scholarly journals Effect of Genetic and Laboratory Findings on Clinical Course of Antisynthetase Syndrome in a Hungarian Cohort

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Katalin Szabó ◽  
Levente Bodoki ◽  
Melinda Nagy-Vincze ◽  
Anett Vincze ◽  
Erika Zilahi ◽  
...  
Keyword(s):  
Prognostic Markers ◽  
Clinical Course ◽  
Disease Onset ◽  
Skin Lesions ◽  
Clinical Database ◽  
Laboratory Findings ◽  
Disease Phenotypes ◽  
Genetic Features ◽  
Hla Dqa1

The aim of this study was to determine the clinical, serological, and genetic features of anti-Jo-1 positive antisynthetase patients followed by a Hungarian single centre to identify prognostic markers, which can predict disease phenotypes and disease progression. It was a retrospective study using clinical database of 49 anti-Jo-1 positive patients. 100% of patients exhibited myositis, 73% interstitial lung disease, 88% arthritis, 65% Raynaud’s phenomenon, 43% fever, 33% mechanic’s hand, and 12% dysphagia. We could detect significant correlation between anti-Jo-1 titer and the CK and CRP levels at disease onset and during disease course. HLA DRB1⁎03 positivity was present in 68.96% of patients, where the CK level at diagnosis was significantly lower compared to the HLA DRB1⁎03 negative patients. HLA DQA1⁎0501-DQB1⁎0201 haplotype was found in 58.62% of patients, but no significant correlation was found regarding any clinical or laboratory features. Higher CRP, ESR level, RF positivity, and the presence of fever or vasculitic skin lesions at the time of diagnosis indicated a higher steroid demand and the administration of higher number of immunosuppressants during the follow-up within anti-Jo-1 positive patients. The organ involvement of the disease was not different in HLA-DRB1⁎0301 positive or negative patients who were positive to the anti-Jo-1 antibody; however, initial CK level was lower in HLA-DRB1⁎0301 positive patients. Distinct laboratory and clinical parameters at diagnosis could be considered as prognostic markers.

Clinical course in children and adolescents with ventricular septal defect

2019 ◽  
Vol 27 (7) ◽  
pp. 529-534
Author(s):  
Noor Mohammad Noori ◽  
Alireza Teimouri
Keyword(s):  
Pulmonary Hypertension ◽  
Ventricular Septal Defect ◽  
Septal Defect ◽  
Clinical Course ◽  
Defect Size ◽  
Eisenmenger Syndrome ◽  
Ventricular Septal Defects ◽  
Laboratory Findings ◽  
Septal Defects

Background Ventricular septal defect, the most common congenital heart defect, is characterized by an opening between the ventricles. This study aimed to evaluate the clinical course and associations between the characteristics of ventricular septal defect. Methods This cross-sectional study was conducted on 1498 children with ventricular septal defects, aged <19 years, who were referred to our center between 2003 and 2018. The diagnosis was suspected from a combination of clinical and laboratory findings, and confirmed by transthoracic echocardiography. Results Of the 1498 children, 54.9% were boys, 78.4% of defects were perimembranous, 30.4% of patients had pulmonary hypertension, 67.5% had regular follow-up, and 76 (5.1%) had complications including 28 (1.9%) with Eisenmenger syndrome; 10 died due to Eisenmenger syndrome during follow-up. The defects closed spontaneously in 38.9% and after surgery in 20.9%. Boys tended to have more perimembranous, inlet, and outlet forms (56.40%, 50.60%, 51.90%, respectively), whereas girls had more muscular types (51.80%). Most patients with pulmonary hypertension had perimembranous defects (83.10%). The majority of patients with pulmonary hypertension had large (63.40%) or moderate (36.60%) defects. Pulmonary hypertension had a significant association with defect size ( p < 0.001). After surgery, residual defects were found mostly in cases of large defects (84.60%). Most patients with spontaneous closure were younger than 4 years. Conclusion Almost four-fifths of children with ventricular septal defects had perimembranous types, and almost one-third had pulmonary hypertension which was associated with defect size. Two-fifths of the defects closed spontaneously. There was a low incidence of complications after surgery.

scholarly journals Non-Hodgkin lymphomas in childhood: How to move on?

