Understanding global changes in fine-mode aerosols during 2008-2017 using statistical methods and deep learning approach.

Despite their extremely small size, fine-mode aerosols have significant impacts on the environment, climate, and human health. However, current understandings of global changes in fine-mode aerosols are limited. In this study, we employed newly developed satellite retrieval data and an attentive interpretable deep learning model to explore the status, changes, and association factors of the global fine-mode aerosol optical depth (fAOD) and aerosol fine-mode fraction (FMF) from 2008 to 2017. At the global scale, the results show a significant increasing trend in land FMF (2.34 × 10-3/year); however, the FMF over the ocean and the fAOD over land and ocean did not reveal significant trends. Between 2008 and 2017, high levels of both fAOD (>0.30) and FMF (>0.75) were identified over China, southeastern Asia, India, and Africa. Seasonally, global land FMF showed high values in summer (>0.70) and low values in spring (<0.65), while land fAOD was high in summer (>0.15) but low in winter (<0.13). Importantly, Australia and Mexico experienced significant increasing trends in FMF during all four seasons. At the regional scale, a significant decline in fAOD was identified in China, which indicates that government emission controls and reductions have been effective in recent decades. The deep learning model was used to interpret the result and showed that O3 was significantly associated with changes in both the FMF and fAOD. This finding suggests the importance of synergizing the regulations for both O3 and fine particles. Our work comprehensively examined global spatial and seasonal fAOD and FMF changes and provides a holistic understanding of global anthropogenic impacts.

Colchicine and Leukopenia: Clinical Implications.

Colchicine is the mainstay of treatment for familial Mediterranean fever. We investigated the frequency of leukopenia in 213 patients with familial Mediterranean fever treated with standard doses of colchicine (0.5-2.0 mg/day). We found that 23 patients (10.8%) had reversible leukopenia, 3 moderate, and none severe and that their rate of infections was not increased.

Assessment of effectiveness of anakinra and canakinumab in patients with colchicine-resistant/unresponsive familial Mediterranean fever

Abstract İntroduction: Familial Mediterranean fever (FMF) is a hereditary auto-inflammatory disease characterized by recurrent fever and serosal inflammation. Anti-interleukin-1 (Anti-IL-1) treatments are recommended in colchicine resistant and/or intolerant FMF patients. This study aims to evaluate the efficacy of anakinra and canakinumab in FMF patients that are resistant/intolareted to colchicine or complicated with amyloidosis. Methods: Between January 2014 and March 2019, 65 patients following-up at Sivas Cumhuriyet University (Medical Faculty Rheumatology-Internal Medicine Department) who were diagnosed with FMF according to the criteria of Tel-Hashomer were included in the study. The laboratory values and clinical features of patients and disease activities were recorded at least every 3 months, and these data were analyzed. Results: Forty-one (63.1%) patients used anakinra (100 mg/day) and 24 (36.9%) patients used canakinumab (150 mg/8 week). The median duration of anti-IL-1 agents use was 7 months (range, 3-30). Fifteen (23.1%) cases were complicated with amyloidosis. Seven (10.8%) patients had renal transplantation. Overall, the FMF 50 score response was 96.9%. In the group that had a glomerular filtration rate (GFR) ≥ 60 ml/min/m2, the median proteinuria decreased from 2390 mg/day (range, 1400-7200) to 890 mg/day (range, 120-2750) (p = 0.008). No serious infections were detected, except in one patient. Conclusions: Anti-IL-1 agents are effective and safe in the treatment of FMF patients. These agents are particularly effective at reducing proteinuria in patients with GFR ≥ 60 ml/min/m2, but less effective in cases with FMF associated with arthritis and sacroiliitis. Large and long follow-up studies are now needed to establish the long-term effects of these treatments.

Familial Mediterranean Fever Is Commonly Diagnosed in Children in Israel with Periodic Fever Aphthous Stomatitis, Pharyngitis, and Adenitis Syndrome.

OBJECTIVES: To describe a cohort of pediatric patients diagnosed with periodic fever aphthous stomatitis, pharyngitis and adenitis (PFAPA) and familial Mediterranean fever (FMF) and compare them with children diagnosed solely with PFAPA (sPFAPA). STUDY DESIGN: Clinical, laboratory, and genetic data of all pediatric patients diagnosed with sPFAPA or PFAPA/FMF were retrospectively collected from 2 primary Israeli medical referral centers and compared. RESULTS: Of 270 patients with PFAPA, more than one-half were of Mediterranean ancestry. Among patients with PFAPA, 51 (18.9%) also were diagnosed with FMF (PFAPA/FMF). Genetic data on the 9 most common MEFV variants were available for 45 children (88%) in the PFAPA/FMF group. Two variants were found in 15 children (33.3 %), 1 variant was found 27 patients (60%), and 3 patients (6.6%) had no variants. Abdominal pain, myalgia, and arthralgia each were more commonly reported in the PFAPA/FMF group compared with the sPFAPA group (90% vs 49% [P < .0001]; 46% vs 23% [P = .02]; and 30% vs 17% [P = .049], respectively). Colchicine was more commonly prescribed for the PFAPA/FMF group compared with the sPFAPA group (82% vs 29%; P < .0001), but alleviation of PFAPA symptoms with colchicine was similar between groups (75% vs 63%; P = .23). CONCLUSION: We show a strong association between 2 common autoinflammatory syndromes, PFAPA and FMF, in patients from Mediterranean ancestry. Clinicians should be aware that presentation of 1 disease may clinically evolve into another. The association between PFAPA and FMF poses the question similar pathogenesis and genetic influence of the MEFV gene on PFAPA.

