Involvement In Adult Patients Research Articles

Myositis-associated antibodies predict the severity of lung involvement in adult patients with inflammatory myositis - a cohort study of 70 adult patients with myositis in a single center.

Idiopathic inflammatory myopathies (IIMs) encompass a diverse group of diseases characterized by considerable variability in clinical manifestations, antibody profiles, and responsiveness to immunosuppressive therapies. This study aimed to investigate the association between organ involvement and distinct myositis autoantibodies in individuals with IIM in a single-center cohort. Patients with ICD diagnoses M33.1, M33.2, M33.9, or M609 who (1) had been tested with Euroline blot assay for myositis autoantibodies and (2) met the classification criteria of definite/probable polymyositis (PM) or dermatomyositis (DM), anti-synthetase syndrome (ASS), or inclusion body myositis (IBM) were included. Medical journals were retrospectively examined with respect to clinical disease features. Seventy patients (median age 58 years; 66% females) were included and represented the following diagnosis: PM (n = 23), DM (n = 21), ASS (n = 23), and IBM (n = 3). Most of the patients (87%) presented a muscle biopsy indicative of myositis. The presence of autoantibodies was as follows: myositis-specific antibodies, MSA (n = 53), myositis-associated antibodies, MAA (n = 33), both MSA + MAA (n = 24), MSA only (n = 29), MAA only (n = 9), no MSA, or MAA (n = 8). Anti-Jo-1 was the most common MSA (19%), whereas the most common MAA was anti-Ro/SSA52 (31%). We observed a significant association between antibody patterns and lung disease. In our cohort, 47% of the patients in the whole study group, 86% of patients with anti-SSA52, and 100% with anti-Jo-1 had pulmonary involvement. Patients with both MSA and MAA had a higher incidence of lung disease and decreased CO-diffusion capacity. This was especially prominent in anti-Ro/SSA52-positive patients. Interestingly, none of the patients suffered from lung disease if only antibodies against Mi-2α, Mi-2β, NXP2, HMGCR, and TIF1γ were present or no MSA/MAA were detected. The simultaneous presence of both MAA and MSA indicates an increased risk of lung involvement in patients with inflammatory myopathies. The presence of any MAA, and especially anti-Ro/SSA52, is associated with more severe pulmonary disease. Our data suggest that MAA antibodies might be relevant markers for early detection and treatment of lung involvement in IIM.

Incidence, risk factors, and outcome of asymptomatic central nervous system involvement in adult patients with acute myeloid leukemia.

Examination of central nervous system (CNS) involvement is not routine diagnostic practice in adult patients with acute myeloid leukemia (AML). Therefore, many asymptomatic patients with CNS involvement might go undetected. The effect of CNS involvement on the AML disease course is not well defined, with conflicting results regarding clinical outcome. This study aimed to determine the incidence of asymptomatic CNS involvement in AML estimated by multiparametric flow cytometry of cerebrospinal fluid (MFC-CSF) at diagnosis, the related potential risk factors, and prognosis. In total, 645 patients with de novo AML were screened; 183 (28.4%) of them fulfilled institutional practice for MFC-CSF analysis based on presence of CNS symptoms and/or clinical features. CNS symptoms and signs were observed in 8/183 (4.4%) patients, but most patients (175/183, 95.6%) were asymptomatic. In the asymptomatic group, 73/175 (41.7%) patients had positive or suspicious cerebrospinal fluid (CSF) findings categorized as CNS positive (CNSpos) and 102/175 (58.3%) had normal CNS findings categorized as CNS negative (CNSneg). The presence of leukemic blasts was confirmed in 81/183 (44.3%) patients; the total incidence of CNS involvement in the whole AML group was 12.6% (81/645). Compared with asymptomatic patients with CNSneg, those with CNSpos had a significantly higher frequency of lymphadenopathy, white blood cell count ≥30×109/L, presence of the monocytic phenotype, and a high percentage of bone marrow (BM) blasts. The multivariate logistic regression model identified monocytic phenotype (p=0.047) and high percentage of BM blasts (p=0.042) as predictors for CNSpos. CNSpos did not affect overall survival in patients with AML. There was a higher incidence of CNS involvement in asymptomatic adult patients with de novo AML, emphasizing possible undervalued rates of CNS disease at diagnosis. Prospective studies should determine whether diagnostic lumbar puncture for MFC-CSF analysis and CNS prophylaxis could contribute to better selection and prognosis in this patient population.

