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BackgroundOrofacial granulomatosis [OFG] is a rare syndrome that may be associated with Crohn’s disease [CD]. We aimed to characterise this relationship and the management options in the biologic era.MethodsThis multicentre case series was supported by the European Crohn’s and Colitis Organisation [ECCO], and performed as part of the Collaborative Network of Exceptionally Rare case reports [CONFER] project. Clinical data were recorded in a standardised collection form.ResultsThis report includes 28 patients with OFG associated with CD: 14 males (mean age of 32 years, ±12.4 standard deviation [SD]) and 14 females [40.3 years, ±21.0 SD]. Non-oral upper gastrointestinal tract involvement was seen in six cases and perianal disease in 11. The diagnosis of OFG was made before CD diagnosis in two patients, concurrently in eight, and after CD diagnosis in 18. The distribution of OFG involved the lips in 16 cases and buccal mucosa in 18. Pain was present in 25 cases, with impaired swallowing or speaking in six. Remission was achieved in 23 patients, notably with the use of anti-tumour necrosis factors [TNFs] in nine patients, vedolizumab in one, ustekinumab in one, and thalidomide in two. A further five cases were resistant to therapies including anti-TNFs.ConclusionsOFG associated with CD may occur before, concurrently with, or after the diagnosis of CD. Perianal and upper gastrointestinal [UGI] disease are common associations and there is a significant symptom burden in many. Remission can be obtained with a variety of immunosuppressive treatments, including several biologics approved for CD.

Li-Hong Lu, Yu-Qing Song, Qi-Ming Wu, Zhao Wang, Yong-Fu Chen, Qian Dong, Xiao-Tao Han Department of Cardiology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of ChinaCorrespondence: Qi-Ming WuDepartment of Cardiology, Beijing Ditan Hospital, Capital Medical University, No. 8 of Jingshun Street, Chaoyang District, Beijing, 100015, People’s Republic of ChinaTel +86 138 0100 9058Fax +86 10-84322988Email lulihong1954@163.comObjective: To improve our knowledge of cardiac manifestations caused by brucellosis through analyzing abnormal electrocardiograms of patients infected with brucella.Methods: A total of 108 cases were enrolled, and their electrocardiograms were analyzed and summarized retrospectively.Results: Among 108 cases, 77 (71.3%) had a normal electrocardiogram, and 31 (28.7%) had an abnormal electrocardiogram. There were 13 cases with nodal tachycardia (12%), 9 cases with sinus bradycardia (8%), 7 cases with sinus arrhythmia (6%), 8 cases with left ventricular high voltage (7%), 13 cases with abnormal ST segment and T wave (12%), 2 cases with abnormal Q wave (1.85%), 3 cases with complete right bundle branch block (2.78%), 3 cases with ventricular premature beat (2.78%), 1 case with left anterior fascicular block (0.9%), 1 case with first degree a-v block (0.9%), 1 case with QT internal prolongation (0.9%), 1 case with poor R wave progression (0.9%), and 1 case with short PR interval (0.9%).Conclusion: The cardiac manifestations of brucellosis were rare, but the mortality was high. Patients with abnormal electrocardiogram should have improved echocardiography in time. Early detection of the abnormal electrocardiogram could give a hint of cardiac damage to avoid the serious consequences.Keywords: brucella, brucellosis, ECG, manifestations, cardiac manifestations

Introduction Phenylketonuria (PKU) is a rare, treatable inborn error of metabolism with frequent neurological and neuropsychiatric complications, especially in undiagnosed or insufficiently treated individuals. Given the wide range of clinical presentations and the importance of treatment implications, we here delineate the neurological and neuropsychiatric symptom spectrum in a large cohort of previously unreported adults with late-treated PKU. Methods We consecutively evaluated late-treated PKU cases and pooled clinical and paraclinical data, including video-material, from three centers with expertise in complex movement disorders, inborn errors of metabolism and pediatrics. Results 26 individuals were included (10 females, median age 52 years). Developmental delay and intellectual disability were omnipresent with severe impairment of expressive communication noted in 50% of cases. Movement disorders were prevalent (77%), including tremor (38%, mostly postural), stereotypies (38%), and tics (19%). One case had neurodegenerative levodopa-responsive parkinsonism. Mild ataxia was noted in 54% of cases and 31% had a history of seizures. Neuropsychiatric characteristics included obsessive-compulsive (35%) and self-injurious behaviors (31%), anxiety (27%), depression (19%) and features compatible with those observed in individuals with autism spectrum disorder (19%). Neuroimaging revealed mild white matter changes. Adherence to dietary treatment was inconsistent in the majority of cases, particularly throughout adolescence. Conclusion A history of movement disorders, particularly tremor, stereotypies and tics, in the presence of developmental delay, intellectual disability and neuropsychiatric features, such as obsessive-compulsive and self-injurious behaviors in adults should prompt the diagnostic consideration of PKU. Initiation and adherence to (dietary) treatment can ameliorate the severity of these symptoms.

Inborn errors of metabolism (IEMs) are a group of rare genetic disorders which, when emerging later in life, are often characterized by neuropsychiatric manifestations including psychosis. This study aimed to determine whether it would be useful to screen patients presenting with a psychotic disorder for IEMs by a single blood sample using Next Generation Sequencing (NGS), in order to detect rare, treatable causes of psychotic disorders. Blood was drawn from 60 patients with a psychotic disorder, with a duration of illness of less than 5 years. Blood samples were screened for 67 genes using NGS (Illumina® MiSeq sequencing technique). The results were compared to the human reference genome (GoNL, n = 498). The identified variants were classified according to the ACMG classification. For the psychotic patients, 6 variants of a likely pathogenic (class 4, n = 2) or pathogenic (class 5, n = 4) origin were found. As all variants were heterozygous, no patients were considered to be affected by an IEM. For the GoNL control group, 73 variants of a likely pathogenic (class 4, n = 31) or pathogenic (class 5, n = 42) origin were found. All of these found variants were heterozygous. Therefore, these individuals from the control group were considered to be a carrier only. Thus, no patients were identified to have an IEM as an underlying disease using this approach. However, NGS may be useful to detect variants of genes associated with IEMs in an enriched subgroup of psychotic patients.

Apart from conjunctival involvement which is the most well-known ocular manifestation of coronavirus infectious disease 2019 (COVID-19), there are multiple reports of the involvement of other ocular structures by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We comprehensively reviewed PubMed, Scopus, Embase, and Google Scholar for available evidence regarding COVID-19 various ocular manifestations, with special focus on less known and unusual ocular findings. We then categorized the findings based on the parts of the eye which was involved. In anterior sections of the eye, the involvement of the eyelid (tarsadenitis), conjunctiva and cornea (follicular conjunctivitis, pseudomembranous conjunctivitis, and keratoconjunctivitis), episclera (nodular episcleritis), uvea (anterior uveitis) were reported. Also, third, fourth, and sixth nerve palsy, retinal vasculitis, retinal optical coherence tomography (OCT) changes (hyper-reflective lesions and increased retinal nerve fiber layer thickness [RNFLT]), optic neuritis, papillophlebitis, Miller Fisher syndrome, posterior reversible leukoencephalopathy (PRES), ophthalmic artery and central retinal artery occlusion, and polyneuritis cranialis were reported in different studies. Postmortem evaluation of COVID-19 patients detected no viral RNA in different anterior and posterior segments of the eyes. However, another study revealed a 21.4% positivity of the retinal biopsies of dead patients. The results of this study can help ophthalmologists to be vigilant when they see these findings in a suspected case of COVID-19. In addition, wearing face masks and protective goggles or eye shields are recommended, especially in high-risk contacts.

