Primary vs. Secondary Antibody Deficiency: Clinical Features and Infection Outcomes of Immunoglobulin Replacement

<div><p>Secondary antibody deficiency can occur as a result of haematological malignancies or certain medications, but not much is known about the clinical and immunological features of this group of patients as a whole. Here we describe a cohort of 167 patients with primary or secondary antibody deficiencies on immunoglobulin (Ig)-replacement treatment. The demographics, causes of immunodeficiency, diagnostic delay, clinical and laboratory features, and infection frequency were analysed retrospectively. Chemotherapy for B cell lymphoma and the use of Rituximab, corticosteroids or immunosuppressive medications were the most common causes of secondary antibody deficiency in this cohort. There was no difference in diagnostic delay or bronchiectasis between primary and secondary antibody deficiency patients, and both groups experienced disorders associated with immune dysregulation. Secondary antibody deficiency patients had similar baseline levels of serum IgG, but higher IgM and IgA, and a higher frequency of switched memory B cells than primary antibody deficiency patients. Serious and non-serious infections before and after Ig-replacement were also compared in both groups. Although secondary antibody deficiency patients had more serious infections before initiation of Ig-replacement, treatment resulted in a significant reduction of serious and non-serious infections in both primary and secondary antibody deficiency patients. Patients with secondary antibody deficiency experience similar delays in diagnosis as primary antibody deficiency patients and can also benefit from immunoglobulin-replacement treatment.</p></div

Socioeconomic profile of diabetic patients with and without foot problems

Introduction: To identify the differences in a socioeconomic profile between two cohorts of diabetic patients &#x2013; one with diabetic foot problems and another without diabetic foot problems. Materials and methods: The cohort with diabetic foot problems (including cellulitis, abscess, osteomyelitis, septic arthritis, gangrene, ulcers, or Charcot joint disease) consisted of 122 diabetic patients, while the other cohort without foot problems consisted of 112 diabetic patients. Both were seen at the National University Hospital from January to April 2007. A detailed protocol was designed and the factors studied included patient profile, average monthly household income, education, compliance to diabetic medication, attendance at clinics for diabetic treatment, exercise, smoking, alcohol consumption, gender, and glycosylated haemoglobin (HbA1C) level. These were studied for significant differences using univariate and stepwise multivariate logistic regression analysis. Results: With multivariate analysis, Malay ethnicity (p&#60;0.001), education of up to secondary school only (p=0.021), low average monthly household income of less than SGD &#x0024;2,000 (p=0.030), lack of exercise (at least once a week, p=0.04), and elevated HbA1C level (&#x003E;7.0%; p=0.015) were found to be significantly higher in the cohort with diabetic foot problems than the cohort without. Conclusions: There are significant differences in the socioeconomic factors between diabetic patients with diabetic foot problems and those without

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Clinical validation of an AI-based pathology tool for scoring of metabolic dysfunction-associated steatohepatitis

\ua9 The Author(s) 2024.Metabolic dysfunction-associated steatohepatitis (MASH) is a major cause of liver-related morbidity and mortality, yet treatment options are limited. Manual scoring of liver biopsies, currently the gold standard for clinical trial enrollment and endpoint assessment, suffers from high reader variability. This study represents the most comprehensive multisite analytical and clinical validation of an artificial intelligence (AI)-based pathology system, AI-based measurement of metabolic dysfunction-associated steatohepatitis (AIM-MASH), to assist pathologists in MASH trial histology scoring. AIM-MASH demonstrated high repeatability and reproducibility compared to manual scoring. AIM-MASH-assisted reads by expert MASH pathologists were superior to unassisted reads in accurately assessing inflammation, ballooning, MAS ≥ 4 with ≥1 in each score category and MASH resolution, while maintaining non-inferiority in steatosis and fibrosis assessment. These findings suggest that AIM-MASH could mitigate reader variability, providing a more reliable assessment of therapeutics in MASH clinical trials

Evaluation of the efficacy and tolerability of miglitol in Chinese patients with type 2 diabetes mellitus inadequately controlled by diet and sulfonylureas