[Result of 12 years of non-surgical treatment of pectus carinatum]. / Resultado de 12 años de tratamiento no quirúrgico del pectus carinatum.

OBJECTIVE: To report our experience in the treatment of pectus carinatum by using the dynamic compression system. MATERIAL AND METHODS: Retrospective study during the period from January 2005 to September 2017. Patients with typical condrogladiolar pectus carinatum and correction pressure (PC) ≤ 14 PSI (pound square inch) were included. Exclusion criteria: patients with previous thoracic surgery, mixed malformations and chondromanubrial pectus carinatum. For the treatment, the Dynamic Thoracic Compressor System (FMF) with pressure meter in PSI was used. The PC, the treatment pressure (PT), the correction time (TC) and the maintenance time (TM), recurrences and complications were analyzed. A qualitative scale was measured in three grades: where A is excellent or very good, B is regular and C is bad. RESULTS: We treated 104 patients under 18 years of age. The PT was 2.26. The average of the TC was 8.8 months. The TM was on average 8 months. 36.5% of the patients finished the treatment, 36.5% still continue in treatment and 26.9% of the patients lost the follow-up due to desertion. The qualitative assessment was positive in 95.5% of our patients, and unfavourable in 4.5%. CONCLUSION: The non-surgical treatment of pectus carinatum is efficient, non-invasive and of low morbidity. Regarding the high dropout rate, we must analyze the variables to be modified to reduce it. This treatment should be considered as the first option to correct pectus carinatum in patients with flexible thorax.

OBJETIVO: Describir nuestra experiencia en el tratamiento del pectus carinatum mediante el uso del sistema de compresión dinámico. MATERIALES Y METODOS: Estudio retrospectivo durante el período de enero de 2005 a septiembre de 2017. Se incluyeron pacientes con pectus carinatum condrogladiolar típico y presión de corrección (PC) ≤ 14 PSI (pound per square inch). Criterios de exclusión: pacientes con cirugía torácica previa, malformaciones mixtas y condromanubriales. Para el tratamiento se utilizó el sistema compresor torácico dinámico (FMF) con medidor de presión en PSI. Se analizaron la PC, la presión de tratamiento (PT), el tiempo de corrección (TC) y el tiempo de mantenimiento (TM), recidivas y complicaciones. Se realizó una escala cualitativa medida en tres grados: donde A es excelente o muy bueno, B regular y C malo. RESULTADOS: Tratamos 104 pacientes menores de 18 años. La PT fue de 2,26. El promedio del TC fue de 8,8 meses. El TM fue en promedio de 8 meses. El 36,5% de los pacientes finalizaron el tratamiento, 36,5% aún continúan en tratamiento y 26,9% de los pacientes se perdió el seguimiento por deserción del mismo. La valoración cualitativa fue positiva en el 95,5% de nuestros pacientes, y desfavorable en el 4,5%. CONCLUSION: El tratamiento no quirúrgico del pectus carinatum es eficiente, no invasivo y de baja morbilidad. Respecto a la alta tasa de deserción, debemos analizar las variables a modificar para disminuirla. Este tratamiento debe ser considerado una opción de primera elección, para corregir el pectus carinatum en pacientes con tórax flexible.

[Autoinflammatory diseases]. / Enfermedades autoinflamatorias.

The monogenic autoinflammatory diseases are rare, genetic disorders resulting in constitutive innate immune defects leading to excessive response to danger signals, spontaneous activation of inflammatory mediators or loss of inhibitory regulators. During the past 15 years, a growing number of monogenic inflammatory diseases have been described and their respective responsible genes identified. The proteins encoded by these genes are involved in the regulatory pathways of inflammation and are mostly expressed in cells of the innate immune system. Although a group of patients exhibit episodic systemic inflammation (periodic fevers), these disorders are mediated by continuous overproduction and release of pro-inflammatory mediators, notably IL-1ß, and are best considered as autoinflammatory diseases rather than periodic fevers. The most common autoinflammatory diseases are familial Mediterranean fever (FMF), TNF receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyperimmunoglobulin D syndrome (MKD/HIDS) and the cryopyrin-associated periodic syndromes (CAPS). Clinical features often include fever, cutaneous rash, serosal involvement and acute phase reactants. Autoantibodies are usually absent but may accompany certain syndromes. Diagnosis remains clinical and is based on the different phenotypic features. Genetic diagnosis is of utmost importance, but must be performed judiciously and interpreted cautiously. Treatment with biologic agents that block proinflammatory cytokines, particularly IL-1, has proved to be dramatically effective in many patients. Still, in many cases of autoinflammation no genetic abnormalities are detected and treatment remains suboptimal, raising the question of novel pathogenic mutations in unexplored genes and pathways.