Objective: Primary immunodeficiencies (PIDs) consist of genetically heterogeneous disorders. The spectrum can include infectious diseases, malignancy, allergy, and autoimmunity. We aimed to analyze the frequency and variety of autoimmune diseases (ADs) in PIDs and describe their clinical and laboratory features. Materials and Methods: Ninety-two patients with PID followed by Ege University Medical Faculty between 2000 and 2017 were enrolled in this retrospective, cross-sectional study. All patients’ medical records were reviewed using the demographic information, type of PIDs and ADs, ADs-related autoantibodies, and basic and immunologic laboratory findings. ADs were diagnosed using clinical and complementary paraclinical findings by an immunologist and/or a subspecialist related to the affected organ or system. Results: We evaluated 50 male and 42 female PID patients with a mean age of 40.92 (18-86). Twenty-nine (32 %) patients (15 females/14 males) with a mean age of 43.8 (19-78) had ADs. In our study group, the most commonly detected type of PID with AD is common variable immune deficiency (CVID) (n=17); followed by combined immune deficiency (CID) (n=3), CTLA4 deficiency (n=2), selective IgA deficiency (sIgAD) (n=2), specific IgG subgroup deficiency (n=1), autoimmune polyglandular syndrome (APS) with hypogammaglobulinemia (n=1), dyskeratosis congenita (DC) (n=1), Osler-Rendu-Weber (ORW) syndrome with CVID-like PID (n=1), and cartilage-hair hypoplasia (CHH) (n=1). According to systematic assessments, ADs resulted in endocrinologic 14%, dermatologic 10.8%, rheumatologic 9.7%, gastroenterological 9.7%, hematological 8.6%, and neurologic disorders 1%. The frequency of ADs was higher in CVID cases than other types of PIDs (p

The novel coronavirus disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major public health emergency worldwide with over 118.27-million confirmed COVID-19 cases and 2.62-million deaths recorded, as of March 12, 2021. Although this disease primarily targets lungs, damages in other organs, such as heart, kidney, liver, and testis, may occur. Testis is the cornerstone of male reproduction, while reproductive health is the most valuable resource for continuity of the human race. Given the unique nature of SARS-CoV-2, the mechanisms of its impact on the testes have yet to be fully explored. Notably, coronaviruses have been found to invade target cells through the angiotensin-converting enzyme 2 receptor, which can be found in the respiratory, gastrointestinal, cardiovascular, urinary tract, and reproductive organs, such as testes. Coronavirus studies have suggested that testes might be a potential target for SARS-CoV-2 infection. The first etiopathogenic concept proposed by current hypotheses indicates that the virus can invade testes through the angiotensin-converting enzyme 2 receptor. Next, the activated inflammatory response in the testes, disease-associated fever, and COVID-19 medications might be implicated in testicular alterations. Although evidence regarding the presence of SARS-CoV-2 mRNA in semen remains controversial, this emphasizes the need for researchers to pay closer attention to sexually transmitted diseases and male fertility after recovering from COVID-19. In this review the latest updates regarding COVID-19-associated testicular dysfunction are summarized and possible pathogenic mechanisms are discussed.

Background/aim: Autoimmune bullous diseases, if left untreated, are life-threatening conditions affecting primarily skin and mucous membranes. These blistering disorders are characterized by epidermal or subepidermal detachment. Autoimmunity plays a key role in pathogenesis; therefore, immunosuppressive agents are the treatment of choice. The aim of this study is to document relative frequencies of different autoimmune bullous diseases, patient characteristics, treatment options, and side effects in patients presenting to our bullous skin disease center at İstanbul University, Cerrahpaşa, Cerrahpaşa Medical Faculty. Materials and methods: Medical files were examined retrospectively for all patients with autoimmune bullous diseases who were followed up between 2003 and 2019 at the Bullous Skin Disease Center at İstanbul University, Cerrahpaşa. Results: A total of 346 patient files were examined. Pemphigus vulgaris was the most frequent autoimmune bullous disease, followed by bullous pemphigoid and pemphigus foliaceus, according to our study. There is a general female predominancy for all autoimmune bullous diseases. The most commonly preferred treatment options were high-dose daily corticosteroids. Conclusion: This retrospective study summarizes the patient characteristics, comorbidities, treatment choices, and side effects during 16 years of clinical practice.

Background Crimean-Congo Hemorrhagic Fever (CCHF) is a particular regional concern because of endemicity in Afghanistan and many neighboring countries. The prevalence of CCHF has been increasing in this region. These concerns are compounded because there is no vaccine or therapeutic for CCHF and Afghanistan lacks adequate public health infrastructure in preventing, detecting, and containing cases. This investigation aimed to study the epidemiological, clinical, and laboratory features of CCHF in Afghanistan that might be useful in prevention and case detection, particularly in a limited resource setting. Method A descriptive and analytic retrospective study of epidemiological, clinical, and laboratory features of confirmed patients (enzyme-linked immunosorbent assay (ELISA)-positive for CCHF) who were admitted to referral infectious center of Afghanistan from March 2017, to December 2018, was carried out. Results There were 51 ELISA-confirmed CCHF patients, comprised of 14 females and 37 males. The mean age was 30 years of age, and there were 11 deaths. The case fatality rate (CFR) was 21.6% and was not significant between sexes (p = 0.8). Most cases were recorded from June to September, which is the period containing Eid-al-Adha. With regard to occupation, 13.7% and 11.8% of subjects were butchers and shepherds, respectively. The leading clinical manifestations were fever, hemorrhage, and myalgia. The mean time between onset of symptoms and admission to the hospital was 4.9 days in recovered cases and 4.7 days for expired cases. Conclusion The prevalence of CCHF is increasing in Afghanistan. The majority of cases visited the hospital during the late phase of infection. This delay can negatively affect the efficacy of treatment and lead to severe health outcomes. Our findings reveal that impaired Alanine aminotransferase (ALT), hemorrhagic manifestations (including epistaxis), and impaired consciousness were factors associated with a higher mortality rate. These biomarkers may provide a clue to possible early effective interventions and increasing the chance of survival of the patients.

Background Paediatric rhinosinusitis is mostly different than that in adults. More frequently, children presented with cough, bad breath, crankiness, low energy, and swelling around the eyes, besides a thick yellow-green nasal or post-nasal discharge. About 5- 13% of childhood viral upper respiratory tract infections may advance to acute rhinosinusitis, with some of them developing a chronic condition. Aim To assess prevalence and clinical presentation of sinusitis in the paediatric age group in Aseer, Saudi Arabia. Methodology A retrospective record-based study was conducted in Abha Maternity and Children Hospital in Abha city, Saudi Arabia between January 2015 and January 2018. All medical records during the study period for children whose from to 15 years old attended the hospital and diagnosed as having sinusitis were included. Results The study included 100 children with complete files whose ages ranged from less than 1 year to up to 13 years old with a mean age of 5.3 4.2 years. Nearly 51% of the children aged 4 years or less and male were 53 (53%). Past history for chronic rhinosinusitis (CRS) was positive among 30 children. Regarding clinical presentations of rhinosinusitis (RS) as reported by the children caregivers, fever was the most reported complaint (50%) followed by red eye (44%), ringing nose (42%), cough (41%) and headache (36%). Mucous culture was positive among 58 cases. The most isolated pathogens were streptococcus pneumoniae (45.6%), Haemophilis influenza (24.6%). Conclusions In conclusion, the study revealed that CRS is a common disease in children at different ages, especially, maxillary and frontal sinuses. In most of the cases, medical treatment is highly appreciated; though, surgical intervention may be needed in a small percentage.

OBJECTIVE: Utilizing data obtained from a prospective, international, juvenile systemic sclerosis (SSc) cohort, the present study was undertaken to determine if pulmonary screening with forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLco) is sufficient to assess the presence of interstitial lung disease (ILD) in comparison to high-resolution computed tomography (HRCT) in juvenile SSc. METHODS: The juvenile SSc cohort database was queried for patients enrolled from January 2008 to January 2020 with recorded pulmonary function tests (PFTs) parameters and HRCT to determine the discriminatory properties of PFT parameters, FVC, and DLco in detecting ILD. RESULTS: Eighty-six juvenile SSc patients had both computed tomography imaging and FVC values for direct comparison. Using findings on HRCT as the standard measure of ILD presence, the sensitivity of FVC in detecting ILD in juvenile SSc was only 40%, the specificity was 77%, and area under the curve (AUC) was 0.58. Fifty-eight juvenile SSc patients had both CT imaging and DLco values for comparison. The sensitivity of DLco in detecting ILD was 76%, the specificity was 70%, and AUC was 0.73. CONCLUSION: The performance of PFTs in juvenile SSc to detect underlying ILD was quite limited. Specifically, the FVC, which is one of the main clinical parameters in adult SSc to detect and monitor ILD, would miss ~60% of children who had ILD changes on their accompanying HRCT. The DLco was more sensitive in detecting potential abnormalities on HRCT, but with less specificity than the FVC. These results support the use of HRCT in tandem with PFTs for the screening of ILD in juvenile SSc.

