Prolonged Disease Duration Research Articles

Carotid intima-media thickness measurements in patients with multiple sclerosis

ObjectivesThe goal of this study was to evaluate the mean carotid intima-media thickness (CIMT) in patients with Multiple Sclerosis (MS). MethodsIn this cross-sectional study, 100 patients with MS were enrolled. Carotid intima-media thickness was measured by Doppler Ultrasonography. The mean CIMT was then compared between different groups of sex, age, body mass index (BMI), medications, and site of the MS plaques in the brain and cervical MRI. In addition, disease duration, annual relapse rate, and Expanded Disability Status Scale (EDSS) were compared between high and normal CIMT groups. ResultsAmong 100 patients, Sixty-two percent of the patients were female. The mean age was 35.95 ± 9.32 years. Mean CIMT was 0.38 ± 0.2 mm, and 22% of the patients had abnormal CIMT measures. CIMT was significantly associated with higher age (P = 0.01) and prolonged disease duration (P < 0.001). CIMT was not associated with other disease factors or types of the disease-modifying drug (P > 0.05). ConclusionMultiple Sclerosis might be associated with carotid atherosclerotic vascular disease.

Self-perceived quality of sleep among COPD patients in Greece: the SLEPICO study

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide accompanied by a substantial social and economic burden for the patient and the society. Poor sleep quality among COPD patients is frequently unnoticed and unaddressed by physicians and patients themselves, although it is a major source of further deterioration of these patients’ quality of life. The aim of the present study was to record the quality of sleep in COPD patients among the Greek population and correlate these findings with various features of these patients, using the COPD and Asthma Sleep Impact Scale (CASIS). This was a cross-sectional observational study. Forty different variables (demographics, vital sign measurements, COPD-related medical history parameters, comorbidities, CASIS questionnaire results, COPD assessment test, COPD severity based on spirometry measurements, COPD stage based on the ABCD assessment approach, inhaled COPD treatment report) were collected from 3454 nation-wide COPD patients (Greece). The study sample consisted of COPD patients, mainly male (73%) with a median age of 69 years and a median BMI of 27.2. More than half of COPD patients (60.6%) suffered from moderate disease severity and 23.8% from severe disease, while less than half (42.1%) suffered from at least one exacerbation of the disease over the last year prior study enrollment. About 14% reported frequent to very frequent issues affecting their sleep quality, between a fourth and a third of them reported occasional night sleep disturbances, and at least half of them reported no or very infrequent problems in their night sleep. Our study indicates that the COPD assessment test (CAT) and the spirometry-based disease severity can predict the poorness in the quality of sleep (F2,3451 = 1397.5, p < 0.001, adj. R2 = 0.45) as assessed by CASIS score, and that the latter also correlates with age (ρ = 0.122, p < 0.001) and disease duration (ρ = 0.104, p < 0.001). On the contrary, there appears to be no correlation between sleep quality and number of exacerbations. Finally, untreated patients with COPD suffer from poorer quality of sleep compared to treated subjects, independently of the use of inhaled corticosteroids (F2,3451 = 21.65, p < 0.001). The results of the SLEPICO study show that increased age, prolonged disease duration, and especially CAT score ≥ 10, and severe COPD stage, might act as important indicators for deterioration in the quality of sleep, with potential consequences in the daily routine of those patients, thus urging potentially for further pharmacological interventions or modifications.

Association of Prolonged Disease Duration and TG/HDL-C Ratio in Accelerating Atherosclerosis in Patients with Takayasu's Arteritis.