Enfermedades autoinflamatorias / Autoinflammatory diseases

Las enfermedades autoinflamatorias monogénicas son desórdenes raros que resultan en defectos del sistema inmune innato, originando excesiva respuesta a señales de peligro, activación espontánea de vías inflamatorias o pérdida de reguladores inhibitorios. En los últimos 15 años un creciente número de enfermedades inflamatorias monogénicas han sido descriptas y sus respectivos genes responsables identificados. Las proteínas codificadas por estos genes están involucradas en las vías regulatorias de la inflamación y están expresadas fundamentalmente en las células del sistema inmune innato. Si bien un grupo de pacientes exhibe inflamación sistémica episódica (fiebres periódicas), estos desórdenes están mediados por una continua sobreproducción y liberación de mediadores pro-inflamatorios -especialmente la interleucina 1beta- y su conceptualización como enfermedades autoinflamatorias es preferible por sobre la de fiebres periódicas. Las enfermedades más frecuentes son fiebre mediterránea familiar (FMF), TRAPS, deficiencia de mevalonatocinasa/síndrome de hiper IgD (MKD/HIDS) y los síndromes periódicos asociados a criopirina (CAPS). Sus características clínicas frecuentemente incluyen fiebre, erupciones cutáneas, compromiso de serosas y reactantes de fase aguda. Los autoanticuerpos están usualmente ausentes pero pueden observarse en ciertos síndromes. El diagnóstico es clínico y se basa en las características fenotípicas. El diagnóstico genético es muy importante pero debe ser realizado de manera juiciosa e interpretado con cautela. El tratamiento con agentes biológicos que bloquean citocinas pro-inflamatorias, particularmente IL-1, ha demostrado ser efectivo en muchos pacientes. Sin embargo, en otros tantos casos no se descubren anormalidades genéticas y el tratamiento es subóptimo, planteando la posibilidad de mutaciones patogénicas en genes y vías aún no explorados.

The monogenic autoinflammatory diseases are rare, genetic disorders resulting in constitutive innate immune defects leading to excessive response to danger signals, spontaneous activation of inflammatory mediators or loss of inhibitory regulators. During the past 15 years, a growing number of monogenic inflammatory diseases have been described and their respective responsible genes identified. The proteins encoded by these genes are involved in the regulatory pathways of inflammation and are mostly expressed in cells of the innate immune system. Although a group of patients exhibit episodic systemic inflammation (periodic fevers), these disorders are mediated by continuous overproduction and release of pro-inflammatory mediators, notably IL-1β, and are best considered as autoinflammatory diseases rather than periodic fevers. The most common autoinflammatory diseases are familial Mediterranean fever (FMF), TNF receptor-associated periodic syndrome (TRAPS), mevalonate kinase deficiency/hyperimmunoglobulin D syndrome (MKD/HIDS) and the cryopyrin-associated periodic syndromes (CAPS). Clinical features often include fever, cutaneous rash, serosal involvement and acute phase reactants. Autoantibodies are usually absent but may accompany certain syndromes. Diagnosis remains clinical and is based on the different phenotypic features. Genetic diagnosis is of utmost importance, but must be performed judiciously and interpreted cautiously. Treatment with biologic agents that block proinflammatory cytokines, particularly IL-1, has proved to be dramatically effective in many patients. Still, in many cases of autoinflammation no genetic abnormalities are detected and treatment remains suboptimal, raising the question of novel pathogenic mutations in unexplored genes and pathways.

Non-surgical treatment of pectus carinatum with the FMF® Dynamic Compressor System.

Pectus carinatum is a chest wall deformity, sometimes associated with physical signs and symptoms, but always associated to significant psychological distress. Surgical correction used to be the only solution, and was therefore only indicated for the most severe cases. Non-surgical approaches have been developed and improved during the last 15-20 years. A paradigm shift occured when the medical community realized that, despite the wall deformity, the chest wall was not completely rigid, but flexible and capable of remodeling. Several bracing devices and protocols are available as of today. This article will focus specifically in the FMF® Dynamic Compressor System (DCS), which was developed in Argentina in 2001 and is currently used worldwide.