2014 ◽  
Vol 142 (7-8) ◽  
pp. 498-504 ◽  
Author(s):  
Lidija Dokmanovic ◽  
Predrag Rodic ◽  
Nada Krstovski ◽  
Jelena Lazic ◽  
Dragana Janic
Keyword(s):  
Prognostic Markers ◽  
Large Cell ◽  
Treatment Regimens ◽  
Diagnosis And Prognosis ◽  
Dismal Prognosis ◽  
Genetic Features ◽  
Short And Long Term ◽  
Refractory Diseases

Non-Hodgkin lymphomas of childhood represent a diverse group of neoplasms with different clinical, pathological, immunophenotypical and genetic features. A vast majority of childhood non-Hodgkin lymphomas could be classified into one of the three major histological subgroups: mature B-cell neoplasms, lymphoblastic lymphomas or anaplastic large cell lymphomas. Modern therapeutic strategies lead to cure in more than 80% of patients. Conversely, refractory diseases, as well as disease relapse convey a dismal prognosis. This fact requires much better stratification based on prognostic markers which would ideally recognize distinct groups of patients requiring different therapeutic regimens. Defining novel diagnostic and prognostic markers should improve diagnosis and prognosis as well as patient follow-up. It should also allow introduction of individually tailored treatment regimens in selected groups of patients with non-Hodgkin lymphomas, with the main goal of improving treatment results and decreasing short- and long-term complications.

scholarly journals Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD

2019 ◽  
Vol 6 (5) ◽  
pp. e583 ◽  
Author(s):  
Lawrence J. Cook ◽  
John W. Rose ◽  
Jessica S. Alvey ◽  
Anna Marie Jolley ◽  
Renee Kuhn ◽  
...  
Keyword(s):  
African American ◽  
International Research ◽  
Disease Onset ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Control Cohort ◽  
Black African ◽  
Study Circles ◽  
Disease Phenotypes ◽  
Annualized Relapse Rate

ObjectiveTo develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment.MethodsTo illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks.ResultsAs of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female.ConclusionsCollectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD.

Characterization of colorectal cancer (CRC) in Lynch syndrome (LS) patients with MSH6 or PMS2 mutations.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1555-1555
Author(s):  
Jean Kyung Lee ◽  
Jinru Shia ◽  
Rohini Rau-Murthy ◽  
Marina Corines ◽  
Erin E. Salo-Mullen ◽  
...  
Keyword(s):  
Medical Records ◽  
High Frequency ◽  
Disease Onset ◽  
Stage Iv ◽  
Clinical Genetics ◽  
Crc Screening ◽  
Genetic Features ◽  
Revised Bethesda Guidelines

