Summary Tuberculosis (TB), caused by Mycobacterium tuberculosis (M.tb) and a few related mycobacteria, is a devastating disease, killing more than a million individuals per year worldwide. However, its pathogenesis remains largely elusive, as only a small proportion of infected individuals develop clinical disease either during primary infection or during reactivation from latency or secondary infection. Subacute, hematogenous, and extrapulmonary disease tends to be more frequent in infants, children, and teenagers than in adults. Life-threatening primary TB of childhood can result from known acquired or inherited immunodeficiencies, although the vast majority of cases remain unexplained. We review here the conditions conferring a predisposition to childhood clinical diseases caused by mycobacteria, including not only M.tb but also weakly virulent mycobacteria, such as BCG vaccines and environmental mycobacteria. Infections with weakly virulent mycobacteria are much rarer than TB, but the inherited and acquired immunodeficiencies underlying these infections are much better known. Their study has also provided genetic and immunological insights into childhood TB, as illustrated by the discovery of single-gene inborn errors of IFN-γ immunity underlying severe cases of TB. Novel findings are expected from ongoing and future human genetic studies of childhood TB in countries that combine a high proportion of consanguineous marriages, a high incidence of TB, and an excellent clinical care, such as Iran, Morocco, and Turkey.
Inflammatory cells, particularly neutrophil granulocytes, have been implicated in the pathogenesis of the adult respiratory distress syndrome (ARDS). In this study, we investigated whether a relationship exists between neutrophil elastase in the plasma of multiple-trauma patients on initial hospital presentation and the subsequent development of lung injury and ARDS. Sixty-one multiple-trauma patients were enrolled prospectively. Neutrophil elastase was measured by a specific radioimmunoassay, and analysis was performed by nonparametric statistical methods. A highly significantly elevated plasma elastase level was found in patients who progressed to ARDS (median 217 ng/ml, range 127 to 480) (n = 8) compared with those who did not (median 117 ng/ml, range 21.4 to 685) (n = 53) (p = 0.009). Significant correlation was found between initial elastase values and subsequent requirement for mechanical ventilation (p = 0.01), lowest arterial oxygen saturation/oxygen supplementation recorded (p = 0.003), and organ failure score (p = 0.006). This study shows that within minutes of the initiating trauma event, there is evidence of enhanced neutrophil degranulation as manifested by elevated levels of immunoreactive neutrophil elastase in the peripheral blood. The level of this enzyme correlates with the degree of subsequent lung injury and ARDS. These findings reinforce the importance of neutrophils and their secretory products in early ARDS disease pathogenesis.
Background/AimsLong COVID is characterised by a range of potentially debilitating symptoms which develop in at least 10% of people who have recovered from acute SARS-CoV-2 infection. This study has quantified corneal sub-basal nerve plexus morphology and dendritic cell (DC) density in patients with and without long COVID.MethodsForty subjects who had recovered from COVID-19 and 30 control participants were included in this cross-sectional comparative study undertaken at a university hospital. All patients underwent assessment with the National Institute for Health and Care Excellence (NICE) long COVID, Douleur Neuropathique 4 (DN4) and Fibromyalgia questionnaires, and corneal confocal microscopy (CCM) to quantify corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD), corneal nerve fibre length (CNFL), and total, mature and immature DC density.ResultsThe mean time after the diagnosis of COVID-19 was 3.7±1.5 months. Patients with neurological symptoms 4 weeks after acute COVID-19 had a lower CNFD (p=0.032), CNBD (p=0.020), and CNFL (p=0.012), and increased DC density (p=0.046) compared with controls, while patients without neurological symptoms had comparable corneal nerve parameters, but increased DC density (p=0.003). There were significant correlations between the total score on the NICE long COVID questionnaire at 4 and 12 weeks with CNFD (ρ=−0.436; p=0.005, ρ=−0.387; p=0.038, respectively) and CNFL (ρ=−0.404; p=0.010, ρ=−0.412; p=0.026, respectively).ConclusionCorneal confocal microscopy identifies corneal small nerve fibre loss and increased DCs in patients with long COVID, especially those with neurological symptoms. CCM could be used to objectively identify patients with long COVID.
Leptin levels and lipid profile of overweight subjects with and without OSAS were not different, and our results suggest that OSAS-related parameters and CPAP treatment do not play a significant role in the serum leptin levels.
Objective To investigate the effects of pulmonary rehabilitation (PR) and combined nutritional support therapy on quality of life (QoL) and functional status in patients with chronic obstructive pulmonary disease (COPD). Methods This pre-and post-intervention prospective exploratory study involved 64 patients with stable stage three to four COPD. Oral nutritional support and personalized diet were combined with an intense and comprehensive PR program. Baseline and 8-week follow-up scores were compared for the 6-minute walk test (6MWT), incremental shuttle walking test (ISWT), St. George’s Respiratory Questionnaire (SGRQ), pulmonary function tests (PFT), PImax-PEmax, arterial blood gas (ABG), respiratory rate (RR), handgrip strength, Borg and modified Medical Research Council dyspnoea scale scores and fat-free mass index. Results Significant improvements were found in functional status (6MWT: 86.72 m, ISWT: 76.24 m), QoL (SGRQ total: 13.86), PFT, ABG, RR, dyspnoea, upper extremity muscle strength and hand-body composition. Conclusion Nutritional support with comprehensive and intensive PR can significantly improve physical performance, QoL, dyspnoea and body composition in COPD. The improvement in QoL was greater than that reported in previous studies. Because two modalities were combined in this study, future randomized controlled studies are needed to confirm the extent and contribution of these modalities to the outcomes.
Background/aim: We aimed to evaluate the prevalence of sarcopenia and associated outcomes in patients with chronic obstructive pulmonary disease (COPD). Materials and methods: This cross-sectional study was performed on 219 patients aged 50 years and over who were diagnosed with chronic obstructive pulmonary disease (COPD) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. The study included 196 (89.5%) male and 23 (10.5%) female patients. The mean age of the patients was 66.9 ± 10.1 years. To diagnose sarcopenia, muscle function was determined by a gait speed test. Muscle strength was assessed with a hand dynamometer and muscle mass was measured with a bioelectrical impedance analysis device. Pulmonary function tests and six-min walking tests were also performed. The modified Medical Research Council (mMRC) dyspnoea scale was used to evaluate all the participants. Our sample consisted of sarcopenic patients at different stages (17 presarcopenic patients (7.8%), 32 patients with sarcopenia (14.6%), 65 patients with severe sarcopenia (29.7%), and 105 nonsarcopenic patients (47.9%). Results: Sarcopenia was significantly associated with age, BODE (body mass index (BMI), airflow obstruction, dyspnoea, and exercise capacity) index, GOLD spirometric classification, mMRC dyspnoea scale score, BMI, and educational status. Sarcopenia in COPD patients was firmly related to the severity of the disease and its prognosis. The prevalence of sarcopenia increased in severe and very severe COPD cases. The dyspnoea score was higher, and exercise capacities were lower in sarcopenic patients. Conclusions: Sarcopenia in COPD patients was closely related to the severity of COPD and a negative prognosis. The frequency of sarcopenia increased in severe and very severe COPD cases. Dyspnoea scores were higher and exercise capacities were lower in patients with sarcopenia. In patients with COPD, a diagnosis of sarcopenia should be considered, and preventive measures should be taken before irreversible changes develop.
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