Retrospective Immunophenotypic Profile of Acute Leukemias in the State of Rio Grande Do Norte, Northeast, Brazil

INTRODUCTION:The main acute leukemias (ALs) are lymphoid (B or T lineage ALL) and myeloid (AML), in addition to biphenotype AL (BAL) and undifferentiated ALL (IAL), which are rarer. This variation reflects on therapy, requiring methods to characterize these leukemias. Thus, methods such as immunophenotyping by flow cytometry (ICF), multiparametric and quantitative, help in the follow-up of these neoplasms. Objective: The aim of this study was to demonstrate the immunophenotypic diagnostic profiles in patients with AL in Rio Grande do Norte, state, Brazil by FC. Methodology: Bone marrow and peripheral blood samples from 371 patients clinically diagnosed with AL were investigated by CF, using a panel of monoclonal antibodies for the detection of lymphoid (B, T and NK) and myeloid antigens, as well as markers related to cell immaturity such as CD34, Terminal deoxynucleotidyl Transferase (TdT).At the same time, information related to clinical data, age group and sex of patients was also collected. Results: Of all LA investigates 71 were B cell-ALL, 55 T cell-ALL, 239 AML, 04 BAL and 02 IAL. Regarding the immunophenotypic pattern, the main subgroups in relation to age group and were evidenced through the FC. 06/71 were Pro-B ALL, 48/71 Common ALL, 06/71 cyt mü chain ALL and 11/71 mature sIgM+ B-ALL. In B-cell lineage ALL, 51 (71.8%) of the cases were children (less than or equal to 18 years old) and 20 (28.2%) adults (over 18 years old). In T-cell ALL, 9 (16.4%) were pre-T ALL, 12 (21.8%) intermediate ALL and 29 (52.7%) medullary T-type ALL, corresponding to a total of 36.4% children and 63.6% adults. In AML, there was a predominance of involvement in adult patients, corresponding to47 (80.7%) of cases and 192 (80.3%) in children. Biphenotypic and undifferentiated AL were detected in adult patients. DISCUSSION: The B cell-ALL were characterized by natural arrest of B-cells precursors based on the expression of antigens related to this lineage in: i) Pro-B ALL (CD19+, HLA-Dr+, CD34+, TdT+); ii) Common ALL (CD10+, CD19+, cCD79a+, cytCD22+, HLA-Dr+, TdT+/- and CD34+/-); iii) cyt mü chain+ ALL (cyt IgM+, CD19+, HLA-Dr+, cytCD79a+, cytCD22+, CD10-, CD34-) and iv) mature B-ALL (sIgM+, sCD22+, CD10+/-, CD20+ and kappa+ or lambda+). The T-ALL were classified into: i) pre-T-ALL (CD7+, cytCD3+, HLADr+, CD34+ and TdT+), ii) intermediate T-ALL (CD1a+, CD2+, CD7+, cytCD3+, TdT+ and HLADr+, CD4+/CD8+) and Medullary T-ALL (CD4+ or CD8+, sCD3+, CD1a-, TdT+, HLADr+/- and CD34-). It was also possible to observe the aberrant expression of myeloid antigens in B and T-ALL, such as CD13, CD33 and CD66b, mainly related to ALL in the context of KMT2A rearrangement with lineage switching. In addition to transferrin receptors (CD71) and IL-2 receptor (CD25), which have been reported in the context of ALL BCR+/ABL+, as well as the presence of the Philadelphia chromosome. In AMLs, the most observed subtypes were those with little differentiation and with a monocyte component. (CD64+/CD14+). CD15+/CD34+ expression was also observed, indicative of asynchrony of maturation, and phenotypic aberrancy of lymphoid antigens in some cases, predominantly CD7. In addition to other antigens such as CD2 and CD19, CD19 and CD56, In addition, ALL was more frequent in children and males, while AML in adults and females in general, with a predominant incidence in males among adult patient. Conclusion: When properly applied, ICF can have a great impact on the diagnosis, classification and prognostic analysis of neoplastic processes.

Pattern of Autonomic Involvement in Adult Patients with Guillain Barre Syndrome in a Tertiary Hospital

Background: Guillain Barre Syndrome (GBS) is an acute post infectious immune mediated peripheral neuropathy with a marked variation in pathology, clinical presentation and prognosis. Autonomic dysfunction is one of the important manifestations of GBS which may lead to significant morbidity and mortality. Objective: The aim of the study is to assess the autonomic involvement, to determine its frequency and pattern of involvement in adult patients with GBS Methods: An observational, descriptive, cross sectional study was carried out in the Department of Neurology, BSMMU, Dhaka from March, 2015 to September, 2017. Total 43 patients of GBS and 35 apparently healthy controls were recruited as the study population. On the basis of nerve conduction study patients were classified into different groups: acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN) and acute motor sensory axonal neuropathy (AMSAN) and other variants. Disability status at the time of autonomic testing was measured by Hughes functional grading scale. The following tests of autonomic nervous system were performed in both patients and controls 1) resting heart rate and heart rate on changing posture (30: 15 ratio) 2) supine blood pressure and blood pressure on changing posture 3) heart rate response to valsalva maneuver 4) heart rate response to deep breathing and E: I ratio 5) sphincter disturbance by symptoms questionnaire. Results: The mean age of patients was 35±12 years (range18 to 65 years) and 58.1% were male. Around 88.4 % of patients showed some sort of autonomic dysfunction. Variation of heart rate by different maneuver like posture change, deep breathing and valsalva maneuver was found commonly. Among them 30:15 ratio was abnormal in majority of the patients (82.4%) followed by abnormal max-min HR/min (58.1%) and abnormal valsalva ratio (37.2%). Other abnormalities were postural hypotension (38.2%), sinus tachycardia (25.6%), hypertension (16.3%), hypotension (2.7%), sinus arrhythmia (4.7%), constipation (30%), urinary retention (7%) and urinary incontinence (4.7%). Conclusion: In this study different patterns of autonomic dysfunction was found in 88.4% of patients with GBS involving both sympathetic and parasympathetic components. The present study found no significant association between autonomic dysfunction and motor disability scores. Thus autonomic function assessment is essential in every patient with GBS in addition to motor & sensory function. Bangladesh Medical Res Counc Bull 2022; 48(3): 174-179