BACKGROUND: Fragility fractures (FFxs) and osteoporosis are frequent manifestations of indolent systemic mastocytosis (ISM). So far, the effect of antiosteoporotic therapy on FFxs has scarcely been investigated.OBJECTIVE: This study evaluates the long-term effect of bisphosphonate treatment on FFxs, bone mineral density (BMD), and bone resorption in patients with ISM in daily clinical practice.METHODS: Patients with ISM who received bisphosphonates because of osteoporosis and/or FFxs were retrospectively analyzed (n = 58). Fractures were recorded by vertebral fracture assessment, X-rays of the thoracolumbar spine, medical records, and a questionnaire. Five-year analysis (n = 30) was made by comparing observed 5-year FFx risk with MastFx-predicted FFx risk for patients with ISM not treated with antiosteoporotic drugs and analyzing 5-year change in BMD and serum collagen C telopeptide (sCTx) Z-scores.RESULTS: During the median follow-up of 7.3 years, 14 of 58 patients suffered 40 FFxs. Five- and 10-year FFx-free survival were 81.9% (standard error [SE], 5.5%) and 67.0% (SE, 7.7%), respectively. FFx risk was significantly higher in patients with previous vertebral FFxs (P = .004), lower femoral BMD at baseline (P = .042), and history of anaphylaxis (P = .028). No 5-year FFx risk reduction could be proven, possibly due to the small sample size. The lumbar BMD Z-score significantly increased from median (interquartile range [IQR]) -2.20 (-2.80 to -1.50) to -1.50 ( -2.30 to -0.60) (PCONCLUSION: Bisphosphonates significantly increase BMD and decrease sCTx in patients with ISM. However, FFxs still frequently occur. Especially patients with previous FFxs remain at high risk of new FFxs. (C) 2020 American Academy of Allergy, Asthma & Immunology

Purpose: To evaluate the prevalence of dry eye and meibomian gland dysfunction in patients with scleroderma. Methods: A total of 32 patients with scleroderma (study group) and 31 healthy subjects (control group) were enrolled. Besides routine ophthalmologic evaluation, Schirmer 1 test, tear break-up time, tear osmolarity, ocular surface staining with fluorescein (Oxford score), and Ocular Surface Disease Index (OSDI) score, meibomian gland dysfunction evaluation (foamy tears, telangiectasia of the eyelid, eyelid contour abnormalities, and meibomian plugs), and meibography were performed. Results: Sixty-four eyes of 32 patients with scleroderma and 62 eyes of 31 healthy individuals were evaluated. Mean ages of the study group was 48.34 +/- 9.73 years (21-62 years) and of the control group was 45.84 +/- 4.42 years (38-54 years) (P = 0.067). Mean duration of systemic sclerosis or scleroderma in study group was 9.78 +/- 7.40 years (1-30 years). Mean tear break-up time was shorter in study group than that in the control group (P < 0.0005). No statistical differences were detected for osmolarity, OSDI score, and Schirmer 1 values between groups (P = 0.051, P = 0.053, and P = 0.358, respectively). The prevalence of grade 1 and higher Oxford score was higher in the study group (P < 0.0005). Upper meiboscores of grade 1 and higher were found to be more common in the study group than those in the control group (P = 0.036). The presence of foamy tears and telangiectasia of the eyelids were significantly higher in the study group (P = 0.002 and P = 0.002, respectively). OSDI score was the only significantly correlated data with disease duration (Spearman rho coefficient = 0.396, P = 0.001). Conclusions: Evaporative type dry eye is more common in patients with scleroderma than the healthy population., Ege University Scientific Research Projects Coordination Unit [2017-TIP-041], Supported by Ege University Scientific Research Projects Coordination Unit (Project Number: 2017-TIP-041).

Background Anticardiolipin (aCL) and anti-β2 glycoprotein I (aβ2GPI) immunoglobulin A (IgA) antiphospholipid antibodies (aPL) have shown to associate with thrombosis and pregnancy morbidity. However, inclusion of IgA aPL in the classification criteria of the antiphospholipid syndrome (APS) has been debated. We investigated the value of aCL and aβ2GPI IgA aPL in the detection of thrombosis and pregnancy morbidity in addition to the current aPL panel for APS. Methods We included 1,068 patients from eight European medical centers: 259 thrombotic APS patients, 122 obstetric APS patients, 204 non-APS thrombosis patients, 33 non-APS obstetric patients, 60 APS patients with unspecified clinical manifestations, 196 patients with autoimmune diseases, and 194 controls. aCL and aβ2GPI IgG/M/A were detected with four commercial assays and lupus anticoagulant was determined by the local center. Results Positivity for IgA aPL was found in 17 to 26% of the patients with clinical manifestations of APS and in 6 to 13% of the control population. Both aCL and aβ2GPI IgA were significantly associated with thrombosis and pregnancy morbidity. Isolated IgA positivity was rare in patients with clinical manifestations of APS (0.3–5%) and not associated with thrombosis and/or pregnancy morbidity. Addition of IgA to the current criterion panel did not increase odds ratios for thrombosis nor pregnancy morbidity. Conclusion aCL and aβ2GPI IgA are associated with clinical manifestations of APS. However, isolated IgA positivity was rare and not associated with thrombosis or pregnancy morbidity. These data do not support testing for aCL and aβ2GPI IgA subsequent to conventional aPL assays in identifying patients with thrombosis or pregnancy morbidity.

Aim: To determine the frequency of sinopulmonary infections, detect changes in the respiratory system, and measure functional capacity of the lungs in our patients with humoral immunodeficiency. Material and Methods: Fifty-six patients with humoral immunodeficiency were enrolled in this study. The clinical, laboratory, and radiologic data, and pulmonary function tests of the subjects were evaluated from their file records, retrospectively. Results: The distribution of our patients was as follows: 25 patients had common variable immune deficiency, three patients had X-linked agammaglobulinemia, five patients had hyper immunoglobulin M syndrome, 19 patients had deficiency of immunoglobulin G subset, and four patients had selective immunoglobulin A deficiency. The most common symptom of the patients was chronic cough (n=47, 83.9%). The most common pathologies on high-resolution computed tomography of the chest were atelectasis and bronchiectasis (27.7%). The most common pathology in pulmonary function tests was the presence of moderate obstructive patterns along with restrictive patterns (n=6,12.5%). The FEV 1, FVC, and FEF 25-75 values were significantly lower in patients with common variable immunodeficiency compared with the patients who had IgG subset deficiencies (p=0.001, p=0.01, p=0.01). Among the patients who were treated with intravenous immunoglobulin, the age at the diagnosis of immunodeficiency was higher in patients with bronchiectasis (14.2 +/- 8.4 years) compared with those without bronchiectasis (10.1 +/- 11.4 years) (p=0.04). Conclusion: Clinical findings are not sufficient to monitor the structural and functional changes in the respiratory system, and patients should be evaluated using high-resolution computed tomography of the chest and pulmonary function tests. Amaç: Humoral immün yetmezlik tanılı olgularımızda, sinopulmoner enfeksiyonların sıklığı ve bunların sonucunda solunum sisteminde meydana gelen değişikliklerin saptanması ve fonksiyonel akciğer kapasitelerinin ölçülmesi amaçlanmıştır. Gereç ve Yöntemler: Çalışmaya humoral immün yetmezlik tanılı 56 olgu alındı. Olguların dosya kayıtlarından klinik, laboratuvar, radyolojik görüntüleme bulguları ve solunum fonksiyon testi verileri geriye dönük olarak incelendi. Bulgular: Olguların tanılara göre dağılımı; yaygın değişken immün yetmezlik tanılı 25 olgu, X’e bağlı agamaglobulinemi tanılı üç olgu, Hiper immunoglobulin M sendromu tanılı beş olgu, İgG alt grup eksikliği tanılı 19 olgu ve selektif immunoglobulin A eksikliği tanılı dört olgu şeklindedir. Olguların 37’si (%66,1) erkek 19’u (%33,9) kadın, yaş ortalaması 14,1±10,6 yıldı. Olguların en sık yakınması kronik öksürük idi (n=47, %83,9). Akciğerlerin yüksek çözünürlüklü bilgisayarlı tomografilerinde en sık görülen patoloji atelektazi ve bronşiektaziydi (%27,7). Solunum fonksiyon testlerinde en sık görülen anormallik orta obstrüktif ve orta restriktif patern birlikteliğiydi (n=6,%12,5). Solunum fonksiyon testi bulguları ile radyolojik bulguların her zaman tutarlı olmadığı görüldü. İntravenöz immünglobulin alan olgular arasında yaygın değişken immün yetmezlik tanılı olgularda, immünglobulin G alt grup eksikliği olan olgulara göre solunum fonksiyon testlerinde; FEV 1, FVC ve FEF 25–75 değerlerinin anlamlı düşük olduğu saptandı (p=0,001, p=0,01, p=0,01). İntravenöz immünglobulin tedavisi alan olgularda; bronşiektazisi olanların immün yetmezlik tanı yaşı (14,2±8,4 yıl), olmayanlara (10,1±11,4 yıl) göre anlamlı olarak büyüktü (p=0,04). Çıkarımlar: Klinik bulgular solunum sistemindeki yapısal ve fonksiyonel değişiklikleri izlemek için yeterli değildir ve olgular gereğinde akciğer yüksek çözünürlüklü bilgisayarlı tomografi ve solunum fonksiyon testleri ile değerlendirilmelidir.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – also known as COVID-19 – is primarily known for respiratory illness. While it is clear that patients with moderate to severe cases of COVID-19 will require pulmonary rehabilitation, physiatrists will need to consider effective management plans for COVID-19 survivors with extra-pulmonary involvement. This report will summarize key non-pulmonary considerations to guide rehabilitation clinicians who may be involved in the care of COVID-19 survivors with the best available early evidence.