The objective of this study is to examine the efficacy and tolerability of miglitol with respect to improving glycemic control in Chinese patients with type 2 diabetes mellitus inadequately controlled by diet and sulfonylurea treatment. This was a randomized, double-blinded, placebo-controlled, multicenter study. A total of 105 patients were randomized to receive 24 weeks of treatment with miglitol (n = 52; titrated from 50 mg to 100 mg 3 times daily) or placebo (n = 53). Concomitant sulfonylurea treatment and diet remained unchanged. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline at 24 weeks. Secondary endpoints were changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and postprandial serum insulin (PSI). The miglitol treatment group showed significantly greater reductions in HbA1c and PPG levels compared with the placebo group. With respect to adverse events, abdominal discomfort, diarrhea, and hypoglycemia occurred with similar frequency in both groups. Results of this study indicate that miglitol significantly improves metabolic control in Chinese patients with type 2 diabetes mellitus. Miglitol is safe and well tolerated, with the exception of abdominal discomfort. Therefore, miglitol may be a useful adjuvant therapy for Chinese patients with type 2 diabetes mellitus inadequately controlled by diet and sulfonylurea treatment

Prevalence of the metabolic syndrome in Luxembourg according to the Joint Interim Statement definition estimated from the ORISCAV-LUX study

ABSTRACT: BACKGROUND: The prevalence of the metabolic syndrome (MS) has been determined in many countries worldwide but never in Luxembourg. This research aimed to 1) establish the gender- and age-specific prevalence of MS and its components in the general adult population of Luxembourg, according to the most recent Joint Interim Statement (JIS) definition, by using both the high and low cut-off points to define abdominal obesity, and 2) compare and assess the degree of agreement with the Revised National Cholesterol Education Programme-Adult Treatment Panel III (R-ATPIII) and the International Diabetes Federation (IDF) definitions. METHODS: A representative stratified random sample of 1349 European subjects, aged 18-69 years, participated to ORISCAV-LUX survey. Logistic regression and odds ratios (OR) were used to study MS prevalence with respect to gender and age. The Framingham risk score (FRS) to predict the 10-year coronary heart disease (CHD) risk was calculated to compare the proportion of MS cases below or above 20%, according to both high and low waist circumference (WC) thresholds. Cohen's kappa coefficient (kappa) was utilized to measure the degree of agreement between MS definitions. RESULTS: The prevalence of the MS defined by the JIS was 28.0% and 24.7% when using the low (94/80) and the high (102/88) WC cut-off points, respectively. The prevalence was significantly higher in men than in women (OR = 2.6 and 2.3 for the low and high WC thresholds), as were all components of the MS except abdominal obesity measured by both thresholds. It also increased with age (OR values in age categories ranging from 2.7 to 28 when compared to the younger subjects for low WC and from 3.3 to 31 for the high WC cut-offs). The 10-year predicted risk of CHD by FRS did not depend on the threshold used. Globally, excellent agreement was observed between the three definitions of MS (kappa= 0.89), in particular between JIS and IDF (kappa = 0.93). Agreement was significantly higher in women than in men, and differed between age groups. CONCLUSION: Regardless of the definition used, the adult population of Luxembourg reveals a high MS prevalence. Our findings contribute to build evidence regarding the definitive construct of the MS, to help selecting the waist circumference thresholds for Europid populations, and to support the need to revise the guidelines for abdominal obesity levels

Race/Ethnicity and gender differences in health intentions and behaviors regarding exercise and diet for adults with type 2 diabetes: A cross-sectional analysis

<p>Abstract</p> <p>Background</p> <p>Self-management is the cornerstone of diabetes control and prevention of complications; however, it is undetermined whether differences in intention to adopt healthy lifestyles and actual healthy behavior exist across race/ethnic groups. This study evaluated the differences across racial-ethnic groups in self-reported medical advice received and health intentions and behaviors among adults with type 2 diabetes mellitus.</p> <p>Methods</p> <p>A cross-sectional analysis of the 2007 SHIELD US survey ascertained self-reported health intentions and behaviors for regular exercise, diet, and weight management among Non-Hispanic Caucasian (n = 2526), Non-Hispanic African-American (n = 706), and Hispanic (n = 179) respondents with type 2 diabetes.</p> <p>Results</p> <p>A similar proportion of respondents from each race-gender group (43%-56%) reported receiving healthcare advice to increase their exercise (P = 0.32). Significantly more minorities reported an intention to follow the exercise recommendation compared with Non-Hispanic Caucasians (P = 0.03). More Non-Hispanic African-American (29%) and Hispanic (27%) men reported exercising regularly compared with other race-gender groups (P = 0.02). Significantly more Non-Hispanic Caucasian women (74%) and Hispanic women (79%) reported trying to lose weight compared with other groups (P < 0.0001).</p> <p>Conclusions</p> <p>Differences in health intentions and healthy behaviors were noted across race-gender groups. More Non-Hispanic African-American men reported an intention to follow advice on exercising and self-report of exercising regularly was also higher compared with other race-gender groups. More Hispanic men reported high physical activity levels than other groups. Despite an increased willingness to follow healthcare recommendations for diet, >50% of respondents were obese among all race-gender groups.</p

