Clinical Course Of Disease Research Articles

Clinicoradiological Correlation of Serum Procalcitonin Values in Degenerative Lumbar Disc Disease

Introduction: Low back pain (LBP) as a result of prolapsed intervertebral disc is one of the common causes of the morbidity and disability in current population. We assessed any association of inflammatory marker serum procalcitonin in degenerative disc disease. Materials & Methods: A prospective analytical study carried out at our tertiary care institute over one year from Dec 2021 to Dec 2022 after clearance from institute ethical committee. Total of 68 patients aged 18 to 65 years with low back pain with lumbar disc herniation on MRI imaging were included in the study. Serum procalcitonin levels were assessed using electrochemiluminescence technique on e411 Elecsys 2010. Results: The median values of serum procalcitonin were higher in early phase of disease tends to stabilising with chronicity of symptoms. There was a positive correlation between mean VAS scores and procalcitonin levels, those patients with higher procalcitonin values clinically had positive straight leg raising test and in the long run required more operative interventions. Conclusions: Lumbar degenerative disc disease has a strong inflammatory basis and serum values of procalcitonin can be useful objective marker to predict extent of inflammation with prediction of possible clinical course of disease.

Патоморфологічні та морфометричні особливості гострого апендициту в дітей з цукровим діабетом І типу

Metabolic disorders caused by chronic hyperglycemia in the gastrointestinal tract of patients with type I diabetes mellitus (T1DM) not only affect natural course of this disease but also modify clinical course of concomitant abdominal purulent-inflammatory diseases in children due to changes of the internal intestinal wall. Purpose - to analyze pathomorphological and morphometric features of acute appendicitis in children with T1DM. Materials and methods. We carried out a pathomorphological and morphometric case-control study of the surgical specimens (appendices and fragments of the peritoneum). Two groups were created: the Group I (n=11) - patients with acute appendicitis, peritonitis and T1DM; the Group II (n=24) - patients with acute appendicitis, peritonitis but without T1DM. Statistical analysis was performed using software package STATISTICA v.10.0 (StatSoft, USA). Results. There were signs of diabetic angiopathy in the Group I and a significant number of inflammatory cells, represented by a large number of segmented nuclear leukocytes - 431±18.2 in 1 mm2, plasma cells - 146±11.13 in 1 mm2, lymphohistiocytic elements - 196±23,32 in 1 mm2. The density of the inflammatory cell infiltrate was 773±36.2 cells in 1 mm2. Morphometric features of the Group II are as follows, number of segmented nuclear leukocytes - 228±15,7 in 1 mm2, plasma cells - 112±10,41 in 1 mm2, lymphohistiocytic elements - 132±21,2 in 1 mm2. The density of the inflammatory cell infiltrate was 773±36.2 cells in 1 mm2. Conclusions. There is an increase in the density of the inflammatory cell infiltrate, the number of neutrophils, plasma cells, and lymphohistiocytic elements in samples of appendices and peritoneum in children with acute appendicitis and T1DM in comparison with the Group II (p˂0.001). Furthermore, those specimens feature presence of hyalinosis, thickening of the vascular wall and partial obliteration of small caliber vessels. In the Group II (patients without T1DM), the parietal and visceral peritoneum had a large number of inflammatory elements and presence of macrophage elements upon normal histological structure of the microcirculatory vessels. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors.

Hepatocellular carcinoma in cirrhotic versus non-cirrhotic liver: Treatment and survival differences in a nationwide cohort.