Background and aim: Takayasu's arteritis (TA) is a chronic inflammation that frequently involves the aorta and its major branches. It has been known that atherosclerosis can occur in some TA patients. Objectives: This study aimed to identify the risk factors associated with the development of atherosclerosis in TA. Methods: This retrospective study enrolled a total of 101 TA patients. All patients were divided into two groups according to the absence or presence of atherosclerosis. Baseline demographic features and clinical characteristics were compared between two groups. A logistic model was applied to determine the risk factors associated with the development of atherosclerosis. Results: Our data suggested that the disease duration of patients in the atherosclerosis group was significantly longer than that of patients in the non-atherosclerosis group [96(18.00, 180.00) versus 48.00(12.00, 111.00) months] (P = .015). In addition, the average age of patients with atherosclerosis was significantly older compared to patients without atherosclerosis [44.00(38.00, 48.00)versus 28.50(24.00，37.00)years] (P < .001). Logistic regression analysis showed that the risk of developing atherosclerosis increased by 9.2% per 1 year increase in the disease duration (P = .005, OR 1.092, 95%CI: 1.027-1.162). Patients with TG/HDL-C ratio more than 0.8875 were associated with a 5.861fold increase of risk developing atherosclerosis (P < .001, OR 5.861, 95%CI: 2.299-14.939). Conclusion: Our study indicated that prolonged disease duration and elevated TG/HDL-C ratio are associated with the development of atherosclerosis in TA patients.

Efficacy and Safety of Sofosbuvir and Velpatasvir Combination for the Treatment of Chronic Hepatitis C in Patients With or Without Cirrhosis.

Background and aimFor years, interferon-based treatment has been offered to patients with chronic hepatitis C virus (HCV) infection; however, the complexity of the treatment, efficacy, and adverse effects were the primary concerns. All these concerns were addressed with the introduction of directly acting antivirals (DAAs) to treat chronic HCV. Sofosbuvir and velpatasvir are second-generation DAAs used in combination for the treatment of chronic HCV infection. The aim of our study was to determine and compare the efficacy and safety profile of the sofosbuvir and velpatasvir combination in treating patients with chronic hepatitis C with or without cirrhosis.Materials and methodsThis descriptive study was conducted at the Department of Medicine, Khyber Teaching Hospital, Peshawar, from March 15th to September 15th, 2021 after approval from the Institution Research and Ethical Review Board (IREB). Diagnosis of HCV was based on the detection of hepatitis C ribonucleic acid (RNA) fragments by reverse transcription-polymerase chain reaction (RT-PCR). Liver status was assessed with liver function tests and imaging. Sofosbuvir (400 mg) and velpatasvir (100 mg) were administered once daily for 12 weeks, followed by polymerase chain reaction (PCR) for HCV RNA after 12 weeks of completion of treatment for determination of sustained virologic response at 12 weeks (SVR12). Patients with cirrhosis also received weight-based ribavirin. Adverse events experienced by the study participants during the course of treatment were recorded. Data were collected regarding patients' demographics, laboratory parameters, SVR12, and adverse events, and were then analyzed using SPSS, version 22 (IBM SPSS Statistics, Armonk, NY).ResultsA total of 58 patients with cirrhosis and 58 patients without cirrhosis with chronic HCV were enrolled. The rate of SVR12 in patients with cirrhosis was 89.7% (52 patients achieved SVR12), compared to 98.3% in patients without cirrhosis (57 patients achieved SVR12). Subgroup analysis of patients with cirrhosis revealed that patients who have failed to achieve SVR12 were mostly males, had prolonged disease duration, and low hemoglobin at baseline; however, the association of these factors with SVR12 was not significant. The incidence of adverse events among all study participants was 46.5%. Among the cirrhotic cohort, 37 (63.8%) patients experienced adverse events, while only 17 (29.3%) patients among the non-cirrhotic cohort had adverse events. A total of 24 patients with cirrhosis (41.37%) reported mild complaints. The most commonly reported adverse event was gastrointestinal (GI) upsets (46.2%), followed by fatigue (33.9%), while 19.9% developed miscellaneous adverse events such as headaches, rash, and insomnia.ConclusionThe combination of sofosbuvir and velpatasvir is highly effective and safe in patients with HCV with or without cirrhosis. However, this combination's efficacy was slightly higher in non-cirrhotic patients (98.3%) than in cirrhotic patients (89.7%).