MicroRNAs in Renal Cell Carcinoma: Diagnostic Implications of Serum miR-1233 Levels

BACKGROUND: MicroRNA expression is altered in cancer cells, and microRNAs could serve as diagnostic/prognostic biomarker for cancer patients. Our study was designed to analyze circulating serum microRNAs in patients with renal cell carcinoma (RCC). METHODOLOGY/PRINCIPAL FINDINGS: We first explored microrna expression profiles in tissue and serum using taqman low density arrays in each six malignant and benign samples: Although 109 microRNAs were circulating at higher levels in cancer patients' serum, we identified only 36 microRNAs with up-regulation in RCC tissue and serum of RCC patients. Seven candidate microRNAs were selected for verification based on the finding of up-regulation in serum and tissue of RCC patients: miR-7-1*, miR-93, miR-106b*, miR-210, miR-320b, miR-1233 and miR-1290 levels in serum of healthy controls (n = 30) and RCC (n = 33) patients were determined using quantitative real-time PCR (TaqMan MicroRNA Assays). miR-1233 was increased in RCC patients, and thus validated in a multicentre cohort of 84 RCC patients and 93 healthy controls using quantitative real-time PCR (sensitivity 77.4%, specificity 37.6%, AUC 0.588). We also studied 13 samples of patients with angiomyolipoma or oncocytoma, whose serum miR-1233 levels were similar to RCC patients. Circulating microRNAs were not correlated with clinical-pathological parameters. CONCLUSIONS/SIGNIFICANCE: MicroRNA levels are distinctly increased in cancer patients, although only a small subset of circulating microRNAs has a tumor-specific origin. We identify circulating miR-1233 as a potential biomarker for RCC patients. Larger-scaled studies are warranted to fully explore the role of circulating microRNAs in RCC

Serum MicroRNAs as Biomarkers for Hepatocellular Carcinoma in Chinese Patients with Chronic Hepatitis B Virus Infection

BACKGROUND: MicroRNAs (miRNAs) have been shown to anticipate great cancer diagnostic potential. Recently, circulating miRNAs have been reported as promising biomarkers for various pathologic conditions. The objective of this study was to investigate the potential of serum miRNAs as novel biomarkers for hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS: This study was divided into four phases: (I) Ten candidate serum miRNAs were detected by using real-time RT-PCR, corresponding 10 HCC patients with chronic hepatitis B virus (HBV) infection and 10 age- and sex-matched healthy subjects. (II) Marker validation by real-time RT-PCR on HBV patients with (n = 48) or without HCC (n = 48), and healthy subjects (n = 24). (III) Marker detection by real-time RT-PCR in sera from another 14 HCC patients before and 1 month after surgical resection. (IV) We examined the correlation between the expressions of candidate serum miRNAs with clinical parameters of HCC patients. Although miR-222, miR-223 or miR-21 were significantly up- or down-regulated between HCC patients and healthy controls, no significant difference was observed in the levels of these miRNAs between HBV patients without and with HCC. MiR-122 in serum was significantly higher in HCC patients than healthy controls (p<0.001). More importantly, it was found that the levels of miR-122 were significantly reduced in the post-operative serum samples when compared to the pre-operative samples. Although serum miR-122 was also elevated in HBV patients with HCC comparing with those without HCC, the difference was at the border line (p = 0.043). CONCLUSIONS/SIGNIFICANCE: Our results suggest that serum miR-122 might serve as a novel and potential noninvasive biomarker for detection of HCC in healthy subjects, moreover, it might serve as a novel biomarker for liver injury but not specifically for detection of HCC in chronic HBV infection patients