Clinical Presentation and Pattern of Cardiac Involvement in Patients with Rheumatic Heart Disease: A Prospective Observational Study

Context: Rheumatic heart disease (RHD). Aim: The aim of the study was to study the clinical presentation and pattern of cardiac involvement in adult patients with RHD. Settings and Design: This was a prospective observational study from a tertiary care hospital in South India. Subjects and Methods: Consecutive adult patients diagnosed with and treated for RHD in our tertiary care teaching hospital in Tirupati were screened for inclusion. In all patients, details of appropriate laboratory and imaging investigations that have been carried out were noted. Statistical Analysis Used: Descriptive statistics (frequencies, mean standard deviation, and median [interquartile range (IQR)]) were reported. Results: A total of 120 patients were enrolled. Their mean age was 45.7–12.2 years; there were 79 females. The median (IQR) follow-up was 364 (156–702) weeks. Single-valve disease was seen in 51.7% (n = 62); others (n = 58) had multivalvular disease (mitral stenosis [MS] + aortic regurgitation [AR] [n = 47, 81%] and mitral regurgitation + AR [n = 11, 19%]). Among patients with single-valve involvement, 58 (93.5%) had mitral valve disease. Overall, 116 of 120 (96.6%) patients had mitral valve involvement. Among patients with mitral valve disease (n = 116), MS was severe in 62 (51.6%). Atrial fibrillation was evident in 59 (49.2%) patients; of these, 8 had cardioembolic strokes. Forty-four (36.7%) had undergone percutaneous transvenous mitral commissurotomy. Prosthetic mitral valve obstruction was observed in 2/20 patients who had undergone mitral valve replacement or double-valve replacement. Conclusions: In patients with RHD, mitral valve involvement (either alone or in combination with the aortic valve) was most common; MS was most common.

Atypical exanthem with acral involvement in adult patients associated with human herpesvirus 7 active replication: A case series.

An "atypical exanthem" (AE) is an eruptive skin eruption that differs in morphology and etiology from classical exanthems and is often a reason for urgent medical evaluation. The most frequent cause of AEs is a viral infection, but an accurate etiology cannot be established basing on the sole clinical features. Human herpesviruses (HHV) have been often suspected as etiologic agents or cofactors in atypical rashes. We performed a retrospective analysis of adult patients presenting an atypical exanthem associated with HHV-7 active replication in our center. The charts of patients were reviewed and the demographic, clinical and laboratory data collected. Nine patients (six males and three females) were included in the study, with a mean age of 43 years for men and of 26 years for women. All patients presented active HHV-7 replication in plasma during the rash, which turned negative after the exanthem resolved. The exanthem displayed a maculopapular pattern involving the trunk, limbs and, notably, the acral regions, in six patients. In three cases the exanthem was confined to only the acral sites. In most cases, there was no fever and the inflammatory indices remained unchanged. Antihistamines, topical and systemic corticosteroids were used as treatment, with excellent symptom control. We propose adding skin manifestation associated with HHV-7 to the concept of atypical exanthems, in particular those localized to the acral regions.

Neurologic Presentations of COVID-19: A Case Series

Introduction: The new pandemic of coronavirus disease 2019 (COVID-19) has evolved certain neurologic syndromes as a presentation of this disease that should be integrated into the whole disease process. Case Presentations: We present cases of neurologic involvement in adult patients with documented bronchopulmonary COVID-19. Certain signs and symptoms are introduced, including new onset seizures, ischemic stroke, and altered mental status in otherwise minimal clinical signs and symptoms of COVID-19. Conclusions: Many neurologic presentations are diagnosed in resolving COVID respiratory infections or in an otherwise asymptomatic individual.

