites involved, from the Karl Wurm and Guy Scadding's chest x-ray staging through the ACCESS, the WASOG Sarcoidosis Organ Assessment Instruments, and the GenPhenReSa study to the 18F-FDG PET/CT scan phenotyping and far beyond to new technologies and/or the current "omics." The hybrid molecular imaging of the 18F-FDG PET/CT scan, by unveiling the glucose metabolism of inflammatory cells, can identify high sensitivity inflammatory active granulomas, the hallmark of sarcoidosis-even in clinically and physiologically silent sites-and, as recently shown, is successful in identifying an unexpected ordered stratification into four phenotypes: (I) hilar-mediastinal nodal, (II) lungs and hilar-mediastinal nodal, (III) an extended nodal supraclavicular, thoracic, abdominal, inguinal, and (IV) all the above in addition to systemic organs and tissues, which is therefore the ideal phenotyping instrument. During the "omics era," studies could provide significant, distinct, and exclusive insights into sarcoidosis phenotypes linking clinical, laboratory, imaging, and histologic characteristics with molecular signatures. In this context, the personalization of treatment for sarcoidosis patients might have reached its goal.

Sex differences in the genetics of sarcoidosis across European and African ancestry populations.

Background: Sex differences in the susceptibility of sarcoidosis are unknown. The study aims to identify sex-dependent genetic variations in two clinical sarcoidosis phenotypes: Löfgren's syndrome (LS) and non-Löfgren's syndrome (non-LS). Methods: A meta-analysis of genome-wide association studies was conducted on Europeans and African Americans, totaling 10,103 individuals from three population-based cohorts, Sweden (n = 3,843), Germany (n = 3,342), and the United States (n = 2,918), followed by an SNP lookup in the UK Biobank (UKB, n = 387,945). A genome-wide association study based on Immunochip data consisting of 141,000 single nucleotide polymorphisms (SNPs) was conducted in the sex groups. The association test was based on logistic regression using the additive model in LS and non-LS sex groups independently. Additionally, gene-based analysis, gene expression, expression quantitative trait loci (eQTL) mapping, and pathway analysis were performed to discover functionally relevant mechanisms related to sarcoidosis and biological sex. Results: We identified sex-dependent genetic variations in LS and non-LS sex groups. Genetic findings in LS sex groups were explicitly located in the extended Major Histocompatibility Complex (xMHC). In non-LS, genetic differences in the sex groups were primarily located in the MHC class II subregion and ANXA11. Gene-based analysis and eQTL enrichment revealed distinct sex-specific gene expression patterns in various tissues and immune cell types. In LS sex groups, a pathway map related to antigen presentation machinery by IFN-gamma. In non-LS, pathway maps related to immune response lectin-induced complement pathway in males and related to maturation and migration of dendritic cells in skin sensitization in females were identified. Conclusion: Our findings provide new evidence for a sex bias underlying sarcoidosis genetic architecture, particularly in clinical phenotypes LS and non-LS. Biological sex likely plays a role in disease mechanisms in sarcoidosis.

Maternal rheumatoid arthritis and risk of autism in the offspring.

BACKGROUND: Maternal Rheumatoid Arthritis (RA) is suggested to increase the risk of Autism Spectrum Disorder (ASD) in the offspring, mainly through inflammation/autoimmunity, but the association is unclear. A prospective population-based cohort study was implemented to examine the association between maternal RA and offspring ASD. METHODS: We included all children born alive in Sweden from 1995 to 2015, followed up through 2017. Diagnoses of ASD and RA were clinically ascertained from National Patient Register. We quantified the association by hazard ratios (HR) and two-sided 95% confidence intervals (CI), from Cox regression after detailed adjustment for potential confounders. We examined RA serostatus, etiological subgroups and the timing of exposure. To closer examine the underlying mechanism for the association, we included a negative control group for RA, arthralgia, with similar symptomology as RA but free from inflammation/autoimmunity. RESULTS: Of 3629 children born to mothers with RA, 70 (1.94%) were diagnosed with ASD, compared to 28 892 (1.92%) of 1 503 908 children born to mothers without RA. Maternal RA before delivery was associated with an increased risk of offspring ASD (HR = 1.43, 95% CI 1.11-1.84), especially for seronegative RA (HR = 1.61, 95% CI 1.12-2.30). No similar association was observed for paternal RA, maternal sisters with RA, or RA diagnosed after delivery. Maternal arthralgia displayed as high risks for offspring ASD as did maternal RA (HR = 1.41, 95% CI 1.24-1.60). CONCLUSIONS: In Sweden, maternal RA before delivery was associated with an increased risk of offspring ASD. The comparable association between maternal arthralgia and ASD risk suggests other pathways of risk than autoimmunity/inflammation, acting jointly or independently of RA.