Numerous studies have reported superior outcome for patients with hepatocellular carcinoma (HCC) in non-cirrhotic compared to cirrhotic livers. This cohort study aims to describe the clinical presentation, disease course, treatment approaches, and survival differences in a population-based setting. Data on patients diagnosed with HCC in Sweden between 2008 and 2018 were identified and extracted from the Swedish Liver registry (SweLiv). Descriptive and survival statistics were applied. Among the 4259 identified patients, 34% had HCC in a non-cirrhotic liver. Cirrhotic patients presented at a younger age (median = 64 vs 74 years, p < 0.001) and with a poorer performance status (Eastern Cooperative Oncology Group (ECOG) = 0-1: 64% vs 69%, p = 0.024). Underlying liver disease was more prevalent among cirrhotic patients (81% vs 19%, p < 0.001). Tumors in non-cirrhotic livers were diagnosed at a more advanced stage (T3-T4: 46% vs 31%) and more frequently with metastatic disease at diagnosis (22% vs 10%, p < 0.001). Tumors were significantly larger in non-cirrhotic livers (median size of largest tumor 7.5 cm) compared to cirrhotic livers (3.5 cm) (p < 0.001). Curative interventions were more commonly intended (45% vs 37%, p < 0.001) and performed (40% vs 31%, p < 0.001) in the cirrhotic vs non-cirrhotic patients. Median survival was 19 months (95% confidence interval (CI) = 18-21 months), in patients with cirrhosis as compared to 13 months in non-cirrhotic patients (95% CI = 11-15) (p < 0.001). In the multivariable Cox regression model, cirrhosis was not an independent predictor of survival, neither among curatively nor palliatively treated patients. These population-based data show that patients with HCC in a cirrhotic liver receive curative treatment to a greater extent and benefit from superior survival compared to those with HCC in a non-cirrhotic liver. The differences in survival are more attributable to patient and tumor characteristics rather than the cirrhotic status itself. not applicable. Patient confidentially: not applicable.

Trends in prevalence among children in secondary schools under the contemporary educational process and exposure to environmental factors

Introduction. Trends in of schoolchildren’s health highlights the importance of performing complex estimates aimed at identifying what influence of the contemporary education process and environmental factors have on prevalence among children and adolescents. &#x0D; Materials and methods. The research involved examining data obtained by a profound medical examination of three hundred thirty nine schoolchildren attending municipal secondary schools with different educational programs. In this research, the test group (146 schoolchildren who attended a gymnasium) and the reference group (193 schoolchildren who attended an ordinary secondary school) were divided into several sub-groups based on their age group. We analyzed data of medical and social questioning, ‘Weekly Rations of a school student’ and school schedules covering classes and breaks between them. All the data were analyzed using conventional statistical procedures and logistic modelling together with calculation of relative risks. &#x0D; Results. We established different ratios of harmful components related to the educational process, lifestyle, diets, and the environment in schools with different educational programs. This fact indicates the examined exposure to be multi-factorial and determines some peculiarities of incidence and unfavourable age periods in clinical courses of diseases among schoolchildren attending a gymnasium or an ordinary secondary school. Causation of negative health outcomes in schoolchildren by lifestyle factors equaled R2 = 0.11–0.86; &#x0D; the educational process, R2 = 0.10–0.84; environmental factors, R2 = 0.13–0.58. &#x0D; Limitations: a rather small sample. &#x0D; Conclusion. Schoolchildren in gymnasium have 3.1–4.8 higher risks of diseases of the endocrine and musculoskeletal system in primary school; diseases of the nervous system, in senior school; ophthalmic pathologies, during the whole school period. Likelihood of digestive diseases and diseases of the musculoskeletal system grows by 4.6–41.0 times in middle and senior school. Greater effectiveness of medical check-ups and timely identification of risk factors are the most important tools for creating an integral preventive environment.

MiRNA-133 and lncRNA-H19 expressions and their relation to serum levels of PKM2 and TGF-β in patients with systemic sclerosis

Background and aimsSystemic sclerosis (SSc) is a common autoimmune disorder involving the skin, blood vessels, and internal organs with an elusive pathophysiology. SSc is believed to be a genetically prone T-cell-mediated autoimmune disease. miRNAs and lncRNAs were thought to be involved in the etiology of several immunological diseases including SSc. This work aimed to assess the expression of miRNA-133, lncRNA-H19, PKM2, and TGF-β levels in SSc in comparison to controls and their relationship to the clinical course and severity of disease. Patients and methodsFifty patients with SSc and 40 healthy age and sex-matched controls were included in this study. miRNA-133 and H19 expression levels were detected using quantitative RT-PCR while serum levels of PKM2 and TGF-β were measured using ELISA techniques. Patients’ clinical data and treatments received were extracted and correlated with proteins investigated. ResultsOur results showed that miRNA-133 was significantly downregulated in SSc patients in comparison to controls (Mean + SD of SSc = 0.61 ± 0.22, Mean ± SD of HC = 0.97 ± 0.007, p = 0.003). However, there was significant upregulation of the serum expressions of all other tested biomarkers in SSc patients in comparison to controls; H19 (Mean + SD of SSc = 10.37 ± 3.13, Mean ± SD of HC = 1.01 ± 0.01, p = 0.0001), PKM2 (Mean + SD of SSc = 28.0 ± 4.84, Mean ± SD of HC = 16.19 ± 1.32, p = 0.005) and TGF-β (Mean + SD of SSc = 150.8 ± 6.36, Mean ± SD of HC = 23.83 ± 0.93, p = 0.0001). We also detected several correlations between serum levels of the investigated proteins in patients with SSc. ConclusionAlong with TGF-β, our results show that miRNA-133, H19, and PKM2 seem to be potential contributors to SSc pathogenesis and could be promising biomarkers in the diagnosis of SSc patients. The lncRNA-H19 correlations with TGF- β, miRNA-133, and PKM2 suggest a possible influential effect of this RNA molecule on the pathogenesis of SSc.