Purpose To explore the characteristics, medical treatments, and long-term facial palsy outcome in Ramsay Hunt syndrome. Methods Patient questionnaire including self-assessment of long-term facial palsy outcome and retrospective chart review. Initial facial palsy grade was compared to self-assessed or patient record stated palsy outcome. Occurrence of different characteristics (blisters, hearing loss, vertigo, etc.) of the syndrome were assessed. Results Altogether 120 patients were included of which 81 answered the questionnaire. All but one patient had received virus medication (aciclovir, valaciclovir), and half received simultaneous corticosteroids. If the medication was started within 72 h of Ramsay Hunt diagnosis, facial palsy recovered totally or with only slight sequelae in over 80% of the patients. Only a minority of the patients experienced varicella blisters simultaneously with facial palsy, blisters more often preceded or followed the palsy. Approximately 20% of the patients had their blisters in hidden places in the ear canal or mouth. Conclusions The long-term outcome of facial palsy in medically treated Ramsay Hunt syndrome was approaching the outcome of Bell’s palsy. It is crucial to ask and inform the patient about the blisters and look for them since, more often than not, the blisters precede or follow the palsy and can be in areas not easily seen.

Throughout much of the African continent, healthcare systems are already strained in their efforts to meet the needs of a growing population using limited resources. Climate change threatens to undermine many of the public health gains that have been made in this region in the last several decades via multiple mechanisms, including malnutrition secondary to drought-induced food insecurity, mass human displacement from newly uninhabitable areas, exacerbation of environmentally sensitive chronic diseases, and enhanced viability of pathogenic microbes and their vectors. We reviewed the literature describing the various direct and indirect effects of climate change on diseases with cutaneous manifestations in Africa. We included non-communicable diseases such as malignancies (non-melanoma skin cancers), inflammatory dermatoses (i.e. photosensitive dermatoses, atopic dermatitis), and trauma (skin injury), as well as communicable diseases and neglected tropical diseases. Physicians should be aware of the ways in which climate change threatens human health in low- and middle-income countries in general, and particularly in countries throughout Africa, the world's lowest-income and second most populous continent.

Tam Metin / Full Text Behçet’s syndrome (BS) is a multisystem variable vessel vasculitis characterized by skin-mucosal lesions. It can also involve the eyes, blood vessels, joints, gastrointestinal system, urogenital system, and central nervous system. BS starts in the third or fourth decade and affects both genders equally. The disease is more severe in young men. Although the sensitivity of the pathergy test (PT) is decreasing today, it is still an important clue in the diagnosis of BS. We describe the characteristics of BS in our region, retrospectively. We also analyzed the effect of gender, age, family history, and skin PT positivity status on the difference of clinical involvement. Methods A total of 777 BS patients (391 women and 386 men; 40.0 ± 11.6 years old) who applied to our Rheumatology Department between January 2010 and June 2020 were included in the study. Results: Of the 777 patients, 391 were female (50.3%) and 386 were male (49.7%). The mean age at diagnosis was 30.3 ± 9.8 years. The proportion of patients with BS in their family was 10.2%. Of the 777 patients, 310 (39.9%) had only mucocutaneous symptoms. Other 467 patients (60.1%) had at least one of the ocular, musculoskeletal, vascular, neurologic, intestinal, or genitourinary involvement. Serious involvements such as eye, cardiovascular, and neurologic involvement were more common in male patients. Conclusion: BS has the different clinical phenotypes according to gender, age of onset, and skin PT positivity status. Gender influences on the major organ involvements such as eye, neurologic, and vascular.

INTRODUCTION: Gastrointestinal (GI) symptoms in coronavirus-19 disease (COVID-19) have been reported with great variability and without standardization. In hospitalized patients, we aimed to evaluate the prevalence of GI symptoms, factors associated with their occurrence, and variation at 1 month. METHODS: The GI-COVID-19 is a prospective, multicenter, controlled study. Patients with and without COVID-19 diagnosis were recruited at hospital admission and asked for GI symptoms at admission and after 1 month, using the validated Gastrointestinal Symptom Rating Scale questionnaire. RESULTS: The study included 2036 hospitalized patients. A total of 871 patients (575 COVID+ and 296 COVID-) were included for the primary analysis. GI symptoms occurred more frequently in patients with COVID-19 (59.7%; 343/575 patients) than in the control group (43.2%; 128/296 patients) (P < 0.001). Patients with COVID-19 complained of higher presence or intensity of nausea, diarrhea, loose stools, and urgency as compared with controls. At a 1-month follow-up, a reduction in the presence or intensity of GI symptoms was found in COVID-19 patients with GI symptoms at hospital admission. Nausea remained increased over controls. Factors significantly associated with nausea persistence in COVID-19 were female sex, high body mass index, the presence of dyspnea, and increased C-reactive protein levels. DISCUSSION: The prevalence of GI symptoms in hospitalized patients with COVID-19 is higher than previously reported. Systemic and respiratory symptoms are often associated with GI complaints. Nausea may persist after the resolution of COVID-19 infection., Fondazione Cassa di Risparmio in Bologna; Italian Ministry of Education, University and Research; Fondazione del Monte di Bologna e Ravenna [SC1-BHC-01-2019]; European Grant H2020, DISCOvERIE [SC1-BHC-01-2019]; Italian Ministry of Health [Ricerca Finalizzata GR-2018-12367062], G.B. contribution to this research was permitted in part by funding from Fondazione Cassa di Risparmio in Bologna; the ItalianMinistry of Education, University and Research; and Fondazione del Monte di Bologna e Ravenna and European Grant H2020, DISCOvERIE, SC1-BHC-01-2019. M.R.B. is a recipient of a grant from the Italian Ministry of Health (Ricerca Finalizzata GR-2018-12367062). None of the funding organizations have had any role in the design and conduct of the study; in the collection, management, and analysis of the data; or in the preparation, review, and approval of the article.

Objectives: Adult studies suggest that patients with isolated colonic Crohn disease (L2 CD) exhibit unique characteristics differentiating them from patients with ileo-caecal (L1) CD and ulcerative colitis (UC). We aimed to characterize clinical features and outcomes of paediatric patients with L2. Methods: Retrospective data was collected through the Porto Inflammatory Bowel Disease group of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) on Paediatric patients with L2, L1 or UC at different time-points. Outcome measures included time to first flare, hospital admissions, initiation of anti-tumor necrosis factor-alpha (TNF alpha) drug, stricture and surgery. Results: Three hundred patients were included: 102 L1, 94 L2 and 104 UC. Rates of hematochezia at presentation were 14.7%, 44.7% and 95.2%, while rates of fever were 12.7%, 26.6% and 2.9%, for patients with L1, L2 and UC, respectively (P < 0.001 for all comparisons). Skip lesions were identified in 65% of patients with L2, and granulomas in 36%, similar to L1 patients. Rates of anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic (pANCA) positivity significantly differed between the three groups: 25.4% and 16.7% for patients with L2, compared with 55.2% and 2.3%, and 1.8% and 52.9% for patients with L1 and UC, respectively. Response rates to exclusive enteral nutrition were comparable between L1 and L2 (78.3-82.4%), as was the response to oral steroids (70.4-76.5%) in the three groups. While times to first flare and admission were similar between groups, patients with L1 were commenced on anti-TNF alpha earlier. Moreover, stricturing phenotype and need for colectomy were very rare in patients with L2. Conclusions: Significant differences are observed in the clinical presentation and outcomes of Paediatric patients with L2, compared to patients with L1 and UC.

Supplemental Digital Content is available in the text., Refractory stage M neuroblastoma (NB) is associated with a poor prognosis and a progressive course of disease. Here, we describe a unique group of patients with a discrepant clinical course. Seven histologically confirmed ganglioneuroblastoma (GNB) (n=6) and differentiating NB (n=1) patients were identified who were diagnosed with stage M disease based on iodine-123-metaiodobenzylguanidine avid bone metastases. Six patients started on high-risk treatment, without tumor response (stable disease). Treatment was discontinued before the start of consolidation treatment because of refractory response in all patients. Unexpectedly, after cessation of treatment no progression of disease occurred. In 2 patients, the primary tumors expanded (>25%) very slowly during 1.5 and 3 years, and remained stable thereafter. Metabolically, a slow decrease of urinary homovanillic acid and vanillylmandelic acid levels and iodine-123-metaiodobenzylguanidine avidity was observed. All patients are alive with presence of metastatic disease after a median follow-up of 17 years (range: 6.7 to 27 y). Interestingly, at diagnosis, 6 patients were asymptomatic, 6 patients had GNB morphology, and 5 patients had meningeal metastases. These are all features seen in only a small minority of stage M patients. This GNB entity illustrates the clinical heterogeneity of neuroblastic tumors and can be used to further study the developmental origin of different NB subtypes.