Eumycetoma Medical Treatment: Past, Current Practice, Latest Advances and Perspectives

Mycetoma is a neglected tropical disease that is associated with poor communities and socioeconomically impaired individuals in the tropical and sub-tropical areas. Interestingly, the disease is caused by either bacteria (actinomycetoma) or fungus (eumycetoma). The latter form of the disease, eumycetoma, is the most common type in Africa. Eumycetoma is characterized by a prolonged disease duration and low cure rate. The effective case management of eumycetoma largely depends on the accurate diagnosis and identification of the causative agent to the species level and evaluating its susceptibility to the available drugs. This review summarizes the currently available and used antifungal agents for the treatment of eumycetoma and discusses optimizing the newly developed antifungals as a potential second line for eumycetoma treatment.

COVID-19. Understanding of the consequences

The new coronavirus infection known as SARS‑CoV‑2 and firstly registered in Wuhan, China in late 2019, resulted in the severe crisis and a great number of lethal outcomes worldwide. Processes occurring in a body with virus infecting are quite polymorphic and involve all organs and systems. The first step in the infection is the virus binding with the host cell via target ACE‑2 receptors with resulting virus‑inducted down‑regulation of these receptors which, through a number of signaling pathways, leads to COVID‑related damage to an organ or system. Since ACE‑2 receptors play a leading role as an entrance gate for the virus, understanding of an axis of ACE/angiotensin receptor and ACE‑2/MAS‑receptor has the crucial significance in the investigation of infection role. The article presents review of the data from patients with delayed recovery after COVID‑19. The prolonged disease duration and disability are often inherent to the patients, hospitalized due to severe and critically severe disease forms. There is no universally accepted definition of «Long Covid», or post‑covid syndrome, but for convenience it was conditionally distinguished a subacute condition that lasts more than 3 weeks from the onset of the disease, and a chronic condition that lasts more than 12 weeks. Among the pathogenetic peculiarities, the activation of renin‑angiotensin‑aldosterone system, cytokine system, anti/prooxidant stress, coagulopathy, endothelial disfunction have been examined. Better understanding of the mechanisms that are realized at COVID‑19, will enable the rational use of the medicines for the disease treatment on all stages that may possibly prevent complications and prolonged consequences of the infection as well as improve the quality of life of patients.

A Rabbit Model for the Evaluation of Drugs for Treating the Chronic Phase of Botulism.

Antitoxin, the only licensed drug therapy for botulism, neutralizes circulating botulinum neurotoxin (BoNT). However, antitoxin is no longer effective when a critical amount of BoNT has already entered its target nerve cells. The outcome is a chronic phase of botulism that is characterized by prolonged paralysis. In this stage, blocking toxin activity within cells by next-generation intraneuronal anti-botulinum drugs (INABDs) may shorten the chronic phase of the disease and accelerate recovery. However, there is a lack of adequate animal models that simulate the chronic phase of botulism for evaluating the efficacy of INABDs. Herein, we report the development of a rabbit model for the chronic phase of botulism, induced by intoxication with a sublethal dose of BoNT. Spirometry monitoring enabled us to detect deviations from normal respiration and to quantitatively define the time to symptom onset and disease duration. A 0.85 rabbit intramuscular median lethal dose of BoNT/A elicited the most consistent and prolonged disease duration (mean = 11.8 days, relative standard deviation = 27.9%) that still enabled spontaneous recovery. Post-exposure treatment with antitoxin at various time points significantly shortened the disease duration, providing a proof of concept that the new model is adequate for evaluating novel therapeutics for botulism.

Association of HLA genotypes, AB0 blood type and chemokine receptor 5 mutant CD195 with the clinical course of COVID-19