Patterns of neuromyelitis optica spectrum disorder attacks in different age groups and sexes depending on the status of immunosuppressive therapy: A retrospective cohort study.

The association between onset age and sex with relapse risk in neuromyelitis optica spectrum disorder (NMOSD) remains inconclusive. We aimed to describe the clinical features of patients with NMOSD in different age groups and sexes and to analyse relapse characteristics pre- and post-immunosuppressive therapy (IST). Patients with NMOSD were retrospectively reviewed from our clinical centre's database. Demographic and clinical data, attack presentation, and disease course pre- and post-IST were investigated. We also analysed the effect of onset age on the annualized relapse rate and relapse risk according to sex and IST status. Interactions on the additive scale between onset age and sex were analysed. A restricted cubic spline was used to analyse potential nonlinear correlations. Longitudinal changes in the Expanded Disability Status Scale score across NMOSD attacks were analysed using linear mixed-effect models. In total, 533 patients experienced 1394 attacks pre-IST and 753 relapses post-IST. Older age at onset was correlated with more myelitis attacks but fewer optic neuritis attacks, with no sex-related differences in attack presentation. Pre-IST, relapse risk increased with age at onset in women, while a U-shaped correlation between onset age and relapse risk was found in men. Post-IST, an inverted U-shaped association between the predicted relapse risk and onset age was observed in women. Conversely, a negative correlation between the predicted relapse risk and onset age was found in men. Overall, a higher ratio of myelitis attacks was found post-IST. Patients of different onset ages and sexes had different relapse patterns before and after IST.

Seorang Wanita Usia 23 Tahun Dengan Anemia Mikrositik Hipokromik Suspect Systemic Lupus Erythematosus (SLE)

Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory disease with diverse clinical manifestations, disease course and prognosis, and it is difficult to predict the onset of acute and subtle manifestations, can attack various organs of the body, and can recur. Hematological manifestations in SLE occur frequently and are one of the criteria for ACR. Thrombocytopenia occurs in 25% - 50% of patients, leukopenia occurs in around 50% and hemolytic anemia with positive Coombs test results in around 10%. Cytopenia that occurs is usually the result of peripheral damage mediated by autoantibodies that cause bone marrow hypercellularity. In rare cases, hypocellularity occurs in the bone marrow due to mediation of T cells that inhibit hemopoetic cells, which causes bone marrow failure and causes anemia gravis. A 23 year old woman came with complaints of paleness, fatigue, decreased appetite, joint pain, nausea, vomiting, headaches, dizzy eyes. On laboratory examination on June 12 2023, microcytic hypochromic anemia was found, on June 13 2023, microcytic hypochromic anemia was found, on peripheral blood morphology examination, anemia was suspected due to iron deficiency, and there was a bacterial and parasitic infection process, on June 15 2023, hypokalemia was found. , hyperchloremia, hypocalcemia. On June 16, 2023, microcytic hypochromic anemia was found. On ECG examination, benign Ves arrhythmia was found. On chest examination, the lung showed no abnormalities, the cast size was normal. On ultrasound examination, Nephrolithiasis Dextra was found. So it was found on physical examination, and the patient's supporting examination was confirmed as microcytic hypochromic anemia suspect systemic lupus erythematosus, however in the patient in this case report it could not be established as systemic lupus erythematosus, because the patient was not willing to be referred to Zainal Abidin General Hospital, Banda Aceh for treatment. further examination.

Fungal Microbiota Composition in Inflammatory Bowel Disease Patients: Characterization in Different Phenotypes and Correlation With Clinical Activity and Disease Course.