Clinical Characteristics of Hemophagocytic Lymphohistiocytosis in Adults with Central Nervous System Involvement

Purpose: Central nervous system (CNS) involvement in hemophagocytic lymphohistiocytosis (HLH) is characterized by neurological symptoms/signs, CNS imaging changes, and cerebrospinal fluid abnormalities. However, most reports of CNS-HLH focused on pediatric patients, and there were few clinical studies in adult patients. Therefore, we carried out this study to investigate clinical characteristics and prognosis of adult patients with CNS-HLH. Methods: A retrospective analysis of adult patients with HLH from January 2010 to December 2021 was conducted. Clinical characteristics, assistant examination, treatment, and prognosis were analyzed. Results: Among 166 HLH patients in our center, 16 patients (9.6%) had neurological symptoms and/or assistant examinations of CNS involvement. 1 was primary HLH; 11 were secondary to malignant tumor; 3 were secondary to infection; 1 was secondary to autoimmune disease. 13 patients (81.3%) showed CNS symptoms, and the most common symptom was dizziness/headache (43.8%). 12 patients underwent cranial CT or MRI, and 9 (75%) showed changes. 7 patients underwent cerebrospinal fluid examination, and 5 (71.4%) showed abnormal results. 5 patients underwent PET-CT, and all were normal. 7 patients underwent HLH genetic testing, 1 showed homozygous mutation of UNC13D C.2588G&GT; 5 showed unknown significance heterozygous mutations of HLH related genes. For patients who received anti-HLH and/or anti-lymphoma chemotherapy, who achieved CR/PR had significantly better OS than those with NR (Not reached V.S. 8 days, P<0.001). However, Patients who received CNS-HLH therapy had no statistically significant long-term survival compared with patients who received general HLH therapy (P=0.290). As for the analyses of effective factors on survival time, rash was the only independent risk factor. Conclusions: CNS involvement in adult patients with HLH is not rare and the prognosis is poor. The clinical manifestations and etiology of these patients are heterogeneous. Early diagnosis through CNS examinations and treatment in time are essential to improve the prognosis of patients with CNS-HLH. This work was supported by 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (No. ZYJC21007). Key words: Hemophagocytic Lymphohistiocytosis; Adults; Central Nervous System; Prognosis; Retrospective Study

Prevalence, Risk Factors, and Prognosis of Liver Involvement in Adult Patients with Chikungunya in Thailand.

Chikungunya is a mosquito-borne disease mainly characterized by fever with polyarthralgia. Currently, liver complications of chikungunya remain rarely described. This study assesses the prevalence, severity, and risk factors of liver involvement, and the association between liver involvement severity and prognosis. We conducted a retrospective cohort study at two referral centers for tropical infectious diseases-the Hospital for Tropical Diseases and Bamrasnaradura Infectious Diseases Institute in Thailand-from January 2016 to April 2021. The study included 400 patients diagnosed with chikungunya. Of them, 254 (63.5%) were female with a mean age of 41.5 ± 14.1 years, and 98.5% of them presented with fever with arthralgia. Gastrointestinal presentations included nausea or vomiting (n = 62, 15.5%), diarrhea (n = 33, 8.3%), and abdominal pain (n = 4, 1%). Of 88 patients with available liver function tests, 39.8% had hepatitis (abnormal alanine aminotransferase levels), of whom 5.7% had moderate hepatitis. Nausea or vomiting is a clinical risk factor associated with liver involvement (adjusted odds ratio, 5.17; 95% CI, 1.20-22.34). Liver involvement was usually observed during the first 2 weeks of illness and resolved eventually. None of the patients experienced severe hepatitis, liver failure, or death caused by a liver problem. In conclusion, most of the patients with chikungunya did not have significant liver involvement. In those patients with severe liver injury, coexisting causes should be considered.

Spinal Cord Involvement in Adult Mitochondrial Diseases: A Cohort Study.

The central nervous system is metabolically very demanding and consequently vulnerable to defects of the mitochondrial respiratory chain. While the clinical manifestations and the corresponding radiological findings of the brain involvement in mitochondrial diseases (e.g., stroke-like episodes, signal changes of the basal ganglia, cerebral and cerebellar atrophy) are well known, at present there are few data on the spinal-cord abnormalities in these pathologies, in particular in adult subjects. In this study, we present a cross-sectional cohort study on the prevalence and characterization of spinal-cord involvement in adult patients with genetically defined mitochondrial diseases.

Impact of Central Nervous System Involvement in Adult Patients with Acute Lymphoblastic Leukemia Treated in a Pediatrics-Inspired Protocol - a Graall Study