BackgroundCOVID-19, the pandemic disease caused by infection with SARS-CoV-2, may take highly variable clinical courses, ranging from symptom-free and pauci-symptomatic to fatal disease. The goal of the current study was to assess the association of COVID-19 clinical courses controlled by patients’ adaptive immune responses without progression to severe disease with patients’ Human Leukocyte Antigen (HLA) genetics, AB0 blood group antigens, and the presence or absence of near-loss-of-function delta 32 deletion mutant of the C–C chemokine receptor type 5 (CCR5).Patient and methodsAn exploratory observational study including 157 adult COVID-19 convalescent patients was performed with a median follow-up of 250 days. The impact of different HLA genotypes, AB0 blood group antigens, and the CCR5 mutant CD195 were investigated for their role in the clinical course of COVID-19. In addition, this study addressed levels of severity and morbidity of COVID-19. The association of the immunogenetic background parameters were further related to patients’ humoral antiviral immune response patterns by longitudinal observation.ResultsUnivariate HLA analyses identified putatively protective HLA alleles (HLA class II DRB1*01:01 and HLA class I B*35:01, with a trend for DRB1*03:01). They were associated with reduced durations of disease instead decreased (rather than increased) total anti-S IgG levels. They had a higher virus neutralizing capacity compared to non-carriers. Conversely, analyses also identified HLA alleles (HLA class II DQB1*03:02 und HLA class I B*15:01) not associated with such benefit in the patient cohort of this study. Hierarchical testing by Cox regression analyses confirmed the significance of the protective effect of the HLA alleles identified (when assessed in composite) in terms of disease duration, whereas AB0 blood group antigen heterozygosity was found to be significantly associated with disease severity (rather than duration) in our cohort. A suggestive association of a heterozygous CCR5 delta 32 mutation status with prolonged disease duration was implied by univariate analyses but could not be confirmed by hierarchical multivariate testing.ConclusionThe current study shows that the presence of HLA class II DRB1*01:01 and HLA class I B*35:01 is of even stronger association with reduced disease duration in mild and moderate COVID-19 than age or any other potential risk factor assessed. Prospective studies in larger patient populations also including novel SARS-CoV-2 variants will be required to assess the impact of HLA genetics on the capacity of mounting protective vaccination responses in the future.

The Extent and Diverse Trajectories of Longitudinal Changes in Rheumatoid Arthritis Interstitial Lung Diseases Using Quantitative HRCT Scores

We aimed to validate quantitative high-resolution computed tomography (HRCT) imaging analyses of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients, and to delineate a broad spectrum of annual longitudinal changes of ILD severity in the RA-ILD cohorts. Retrospective cohort 1 (n = 26) had matched PFT results and prospective cohort 2 (n = 34) were followed for over two years with baseline serum specimen. Automated quantitative analysis of HRCT was expressed as the extent of ground-glass opacity, lung fibrosis, honeycombing, and their summation—the total extent of quantitative ILD (QILD). Higher QILD score was associated with lower pulmonary function especially for DLCO% (ρ = −0.433, p = 0.027). Higher serum level of Krebs von den Lungen 6 were significantly associated with high QILD scores (ρ = 0.400, p = 0.026). Regarding QILD score changes in whole lung, even a single point increase was significantly associated with interval progression detected by the radiologist. Four distinct patterns (improvement, worsening, convex-like, and concave-like) during the 24 months were described by QILD scores. Prolonged disease duration of ILD at baseline was significantly associated with worsening of QILD scores. QILD has the potential to reliably evaluate the dynamic severity changes in patients with RA-ILD.

Drug efficacy and safety of biologics and Janus kinase inhibitors in elderly patients with rheumatoid arthritis.

Elderly patients with rheumatoid arthritis (RA) are frequently associated with higher disease activity and impaired physical function, although they show intolerance for conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), such as methotrexate, because of their comorbidities. However, the present treatment recommendation based on randomized controlled trials is not distinguished by age or comorbidities. Therefore, this review aimed to investigate the efficacy and safety of biological DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi) in elderly patients. Present bDMARDs, including tumor necrosis factor inhibitors (TNFi), cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (abatacept), interleukin (IL)-6 receptor antibody (tocilizumab and salirumab), and anti-CD20 antibody (rituximab), may be similarly or slightly less effective or safe in elderly patients compared with younger patients. Oral glucocorticoid use, prolonged disease duration, and very old patients appear to be associated with an increased risk of adverse events, such as serious infection. Some recent cohort studies demonstrated that non-TNFi showed better retention than TNFi in elderly patients. Both TNFi and non-TNFi agents may not strongly influence the risk of adverse events such as cardiovascular events and malignancy in elderly patients. Regarding JAKi, the efficacy appears to be similar, although the safety (particularly for serious infections, including herpes zoster) may be attenuated by aging.