Functional link between sarcoidosis-associated gene variants and quantitative levels of bronchoalveolar lavage fluid cell types.

Background: Sarcoidosis is an inflammatory disease that affects multiple organs. Cell analysis from bronchoalveolar lavage fluid (BALF) is a valuable tool in the diagnostic workup and differential diagnosis of sarcoidosis. Besides the expansion of lymphocyte expression-specific receptor segments (Vα2.3 and Vß22) in some patients with certain HLA types, the relation between sarcoidosis susceptibility and BAL cell populations' quantitative levels is not well-understood. Methods: Quantitative levels defined by cell concentrations of BAL cells and CD4+/CD8+ ratio were evaluated together with genetic variants associated with sarcoidosis in 692 patients with extensive clinical data. Genetic variants associated with clinical phenotypes, Löfgren's syndrome (LS) and non-Löfgren's syndrome (non-LS), were examined separately. An association test via linear regression using an additive model adjusted for sex, age, and correlated cell type was applied. To infer the biological function of genetic associations, enrichment analysis of expression quantitative trait (eQTLs) across publicly available eQTL databases was conducted. Results: Multiple genetic variants associated with sarcoidosis were significantly associated with quantitative levels of BAL cells. Specifically, LS genetic variants, mainly from the HLA locus, were associated with quantitative levels of BAL macrophages, lymphocytes, CD3+ cells, CD4+ cells, CD8+ cells, CD4+/CD8+ ratio, neutrophils, basophils, and eosinophils. Non-LS genetic variants were associated with quantitative levels of BAL macrophages, CD8+ cells, basophils, and eosinophils. eQTL enrichment revealed an influence of sarcoidosis-associated SNPs and regulation of gene expression in the lung, blood, and immune cells. Conclusion: Genetic variants associated with sarcoidosis are likely to modulate quantitative levels of BAL cell types and may regulate gene expression in immune cell populations. Thus, the role of sarcoidosis-associated gene-variants may be to influence cellular phenotypes underlying the disease immunopathology.

COVID-19, rinovirus y asma... ¿Una mala combinación? / COVID-19, rhinovirus and asthma... a bad conmbination?

La pandemia de COVID-19 enfrentó a la humanidad a un gran desafío y hemos ido aprendiendo a medida que avanzó. La aparición de este virus, su comportamiento por si solo y en conjunto con los otros virus nos mantuvo alerta.. Los pacientes pediátricos asmáticos, a pesar de lo que se pensó en un principio, son menos afectados y hacen un cuadro clínico más leve. Objetivo: presentar un caso clínico de un paciente asmático, con una evolución tortuosa por co-infección SARS-CoV-2 y Rinovirus (RV) y revisión de la litaratura. Se trata de un escolar de 6 años, asmático con mal control, con 2 dosis de vacuna anti SARS-CoV-2, que presento un estado asmático por rinovirus y posterior evolución con neumonía grave por SARS-CoV-2, requiriendo ventilación mecánica invasiva y estadía en UCI Pediátrica. Es probable que la gravedad del caso presentado se deba al mal control del asma antes de la infección, ya que se ha visto que los niños asmáticos alérgicos presentan un factor protector para infección grave por SARS-CoV-2, lo cual esta supeditado a un buen control de su enfermedad basal.

The COVID-19 pandemic presented a great challenge and we have been learning as it has progressed. The appearance of this virus, its behavior by itself and in conjunction with the other viruses kept us alert. Pediatric asthmatic patients, despite what was initially thought, are less affected and present a milder clinical picture. Objective: to present a clinical case of an asthmatic patient, with a tortuous evolution due to SARS-CoV-2 and Rhinovirus (RV) co-infection and a literature review. This is a 6-year-old schoolboy, asthmatic with poor control, with 2 doses of the SARS-CoV-2 vaccine, who presents asthmatic status due to rhinovirus and subsequent evolution with severe pneumonia due to SARS-CoV-2, requiring invasive mechanical ventilation and stay in Pediatric ICU. It is likely that the severity of the case presented is due to poor asthma control before infection, since it has been seen that allergic asthmatic children present a protective factor for severe infection by SARS-CoV-2, which is subject to good control of his basal disease.