▪Background: The prognosis of central nervous system (CNS) involvement in adult patients with acute lymphoblastic leukemia (ALL) has been historically associated with a dismal outcome. Whereas the prognosis of adult patients with ALL has greatly improved since the advent of pediatrics-inspired regimens, the prognostic impact of CNS involvement has not been formerly reevaluated. We report herein the impact of CNS involvement in patients included in the pediatric-inspired prospective GRAALL-2005 study.Methods: All patients received a 5-drug induction therapy with native E. Coli-ASP intravenous injections. Patients in complete remission (CR) received two consolidation courses with alternating cycles including high dose cytarabine (2g/m2/12h on days 1 and 2), high dose methotrexate (3 g/m2 on day 1), and cyclophosphamide. All patients in persistent CR and with no indication for allogeneic stem cell transplantation (SCT) received late intensification, followed by one last consolidation course. Patients with initial CNS involvement, clinically and/or cytologically (cerebrospinal fluid), were recommended to receive an increased number of triple intrathecal therapy, CNS irradiation, and were eligible for allogeneic SCT in first CR. They received less Asp injections during induction therapy to avoid CNS adverse events. CNS irradiation included two lateral fields encompassing the skull, facial, the base of the skull, and the first two cervical vertebrae at a dose of 24 grays for those not receiving allogeneic SCT and 15 grays for those receiving allogeneic SCT.Results: Between 2006 and 2014, 784 adult patients with newly diagnosed Philadelphia-negative ALL were included with 55 (7%) having initial CNS involvement. These patients were more likely to be of T-phenotype (51 versus 32%, p=.004) and had more white blood cells at diagnosis (median 23 G/l versus 11 G/l, p=.02). Most patients (36 pts, 66%) were classified as CNS-3 (> 5 white blood cells/µl and a positive cytospin and/or clinical signs) whereas 5 patients (9%) were CNS-2 (< 5 white blood cells/µl and a positive cytospin), and 14 (25%) have data pending. Among patients with details regarding CNS involvement, 25/41 (61%) had clinical signs including trigeminal anesthesia (9 pts, 36%), facial paralysis (4 pts, 16%), extremities paresthesia (4 pts, 16%), visual signs (2 pts, 8%), meningeal syndrome (2 pts, 8%), and motor deficit (2 pts, 8%), and 4/18 (22%) had radiological signs. Induction death, CR1 rate, and negative minimal residual disease after induction were similar whether patients had CNS involvement or not (6 vs 6%, 89 vs 89%, 73 vs 62%, 26 vs 22%, respectively). Patients with CNS involvement had a worse outcome than those without with a median event-free survival (EFS) of 391 days (versus not reached for patients without CNS involvement, HR: 1.7, 95% CI: 1.2 - 2.5, p=.002) and a median overall survival (OS) of 608 days (versus not reached for patients without CNS involvement, HR: 1.8, 95% CI: 1.3 - 2.6, p=.001) (figure). Similar results were observed when patients who received allogeneic SCT in CR1 were censored at the time of graft. As recommended, patients with CNS involvement were more likely to receive allogeneic SCT than those without (53 versus 34%, p=.01), with a median time of 169 days. A 150-day landmark analysis, excluding 12 patients with an EFS event before 150 days, was performed to study the impact of allogeneic SCT on the outcome of patients with CNS involvement. Allogeneic SCT had no impact on either EFS (HR: .5, 95% CI: .2 - 1.2, p=.15) or OS (HR: .8, 95% CI: .3 - 1.8, p=.53).Conclusion: Despite improved outcome in young adult ALL patients with pediatrics-inspired protocols, CNS involvement remains a poor-risk feature. The historical use of allogeneic SCT does not improve outcome. Specific regimens should be developed for adult ALL patients with CNS involvement. [Display omitted] DisclosuresHuguet: Amgen: Other: Advisor; BMS: Other: Advisor; Celgene: Other: Advisor; Jazz Pharmaceuticals: Other: Advisor; Novartis: Other: Advisor; Pfizer: Other: Advisor. Barbieux: ASTRA-ZENECCA: Consultancy. Vey: Amgen: Honoraria; BMS: Honoraria; BIOKINESIS: Consultancy, Research Funding; NOVARTIS: Consultancy, Honoraria, Research Funding; SERVIER: Consultancy; JAZZ PHARMACEUTICALS: Honoraria; JANSSEN: Consultancy. Dombret: Amgen: Honoraria, Research Funding; Incyte: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Novartis: Research Funding; Pfizer: Honoraria, Research Funding; Servier: Research Funding; Abbvie: Honoraria; BMS-Celgene: Honoraria; Daiichi Sankyo: Honoraria. Boissel: Bristol-Myers Squibb: Honoraria, Research Funding; Servier: Consultancy, Honoraria; Incyte: Honoraria; Amgen: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; JAZZ Pharma: Honoraria, Research Funding; CELGENE: Honoraria; SANOFI: Honoraria; PFIZER: Consultancy, Honoraria. Mathilde: ABBVIE: Consultancy; SERVIER: Consultancy.

Ophthalmologic manifestations of adult patients with cystic fibrosis.