Root Extract of Lindera aggregata (Sims) Kosterm. Modulates the Th17/Treg Balance to Attenuate DSS-Induced Colitis in Mice by IL-6/STAT3 Signaling Pathway

Ulcerative colitis (UC) is a chronic, idiopathic and relapsing inflammatory disease of the gastrointestinal tract that has a prolonged disease duration. Lindera aggregata (Sims) Kosterm. is a traditional Chinese herb which has been used to treat gastrointestinal diseases for thousand years. However, there are few reports about the application of L. aggregata in the treatment of UC at present. Herein, we investigated the therapeutic effect of the root extract of L. aggregata (LREE) against UC and explored its underlying mechanisms based on IL-6 signaling pathway and the balance of T helper (Th) 17 and regulatory T (Treg) cells. Results showed that LREE could not only decrease the production and secretion of IL-6, but also could inhibit the signal transduction of IL-6/STAT3 signaling pathway. Moreover, LREE could significantly inhibit the differentiation of CD4+ T cells to Th17 cells in vitro and decrease the proportion of Th17 cells in mesenteric lymph nodes (MLNs) of model mice in vivo. Besides, LREE could also alleviate the disease symptoms, reduce intestinal permeability and improve histopathological changes of colitis model mice. Together, LREE can significantly inhibit the production and secretion of IL-6, regulate IL-6/STAT3 signal transduction, and modulate the balance of Th17 and Treg cells and effectively attenuate UC.

Early and late manifestations of neuropathy due to HSPB1 mutation in the Jewish Iranian population.

ObjectiveMutations in the HSPB1 gene are associated with a distal hereditary motor neuropathy type 2 (dHMN2) or Charcot‐Marie‐Tooth disease type 2F (CMT2F), usually with autosomal dominant inheritance. This study aimed to describe the phenotype of the HSPB1 c.407G>T (p.Arg136Leu) mutation at early and late stages of the disease course.MethodsWe identified this mutation (previously reported in patients from Italy) in a heterozygous state, among 14 individuals from eight families of Jewish Iranian descent. The clinical, electrophysiological and ultrasonographic features were evaluated during early (less than 5 years, N = 9) or late disease course (N = 5).ResultsThe majority of subjects were males with a mean age at onset of 43.4 years (range 21‐67). Common initial symptoms were gait imbalance, distal (often asymmetric) lower limb weakness and feet numbness. Neurological examination in early disease course showed distal lower extremity weakness in nearly all cases, and absent Achilles tendon reflex in about half. A minority had distal loss of pain, vibration or position sensation. These findings were more prevalent in late disease stage. Electrodiagnostic studies demonstrated a length‐dependent axonal motor neuropathy, with typical preferential involvement of the tibial nerve. Muscle ultrasound showed a corresponding length‐dependent increase of homogeneous echo‐intensity, most noticeably in the gastrocnemius. One patient had a dual diagnosis of CMT2F and CMT2W.InterpretationThe HSPB1 c.407G>G (p.Arg136Leu) mutation causes an adult‐onset, predominantly motor, axonal neuropathy in individuals of Jewish Iranian descent. Variable manifestations are noticed, and sensory involvement is more prominent in prolonged disease duration.

Plasma amino acids and oxylipins as potential multi-biomarkers for predicting diabetic macular edema