Taquicardia ventricular asociada a mutación en el gen de ankirina B / Ventricular tachycardia associated to a mutation in the ankyrin B gen

Resumen Se presenta el caso de una mujer de 14 años, con taquicardiomiopatía secundaria a taquicardia ventricular. Se evidenció la presencia de una variante de significado incierto en el gen ANK2, por lo que se consideró un posible síndrome de ankirina B. La paciente fue tratada con éxito a través de ablación con radiofrecuencia. Tras dicho procedimiento, tuvo recuperación completa de su función ventricular izquierda y resolución de los complejos ventriculares prematuros y los episodios de taquicardia ventricular.

Abstract We report a case of a 14-year-old with tachycardiomyopathy due to ventricular tachycardia. A variant of uncertain significance of the ANK2 gene was identified, which is suggestive of a possible ankyrin-B syndrome. The patient underwent a successful radiofrequency ablation. After the procedure, the patient completely recovered her left ventricular function and there was resolution of the premature ventricular complexes and ventricular tachycardia.

Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention.

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention.

Sarcopenic Dysphagia Is Associated With Mortality in Institutionalized Older Adults.

OBJECTIVE: To estimate mortality associated with sarcopenic dysphagia. DESIGN: A 3-year follow-up cohort. SETTING AND PARTICIPANTS: Ninety-five nursing home residents were evaluated to determine the baseline presence or absence of oropharyngeal dysphagia and followed up for 3 years. METHODS: The primary outcome was the risk of death. Dysphagia was assessed using a volume-viscosity swallow test. We used an algorithm to determine sarcopenic dysphagia based on grip strength, walking speed, calf circumference, and exclusion of neurologic or structural causes of dysphagia. We constructed 3 subgroups: without dysphagia, nonsarcopenic dysphagia, and sarcopenic dysphagia. Cox proportional regression analyses were used to predict the risk of death. RESULTS: Thirty-five percent of participants had no dysphagia, 20% nonsarcopenic dysphagia, and 45% sarcopenic dysphagia. Sarcopenic dysphagia was independently associated with a higher risk of death [hazard ratio (HR) 2.44, 95% CI 1.02-5.80, P = .043] than without dysphagia. In addition, a higher Charlson Comorbidity Index score was associated with a higher risk of death (HR 1.33, 95% CI 1.01-1.75, P = .040). CONCLUSIONS AND IMPLICATIONS: This study shows that sarcopenic dysphagia was associated with increased mortality among institutionalized older adults. These deaths could be potentially preventable.

Hipertensión arterial esencial: ¿cuál agente antihipertensivo elegir? / Essential hypertension: which antihypertensive agent to choose?

Resumen Introducción: La hipertensión arterial sistémica (HTA) constituye el principal factor de riesgo para morbilidad y mortalidad cardiovascular a nivel global, afecta a todas las edades, sin distinción de género y etnicidad. Su tratamiento continúa constituyendo un reto, dada la persistencia del pobre control, especialmente en países como Colombia. Objetivo: Mostrar la evidencia disponible respecto al tratamiento actualizado de la HTA y la elección certera de los agentes antihipertensivos acorde con la individualidad de cada paciente. Asimismo, consolidar y comparar el efecto hipotensor de cada agente antihipertensivo más usado. Metodología: Se realizó una búsqueda avanzada con los términos DeCS y MeSH: hipertensión, agentes antihipertensivos, hipertensión esencial y terapia combinada, en los motores de búsqueda PubMed, Clinical Key, Lilacs, Scielo. Un total de 109 artículos se seleccionaron para elaborar en la presente revisión de la literatura. Conclusiones: La individualización del manejo de la HTA lleva al reconocimiento de los distintos fenotipos, la presencia de complicaciones, el examen físico, el género y la raza como puntos fundamentales para elegir el agente antihipertensivo más adecuado que permita alcanzar las metas de control y propenda por la reducción y prevención de las complicaciones derivadas de un control no óptimo.