Cystic fibrosis (CF) is the most common life-shortening recessive genetic disease in Caucasians, affecting primarily the lungs. The objective of our study was to investigate potential ophthalmologic involvement in adult patients with CF. Fifty adult patients with cystic fibrosis and 60 age- and sex-matched controls underwent complete ophthalmologic examination including tear-film Break-Up Time (BUT), Macular Thickness, and peripapillary Retinal Nerve Fiber Layer (pRNFL) thickness measurements using Spectral Domain-OCT. CF patients had significantly lower nasal-inferior pRNFL thickness (median 82 IQR 67-102 vs 92.5 IQR 82-107, p = 0.005) and lower percentage of normal tear Break-Up Time (56.0% vs 96.7%, p = 0.001) than healthy controls. All CF patients with BUT <10 s were diagnosed with blepharitis at the time of our assessement. The subgroup of patients homozygous for the most common CF mutation, F508del, had lower nasal-inferior pRNFL thickness (p = 0.014) and lower percentage of normal tear Break-Up Time (p = 0.001) compared to the control group. Additional findings, present in the CF group only, were punctuate retinal hemorrhages (four patients), vessel tortuosity (four patients), snail-track degeneration, and retinal tufts (two patients without refractive error). There were no significant differences in visual acuity, refractive errors, gonioscopic findings, or intraocular pressure between the groups. Our study is, to the best of our knowledge, the largest ophthalmologic study of patients with cystic fibrosis. We found that CF patients had significantly decreased inferior-quadrant peripapillary retinal nerve fiber layer thickness and decreased tear-film break-up time compared to controls. We highlight the importance of careful regular ophthalmologic assessment and follow-up of these patients.

Deoxynucleoside therapy for respiratory involvement in adult patients with thymidine kinase 2-deficient myopathy

BackgroundRecessive mutations in the thymidinekinase 2 (TK2) gene cause a rare mitochondrial myopathy, frequently with severe respiratory involvement. Deoxynucleoside therapy is currently under investigation.Research questionWhat is the impact of nucleosides...

COVID-19 and Kawasaki Disease: Finding the Signal in the Noise.

On April 7, 2020, Hospital Pediatrics published a case report describing an infant who was diagnosed with and treated for Kawasaki disease (KD) and also happened to test positive for severe acute respiratory syndrome coronavirus 2, the causative agent of coronavirus disease (COVID-19).1 Before this publication, we had been reading multiple reports of vascular and multisystem inflammatory involvement in adult patients with COVID-19. Although our journal does not traditionally publish case reports, we felt that this case could help spark awareness of a possible association and trigger further investigations in children. However, we were also cognizant that the COVID-19 positivity and the KD in the published case may have been “true, true and unrelated.” We also recognized (as did the article authors) that the association, if true, had few if any clinical implications for the case in question. Since then, attention over a possible association between COVID-19 and KD and other hyperinflammatory states has mounted. On April 26, an alert was sent to general practitioners in London advising them of rising numbers of cases of a multisystem inflammatory state in children with overlapping features of toxic shock syndrome (TSS) and atypical KD. These cases were subsequently described in a correspondence in the Lancet on May 7, 2020, in which researchers detailed 8 children with critical illness characterized by severe inflammation, although not all had confirmed COVID-19 infection or exposure.2 In Bergamo, Italy, KD was diagnosed in 20 children over a short period, roughly equivalent to the total number of cases that …

Utility of the EULAR Sj\xf6gren syndrome disease activity index in Japanese children: a retrospective multicenter cohort study

BackgroundThe European League Against Rheumatism (EULAR) Sjögren Syndrome Disease Activity Index (ESSDAI) has been utilized to assess Sjögren syndrome-related systemic involvement in adult patients. To date, however, the ESSDAI has not been validated in children with primary Sjögren’s syndrome. This study evaluated the applicability of the ESSDAI to Japanese children with primary Sjögren’s syndrome.MethodsThe medical records of children who had been diagnosed with Sjogren syndrome at age ≤ 16 years between June 2011 and October 2016 were collected, and their ESSDAIs at initial presentation were calculated. Clinical symptoms and treatment regimens were surveyed by questionnaire, and patients were divided into groups based on ESSDAI and glucocorticoid dosages. The associations of ESSDAI scores with treatment regimens were analyzed statistically.ResultsThe study subjects included 31 children (3 boys, 28 girls) with primary Sjögren’s syndrome. Their median age at disease onset was 10 years (interquartile range [IQR], 8–13 years), and their median initial ESSDAI was 7.0 (IQR; 5.0–15.0). ESSDAI-determined disease activity was high in nine patients (29.0%), moderate in 15 (48.4%), and low in seven (22.6%). During the first year after their initial visit, 14 patients (45.2%) were treated with prednisolone (PSL) and six (19.4%) with immunosuppressants. Dose of PSL was significantly associated with ESSDAI score. Median ESSDAI score was significantly higher in patients treated with high/medium- than with no/low-dose PSL (16.5 [IQR 10.5–18.0] vs 5.0 [IQR 3.0–8.5]). Eight (66.7%) of 12 patients administered medium/high-dose PSL and one (5.3%) of 19 administered no/low-dose PSL had high disease activity on ESSDAI.ConclusionDisease activity assessed by ESSDAI tended to be consistent with disease activity assessed by pediatric rheumatologists in determining treatment regimens. ESSDAI is useful for assessing disease activity in Japanese children with primary Sjögren’s syndrome.