There is growing evidence of the role of the mycobiome in inflammatory bowel disease (IBD). Variations within phenotypes and activity and with prognosis have been poorly studied. A total of 111 individuals were prospectively enrolled: 89 IBD patients (52 ulcerative colitis and 37 Crohn's disease [CD]) and 22 healthy individuals. Disease characteristics were collected and a fecal calprotectin >100 μg/mg was considered indicative of activity. A subset of patients was followed for 6 ± 2 years. Disease course was designated as either complicated or uncomplicated based on the need of intensified medication and/or surgery. ITS sequencing was performed targeting the ITS1 region. We found lower Ascomycota/Basidiomycota ratio in IBD. Patients showed a marked increase in Candida dublinensis and Ca albicans and were depleted of Aspergillus rubrobrunneus and Penicillium brevicompactum (P ≤ .001) Saccharomyces was predominant in total colitis and Penicillium in proctitis. Several Penicillium species were depleted in total colitis vs proctitis. Ileal CD patients were enriched in Debaromyces hansenii and depleted of Ca tropicalis (P ≤ .001). Ca albicans was overrepresented in inflammatory (B1) vs fibrostenosing (B2) CD. Ca dublinensis was more abundant in active patients and correlated positively with fecal calprotectin and neutrophil gelatinase-associated lipocalin, while S pastorianus correlated inversely with activity. Ca sake was associated with complicated disease and increased abundance of Cryptococcus carnescens with the need for surgery in CD. This study shows important differences in the mycobiome in IBD and within phenotypes. Selected fungal species were associated with complicated disease and the need of surgery in CD. This work adds to our understanding of the role of fungi in IBD, with potential clinical implications.

Diagnostic and therapeutical approaches to H3K27M-altered diffuse midline glioma in children: a review

H3K27M-altered diffuse midline gliomas are the most devastating pediatric brain tumors. These tumors are characterized by lesion of central nervous system midline structures, diffuse infiltrative growth and fatal prognosis. The pathogenesis of H3K27M-altered diffuse midline glioma is based on unique epigenetic and genetic changes which are associated with histone 3 (H3) alterations. Clinical disease course usually is non-specific, that could hamper diagnosis establishment and defines high prevalence of disseminated tumor stages. Diagnostic approach includes neuroimaging, various laboratory and molecular methods, including high throughput sequencing, which allows finding potential targets for precise therapy. Despite the availability of anti-tumor technologies, including targeted therapy and immunotherapy, the standard of care for H3K27M-altered diffuse midline glioma is radiation therapy, which does not allow achieving long-term event-free survival. A dismal prognosis and absence of curative options for these tumors determine the necessity of new treatment methods search that could improve patients’ outcome. In this article we present current worldwide data of the diagnosis and treatment trends in H3K27M-altered diffuse midline glioma.

Systemic lupus erythematosus and diabetic mellitus is it single or two entity(es)

Introduction: Systemic lupus erythematosus (SLE) is a complex and chronic autoimmune disease with varied clinical manifestations and multi-organ involvement. The disease may present with acute, severe, and life-threatening symptoms or present as a fluctuating and chronic process that impacts several systems and increases the risk of malignancy. Systemic lupus erythematosus (SLE) often coexists with other diseases. Diabetes mellitus (DM) is an example and patients with SLE-DM can present with clinical features common to both disorders. Type 2 diabetes (T2D) is characterized by insulin resistance the inability of tissues to respond to insulin, and a progressive pancreatic beta cell dysfunction in response to glucose levels. The disease is thought to be caused by environmental and inherited factors in about equal proportions. Many environmental risk factors are known, including obesity, sedentary lifestyle, stress, nutritional factors and toxins. The report aims to describe Systemic Lupus Erythematosus and Diabetes mellitus as single or two entity(es). Case presentation: A 14-year-old female patient who was admitted to the hospital with complaints of weakness and drowsiness was getting worse 3 days before admitted from hospital. There have been complaints of fatigue for last 3 years accompanied by a lot of eating and drinking and urinating. Complaints of pain in both joints of the hands and both knees appeared in the last 3 months and had been getting worse. Hair loss existed in the past 4 months before being admitted to the hospital. Blurred vision in the right eye in the last 6 months has worsened in the last 1 month. Vision loss in the last 3 months. Body weight was reduced 4 kilograms within 3 months without any loss of appetite. Initial laboratory results revealed hyperglycemia, antinuclear antibodies (ANA) IF 1:100 and ANA Profile Sm (+), dyslipidemia, increase of creatinine serum with glomerular filtration rate 72.41 m2/BSA (decreased 38%). Other examinations showed that C-peptide is normal and beta islet antibody is negative. Echocardiography resulted tricuspid regurgitation with normal ventricle function. Conclusion: Systemic Lupus Erythematosus and Diabetes mellitus is a rare condition that warrants a thorough evaluation to both determine the diagnosis and predict the clinical course of disease.