1555 Background: The majority of LS patients harbor germline mutations in the MLH1 or MSH2 genes. However, ~10% have MSH6 and ~<5% PMS2 mutations. An attenuated form of LS has been suggested in MSH6/PMS2 carriers with decreased CRC risk and older age of disease onset. As recent guidelines suggest that initiation of CRC screening may be delayed in such patients, we characterized our patients with MSH6/PMS2-associated CRC. Methods: We obtained an IRB waiver to identify all LS patients with CRC, defined as the presence of a deleterious germline mutation in a MMR gene, from the Clinical Genetics database at MSKCC. Clinical, pathologic, and genetic features were extracted from medical records and Progeny software. Results: Of 147 LS patients with CRC, 23 had mutations in the MSH6 (n=16, 11%) or PMS2 (n=7, 5%) genes. Mean age at CRC diagnosis was 48.5 yrs (range 32-70) in MSH6 and 40.7 (range 22-57) in PMS2 carriers. 16 (70%) and 5 (22%) were diagnosed at age ≤50 or ≤35, respectively. 4 (17%) had metachronous and 3 (13%) synchronous primary CRCs, and 5 (22%) had additional LS-associated cancer. Although all 23 LS patients met Revised Bethesda guidelines, only 50% of MSH6 and 0 of the PMS2 carriers met Amsterdam I/II criteria (AC). Of 32 independent primary CRCs, 18 (56%) were stage I/II, 9 (28%) stage III, and 1 (3%) stage IV. 9/9 MSH6 and 4/4 PMS2 CRCs had high-frequency microsatellite instability. In MSH6 carriers, 11/13 had absence of MSH6protein expression only on IHC, 1 had inconclusive MSH6 staining, and 1 had absence of both MSH6 & MSH2 proteins. In PMS2carriers, 7/7 had absence of PMS2 on IHC, 2 also had equivocal/focal MLH1 staining. Right-sided CRC was present in 50% and at least 40% had mucinous features. 26/29 (90%) of tumors underwent segmental resection. 6/11 stage II patients received adjuvant chemotherapy including 2 with pT4N0 tumors. With a mean follow-up of 5.6 yrs to date, 1 patient is known to have developed recurrent CRC. Conclusions: Although the majority of MSH6/PMS2 CRC patients do not meet AC, 70% of CRCs were diagnosed at age ≤50, 22% at age ≤35, and 30% had synchronous/metachronous CRCs. These findings have important implications for CRC surveillance and may not support delaying colonoscopy initiation in MSH6/PMS2 LS families.

scholarly journals Predictors of unfavorable course of acute myocarditis with reduced left ventricular ejection fraction

2019 ◽  
Vol 23 (2) ◽  
pp. 251-256
Author(s):  
S. V. Cherniuk
Keyword(s):  
Ejection Fraction ◽  
Cardiovascular Events ◽  
Clinical Course ◽  
Acute Myocarditis ◽  
Disease Onset ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Systolic Strain ◽  
Ventricular Ejection Fraction

Early prediction of myocarditis clinical course still remains one of the actual tasks of cardiological science, which has a significant practical value. The purpose of the study was to determine the predictors of unfavorable course of myocarditis with reduced ejection fraction (EF) of the left ventricle (LV) on the basis of follow-up during 24 months. The study included 90 patients with acute myocarditis and reduced LV EF, who were examined in the first month after the disease onset, after 6, 12 and 24 months of follow-up. All patients underwent for echocardiography, Holter monitoring of the electrocardiogram and cardiac magnetic resonance imaging. Statistical processing of the results was performed using the Excel XP software (Місrosoft Office, USA) and Statistica for Windows v. 6.0 (Statsoft, USA). It was found that restoration of cardiac contractility in patients with myocarditis and reduced LV EF began with an increase in the index of LV longitudinal global systolic strain, which occurred 6 months after the debut of the disease and was associated with a decrease in the number of LV segments affected by the inflammatory process, and a significant increase of LV EF and a decrease of LV end-diastolic volume were observed only 1 year after the disease onset. The predictors of cardiovascular events in patients with acute myocarditis during the next 24 months from the onset of the disease, were detected in the 1st month from the debut of the disease and included following pathological changes: value of the LV EF ≤ 30%; reduction of LV longitudinal global systolic strain ≤ 7.0%; evidence of non-sustained ventricular tachycardia, presence of inflammatory changes in ≥6 LV segments, presence of delayed enhancement in ≥ 5 LV segments. Prospects for further research are the creation of registries of patients with myocarditis on the basis of multicenter clinical trial results on a large number of patients surveyed in order to improve diagnosis, prediction of clinical course and identification of early diagnostic markers of cardiovascular events and quantitative risk assessment of their development.

scholarly journals Congenital syphilis in Argentina: experience in a pediatric hospital