To investigate the pathophysiologic characteristics of diabetic complications, we identified differences in plasma metabolites in subjects with type 2 diabetes (T2DM) with or without diabetic macular edema (DME) and a disease duration > 15 years. An cohort of older T2DM patients with prolonged disease duration was established, and clinical information and biospecimens were collected following the guidelines of the National Biobank of Korea. DME phenotypes were identified by ophthalmologic specialists. For metabolomics studies, propensity matched case and control samples were selected. To discover multi-biomarkers in plasma, non-targeted metabolite profiling and oxylipin profiling in the discovery cohort were validated in an extended cohort. From metabolomic studies, 5 amino acids (asparagine, aspartic acid, glutamic acid, cysteine, and lysine), 2 organic compounds (citric acid and uric acid) and 4 oxylipins (12-oxoETE, 15-oxoETE, 9-oxoODE, 20-carboxy leukotriene B4) were identified as candidate multi-biomarkers which can guide DME diagnosis among non-DME subjects. Receiver operating characteristic curves revealed high diagnostic value of the combined 5 amino acids and 2 organic compounds (AUC = 0.918), and of the 4 combined oxylipins (AUC = 0.957). Our study suggests that multi-biomarkers may be useful for predicting DME in older T2DM patients.

Camptocormia in patients with multiple system atrophy at different disease durations: frequency and related factors

BackgroundCamptocormia is common in patients with multiple system atrophy (MSA). The current study was aimed at assessing the frequency of camptocormia and its related factors in MSA patients with different disease durations. Also, the impact of camptocormia on disability was evaluated.MethodsA total of 716 patients were enrolled in the study. They were classified into three groups based on disease duration (≤ 3, 3–5, ≥ 5 years). Specific scales were used to evaluate the motor and non-motor symptoms. Disease severity was assessed using the Unified Multiple System Atrophy Rating Scale (UMSARS). The binary logistic regression model was used to explore the factors related to camptocormia. To analyze the impact of camptocormia on disability in patients with disease duration less than 5 years, propensity score matching (PSM) and stratified Cox regression analysis were used.ResultsIn the current study, we found that the frequency of camptocormia was 8.9, 19.7 and 19.2% when the disease duration was ≤3, 3–5, ≥ 5 years, respectively. In the disease duration ≤3 years group, we found that MSA-parkinsonian subtype (MSA-P) (OR = 2.043, P = 0.043), higher total UMSARS score (OR = 1.063, P < 0.001), older age of onset (OR = 1.047, P = 0.042), and lower score on the frontal assessment battery (FAB) (OR = 0.899, P = 0.046) were associated with camptocormia. Only greater disease severity was associated with camptocormia in the group of patients with disease duration 3–5 years (OR = 1.494, P = 0.025) and in the group of patients with disease duration ≥5 years (OR = 1.076, P = 0.005). There was no significant impact of camptocormia on disability in patients with a disease duration of < 5 years (HR = 0.687, P = 0.463).ConclusionThe frequency of camptocormia increased with prolonged disease duration. Disease severity was related to camptocormia at different stages of the disease. The MSA-P subtype, older age of onset, and lower FAB score were associated with camptocormia in the early stage of the disease.

Sakrokoksigeal Pilonidal Sinüs Spesmenlerinde Patolojik Değerlendirme Gerekli midir?

In some surgical methods, the cavity of the sacrococcygeal pilonidal sinus remains in the patient. This situation leads us to question the necessity of routine pathological examination. Patients undergoing surgical excision for sacrococcygeal pilonidal sinus between January 2016 and March 2020 at Gaziantep Dr. Ersin Arslan Training and Research Hospital were retrospectively screened. Patients with pilonidal sinus in the non-sacrococcygeal region and patients with minimally invasive treatment and without histopathological examination were excluded. Gender, age, operation notes, and pathology results of the patients were analyzed. For all patients, an excision plus flap (Limberg or Karydakis) procedure was performed and the specimen was sent to routine histopathological examination. Of 1971 patients who underwent surgery for sacrococcygeal pilonidal sinus, 1551 (79%) were male and 420 (21%) were female, with an average age of 24 years (13-66). None of the pathological findings revealed any malignancy. The rate of malignancy reported in the literature is not in concordance with minimally invasive procedures in which pathology samples are not taken. Except in cases of prolonged duration of disease, elderly age, macroscopic suspicion, or recurrence, we believe that routine pathological examination of the pilonidal sinus may be unnecessary.

Advances in Research on the Cardiovascular Complications of Acromegaly.