Anti-MDA5 antibody-positive dermatomyositis: pathogenesis and clinical progress.

Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is a subtype of dermatomyositis. Although the aetiology and pathology remain unclear, increasing evidence suggests that viral infection is a potential trigger of MDA5-DM. Multiple factors, including T cells, B cells, neutrophils and macrophages, are implicated in the pathophysiology of MDA5-DM. Distinctive skin rashes, rapidly progressive interstitial lung disease, peripheral lymphopenia and elevated serum ferritin levels are the most prominent clinical and laboratory features of MDA5-DM. Concomitant infection is a common complication of MDA5-DM. The proper evaluation of patients with MDA5-DM requires knowledge of the disease heterogeneity and clinical course variability. Several biomarkers, including serum levels of anti-MDA5 antibodies and biomarkers related to macrophage activation, have been identified as useful tools for monitoring disease activity and prognosis. MDA5-DM shows a poor response to conventional glucocorticoid and immunosuppressant therapy and has a poor overall prognosis. Therefore, there is an urgent need to explore the key pathogenic mechanisms of MDA5-DM and develop novel therapeutic options for patients. This Review discusses recent clinical progress and pathogenic findings of MDA5-DM.

Clinical Features and Disease Course of Cancer Patients Infected with Sars-Cov-2 During Anticancer Treatments

Abstract Cancer patients infected with SARS-CoV-2 during their active anticancer treatment represent a highly vulnerable population. We aimed this investigation to show clinical features and outcomes of the patients who had mild to moderate COVID-19 symptoms or were asymptomatic at the admission to the COVID Center. The retrospective study included 25 cancer patients confirmed with SARS-CoV-2 within seven days of their last anticancer treatment. Clinical data were collected from medical records and processed by methods of descriptive and inferential statistics. Patients' mean age was 68.1±10.4 years. More than 2/3 of the patients were with ECOG PS 0 and 1, and about 4/5 of patients were in III or IV cancer stage. The most frequently applied types of therapy were radiotherapy and combined radio/chemotherapy. Eleven (44.0%) patients had bilateral while 4 (16%) had unilateral pneumonia. The most frequent symptoms were fever (72%), fatigue (72%), dyspnea (32%), and cough (32%). 1/5 of the patients needed oxygen support. Mean neutrophil (2.6±1.2), lymphocyte (0.9±0.6) and platelets (200.1±88.1) number significantly increased from admission to discharge (p=0.004, p=0.005, p&lt;0.001). Median CRP significantly decreased from 40.4 (6.2-96.2) at admission to 11.35 (3.75-27.65) at discharge (p=0.008). Twenty-four patients were cured, and one patient died. Naso-pharyngeal SARS-CoV-2 clearance time was 19.4±6.9 days; the minimum was seven, and the maximum was 39 days. Cancer patients infected with SARS-CoV-2 during active anticancer treatment can successfully overcome COVID-19 without developing further respiratory or other complications during hospitalization. An increase in lymphocyte and neutrophil counts, with a decrease in CRP, may be markers of a favorable prognosis.

Clinical and Diagnostic Challenges in Patients with Concomitant Plasma Cell Disorders and Myeloproliferative Neoplasms

