Adult Primary Immune Deficiency: What Are We Missing?

BackgroundMore than 200 primary immune deficiencies have been described. In adults, their identification can be difficult. The lack of timely referrals, diagnostic facilities, and available expertise often delay appropriate treatment. Because an increasing number of adults are now diagnosed with immune deficiencies, there is a need to better understand the immune deficits in this age group. The study objective was to analyze the diagnostic spectrum of adults with primary immune deficiency and to determine the presumptive diagnostic accuracy of the referring physicians.MethodsWe conducted a retrospective chart review over a 10-year period of all individuals referred to a dedicated center for adults with primary immune deficiency. Suspected cases were confirmed using standard clinical criteria and state of the art immune assays.ResultsOf the 381 individuals studied, 244 were diagnosed as immune deficient. Of these, 210 had primary immune deficiency classified as novel, defined, and undefined. Forty-three patients had a prior diagnosis and were referred for follow-up care, and 201 patients were newly diagnosed. Most patients had common variable immune deficiency. Despite an apparent high index of suspicion in initiating the referrals, only one third of these patients had a prior quantitative assessment of serum immunoglobulins.ConclusionsIn this first known analysis of a large cohort of adults with suspected immune deficiency using established diagnostic criteria, we confirmed the diagnosis in two thirds of all patients. Our findings highlight the wide spectrum of primary immune deficiency states seen in adult medical practices and the need for increased awareness of their existence.     

Effect of orthodontic forces on cytokine and receptor levels in gingival crevicular fluid: a systematic review

This systematic review aimed to generate evidence on role of potent markers of inflammation [cytokines, chemokines, their associated receptors and antagonists] following the application of orthodontic forces. Subsequent to registration with PROSPERO, literature search followed a predetermined search strategy to key databases along with hand search (HS). Seventy-seven articles from PubMed (P), 637 from Scopus (S), 51 from Embase (E), and 3 from hand search (HS) were identified. A total of 39 articles were shortlisted that met strict inclusion and exclusion criteria and quality assessment. Each study was evaluated for participant characteristics, study design, oral hygiene regimen, and gingival crevicular fluid (GCF) handling. Among these studies, biomarkers in the order of frequency were interleukin (IL)-1β (N = 21), tumor necrosis factor (TNF)-α (N = 10), IL-8,IL-6(N=8), receptor activator of nuclear factor kappa-B ligand (RANKL) (N = 7), monocyte chemoattractant protein (MCP)-1 (N = 3), IL-2 (N=4), IL-4, IL-10, RANTES (N = 2), IL-1, IL-5, IL-1α, IP-10, osteopontin (OPN) (N = 1) and receptors and their antagonists in the order of osteoprotegerin (OPG) (N = 8), IL-1RA (N = 5), and RANK (N = 1). Results revealed an immediate release of inflammatory bone-resorptive mediators, IL-1β and TNF-α, where IL-1β increased as early as 1 min to 1 h reaching peak at 24 h while TNF-α increased at 1 h or 1 day. This was accompanied by a fall in bone-protective mediator (OPG) levels at 1 h and 24 h after orthodontic force application. Continuous forces were accompanied by a decrease in mediator levels after attaining peak levels (most commonly at 24 h) while repeated activations in interrupted force upregulated their secretion. Significant correlations of IL-1β levels with pain intensity, rate of orthodontic tooth movement (OTM) and of activity index (AI) (IL-1β/IL-1RA) with velocity of tooth movement and growth status of individuals have also been deduced. A greater AI and RANKL/OPG ratio was seen in juveniles as compared to adults or non-growers that were associated with faster rate of OTM in juveniles. None of the studies addressed the effect of estrous cycle in female subjects. Lack of homogeneity in several parameters calls for a better controlled research on the biology of OTM.

Electronic supplementary material

The online version of this article (doi:10.1186/s40510-014-0065-6) contains supplementary material, which is available to authorized users.     

Prevalence of opportunistic infections in AIDS patients in Mangalore, Karnataka

A study was conducted to determine the prevalence of opportunistic infections in HIV-seropositive patients at Kasturba Medical College Hospital, Mangalore. Three hundred and seven HIV-positive patients were screened for various opportunistic pathogens. Tuberculosis was the most common infection followed by candidiasis, cryptosporidiosis and cryptococcal meningitis.     