Cardiovascular-related complications are one of the most common complications in patients with acromegaly, and can lead to an increased risk of death. Hypertension and cardiomyopathy are the main cardiovascular complications. The characteristics of acromegalic cardiomyopathy are concentric biventricular hypertrophy and diastolic dysfunction. In addition, arrhythmia and heart valve disease are common cardiac complications in acromegaly. Although the underlying pathophysiology has not been fully elucidated, the spontaneous overproduction of GH and IGF-1, increasing age, prolonged duration of disease and the coexistence of other cardiovascular risk factors are crucial to cardiac complications in patients with acromegaly. Early diagnosis and appropriate treatment of acromegaly might be beneficial for the prevention of cardiomyopathy and premature death.

Total cholesterol/high density lipoprotein-cholesterol ratio as an indicator of Dyslipidemia in hypothyroidism

Background: The thyroid hormones are involved in controlling metabolism, growth and functions of various organ systems of our body. Hypothyroidism, a very common endocrinopathy features reduced production of thyroid hormones. In hypothyroidism we encounter abnormal circulating lipid fractions which is termed as ‘Dyslipidemia’. The coexistence of dyslipidemia and hypothyroidism is associated with development of atherosclerosis. Aim: This research is undertaken to assess the potential of TC/HDL-C ratio to disclose dyslipidemia in hypothyroidism. Methodology: The study consists of two major groups, the ‘Cases’ comprising of Fifty hypothyroid patients and ‘Controls’, with fifty age and gender matched healthy adults. The Cases are further subdivided into Twenty ‘Known cases’ of Hypothyroid patients, already receiving treatment and thirty ‘New cases’. The ‘New cases’ sub group further is subdivided as Twenty-one ‘Overt hypothyroids’(OH) and nine ‘Subclinical Hypothyroids’ (SCH). The Biochemical parameters estimated in all subjects of the study includes, Serum TSH, T3, T4, Total Cholesterol (TC) and High density lipoprotein-cholesterol(HDL-C). TC/HDL ratio was then calculated . Result: The study shows a significant elevation (p = 0.05) in the TC/HDL-C ratio in hypothyroid patients (3.67 ± 1.02) when compared to healthy controls (3.29 ± 0.95). TC/HDL-C ratio is more elevated in OH (4.01 ± 1.28) than in SCH (3.46 ± 0.92). The levels in ‘New cases’ sub-group and OH sub sub group have significantly higher ratio than in healthy controls (p = 0.02 and p = 0.01 respectively). TC/HDL-C ratio value in “known cases’ group who are those hypothyroid patients on Levo-thyroxine therapy is (3.40 ± 0.61) less than those who are newly diagnosed. Conclusion: TC/HDL-C ratio is not only raised in hypothyroid patients but it is seen increasing with severity and prolonged duration of disease. The calculation of TC/HDL-C ratio should be routinely put into practice to detect hypothyroid patients with dyslipidemia.

Modeling Endoscopic Improvement after Induction Treatment With Mesalamine in Patients With Mild-to-Moderate Ulcerative Colitis

Endoscopic improvement is an important treatment target for mild-to-moderate ulcerative colitis (UC). However, early endoscopic evaluation is not always feasible. We aimed to develop a clinical decision support tool to discriminate patients who have achieved endoscopic improvement from those with more severe inflammation following mesalamine induction therapy. We performed a post-hoc analysis of data from a phase 3 non-inferiority trial of 726 adults with mild-to-moderate UC treated with mesalamine. Multivariable logistic regression modeling determined associations between candidate variables and endoscopic improvement (Mayo endoscopic subscore=0-1 according to blinded central reading) at Week 8. Internal model validation was performed using bootstrap resampling. A clinical decision support tool was developed to stratify patients into low, intermediate, and high probability groups for endoscopic improvement. Variables associated with endoscopic improvement at Week 8 included 50% reduction in fecal calprotectin from baseline (odds ratio [OR] 2.64, 95% CI:, 1.81, 3.85), reduction in rectal bleeding (OR 1.79 per point reduction, 95% CI: 1.35, 2.39), and improvement in physician global assessment (OR 2.32 per point improvement, 95% CI: 1.88, 2.85). The baseline Geboes score (OR 0.74 per grade, 95% CI: 0.65, 0.85) and prolonged disease duration (OR 0.95 per year, 95% CI: 0.92, 0.98) were negatively associated with endoscopic improvement. This model strongly discriminated endoscopic improvement in the development dataset (area under the curve [AUC] 0.84, 95% CI: 0.81, 0.87) and during validation (AUC 0.83). We developed and validated a clinical decision support tool that has good discriminative performance for induction of endoscopic improvement in patients with mild-to-moderate UC treated with mesalamine. ClinicalTrials.gov Registration: NCT01903252.