Abstract Introduction: Systemic arterial hypertension (HT) constitutes the main risk factor for cardiovascular morbidity and mortality at a global level, affecting all ages regardless of gender and ethnicity. Its treatment continues to be a challenge, given the persistence of poor control, especially in countries like Colombia. Objective: To show the available evidence regarding the updated treatments of HT and the correct choice of antihypertensive agents according to the individual needs of each patient. Likewise, to consolidate and compare the hypotensive effect of the most used antihypertensive agents. Methodology: An advanced search was carried out with the terms DeCS and MeSH: Hypertension, antihypertensive agents, Essential Hypertension and Combination Therapy through the search engines PubMed, Clinical Key, Lilacs, Scielo. A total of 109 articles were selected to prepare the present literature review. Conclusions: An individualized hypertension treatment plan leads to the recognition of the different phenotypes, the presence of complications, the gender, and race, which are fundamental aspects to consider when choosing the appropriate antihypertensive agents. These findings allow for the achievement of the desired blood pressure target and leads to reduction and prevention of complications derived from suboptimal control.

Definición de displasia broncopulmonar propuesta por la Comisión Neo SOCHINEP / Definition of bronchopulmonary dysplasia proposed by the Neo SOCHINEP Commission

La displasia broncopulmonar (DBP) es la enfermedad crónica más frecuente del recién nacido prematuro. Los avances en su prevención y tratamiento han permitido una mayor sobrevida de prematuros más pequeños, pero su incidencia se ha mantenido estable en el tiempo, con una fisiopatología y presentación clínica que abarca un amplio espectro y que difiere de la DBP descrita originalmente hace más de 50 años. Aún existen controversias en su definición, la que se ha establecido en base al tratamiento, específicamente al requerimiento de soporte respiratorio. Las definiciones más utilizadas son el requerimiento de oxígeno por 28 días y a las 36 semanas de edad gestacional corregida (EGC). Recientemente se ha propuesto definirla en base al requerimiento de ventilación mecánica a las 36 semanas de EGC, lo que identificaría a los prematuros con DBP más grave y mayor probabilidad de complicaciones respiratorias y neurológicas en los 2 primeros años de vida. Nuestro objetivo en la comisión de Neo-SOCHINEP es el de recomendar la definición y clasificación que nos parece más adecuada para identificar a los prematuros portadores de DBP, considerando los aspectos fisiopatológicos, del compromiso de la función pulmonar y consecuencias prácticas de la definición en nuestro medio. También proponemos la definición del requerimiento de oxígeno en el prematuro cuando esta en neonatología, las condiciones e interpretación de la saturometría contínua cuando está pronto al alta y el seguimiento de la oxigenoterapia posterior al alta.

Bronchopulmonary dysplasia (BPD) is the most frequent chronic disease of the premature newborn. Advances in its prevention and treatment have allowed a greater survival of smaller preterm infants, but its incidence has remained stable over time, with a pathophysiology and clinical presentation that covers a wide spectrum and differs from the BPD originally described more than 50 years ago. There are still controversies in its definition, which has been established based on the treatment, specifically the requirement of respiratory support. The most used definitions are the oxygen requirement for 28 days and at 36 weeks of postmenstrual age (PMA). It has recently been proposed a definition based on the requirement of mechanical ventilation at 36 weeks of PMA, which would identify premature infants with more severe BPD and a greater probability of respiratory and neurological complications in the first 2 years of life. Our objective in the Neo-SOCHINEP commission is to recommend the definition and classification that we believe is most appropriate to identify premature infants with BPD, considering the pathophysiological aspects, the compromised lung function, and practical consequences of the definition in our medium. We also propose the definition of the oxygen requirement in premature infants when they are in neonatology, the conditions and interpretation of continuous saturation when they are soon discharged, and the follow-up of post-discharge oxygen therapy.

Angioplastia con balón de venas pulmonares por estenosis tras ablación percutánea de fibrilación auricular / Balloon angioplasty of pulmonary vein stenosis after percutaneous ablation of atrial fibrillation

Resumen Se presenta el caso de un hombre de 31 años, con historia de fibrilación auricular paroxística, a quien se realizó exitosamente una ablación por radiofrecuencia de venas pulmonares guiada por un sistema de mapeo tridimensional EnSite™. Tres meses después del procedimiento presentó hemoptisis y dolor torácico de características pleuríticas, motivo por el cual se le realizó una angiotomografía computarizada coronaria que evidenció una estenosis grave de la vena pulmonar superior izquierda y una estenosis moderada de la vena inferior izquierda. El paciente fue sometido a angioplastia con balón, con la cual se normalizó la perfusión pulmonar.