Background: Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell precursor disease that regularly precedes the development of multiple myeloma (MM). It accounts for about 4.5% in the entire population, however patients with myeloproliferative neoplasms (MPN) seem at a higher risk for MGUS with a reported rate of concomitant disease at 3-14%. The reason for this co-occurrence of MGUS and MPN remains unclear, and a common cell of origin has not yet been defined. Inversely, constant MPN-driven inflammation in the bone marrow microenvironment (BM) may stimulate the expansion of a pre-existing plasma cell clone thereby promoting the transition from MGUS to active MM. Here, we investigated the clinical and molecular characteristics of a comprehensive series of cases treated for MGUS/MPN overlap at our center. Methods: Patients who were diagnosed with concomitant MGUS/MM and MPN between 2006 and 2023 were identified by retrospective chart review, yielding a total of 13 cases. Results: We identified 5/13 patients with a confirmed diagnosis of MGUS and 8/13 cases with active MM, all coinciding with a diagnosis of MPN (5 polycythemia vera (PV), 4 chronic myelomonocytic leukemia (CMMol), 3 primary myelofibrosis (PMF), 1 chronic myelogeneous leukemia (CML)). Median age at diagnosis was 66 (range 44-78) years for MGUS/MM and 64 (range 43-81) years for MPN. Overall survival in our cohort was rather short at a median of 8.2 (range 0-16) years. For clinical management, anti-MM therapy was prioritized over MPN treatment in the majority of patients, with the exception of CMMol. MPN-related organ restrictions significantly limited treatment options for MM, including bleeding disorders, infectious complications and impaired hematopoiesis (in PMF). High-dose concepts were performed in transplant-eligible cases, including autologous in 4 and allogenic stem cell transplantation in 2 patients. Two out of 6 patients died under transplant (1 autologous graft failure), indicating a comparably high transplant-related mortality. Another patient died from MM progression as PMF-induced anemia did not allow for more intense treatment. To examine the evolutionary path from MGUS to MM and the potential impact on this transformation by a concomitant MPN, we next examined the clinical course of disease in each patient. Six out of 13 patients had secondary MPN after prior MGUS/MM diagnosis, 5/13 patients were diagnosed with MPN first, and for 2/13 cases BM assessment revealed coincidental findings of MPN/ MM at the same time. For the cases of secondary MPN after initial diagnosis of MM/MGUS, latency between both diseases was shorter, than vice versa (40.2 vs. 73.6 months, P=0.19). No association was observed between secondary MPN and prior treatment for MM, as only 1/6 patients was diagnosed with PV following high-dose melphalan chemotherapy, potentially pointing towards a negligible role of treatment-induced secondary primary malignancies the context of MM/MPN overlap. In contrast, MGUS progression to active MM was observed in 1 patient with hyperdiploid IgG kappa MM (including trisomy 9) and long-term coexistent JAK2-mutated PV. Another patient was diagnosed with IgG kappa MM and 9p gain along with concomitant JAK2-mutated PMF. Whole-genome sequencing (WGS) is currently ongoing for these patients to decipher the temporal relationship of MM/MGUS and JAK2-mutated MPN. Conclusions: The prevalence of MGUS/MM in MPN patients seems modestly increased as compared to the entire population. From a clinical viewpoint, overlap of both diseases poses significant challenges to healthcare providers as treatment-related mortality tends to be higher than in patients with mutually exclusive MPN/ MM. Improved understanding of the molecular interplay of both diseases will inform risk-adjusted treatment decisions and will lead to improved outcomes in this highly challenging subgroup of patients.

Chronic limping in childhood, what else other than juvenile idiopathic arthritis: a case series

BackgroundLimping is a common clinical symptom in childhood; different clinical conditions may lead to limping and the diagnosis of the underlying cause may often be a challenge for the pediatrician.Case presentationWe describe the clinical manifestations, radiological pictures and disease course of other causes of limping in childhood, through a case series of seven cases and a brief discussion of each disease.Conclusionsalthough trauma is the most common cause of acute limping, when there is no history of traumatic events and the limping has a chronic course, Juvenile Idiopathic Arthritis is usually the most likely clinical diagnosis. However, other some rare conditions should be taken into account if JIA is not confirmed or if it presents with atypical clinical picture.

Clusters of Disease Activity and Early Risk Factors of Clinical Course of Pediatric Crohn's Disease.

This study aimed to define clusters of disease activity and prognostic factors of disease course in a well-characterized cohort of children with Crohn's disease (CD). All patients from the SIGENP IBD (Italian Society of Pediatric Gastroenterology Hepatology and Nutrition Inflammatory Bowel Disease) registry with a 5-year follow-up and 6-monthly evaluation were included. Active disease was defined for each semester as follows: clinical activity (weighted Pediatric Crohn's Disease Activity Index ≥12.5 or Mucosal Inflammation Noninvasive Index ≥8) and active disease on endoscopy (Simple Endoscopic Score for Crohn's Disease >3 or fecal calprotectin >250 µg/g) or imaging. Formula-based clusters were generated based on previously published patterns in adults. Data from 332 patients were analyzed. A total of 105 (32%) experienced a quiescent disease course; 49 (15%) and 31 (9%) a moderate-to-severe chronically active and chronic intermittent disease, respectively; 104 (31%) and 43 (13%) had active disease in the first 2 years after diagnosis and remission thereafter and vice versa, respectively. Surgery at diagnosis was significantly associated with a quiescent course (odds ratio [OR], 10.05; 95% confidence interval [CI], 3.05-25.22; P=.0005), while growth impairment at the diagnosis and active disease requiring corticosteroids at 6 months were inversely related to the quiescent group (OR, 0.48; 95% CI, 0.27-0.81; P= .007; and OR, 0.35; 95% CI, 0.16-0.71; P= .005, respectively). Perianal involvement at diagnosis and moderate-severe activity at 6 months correlated with disease progression (OR, 3.85; 95% CI, 1.20-12.85; P=.02). During the first 5 years of follow-up, one-third of children with CD experience a quiescent course. However, another one-third have a moderate-to-severe disease course. Surgery at the diagnosis is related to a quiescent course, while growth impairment and lack of response to induction therapy correlate with more severe disease activity during follow-up.