A study on the clinico-epidemiological profile of vitiligo patients and its association with endocrine, audiological and ocular abnormalities

Background: Vitiligo is an acquired condition resulting from the progressive loss of melanocytes. It may be associated with disorders of pigmented tissues of the eyes and ears, and withdisorders of the endocrine organs. Aim: To study the clinico-demographic profile of vitiligo patientsand its association with endocrine disorders and audiological and ocular abnormalities. Materials and Methods: This was a case-control study conducted at a tertiary care hospital; 261 vitiligo patients were enrolled together with 100 age- and gender-matched healthy individuals without vitiligo as the controls. A detailed history and clinical examination, including audiological and ocular examination, was undertaken; blood investigations like random blood sugar, thyroid function tests, and serum cortisol levels were requested for all subjects. Results: Vitiligo vulgaris was the most common type of disease detected in 146 (55.93%) patients, followed by focal vitiligo in59 (22.60%), mucosal vitiligo in 31 (11.87%), acrofacial vitiligo in 16 (6.13%), segmental vitiligo in 8 (3.06%), and universal vitiligo in one (0.38%) patient. Endocrine disorders were noted in 40 (15.32%) patients, which included hypothyroidism in 27, hyperthyroidism in 5, and diabetes in 8 patients. Sensorineural hypoacusis andocular abnormalities were noted in 56 (21.45%) and 49 (18.77%) vitiligo patients respectively. The association of hypothyroidism, sensorineural hypoacusis, and ocular abnormalities with vitiligowas statistically significant. Conclusion: Vitiligo is not limited to cutaneous melanocytes; it also affects pigment cells throughout the body. Patients with increased age, prolonged duration of disease, and greater bodysurface area involvement are at increased risk for systemic associations. A thorough clinical evaluation seems necessary for all vitiligo patients.

Elevated Concentrations of Soluble Fas and FasL in Multiple Sclerosis Patients with Antinuclear Antibodies.

Antinuclear antibodies (ANA) are currently considered as an epiphenomenon of apoptotic processes, possibly in control of autoreactivity in patients with multiple sclerosis (MS). Apoptosis of reactive lymphocytes by the Fas/FasL system is described as an effective control mechanism for autoreactivity in MS. We aimed to provide a context to the potential link between ANA and peripheral lymphocyte apoptosis in MS. The presence of ANA was detected in sera by immunofluorescence assay, and concentrations of sFas and sFasL were determined in the sera of 44 and cerebrospinal fluid (CSF) of 11 relapsing-remitting (RR) MS patients using cytometric bead-based array, and their association with the disease characteristics was determined. ANA were detected in the sera of 43.2% of RRMS patients, and their frequency was the highest in patients with disease duration of less than one year (88,89%). In addition, the number of experienced relapses was lower in ANA-positive patients. Concentrations of sFasL were inversely associated with patients’ expanded disability status scale (EDSS) scores. Low concentrations of both soluble factors strongly discriminated patients with moderate to severe disability, from patients with mild or absent disability only in a group of patients with prolonged disease duration (>10 years). Both soluble mediators were significantly higher in ANA-positive patients. FasL concentrations were inversely associated with the number of relapses. There is a potential link between the presence of ANA and peripheral lymphocyte apoptosis mediated by Fas/FasL system in MS, whose precise role and significance needs to be determined by future mechanistic studies.