Objective Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) has variable clinical course. Overall mortality is increased but reasons for this remain largely unknown. Our objective was to assess the causes of death and factors contributing to increased mortality. Design A follow-up study of the Finnish APECED cohort in 1970–2019. Methods In 33 deceased patients with APECED, causes of death and clinical course preceding the death were analyzed using national registry data, death certificates, autopsy reports, and patient records. Results Most common causes leading to death were infections (24%), oral and esophageal malignancies (15%; median age at death 36.7 years; median survival 1.5 years), and diseases of the circulatory system (18%). Adrenal crisis was an independent cause of death in two patients. In addition, in four patients, the adrenal crisis was a complicating factor during a fatal infection. Other APECED manifestations leading to death were hypoparathyroidism, diabetes, and hepatitis. Other causes of death included accidents (12%), alcohol-related causes, and amyotrophic lateral sclerosis. Challenges in overall, and especially in the endocrine, care contributed to deaths related to carcinomas and adrenal crisis. Age at death and year of death correlated (r = 0.345, P = 0.045), suggesting improved longevity. Conclusions Infections, malignancies, and diseases of the circulatory system are the most common primary causes of death in patients with APECED. Adrenal crisis is an independent cause of death but more often a contributing factor in fatal infections. Despite the high overall mortality and the demanding care, our results suggest improved patient survival in recent years.

BackgroundNovel coronavirus SARS-CoV2 is evolving continuously with emergence of several variants of increasing transmission capabilities and pandemic potential. Generation of variants occurs through accumulation of mutations due to the RNA nature of viral genome, which is further enhanced by variable selection pressures of this ongoing pandemic. COVID-19 presentations of SARS-CoV2 are mainly pulmonary manifestations with or without mild gastrointestinal (GI) and hepatic symptoms. However, the virus has evolved beyond pulmonary manifestations to multisystem disorder due to systemic inflammation and cytokine storm. Definitive cause of acute or late onset of inflammation, infection in various organs, and host response to emerging variants lacks clarity and needs elucidation. Several studies have reported underlying diseases including diabetes, hypertension, obesity, cardio- and cerebrovascular disorders, and immunocompromised conditions as significant risk factors for severe form of COVID-19. Pre-existing liver and GI diseases are also highly predominant in the population, which can alter COVID-19 outcome due to altered immune status and host response. We aim to review the emerging variants of SARS-CoV2 and host response in patients with pre-existing liver and GI diseases.MethodsIn this review, we have elucidated the emergence and characteristic features of new SARS-CoV2 variants, mechanisms of infection and host immune response, GI and hepatic manifestation with radiologic features of COVID-19, and outcomes in pre-existing liver and GI diseases.Key FindingsEmerging variants of concern (VOC) have shown increased transmissibility and virulence with severe COVID-19 presentation and mortality. There is a drastic swift of variants from the first wave to the next wave of infections with predominated major VOC including alpha (B.1.1.7, UK), beta (B.1.351, South Africa), gamma (B.1.1.28.1, Brazil), and delta (B1.1.617, India) variants. The mutations in the spike protein of VOC are implicated for increased receptor binding (N501Y, P681R) and immune escape (L452R, E484K/Q, T478K/R) to host response. Pre-existing liver and GI diseases not only have altered tissue expression and distribution of viral entry ACE2 receptor but also host protease TMPRSS2, which is required for both spike protein binding and cleavage to initiate infection. Altered immune status due to pre-existing conditions results in delayed virus clearance or prolonged viremia. Even though GI and hepatic manifestations of SARS-CoV2 are less severe, the detection of virus in patient’s stool indicates GI tropism, replication, and shedding from the GI tract. COVID-19-induced liver injury, acute hepatic decompensation, and incidences of acute-on-chronic liver failure may change the disease outcomes.ConclusionsThe changes in the spike protein of emerging variants, immunomodulation by viral proteins, and altered expression of host viral entry receptor in pre-existing diseases are the key determinants of host response to SARS-CoV2 and its disease outcome.

Introduction: The coronavirus disease-2019 (COVID-19) pandemic has been the most significant event in 2020, with ~86.8 million cases and 1.88 million deaths worldwide. It is a highly infectious disease, wherein the virus (severe acute respiratory syndrome coronavirus 2) rapidly multiplies and spreads to all parts of the body. Therefore, COVID-19 is not only respiratory disease but also a multisystem disease. Many people, including physicians, incorrectly believe that the disease affects only the respiratory tract. In this study, we aimed to describe COVID-19 manifestations and the underlying pathophysiology to provide the readers with a better understanding of this disease to achieve good management and to control the spread of this disease.Methods: Secondary data were obtained from PubMed, Google Scholar, and Scopus databases. The keywords used for the search were as follows: COVID-19, COVID-19 pulmonary manifestations, COVID-19 extra pulmonary manifestations, and pathophysiology of COVID-19. We collected secondary data from systemic reviews, metaanalyses, case series, and case reports in the form of public data that was published on websites of the government, medical corporations, medical peer-reviewed journals, and medical academies, all of which were indexed in PubMed, Google Scholar, or Scopus. Our questions were as follows: Is COVID-19 a respiratory disease only? and What are the extrapulmonary manifestations of COVID-19?Results: From our data, we found that a patient with COVID-19 may be either asymptomatic or symptomatic. Symptomatic cases may have either pulmonary or extrapulmonary manifestations. Pulmonary manifestations occur as mild, moderate, or severe cases. In mild and moderate cases, extrapulmonary manifestations such as gastroenteritis, fever, or vomiting may present alone. Some of these cases may be missed for diagnosis, and the patient may receive symptomatic treatment without a COVID-19 diagnosis, leading to increased spread of the infection. Extrapulmonary manifestations may occur in severe and critical cases as complications of severe infections (high viral overload) or the cytokine storm, such as in acute kidney injury (AKI), heart failure (HF), and venous thromboembolic (VTE) manifestation.Conclusion: COVID-19 is not a respiratory disease alone; rather, it is a multisystem disease. Pulmonary and extrapulmonary manifestations should be considered for early diagnosis and to control the spread of the infection.

Summary Since the Coronavirus disease 2019 (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), our understanding regarding the pathophysiology and clinical manifestations of this disease have been improving. However, we still have limited data on long‐term effects and lingering symptoms of post COVID‐19 recovery. Despite predilection of COVID‐19 for lungs, multiple extra‐pulmonary manifestations appear in multiple organs and biological systems and with continued infection and recovery worldwide. It is necessary that clinicians provide patients with previous SARS‐CoV‐2 infection with expectations of long‐term effects during or after recovery from COVID‐19. Herein, we review the long‐term impact of COVID‐19 on different organ systems reported from different clinical studies. Understanding risk factors and signs and symptoms of long‐term consequences after recovery from COVID‐19 will allow for proper follow‐up and management of the disease post recovery.

Objective To evaluate choroidal thickness (CT), corneal parameters, and scleral thickness (ST) in patients with systemic sclerosis (SSc) and to determine their relationship with disease-related quality of life (QoL). Methods The study included 38 patients with SSc and 40 healthy controls. A detailed ocular examination was performed on all participants. Corneal parameters such as K1, K2, Km, corneal volume (CV), central corneal thickness (CCT), and ST at a distance of 1000, 2000, and 3000 mu m from the scleral spur were measured. CT was measured at five points, including the subfoveal area and the temporal and nasal points at radii of 750.0 and 1500.0 mu m. The scleroderma health assessment questionnaire (SHAQ) was administered to SSc patients to investigate the disease-related QoL. Results Individuals with SSc had thicker ST at all distances from the scleral spur (P=0.008, P=0.001, P=0.002, respectively). All corneal parameters were significantly lower in the SSc group than in the control group (P < 0.05). Moreover, SSc patients had significantly lower median CT at N750.0, N1500.0, T750.0, and T1500.0 points and thinner subfoveal CT than healthy controls (P < 0.05). There was a weak-moderate negative correlation between ST and the components of the SHAQ scale and SHAQ-global. Conclusion Despite not having ocular involvement, SSc patients had thicker ST but thinner CT and corneal parameters than healthy controls. This may indicate subclinical inflammation in patients with SSc. Only ST was affected by organ involvement and QoL among the ocular parameters.