Abstract We report the case of a 31-year-old male patient with a history of paroxysmal atrial fibrillation, who underwent a successful radiofrequency pulmonary vein ablation using EnSite™ three-dimensional mapping system. Three months after the procedure, patient presented with hemoptysis and pleuritic chest pain. A coronary computed tomography angiography was performed, which showed a severe left superior pulmonary vein stenosis and a moderate left inferior pulmonary vein stenosis. A balloon angioplasty was performed with subsequent restoration of pulmonary perfusion.

Effects of infliximab on lung and circulating natural killer cells, CD56+ T cells and B cells in sarcoidosis.

BACKGROUND: Tumour necrosis factor α (TNF-α) is pivotal in sarcoid granuloma formation, and inhibitors of TNF-α offer an attractive third-line treatment option in sarcoidosis. The sarcoid inflammation is characterised by an exaggerated T helper 1 response, and evidence indicates a contribution of dysregulated and/or deficient NK (natural killer) cells, CD56+ T cells and B cells. OBJECTIVES: Insight into how TNF-α inhibitors influence these cells may provide more information on inflammatory mechanisms in sarcoidosis and improve understanding of such treatment. We therefore evaluated treatment effects of the TNF-α inhibitor infliximab on lung and peripheral blood (PB) NK, CD56+ T cells and B cells. METHODS: Fifteen patients were assessed with PB samples, spirometry and CT scan, and 11 of them also underwent bronchoalveolar lavage (BAL) close to start of infliximab treatment. These investigations were repeated after 6 months of treatment. RESULTS: Twelve out of 15 patients disclosed a clinical improvement at follow-up. Median percentage of BAL fluid (BALF) CD56+ T cells increased while a decrease was seen in PB (p<0.05 and 0.005, respectively). No significant changes were observed for NK cells. There was a trend towards increased median percentage of PB B cells (p=0.07), and a negative correlation was observed between PB and BALF B cells after treatment (p<0.05). CONCLUSION: In conclusion, 6 months of infliximab treatment in patients with sarcoidosis, of whom the majority benefited from the treatment, influenced immune cells in the lung and circulation differently, highlighting the importance of investigating several compartments concomitantly when evaluating treatment effects on the inflammatory activity.

HLA-DRB1 alleles associate with hypercalcemia in sarcoidosis.

BACKGROUND: The mechanisms behind and which patients are at risk of developing sarcoidosis associated hypercalcemia (SAHC) have not been addressed. Different human leukocyte antigen (HLA) alleles associate with disease phenotypes in sarcoidosis. Insights into associations between HLA alleles, clinical phenotype and calcium levels may provide clues to mechanisms behind SAHC and help monitoring patients at risk for SAHC. AIMS AND OBJECTIVES: To identify any HLA-association with SAHC, and to phenotypically characterize this patient group. METHODS: 66 patients with SAHC (s-Ca2+>1.33 mmol/L) and 150 normocalcemic patients as controls were identified in a cohort of sarcoidosis patients. Data on HLA-DRB1 alleles, sex, angiotensin-converting enzyme (ACE), creatinine, extrapulmonary manifestations (EPM), age at sarcoidosis diagnosis, and how long after diagnosis SAHC emerged, were retrieved. RESULTS: HLA-DRB1*04 was more common in patients with SAHC and the proportion of patients with HLA-DRB1*04 increased the more pronounced hypercalcemia. In patients with s-Ca2+>1.4 mmol/L, 20 out of 30 carried the HLA-DRB1*04 allele (67%, p < 0.01). Patients with SAHC more often disclosed renal insufficiency, elevated ACE, EPM, and a non-resolving disease than controls. The mean duration between sarcoidosis diagnosis and detection of SAHC was 1.39 years. CONCLUSIONS: SAHC is associated with a more severe disease phenotype, particularly patients carrying the HLA-DRB1*04 allele are at higher risk for SAHC. HLA-assessment in the clinic can be a way to identify these patients. The results provide a basis for future studies on the connection between HLA-DRB1*04 and SAHC mechanisms.