Features of the clinical course of neurodegenerative brain disease caused by mutations in the neurophacitis and succinate dehydrogenase gene: clinical case

Neurodegenerative diseases of the brain pose a serious challenge in diagnosis and treatment. Of particular interest are diseases caused by complex mutations, the clinical picture of which is ambiguous. The article presents a description of a clinical case of a neurodegenerative disease of the brain with symmetrical damage to the cerebellar hemispheres in the projection of the dentate nuclei, in the region of the superior and middle cerebellar peduncles, in the region of the midbrain tegmentum, along the corticospinal tracts, in the subcortical sections of the frontoparietal regions of the brain. It has been shown that these clinical manifestations are caused by the formation of small foci of demyelination in the white matter of the brain. The cause of the disease was revealed to be a deficiency of mitochondrial complex II, nuclear type 4, which is caused by mutations in the NFASC (encoding neurofascin) and SDHB (encoding succinate dehydrogenase) genes. The leading clinical manifestations in this case were motor disorders in the form of persistent bilateral ptosis, external ophthalmoplegia, optic disc atrophy, retinal pigmentary degeneration, subcortical dysarthria, sensorineural hearing loss, and cognitive impairment. However, the clinical picture of this disease developed latently for a long time, which made its diagnosis difficult. The reason for this was a complex genetic defect including mutations in the neurofasciitis and succinate dehydrogenase gene. The paper provides a discussion of currently known effective methods of treating the disease.

Failure to experimentally infect 10 days-old piglets with a cell culture-propagated infectious stock of a classical genotype 1a porcine epidemic diarrhea virus.

Porcine epidemic diarrhea virus (PEDV) causes enteric disease in pigs of all ages. PEDV can be grouped into G1 (classical strains) and G2 (variant strains) based on sequence differences in the spike gene. Although several pathogenesis studies using contemporary strains of PEDV have been conducted to date, there is limited information on the pathogenesis of historical PEDV strains in contemporary pigs. This study aimed to investigate the clinical disease course of 10 days-old pigs infected with a classical European G1a PEDV strain from the 1980s which was last passaged in pigs in 1994. Sequencing results confirmed that the virus inoculum was a PEDV strain closely related to the prototype CV777 strain. The PEDV stock was serially passaged three times in Vero cells, and the P3 infectious virus stock was used to inoculate the pigs. A total of 40 pigs were inoculated using the oral route. Pigs showed no enteric disease signs, and PEDV shedding was not detected for 44 days post-inoculation (dpi). At necropsy at 3 (5 pigs) or 7 dpi (5 pigs), no lesions were observed in intestinal sections, which were negative for PEDV antigen by immunohistochemistry. In addition, no IgG or IgA PEDV-specific antibodies in serum or fecal samples for 35 dpi further indicates a lack of infection. Titration of the leftover thawed and refrozen PEDV virus stock inoculum showed that the virus stock retained its infectivity in Vero cell culture and the porcine small intestine enterocytes cell line IPEC-J2. The reasons for the loss of infectivity in pigs are unknown. In conclusion, we showed that a classical G1a PEDV strain successfully propagated in cell cultures could not orally infect 40 piglets.