Acute intermittent porphyria is one of the most common porphyria subtypes. There is a critical need to diagnose porphyria, given its multisystem nature and the poor prognosis associated with incurable cases. Here we present the case of a 27-year-old female patient who had severe abdominal pain and who was operated on due to ileus with tetraparesis that manifested following an operation. The patient had muscle weakness in four limbs and symptoms of sympathetic hyperactivity and electrolyte imbalance. Moreover, neurophysiological studies supported acute axonal polyneuropathy. Owing to the neurological symptoms, electrophysiological studies, metabolic disorders, and the severe abdominal pain noted, porphyria was suspected. Porphobilinogen and ALA levels increased in the 24-hour urine test, and the patient was diagnosed with acute intermittent porphyria. In patients who have unexplained recurrent abdominal pain with additional autonomic dysfunction, neurological and / or psychiatric findings, porphyria, a rare disease, should come to mind., Akut intermittant porfiri, porfirinin en yaygın alt tiplerinden biridir. Multisistemik bir hastalık olması ve tedavi edilemeyen olgularda prognozun kötü olması nedeniyle tanı koymak çok önemlidir. Burada şiddetli karın ağrısı ile acil servise başvuran ve ileus ön tanısıyla opere edilen, operasyon sonrası tetraparezi gelişen 27 yaşında bayan hasta sunulacaktır. Hastanın dört ekstremitesinde kas güçsüzlüğü, sempatik hiperaktivite bulguları ve elektrolit dengesizliği vardı. Yapılan elektrofizyolojik çalışmalar akut aksonal polinöropatiyi destekledi. Hastanın nörolojik semptomları, elde edilen elektrofizyolojik bulguları, metabolik bozukluklar ile birlikte şiddetli karın ağrısı olan hastada porfiriden şüphelenildi. Bakılan 24 saatlik idrar testinde porfobilinojen ve ALA düzeylerinin yükseldiği gösterilen hastaya akut intermittant porfiri tanısı konuldu. Açıklanamayan tekrarlayan karın ağrısı, otonom disfonksiyon, nörolojik ve/veya psikiyatrik bulguları olan hastalarda, nadir görülen bir hastalık olan porfiri akla gelmelidir.

Background The cervicovaginal microbiota, including sexually transmitted infections (STIs), have not been well described in female genital schistosomiasis (FGS). Methods Women (aged 18–31, sexually active, nonpregnant) were invited to participate at the final follow-up of the HPTN 071 (PopART) Population Cohort in January–August 2018. We measured key species of the cervicovaginal microbiota (Lactobacillus crispatus, L. iners, Gardnerella vaginalis, Atopobium vaginae, and Candida) and STIs (Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Mycoplasma genitalium) using quantitative PCR (qPCR). We evaluated associations of the microbiota and STI presence and concentration with FGS (qPCR-detected Schistosoma DNA in any of 3 genital specimens). Results The presence and concentration of key cervicovaginal species did not differ between participants with (n = 30) or without FGS (n = 158). A higher proportion of participants with FGS had T. vaginalis compared with FGS-negative women (P = .08), with further analysis showing that T. vaginalis was more prevalent among women with ≥2 Schistosoma qPCR-positive genital specimens (50.0%, 8/16) than among FGS-negative women (21.5%, 34/158; P = .01). Conclusions We found weak evidence of an association between the presence of T. vaginalis and FGS, with a stronger association in women with a higher-burden FGS infection. Additional research is needed on potential between-parasite interactions, especially regarding HIV-1 vulnerability.

To understand the current state of the issue of dental manifestations of primary immunodeficiencies, foreign literature on the problem has been analyzed. The article describes the dental manifestations of many primary immunodeficiencies, which can be both secondary and major symptoms. The article presents the data on the following syndromes: severe combined immunodeficiency, hyper IgE, Wiskott - Aldrich, DiGeorge, deficiency of STIM1 and ORAI1, NEMO deficiency and IκBα deficiency, common variable immunodeficiency, X-linked agammaglobulinemia, hyper IgM, selective IgA deficiency, autoimmune lymphoproliferative syndrome, autoimmune polyendocrine syndrome type 1, Chediak - Higashi syndrome, CD70 deficiency, severe congenital neutropenia syndromes, leukocyte adhesion deficiency, localized aggressive periodontitis, Papillon - Lefevre syndrome, chronic mucocutaneous candidiasis, Marshall syndrome, hyper IgD syndrome, Aicardi - Goutières syndrome type 7, cherubism syndrome, CANDLE (chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature), PAPA (pyogenic arthritis, pyoderma gangrenosum and acne), chronic recurrent multifocal osteomyelitis, periodontal Ehlers - Danlos syndrome, and C1 inhibitor deficiency. The role of secretory immunoglobulins of salivary fluid is described. © 2019 Siberian State Medical University. All rights reserved. Ural Branch, Russian Academy of Sciences, UB RAS: АААА-А18-118020590108-7 Sourse of financing. The study was supported by the state order of the Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences (topic No. АААА-А18-118020590108-7) as well as by the decree of the Russian Federation Government No. 211, contract No. 02.A03.21.0006.

Objective: Systemic features influence disease prognosis and choice of treatment in primary Sjogren's syndrome (pSS). Our aim was to investigate the prevalence of pulmonary involvement in pSS patients and to classify patients according to the pulmonary domain of the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI). Methods: This retrospective cohort study included consecutive pSS patients, fulfilling American-European Consensus Group/American College of Rheumatology classification criteria, who visited the Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, in 2015. Data on pulmonary complaints and pulmonary tests were obtained from electronic patient records. Pulmonary involvement was recorded if therapy was needed or follow-up was recommended, and when it was possibly or assumed to be related to pSS instead of coincidental factors. Results: Of the 262 included pSS patients, 88 (34%) had pulmonary complaints, mostly cough or dyspnoea on exertion. Pulmonary diagnostics were performed in 225 patients (86%). Pulmonary involvement was present and assumed to be related to pSS in 25 patients (10%) and possibly related to pSS in 14 (5%). Interstitial lung disease (ILD, n = 15), especially non-specific interstitial pneumonia (n = 7), was present most commonly. In total, 16 patients (6%) were scored as low (n = 4), moderate (n = 11), or high activity (n = 1) on the ESSDAI pulmonary domain. Conclusion: In this cross-sectional study in daily clinical practice, pulmonary involvement was present in 10-15% of pSS patients, of which ILD was most common. Of all pSS patients, 6% were scored as active on the pulmonary domain of the ESSDAI.

Purpose of review To carry out an update on the state of the art of the Mayaro virus (MAYV) infection and its osteoarticular implications. Recent findings There is a wide distribution of MAYV in Latin America and documented exported cases to the United States and Europe. Although osteoarticular involvement is not the most frequent, it is one the most associated with disability. The main mechanisms related to arthropathy involves cellular infiltrates (i.e. macrophages, natural killer cells, lymphocytes) together with production of cytokines, such as IL-6, IL-7, IL8, IL-12p70. Summary MAYV infection is an emerging disease, which has been reported in many and increasing number of countries of Latin America. There is a high risk of epidemic outbreaks, given the inadequate vector control (Aedes mosquitoes). Its main symptoms, like other arbovirus infections, involve the presence of headache, rash, conjunctivitis, and arthralgias. MAYV arthropathy is usually severe, can last in time, and is associated with severe disability. There is currently no treatment for MAYV. Prevention of MAYV as a public health burden will be achieved by integrating vector control with vaccines (still under development).

Background: Hypophosphatasia (HPP) is a rare, inherited, metabolic disease caused by tissue-nonspecific alkaline phosphatase deficiency, characterized by bone mineralization defects and systemic complications. Understanding of the clinical course and burden of HPP is limited by its rarity. This systematic literature review and synthesis of case report data aimed to determine the frequency and timing of clinical HPP manifestations and events. Methods: Case reports and series of patients with HPP who had been followed longitudinally for ≥1 year were identified. Demographics and clinical data of interest, identified through consultation with clinical experts in HPP, were extracted. Occurrences of clinical manifestations/events of interest were categorized, classified by age at first reported occurrence of HPP manifestations and visualized over time. Clinical manifestations/events considered to contribute to the clinical burden of HPP were identified. Kaplan-Meier curves were used to estimate the median (range) age at first occurrence of the most frequently reported manifestations/events. Results: From the 283 studies that met the inclusion criteria, 265 patients with HPP with ≥1 year of longitudinal follow-up were identified (median [interquartile range] age 4 [0-34] years; 45% male). The types of clinical manifestations/events of interest experienced by individuals with ≥1 such manifestation/event (n = 261) often differed between older and younger patients. Most (94%) of the 265 patients experienced ≥1 manifestation/event deemed to contribute to the clinical burden of HPP; premature tooth loss (53.5%), fractures (35.8%), pain (33.6%), and gross motor/ambulation difficulties (30.9%) were most frequently reported. The median (range) age at first reported occurrence of respiratory symptoms, cranial abnormalities, and premature tooth loss ranged from 0.3 to 10 years, whereas the median age at first reported occurrence of fractures, pain, gross motor/ambulation difficulties, and surgery ranged from 33 to 70 years. Conclusions: HPP is associated with a high clinical burden of disease, regardless of age at first reported occurrence of HPP manifestations. Over an individual's lifetime, the types of manifestations/events experienced can change and multiple HPP-related clinical manifestations/events can accumulate. These observations may reflect evolution and progression of the disease., Funding for the conduct of this study and the development of this manuscript was provided by Alexion Pharmaceuticals, Inc.