A study of hepatobiliary involvement in adult patients with sickle cell disease

Background: Sickle cell disease (SCD) encompasses a group of hemoglobinopathies characterized by a single amino acid substitution in the ß-globin chain. Hepatobiliary complications are frequent among sickle cell disease patients. Sickle cell disease has been extensively studied. However, data about hepatobiliary abnormalities among the adult age group are limited. Aim of our study aims to find the prevalence of hepatic-biliary involvement in Sickle cell disease in adult patients admitted to our hospital.Methods: A prospective study was done for a period of two years from October 2017 to October 2019. Subjects of both sexes above the age of 18 years with SCD admitted to our hospital were enrolled. Thorough history taking, full clinical examination, hematological and biochemical parameters assessment, and abdominal ultrasonographic studies were performed to all patients.Results: The results obtained showed that 59% of patients had hepatobiliary involvement. The most common symptom among these patients was bone pain, and the pallor was the most common sign. Biochemical tests revealed reduced hemoglobin concentration, elevated bilirubin, and compromised liver function. The most common ultrasound finding in this study was hepatomegaly, hepatosplenomegaly, cholelithiasis, and gall bladder sludge. The incidence of viral hepatitis was low compared to previous studies. Other hepatobiliary complications were cholelithiasis (14%), benign hyperbilirubinemia (14%), cholecystitis (8%) hepatic crisis (9%), hepatic sequestration (1%) , liver cirrhosis (1%), choledocholithiasis (1%) and cholangitis (1%).Conclusions:Hepatobiliary complications, particularly gallbladder diseases, are frequent among SCD patients. The early detection of hepatobiliary complications by repeated ultrasound screening and liver function tests is significant as their frequency and intensity are related to the patient's age and the duration.

SUN-362 Bone Involvement in Adult Patients Affected with Ehlers-Danlos Syndromes

INTRODUCTION: The Ehlers-Danlos syndrome (EDS) is characterized by abnormalities of the connective tissue leading to ligamentous laxity and skin and tissue fragility, bone involvement is an emerging manifestation. We evaluated the bone metabolism, bone mineral density (BMD) and bone quality (measured by trabecular bone score, TBS), and the prevalence of clinical fractures and morphometric vertebral fractures (mVFx) in a large group of adult EDS patients. METHODS: Two-hundred and sixty-six consecutive Caucasian patients, aged ≥18 years (38.3±11.8) (190 females, 76 males) 58% with classical, 34.9% with hypermobility, 4.5% with vascular and 4.8% undefined EDS were enrolled. We had genetic information of 117 patients (74 patients showed no mutations, 2 COL2 mutations, 8 COL3 mutation, 28 COL5 mutations and 5 other genes mutations). In all subjects’ calcium-phosphorous metabolism, bone turnover, BMD at the lumbar spine (LS) and femur (femoral neck, FN and total femur, FT) and radius and TBS by dual-energy X-ray absorptiometry were assessed. Moreover, we evaluated the history of clinical fragility and the mVFx presence by spine radiograph. RESULTS: The 20.6% of patients showed a Z-score BMD ≤-2.0, the 29.8% ≥1 mVFx and the 24.5% ≥1 clinical fractures. Male patients showed a higher prevalence of reduced BMD (31.9 vs 15.6%; p=0.007) and mVFx (41.4% vs 24.8%; p=0.026). Patients with ≥1 mVFx were older (43.2±12 vs 35.6±12; p=0.0001), showed a lower TBS z-score (-1.4±1.7 vs -0.8±1.2; p=0.013) and lower phosphate levels (3.3±0.6 vs 3.5±0.5; p=0.032) with an higher prevalence of hypophosphatemia (24.5% vs 8.8%; p=0.014). No difference was found in prevalence of EDS subtypes or gene mutations. In EDS patients, the VFx presence was significantly associated with TBS and age, even after adjusting for sex and hypophosphatemia. CONCLUSIONS: EDS patients have reduced BMD and bone quality (as measured by TBS) and increased prevalence of clinical and mVFx associated with age and TBS.