Phenotypic switch in mycosis fungoides: A tertiary cancer center experience

BackgroundChanges in immunophenotype in mycosis fungoides (MF) are rarely reported, making this phenomenon a diagnostic challenge with unclear significance for the disease's biological behavior. This study examines a large series of MF patients who exhibited a phenotype switch (PS) and analyzes their clinical and histopathologic characteristics. DesignInstitutional files were searched for MF cases exhibiting PS between 2010 and 2020. Clinical, follow-up, and histopathological data were collected. ResultsForty-two biopsies from 32 patients (13 women and 19 men, median age 67.5) showed PS. Eight patients (25 %) experienced multiple PS during their disease course. The median time for PS was 22 months from the initial diagnosis. In 5 cases tested, identical TCR clone peaks were detected in the immunophenotypically distinct lesions. Median follow-up was 14.5 months. Among deceased patients, median time from MF diagnosis to PS was 20.6 months, while among the patients who were still alive, median time was 44.1 months. ConclusionMF biopsies can show PS during the course of the disease and may indicate a change in clinical behavior. 28.1 % of patients displayed more than one PS, further indicating high plasticity of MF cells. No obvious association was found between PS and therapy initiation or response. Features that appeared to portend a worse clinical course were earlier PS in the course of the disease and PS from CD4-/CD8-to CD8+, and CD8+ to CD4-/CD8-. Awareness of this phenomenon is crucial to avoid misdiagnosing phenotypically distinct lymphomas as second primaries and to alert clinicians about potential changes in the disease's clinical course.

The effect of TRIM5 variants on the susceptibility to HIV-1 infection and disease progression in the Polish population.

Tripartite motif containing 5α protein is a factor contributing to intracellular defense mechanisms against human immunodeficiency virus-1 (HIV-1) infection. The studies of TRIM5 variants effects on the risk of HIV-1 infection and the clinical course of disease provided inconclusive results in different ethnic groups. The aim of this study was to investigate the influence of TRIM5 variants on susceptibility to HIV-1 infection and clinical parameters among Polish HIV-1-infected patients. In our study, we investigated 301 HIV-1-infected patients and 186 age-matched seronegative controls. Seven variants of the TRIM5 gene (rs7127617, rs3824949, rs3740996, rs11601507, rs10838525, rs11038628, and rs28381981) were genotyped using both sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques. The frequencies of rs7127617 TT genotype and T allele occurrence were lower in HIV-1-infected subjects compared to controls (0.14 vs. 0.26 for T/T genotype and 0.45 vs. 0.54 for T allele), suggesting their possible protective effect (p=0.005 and p=0.007, respectively). Heterozygosity and presence of the T allele at rs3740996 were enriched in controls compared to HIV-1-infected group (0.19 vs. 0.12 for C/T genotype and 0.11 vs. 0.07 for T allele; p=0.03 and p=0.02, respectively). Moreover, rs3824949 CC genotype carriers had a lower viral load than patients bearing rs3824949 GG/CG genotypes (4.0 vs. 4.6 log copies/mL; p=0.049); however, none of the variants affected CD4+ cell count. In conclusion, our data confirm the role of TRIM5 variants in the HIV-1 transmission and the clinical course of HIV-1 infection. The presence of rs7127617 TT genotype and T allele seems to protect against HIV-1 transmission in examined population.

The Frequency and Impact of Self-Imposed Elimination Diets on the Nutritional Status and Clinical Course of Disease in Children with Inflammatory Bowel Disease.

From the patients' perspective, diet has a relevant role in triggering symptoms of inflammatory bowel disease (IBD). There is a lack of prospective studies regarding the diet of children with IBD. The aim of this study was to assess the frequency and impact of self-imposed elimination diets on the nutritional status and clinical course of disease in the pediatric population. This was a prospective case-control study that included newly diagnosed patients with IBD and healthy controls (age/sex-matched peers and siblings) over a one-year period. The participants were examined in three categories: (1) anthropometric data and nutritional status; (2) dietary intake, as obtained by a Food Frequency Questionnaire (FFQ); and (3) dietary beliefs and elimination diets, as obtained by a structured questionnaire. Overall, one-hundred and thirty-seven participants were included (twenty-eight with Crohn's disease, sixteen with ulcerative colitis, three with IBD-unclassified, and seventy healthy controls). Only 15% of patients followed the self-imposed elimination diet upon the diagnosis, which increased to 47.6% by the end of the follow-up. The elimination diet did not influence the nutritional status and quality of the diet. Self-imposed elimination diets were not a risk factor for disease relapse. Most of the patients received nutritional counseling during the follow-up. The number of patients following self-imposed elimination diets had increased during the disease course but with no influence on nutritional status or relapse risk.