Lipoid proteinosis is a rare cause of voice problems. Hoarseness is often the first clinical manifestation of this disorder and can present years before any other symptom. Therefore, it is very important as an otorhinolaryngologist to be familiar with the main characteristics of this disease. We present a case report and a review of current literature to provide a concise overview of this frequently missed diagnosis. ispartof: JOURNAL OF VOICE vol:33 issue:2 pages:155-158 ispartof: location:United States status: published

Background This study evaluated the time course of computed tomography (CT) findings of patients with COVID-19 pneumonia who required mechanical ventilation and were treated with favipiravir and steroid therapy. Results Eleven patients with severe COVID-19 pneumonia were included. CT findings assessed at the three time points showed that all patients had ground-glass opacities (GGO) and consolidation and mixed pattern at intubation. Consolidation and mixed pattern disappeared in most of the patients whereas GGO persisted in all patients at 1-month follow-up. In addition to GGO, a subpleural line and bronchus distortion and bronchial dilatation were frequent findings. The degree of resolution of GGO varied depending on each patient. The GGO score correlated significantly with the time from symptoms onset to initiation of steroid therapy (ρ = 0.707, p = 0.015). Conclusions At 1-month follow-up after discharge, non-GGO lesions were absorbed almost completely, and GGO were a predominant CT manifestation. Starting steroid therapy earlier after onset of symptoms in severe COVID-19 pneumonia may reduce the extent of GGO at 1-month follow-up.

Introduction Sarcoidosis is a chronic granulomatous disease of unknown aetiology and laryngeal involvement is seen in a small percentage of cases. Dysphagia is a common but under-reported symptom. Little is known about how dysphagia typically presents or is managed in the context of this fluctuating disease. We present our case series using an SLT-led model of assessment and management. Methods A literature search was conducted for any articles that reported both laryngeal sarcoidosis and dysphagia. We then analysed a case series of laryngeal sarcoidosis patients treated at Charing Cross Hospital. We report on multidimensional swallowing evaluation and rehabilitative interventions. Results Seventeen papers report both laryngeal sarcoidosis and dysphagia, with only one paper giving details on the nature of the dysphagia and the treatment provided. In our case series (n = 7), patients presented with FOIS Scores ranging from 5 to 7 pre-operatively (median = 6). Aspiration (median PAS Score = 6 and Range = 3–8) and pharyngeal residue were common. Sensory issues were also prevalent with most unaware of the extent of their difficulties. Management interventions included safe swallowing advice, compensatory strategies, exercises and close surveillance given their potential for repeated surgical interventions. Conclusion Laryngeal sarcoidosis is a rare condition. Dysphagia is under-reported and our experience highlights the need for specialist dysphagia intervention. Further research is required to understand dysphagia management requirements in the context of this fluctuating disease process.

Behçet‘s Syndrome (BS) is a variable vessel vasculitis according to the Chapel Hill Consensus Nomenclature (1) and may thus affect any organ, including major and minor arterial and venous vessels to a varying degree and with varying frequency. Although the main features of BS are recurrent oral and genital aphthous ulcers, cutaneous lesions, ocular inflammation and arthritis—major vessel and life—or organ threatening involvement of internal organs and the central and peripheral nervous system occur. In general, BS in Europe appears to form six phenotypes of clinical manifestations (2), which are (1) mucocutaneous only, (2) predominant arthritis/articular involvement, (3) vascular phenotype, (4) ocular manifestations, which are most likely associated with CNS manifestations and HLA-B51, (5) dominant parenchymal CNS manifestations (being associated with the ocular ones), and (6) gastrointestinal involvement. Mucocutaneous manifestations are present in almost all patients/all phenotypes. In the following review, we summarize the current knowledge concerning vascular, neurologic, gastrointestinal and musculoskeletal manifestations of the disease.

To establish practical recommendations for the management of patients with psoriatic arthritis (PsA) with particular clinical situations that might lead to doubts in the pharmacological decision-making. A group of six expert rheumatologists on PsA identified particular clinical situations in PsA. Then, a systematic literature review (SLR) was performed to analyse the efficacy and safety of csDMARDs, b/tsDMARDs in PsA. In a nominal group meeting, the results of the SLR were discussed and a set of recommendations were proposed for a Delphi process. A total of 65 rheumatologists were invited to participate in the Delphi. Agreement was defined if ≥ 70% of the participants voted ≥ 7 (from 1, totally disagree to 10, totally agree). For each recommendation, the level of evidence and grade of recommendation was established based on the Oxford Evidence-Based Medicine categorisation. Particular clinical situations included monoarthritis, axial disease, or non-musculoskeletal manifestations. The SLR finally comprised 131 articles. A total of 16 recommendations were generated, all but 1 reached consensus. According to them, it is crucial to carefully analyse the impact of individual manifestations on patients (disability, quality of life, etc.), but also to recognise the impact of each drug singularities on selected clinical phenotypes to adopt the most appropriate treatment strategy. Early diagnosis and treatment to target approach, along with a close risk management, is also necessary. These recommendations are intended to complement gaps in national and international guidelines by helping health professionals address and manage particular clinical situations in PsA. Supplementary Information The online version contains supplementary material available at 10.1007/s00296-021-04877-5.

Chronic drug-induced liver injury (DILI), defined as DILI with persistent liver injury more than one year after the first onset by the latest European guidelines, is a notable challenge globally with big issues of defining causality and establishing effective treatment. About 20% of patients with DILI develop into chronic DILI. Chronic DILI manifests as persistent or repeated inflammatory or diminishing bile ducts, even progresses to cirrhosis and needs liver transplantation eventually. However, research on chronic DILI over the last decades is still lacking, and the incidence, phenotypes, mechanisms, risk factors, and treatment have not been fully understood. In this paper, we reviewed the definition of chronic DILI, updated clinical studies in terms of incidence, special manifestations, and promising risk factors of chronic DILI, along with the recent progress and challenges in glucocorticoid therapy.

In December 2019 novel coronavirus-Severe Acute Respiratory Syndrome-Corona Virus2 (SARS-CoV2)-originated from Wuhan, China, and spread rapidly around the world. This literature review highlights the dynamic nature of COVID-19 transmission and presentation. Analyzing 59 relevant articles up to May 1st, 2020 reflects that the main reported clinical manifestation of COVID-19 pandemic is fever and respiratory involvement. Also, current literature demonstrates a wide spectrum of different and atypical presentation(s) of COVID-19. The definite route of SARS-CoV2 transmission is respiratory droplets, however, virus nucleic acid has been detected in the stool and urine specimens as well. The severity of symptoms and outcomes of COVID-19 vary based on the patient's medical background, age, sex, and concurrent medical conditions (e.g. pregnancy). This is the first review that classifies all essential points regarding COVID-19 manifestations at a glance to improve the outcome of the patients by a better insight into diagnosis and management.

Systemic embolization has been reported in up to 40% of patients with left atrial myxoma, half of them with cerebral involvement. However, development of intracerebral embolization associated with parenchymal seeding of the myxoma emboli is an extremely rare complication, with only 36 histologically diagnosed cases reported in the published literature. We describe a 69-year-old woman who arrived at the emergency service with hemiparesis associated with drug-resistant epilepsy and a medical history of resection of a left atrial myxoma 10 months previously. Cranial computed tomography revealed multiple large lesions of heterogeneous density and cystic components in the occipital lobes and posterior fossa parenchyma. Histopathological analyses after stereotactic biopsy of the occipital lesion revealed infiltrative myxoma cells with benign histological findings and uniform expression of calretinin similar to that of the primary cardiac myxoma. Additional immunohistochemical studies confirmed brain parenchymal seeding of the myxoma cells with strong expression of interleukin-6 (IL-6) and focal expression of matrix metalloproteinases-2 (MMP-2). Here, we discuss the clinicopathological features of intracerebral embolization of left atrial myxomas associated with progressive parenchymal seeding of the tumor emboli and the potential pathogenic role of IL-6 and MMPs.

Patients hospitalized with COVID-19 are at risk of developing many neuropsychiatric disorders, due to the effects of the disease on the brain and the psychosocial pressures of having the disease. The aim of the present study was to evaluate the characteristics and outcomes of patients who were hospitalized with a diagnosis of COVID-19, who underwent psychiatric consultations. The medical records of 892 patients hospitalized due to COVID-19 and the 89 among them who requested psychiatric consultations were analyzed retrospectively. After the psychiatric consultations, patients were most frequently diagnosed with delirium (38.2 %), adjustment disorder (27.0 %), depressive disorder (19.1 %) and anxiety disorder (11.2 %). Patients with delirium had longer hospital stays (p < 0.001), were transferred more frequently to intensive care units (p < 0.001), and had higher mortality rates during their hospital stays (p < 0.001), than all other patients. The need for oxygen (p < 0.001) and mechanical ventilation (p < 0.001) was also significantly higher in delirium patients, as well as in patients who received other psychiatric diagnoses. Neuropsychiatric disorders develop in patients receiving inpatient treatments in COVID-19 wards, and these disorders negatively affect the prognosis of COVID-19. Our findings suggest that the presence of neuropsychiatric disorders in in-patients with COVID-19 might be associated with the negative outcomes of the disease.