2020 ◽  
Author(s):  
Luciana Noemí Garcia ◽  
Alejandra Destito Solján ◽  
Nicolas Falk ◽  
Nicolás Leonel Gonzalez ◽  
Griselda Ballering ◽  
...  
Keyword(s):  
Medical Records ◽  
Congenital Syphilis ◽  
Delayed Diagnosis ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Penicillin G ◽  
High Morbidity ◽  
Laboratory Findings ◽  
Therapeutic Decisions

AbstractAlthough congenital syphilis (CS) is preventable, it is still an important health problem worldwide. Recently, an increase in the number of primary and congenital syphilis cases has been observed. Fetal infection can be particularly aggressive, but newborns can be asymptomatic at birth and run the risk of developing systemic compromise with a poor prognosis.We conducted a study (1987-2019) analyzing the medical records of CS diagnosis cases assisted at the Buenos Aires Children’ Hospital. Sixty-one patients were included. Information about demographics, clinical and laboratory findings, T. pallidum serology and treatment was collected. Median age at diagnosis was 2 months (IQ 1-6 months). The distribution of cases showed a bimodal curve, with a peak in 1993 and in 2017. The main clinical findings were: bone alterations in 36/61 (59%); hepatosplenomegaly in 33/61 (54.1%); anemia in 32/51 (62.8%); skin lesions 26/61 (42.6%) and renal compromise in 15/45 (33.3%). Cerebrospinal fluid was studied in 50/61 (81.9%); 5 (10%) were abnormal (reactive VDRL and/or cell alteration count). Only 23 (60.5%) patients had nontreponemal titers fourfold higher than their mothers did. Intravenous penicillin G for an average of 10-14 days was prescribed in 60/61 subjects and one patient received ceftriaxone. Remarkably, only 28 (46%) mothers were tested for syphilis during pregnancy.During follow-up, a decrease in RPR titers was observed reaching seroconversion in 31/34 (91%) subjects at a median of 19.2 months after treatment. Treponemal titers (TPHA) remained reactive.Our results highlighted that an increase in the number of cases of CS is occurring in our population with high morbidity related to delayed diagnosis. A good therapeutic response was observed.CS requires a greater effort from obstetricians to adequately screen for the disease during pregnancy and pediatricians should be alert in order to detect cases earlier, to provide an adequate diagnosis and treatment of CS.Author SummaryCS is caused by mother-to child transmission. Although screening of pregnant women and treatments are available, new cases are increasing worldwide. We reviewed the medical records of CS-patients assisted in our hospital over the past 30 years. Our results showed that there was an increase in the number of CS cases. At birth, most children were asymptomatic and later developed CS clinical manifestations. Penicillin treatment, and in one case ceftriaxone, was prescribed with a good clinical response. Nevertheless, one infant died, four had persistent kidney disorders and one showed bone sequelae damage. Spinal lumbar puncture did not modify therapeutic decisions. In the follow-up, a decrease in nontreponemal antibodies was observed as a marker of treatment response. We concluded that the detection and treatment of CS remains a great challenge for clinical practice in our region.It is crucial that pediatricians and obstetricians give greater attention and make a greater effort to detect this neglected disease in an attempt to reverse its upwards trend.

scholarly journals On Two Cases with Autosomal Dominant Hyper IgE Syndrome: Importance of Immunological Parameters for Clinical Course and Follow-Up

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Snezhina Mihailova Kandilarova ◽  
Spaska Stoyneva Lesichkova ◽  
Nevena Todorova Gesheva ◽  
Petya Stefanova Yankova ◽  
Nedelcho Hristov Ivanov ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Clinical Symptoms ◽  
Clinical Course ◽  
Dna Binding Domain ◽  
Disease Course ◽  
Immunological Parameters ◽  
Laboratory Findings ◽  
Hyper Ige Syndrome ◽  
Stat3 Mutation