Altered antioxidant status and lipid peroxidation in Indian patients with urothelial bladder carcinoma

ObjectivesUrothelial carcinoma of bladder is the second most common urological malignancy after prostate cancer. Recently, there has been increased interest in research of the role of free radicals and antioxidant materials in the prevention, treatment, and alleviation of therapy-related side effects of cancer. In the present study, we aimed to assess the alterations in the levels of antioxidant vitamins, activities of defense enzymes, circulating lipid peroxide, and total antioxidant activity (AOA) in patients with urothelial carcinoma of bladder and correlate these changes with the grade and severity of the disease.Materials and methodsThe study cohort consisted of 90 subjects; 50 patients with bladder UC (25, low grade; 10, high grade; 15, muscle invasive) and 40 healthy controls. Vitamins C and E, malondialdehyde (MDA), and AOA were estimated using standard protocols. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) were assayed using commercially available kits.ResultsThe serum levels of vitamins C and E, whole blood levels of SOD and GPx, and serum AOA was significantly lower (P < 0.001) while serum MDA levels were significantly higher (P < 0.001) in patients than in controls, indicating presence of oxidative stress in bladder UC patients. The levels of all the biochemical parameters were correlated with the grade and severity of the disease. There were significant differences between the patients with low grade tumors and muscle invasive tumors for all parameters (P < 0.001); except AOA (P < 0.279).ConclusionsThe observed redox imbalance in UC of bladder in correlation with the grade and stage, as a consequence of decreased levels of antioxidant vitamins, enzymes, and AOA, along with increased MDA levels in circulation, may be important factors in tumor development and growth. Our results suggest that with advancing stage of bladder UC, the levels of oxidative stress increase, while levels of antioxidant molecules decrease. These findings suggest possible use of antioxidant supplementation as prophylactic agents for prevention and treatment of bladder cancer.     

Rapid point-of-care HIV testing in pregnant women: a systematic review and meta-analysis

Rapid, point-of-care human immunodeficiency virus (HIV) testing has the potential to enhance strategies to prevent mother-to-child transmission (MTCT) of HIV infection. Rapid tests need minimal laboratory infrastructure and can be performed by health workers with minimal training. In our systematic review and meta-analysis, we aimed to summarize the overall diagnostic accuracy of rapid HIV tests in pregnancy, and outcomes such as acceptability, patient preference, feasibility and impact of rapid testing. We searched four major databases, identified and screened 1377 citations, and included 17 studies that met our eligibility criteria. Analyses of these studies suggested that the overall sensitivity and specificity of blood-based rapid tests was high compared with oral rapid tests. A two-step testing strategy, particularly parallel testing, was found to be superior to single-test strategy in labour and delivery settings. Acceptability of rapid tests and patient preference was variable across studies. Overall, rapid HIV testing was highly accurate compared with conventional tests and offer a clear advantage of enabling the implementation of timely interventions to reduce MTCT of HIV. To improve diagnostic accuracy and to reduce false-positive results, it may be necessary to use two rapid tests during labour and delivery.     

A systematic review of relative risks for the relationship between chronic alcohol use and the occurrence of disease

Alcohol use is causally linked to the development of and mortality from numerous diseases. The aim of this study is to provide an update to a previous systematic review of meta-analyses that quantify the sex-specific dose–response risk relationships between chronic alcohol use and disease occurrence and/or mortality. An updated systematic search of multiple databases was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria to identify meta-analyses published from January 1, 2017, to March 8, 2021, which quantified the risk relationships between chronic alcohol use and the risk of disease occurrence and/or mortality. This systematic review was not preregistered. The comparator was people who have never consumed at least one standard drink of alcohol. Measurements included relative risks, odds ratios, and hazard ratios of disease occurrence and/or mortality based on long-term alcohol intake measured in grams per day. The systematic search yielded 5953 articles, of which 14 were included in the narrative review. All diseases showed an increased risk of occurrence as alcohol use increased. At all doses examined, alcohol had a significant detrimental effect on tuberculosis, lower respiratory infections, oral cavity and pharyngeal cancers, esophageal cancer, colorectal cancer, liver cancer, laryngeal cancer, epilepsy, hypertension, liver cirrhosis, and pancreatitis (among men). For ischemic heart disease, ischemic stroke, and intracerebral hemorrhage, protective effects from low-dose chronic alcohol use among both men and women were observed. Low-dose alcohol consumption also had a protective effect for diabetes mellitus and pancreatitis among women (approximately to 50 g/day and 30 g/day, respectively). Alcohol use increases the risk of numerous infectious and noncommunicable diseases in a dose–response manner. Higher levels of alcohol use have a clear detrimental impact on health; however, at lower levels of use, alcohol can have both disease-specific protective and detrimental effects.