Spinal Involvement in Adult Patients with Sickle Cell Disease

Background Data: Sickle cell disease (SCD) is the most common inherited blood disease that has obvious effects on the osteoarticular system and the spine. Despite Although vaso-occlusive crises and osteomyelitis are the most frequent complications requiring hospitalization for patients with SCD, the spinal involvement in adult patients with SCD has not been fully explored. Study Design: Retrospective clinical case series. Purpose: To elaborate on various types of spinal affection in adults with SCD and to discuss the effectiveness of conservative management in these patients. Patients and Methods: Between January 2018 and December 2019, a retrospective study was conducted on 21 adults with SCD who presented to the neurosurgery clinic with back pain. The mean age was 27.4±7.84 (range, 17–49) years, while 14 were females and 7 were males. The patients were divided into two groups according to the cause of back pain where Group I (N=12) included the patients who presented with back pain due to SCD related causes like osteonecrosis or infection, while Group II (N=9) included the patients who had back pain due to non-SCD etiologies such as vertebral disc protrusion or facet arthropathy. All patients were offered conservative management as a first-line treatment. Back pain was evaluated using the Wong–Baker Faces Pain Scale. Results: Group I of 12 patients (57.1%) had SCD related causes including 11 patients (91.7%) with vertebral osteonecrosis (4 of them (33.3%) had associated osteoporosis) and one patient (8.3%) with acute lumbar osteomyelitis. Of the 11 patients who presented with osteonecrosis, 7 patients (63.6%) had an acute painful crisis, and the remaining 4 (36.4%) presented with chronic pain due to bone infarcts. In 8 patients (72.7%), the osteonecrosis involved the lumbar spine, while the thoracic and lumbar spines were involved in 3 patients (27.3%). Group II of 9 patients (42.9%) had non-SCD etiologies, including 2 patients (22.2%) who had facet arthropathy, 4 patients (44.4%) disc protrusion, and 3 patients (33.3%) mixed pathology. All patients were managed conservatively. The mean follow-up was 15.2±5.38 (range, 3–24) months. Overall, the mean pre-management Wong–Baker Faces Pain Scale improved from 5.57±1.121 (range, 4–8) to 1.95±0.59 (range, 1–3) at the last follow-up. Conclusion: The most common SCD related spinal pathologies in adults are infarction, infection, and osteoporosis. The majority of SCD patients presenting with low back pain can be managed conservatively regardless of the associated pathology. (2020ESJ202)

A Comprehensive Study of Bone Manifestations in Adult Gaucher Disease Type 1 Patients in Argentina.

Gaucher disease (GD) is the most prevalent lysosomal storage disease, and bone involvement is the most disabling condition. The aim of the present study was to evaluate bone involvement in adult patients with GD, using an observational cross-sectional study. Patients were evaluated using X-rays, bone densitometry (BMD), trabecular bone score (TBS), magnetic resonance imaging (MRI), and biochemical bone markers. Thirty-two type 1GD patients were included (mean age: 40 ± 16years). Patients had received velaglucerase for 2.7 ± 1.4years; 19/32 had been treated previously with imiglucerase. Ninety-four percent of subjects met therapeutic goals for hematological parameters, and eight were splenectomized (SPX). Nineteen patients had irreversible bone lesions (IL), i.e., avascular necrosis, bone infarction, and/or vertebral fractures. MRI showed marrow infiltration in 71% of patients. Patients with IL had higher bone marrow burden than those without (p = 0.001). All SPX patients had IL, a higher prevalence of bone marrow edema (p = 0.02), and lower TBS (p = 0.03) than non-SPX patients. Only 18.7% of patients had abnormal BMD, with no correlation with fractures (FX). TBS values were < 1350 in 53% of patients and tended to be lower in those with FX (p = 0.06). Patients with P1NP in the lower quartile had lower TBS (p = 0.03) than those with P1NP in the higher quartiles. TBS correlated moderately but not significantly with P1NP (r = 0.32) and BMB (r = - 0.44). A high prevalence of IL was documented. Bone quality was more affected than BMD in fracture patients. Low bone formation, active bone marrow infiltration, and splenectomy might be implicated in IL.

Cardiac involvement in adult patients with febrile thrombocytopenia diagnosed by bedside 2-D echocardiography

Background: Febrile thrombocytopenia due to various etiologies is very common in India. Its clinical manifestations range from asymptomatic infections to severe disease. Cardiac involvement in such systemic illness should be evaluated. Aim of present study is to evaluate cardiac involvement in patients with Febrile thrombocytopenia with platelets count less than 50,000/µL with the help of handheld echocardiography.Methods: Two hundred patients who had fever with thrombocytopenia were enrolled in the study. ECG and echocardiogram were done to all the patients. One-way ANOVA, Chi square test and correlation coefficient from Pearson correlation and P value of &lt; 0.05 was taken as significant.Results: Out of 200 patients there were 146 males and 56 females. The mean age was 24.12yrs in males 28.32yrs in females .Rhythm abnormalities were present in 60 patients and the most common abnormality was sinus tachycardia; 17 patients had ascites and right pleural effusion; 24 patients presented with pericardial effusion and incidental diagnosis of CHD, RHD, and CAD were made; two patients had myocarditis as evidenced by global hypokinesia of left ventricle. All of those cardiac manifestations were common in Dengue Shock Syndrome.Conclusions: Cardiovascular manifestation in Febrile thrombocytopenia is relatively common ranging from pericarditis to myocarditis. Clinician should routinely screen patients with pyrexia with thrombocytopenia for cardiac manifestations. Early diagnosis at bed side may improve the outcome. Management of patients with pre-existing cardiac diseases should be individualized.