PURPOSE: Severe coronavirus disease 2019 (COVID-19) pneumonia is associated with high mortality. However, the evolution of computed tomography (CT) manifestations of severe COVID-19 pneumonia remains unclear, more evidence regarding its evolution process is urgently needed. METHOD: The clinical, laboratory and imaging data of eleven patients with severe COVID-19 pneumonia were collected to investigate the evolution process of severe COVID-19 cases. RESULTS: The main initial CT manifestations of severe COVID-19 pneumonia were multiple ground-glass opacities and/or consolidation. The evolution of CT manifestations showed that acute exudative lesions of severe COVID-19 pneumonia could be gradually resolved after the active intervention. CONCLUSIONS: Most of patients with severe COVID-19 pneumonia showed marked improvement of acute exudative lesions on chest imagings and satisfactory prognosis of severe COVID-19 pneumonia could be achieved after active treatment.

Abnormal liver function tests (LFTs) are reported frequently in hospitalized coronavirus disease 2019 (COVID-19) patients. A review of the literature shows that 46% of admitted COVID-19 patients had elevated plasma aspartate aminotransferase (AST) and 35% had elevated alanine aminotransferase (ALT) levels on admission. Elevations of both AST and ALT are mostly below 5 times the upper reference limit and are associated with severe disease and increased inflammatory markers. AST and ALT elevations are more frequent in US patients compared to Chinese patients. Mild elevations in gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP) and total bilirubin are also reported, although less frequently. Significant impairment of liver function or overt liver failure as the cause of death in COVID-19 rarely occur. There is no direct evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) hepatic infection, although a subset of hepatocytes and cholangiocytes express the host receptor utilized for cellular entry by SARS-CoV-2. The presence of pre-existing liver disease in patients with elevated LFTs on admission has not been comprehensively assessed in most studies but is unlikely to account for all abnormalities in LFTs. Although abnormal LFTs are already frequently present upon admission before the start of treatment, drug-induced liver injury should be taken into consideration, especially after the use of acetaminophen, lopinavir/ritonavir and remdesivir, which are potentially hepatotoxic. In conclusion, these initial observations suggest that the prevalence of abnormal LFTs is high in COVID-19 patients, but that the clinical relevance is limited and that treatment is not required. The mechanisms underlying abnormal LFTs in COVID-19 are likely multifactorial and related to a hyper-inflammatory status and thrombotic microangiopathy that are observed in severe COVID-19 disease.

Psoriatic arthritis (PsA) is a chronic inflammatory condition with articular and extra-articular manifestations: peripheral arthritis, axial disease, enthesitis, dactylitis, psoriasis, inflammatory bowel disease and uveitis. Anti-tumour necrosis factors (anti-TNFs) have demonstrated clinical efficacies exceeding those of conventional disease-modifying antirheumatic drugs (DMARDs). New understanding in pathogenic pathways have led to novel therapeutic targets. The current treatment paradigms emphasize early diagnosis and treatment, and treating towards remission and low disease activity status, particularly in long-standing disease. This review addresses the evidence of current treatment options for each of the domains of PsA. We present a simple guide that weighs on clinical efficacies for each PsA domain to aid clinicians in choosing the most appropriate treatment for patients. We highlight the unmet need for biomarkers of treatment response, and future perspectives with precision medicine in PsA.

For decades, tuberculosis (TB), a potentially serious infectious lung disease, continues to be a leading cause of worldwide death. Proven to be conveniently efficient and cost-effective, chest X-ray (CXR) has become the preliminary medical imaging tool for detecting TB. Arguably, the quality of TB diagnosis will improve vastly with automated CXRs for TB detection and the localization of suspected areas, which may manifest TB. The current line of research aims to develop an efficient computer-aided detection system that will support doctors (and radiologists) to become well-informed when making TB diagnosis from patients' CXRs. Here, an integrated process to improve TB diagnostics via convolutional neural networks (CNNs) and localization in CXRs via deep-learning models is proposed. Three key steps in the TB diagnostics process include (a) modifying CNN model structures, (b) model fine-tuning via artificial bee colony algorithm, and (c) the implementation of linear average–based ensemble method. Comparisons of the overall performance are made across all three steps among the experimented deep CNN models on two publicly available CXR datasets, namely, the Shenzhen Hospital CXR dataset and the National Institutes of Health CXR dataset. Validated performance includes detecting CXR abnormalities and differentiating among seven TB-related manifestations (consolidation, effusion, fibrosis, infiltration, mass, nodule, and pleural thickening). Importantly, class activation mapping is employed to inform a visual interpretation of the diagnostic result by localizing the detected lung abnormality manifestation on CXR. Compared to the state-of-the-art, the resulting approach showcases an outstanding performance both in the lung abnormality detection and the specific TB-related manifestation diagnosis vis-à-vis the localization in CXRs.

In connection with the editorial of Mallineni et al. 2020 on the coronavirus disease (COVID‐19) characteristics in children, we aim to demonstrate the emerging Pediatric Multi‐system Inflammatory Syndrome Temporally Associated with SARS‐COV‐2 (PMIS‐TS) from oral health professionals perspective.1 The epidemiological burden of COVID‐19 in children was unexplainably lower than adults; therefore, it was predicted that the clinical course differs between children and adults, such hypothesis was confirmed by the surging cases of PMIS‐TS.2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been initially defined as a disease of the respiratory tract; however, with the increasing number of patients and announcing that the virus became a pandemic, new systemic clinical manifestations are observed, including dermatological manifestations. However, the identification and characteristics of these manifestations are still controversial. This review article aims to evaluate the medical literature and explore the dermatological clinical manifestations in patients with SARS-CoV-2. The literature was reviewed through MEDLINE®, Ovid, PubMed®, and Embase®. Searching terms included were a combination of "dermatological" OR "skin" AND "symptoms" OR "manifestations" AND "SARS-CoV-2". The following step was filtering the results to include only original research studies investigating the different types of skin and dermatological clinical manifestations in patients with SARS-CoV-2. A total of 879 studies were retrieved. Following the exclusion of studies on animals and including only studies on humans, 32 studies emerged. Altogether, seven studies were identified as eligible, covering 555 patients with SARS-CoV-2 who had dermatological symptoms. Three studies were retrospective, two studies were prospective, and two studies were case series. Different types of dermatological lesions can occur in patients with SARS-CoV-2, most commonly erythema, urticaria, and varicella-like rash. Dermatological manifestations with SARS-CoV-2 can be misdiagnosed with other conditions. Further studies with robust design are needed.

Objectives. This study was conducted to investigate the current practices of Asian otolaryngologists for laryngopharyngeal reflux (LPR).Methods. An online survey about LPR was sent to 2,000 members of Asian otolaryngological societies, and a subgroup analysis was performed between Western and Eastern Asian otolaryngologists. The survey was conducted by the Laryngopharyngeal Reflux Study Group of Young Otolaryngologists of the International Federation of Oto-rhino-laryngological Societies.Results. Among approximately 1,600 Asian otolaryngologists, 146 completed the survey (62 from Western Asian countries, 84 from Eastern Asian countries). A substantial majority (73.3%) of the otolaryngologists considered LPR and gastroesophageal reflux disease to be different diseases. The symptoms thought to be closely related to LPR were coughing after lying down, throat clearing, and globus sensation. The findings thought to be closely related to LPR were posterior commissure granulations and hypertrophy, arytenoids, and laryngeal erythema. The respondents indicated that they mostly diagnosed LPR (70%) after an empirical therapeutic trial of proton pump inhibitors (PPIs). Although multichannel intraluminal impedance-pH (MII-pH) monitoring is a useful tool for diagnosing nonacid or mixed LPR, 78% of Asian otolaryngologists never or very rarely used MII-pH. Eastern Asian otolaryngologists more frequently used once-daily PPIs (64.3% vs. 45.2%, P=0.021), whereas Western Asian otolaryngologists preferred to use twice-daily PPIs (58.1% vs. 39.3%, P=0.025). The poor dietary habits of patients were considered to be the main reason for therapeutic failure by Asian otolaryngologists (53.8%). Only 48.6% of Asian otolaryngologists considered themselves to be adequately knowledgeable and skilled regarding LPR.Conclusion. Significant differences exist between Western and Eastern Asian otolaryngologists in the diagnosis and treatment of LPR. Future consensus statements are needed to establish diagnostic criteria and therapeutic regimens.