Autosomal dominant hyper-IgE syndrome (AD-HIES) is a rare disease described in 1966. It is characterized by severe dermatitis, a peculiar face, frequent infections, extremely high levels of serum IgE and eosinophilia, all resulting from a defect in the STAT3 gene. A variety of mutations in the SH2 and DNA-binding domain have been described, and several studies have searched for associations between the severity of the clinical symptoms, laboratory findings, and the type of genetic alteration. We present two children with AD-HIES–a girl with the most common STAT3 mutation (R382W) and a boy with a rare variant (G617E) in the same gene, previously reported in only one other patient. Herein, we discuss the clinical and immunological findings in our patients, focusing on their importance on disease course and management.

scholarly journals Clinical Outcomes for Chronic Lymphocytic Leukemia (CLL) Patients with 11q Deletion in British Columbia (BC), Canada: Results of a Population-Based Cohort

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2648-2648
Author(s):  
Jennifer Goy ◽  
Tanya L. Gillan ◽  
Huang J.T. Steven ◽  
Helene Bruyere ◽  
Monica Anne Hrynchak ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Prognostic Markers ◽  
Clinical Course ◽  
Population Based ◽  
Trial Data ◽  
Disease Course ◽  
First Line ◽  
Prognostic Features ◽  
Significant Difference

Abstract BACKGROUND The 11q22.3 deletion (11q-) encompassing the ATM locus detected by fluorescence in situ hybridization (FISH) is present in up to 20% of CLL patients (pts), and is associated with an aggressive disease course and poor response to treatment (tx). However, there are few clinical studies that have specifically focused on pts with 11q-. Prognostic factors that may explain the variable outcome in this group have not been investigated, nor have survival outcomes in a population-based setting. Furthermore, few clinical studies have described practice patterns within the 11q- group. This study aims to improve our understanding of the prognosis, management and clinical course of CLL pts with 11q-. METHODS The BC Provincial CLL Database, which includes all pts who have undergone CLL FISH testing in a provincially validated laboratory since 2004, was used to identify all pts in BC (population 4.5 million) with a confirmed 11q- >10% found at any point during the disease course, with or without other detectable FISH abnormalities. Overall survival (OS), treatment-free survival (TFS) (time from diagnosis to first tx/death) and time to second-line treatment (tx) were the main outcomes of interest, and were investigated in relationship to age (<60 vs ≥60 years [yrs]), sex, Rai stage (3-4 vs 0-2), CD38 status, % 11q-, and presence of other recurrent FISH abnormalities (17p deletion [17p-], trisomy 12, 13q deletion, and IGH translocation). Multivariate analysis (MVA) was performed using Cox proportional hazard models with a backwards stepwise selection process to determine predictors of OS/TFS. RESULTS 125 out of 1044 (12%) pts were identified with 11q- detected at any point. Median age at CLL diagnosis was 61 yrs (range, 35-80). At a median follow-up of all patients of 6.3 yrs (range 0.5 - 26.2), median OS and TFS for the entire cohort are 12.6 yrs (standard error [SE] = 1.5 yrs) and 2.5 yrs (SE = 0.5 yrs), respectively. In MVA, advanced Rai stage (HR 3.7, 95% CI 1.28-10.8, P=.015), age ≥ 60 yrs (HR 2.2, 95% CI 1.2-4.3, P=.012) and male gender (HR 2.4, 95 % CI 1.5-5.3, P=.024) were significant predictors of OS. Clonal evolution (CE) to 11q- and/or other FISH abnormalities was documented in 12 pts. In 9/12 cases, 11q- developed after one or more tx courses whereas, in 3/12 cases, 11q- developed prior to tx initiation at median 5 yrs (range, 3.8-6.5) from initial FISH test. Sixty-nine pts had a documented 11q- pre-tx. At median follow-up of 5.0 yrs (range, 0.5 to 18.7), this group had median OS and TFS of 14.7 (SE =1.8) and 2.5 yrs (SE= 0.5), respectively (Fig 1). Pts with presence of 11q- and 17p- had a markedly worse prognosis compared to those without, with median OS 4.9 vs. 14.7 yrs (P< .001) and TFS of 0.2 vs. 2.5 yrs (P=0.31). In MVA, co-presence of 17p- (HR = 11.3, 95% CI 2.4-52.5, P=.02) and age ≥ 60 yrs (HR 3.8, 95% CI 0.83-17.1, P=.05) were adverse prognostic markers for OS. Age ≥ 60 yrs (HR =2.0, 95% CI 1.0-3.9, P=.03), presence of > 75% 11q- (vs. < 75 % 11q-) (HR = 1.8, 95%CI 1.0-2.3, P=.03) and advanced Rai stage (HR = 7.1, 95%CI 2.4-21.0, P=.01) were associated with shorter TFS. Of this group of 69, 52 pts (75%) received at least one tx course during follow-up. Thirty-three pts received fludarabine +/- rituximab (FR) as first line, 14 pts received alkylator based tx (FC +/- R in 8; CVP +/- R in 5; CHOP + R in 1) and 5 pts received chlorambucil-based +/- R. Pts treated with FR alone had median OS 12.8 yrs (SE=1.0), which was not statistically different from those treated with alkylators , where median OS was 6.8 yrs (SE=2.1), P=.35 (Fig 2). In MVA, receipt of fludarabine vs alkylator-based treatment was not associated with any significant difference in OS (P=.52) or time to 2nd tx (P=.65). CONCLUSION This study is to our knowledge the largest population-based report of CLL pts with 11q- and further enhances our understanding of the clinical course of such pts in a real world setting. Although median TFS of 11q- pts is short at 2.5 yrs, OS remains long at 12.6 yrs. The importance of combined 11q- and 17p- as adverse prognostic markers in CLL is highlighted. Most pts in BC with 11q- received FR as first line therapy. There is retrospective trial data suggesting that first line tx containing alkylators (ie. cyclophosphamide) can overcome the adverse prognostic features of 11q-. However, most of this trial data is from the pre-R era. Though limited in numbers, our study does not suggest that first line tx without alkylators is associated with negative outcomes. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Toze: Roche: Consultancy, Honoraria, Research Funding. Gerrie:F Hoffmann-La Roche: Other.

scholarly journals Mystery called sarcoidosis: Forty-four years follow-up of chronic systemic disease

2012 ◽  
Vol 140 (11-12) ◽  
pp. 768-771
Author(s):  
Vesna Skodric-Trifunovic ◽  
Violeta Vucinic ◽  
Sanja Simic-Ogrizovic ◽  
Ruza Stevic ◽  
Mihailo Stjepanovic ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Inflammation ◽  
Kidney Biopsy ◽  
Clinical Course ◽  
Systemic Disease ◽  
Body Weight Loss ◽  
Final Diagnosis ◽  
Pulmonary Sarcoidosis ◽  
Laboratory Findings

Introduction. This is a presentation of a 61-year-old female patient. Since 44 years have passed from the onset of her first symptoms until the final diagnosis of sarcoidosis, this was the reason of our decision to publish the case. Case Outline. During the follow-up period of 44 years the patient had ocassional polymorphic complains, such as adynamia, nausea, abdominal pains, myalgia, arthralgia, body weight loss (8-10 kg) etc. The clinical course was predominated by splenomegaly, hepatitis and arthralgia, and later chronic renal failure also developed. Laboratory findings showed elevated markers of acute inflammation and autoantibodies. The patient was hospitalized in different university internal hospitals (gastroenterology, allergology, rheumatology, nephrology and pulmology). Liver biopsy was performed three times, rectum and kidney biopsy once each and finally bronchoscopy and pulmonary biopsy was done. At last, about 40 years from the onset of the first symptoms, in 2006 the diagnosis of lung sarcoidosis was established. Conclusion. The final diagnosis of spleen sarcoidosis was confirmed by pathologically verified sarcoidosis of the lungs. This case is particularly interesting because of the presence of familial sarcoidosis (the patient?s son also had recurrent pulmonary sarcoidosis).

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