Hispanic ethnicity and survival in pediatric acute lymphocytic leukemia (all) patients in Florida

Introduction: Pediatric cancer mortality rates have drastically declined according to analyzed population-based surveillance data; however, incidences of most childhood cancers continue to rise. Recent studies have indicated an association between ethnicity/race and cancer survival. Florida's ethnically/racially diverse population and surging pediatric cancer incidence characterize the state as an ideal setting to study the association between ethnicity/race and pediatric cancer survival. Objective: To determine whether or not an association exists between Hispanic ethnicity and cancer survival in a Floridian population of pediatric patients with Acute Lymphocytic Leukemia (ALL). Methods: We will use data from participants 18 years or younger of Florida Cancer Data System (FCDS). Cox-proportional hazard regression was used to assess independent association between Hispanic ethnicity and time to death (time interval from diagnose of ALL to the last patient contact, as recorded in the database). Survival status (death or alive) was assessed at the date of last contact. Those who are alive at last contact were then censored. Results: In the unadjusted model, ethnicity was not associated with risk of death (HR= 0.87, 95% CI=0.73 - 1.04). After adjustment for sex, race, age at diagnosis, insurance status, geographic area, and immunophenotype) the results showed again no association between Hispanic ethnicity and survival (HR = 1.19, 95% CI=0.82 - 1.72). Conclusions: We found no evidence for differences in survival based on ethnic status. Potential difference in racial-survival disparities in pediatric ALL within various geographic regions might depend on Hispanic ancestries or cancer type. Further research on the topic is still deemed necessary as to clarify the nature of the association between ethnicity and cancer survival

The seasonality of tuberculosis, sunlight, vitamin D, and household crowding.

BACKGROUND: Unlike other respiratory infections, tuberculosis diagnoses increase in summer. We performed an ecological analysis of this paradoxical seasonality in a Peruvian shantytown over 4 years. METHODS: Tuberculosis symptom-onset and diagnosis dates were recorded for 852 patients. Their tuberculosis-exposed cohabitants were tested for tuberculosis infection with the tuberculin skin test (n = 1389) and QuantiFERON assay (n = 576) and vitamin D concentrations (n = 195) quantified from randomly selected cohabitants. Crowding was calculated for all tuberculosis-affected households and daily sunlight records obtained. RESULTS: Fifty-seven percent of vitamin D measurements revealed deficiency (<50 nmol/L). Risk of deficiency was increased 2.0-fold by female sex (P < .001) and 1.4-fold by winter (P < .05). During the weeks following peak crowding and trough sunlight, there was a midwinter peak in vitamin D deficiency (P < .02). Peak vitamin D deficiency was followed 6 weeks later by a late-winter peak in tuberculin skin test positivity and 12 weeks after that by an early-summer peak in QuantiFERON positivity (both P < .04). Twelve weeks after peak QuantiFERON positivity, there was a midsummer peak in tuberculosis symptom onset (P < .05) followed after 3 weeks by a late-summer peak in tuberculosis diagnoses (P < .001). CONCLUSIONS: The intervals from midwinter peak crowding and trough sunlight to sequential peaks in vitamin D deficiency, tuberculosis infection, symptom onset, and diagnosis may explain the enigmatic late-summer peak in tuberculosis

Non-Celiac Gluten Sensitivity: The New Frontier of Gluten Related Disorders

Non Celiac Gluten sensitivity (NCGS) was originally described in the 1980s and recently a “re-discovered” disorder characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected with either celiac disease (CD) or wheat allergy (WA). Although NCGS frequency is still unclear, epidemiological data have been generated that can help establishing the magnitude of the problem. Clinical studies further defined the identity of NCGS and its implications in human disease. An overlap between the irritable bowel syndrome (IBS) and NCGS has been detected, requiring even more stringent diagnostic criteria. Several studies suggested a relationship between NCGS and neuropsychiatric disorders, particularly autism and schizophrenia. The first case reports of NCGS in children have been described. Lack of biomarkers is still a major limitation of clinical studies, making it difficult to differentiate NCGS from other gluten related disorders. Recent studies raised the possibility that, beside gluten, wheat amylase-trypsin inhibitors and low-fermentable, poorly-absorbed, short-chain carbohydrates can contribute to symptoms (at least those related to IBS) experienced by NCGS patients. In this paper we report the major advances and current trends on NCG

Wheat amylase/trypsin inhibitors (ATIs): occurrence, function and health aspects

Amylase/trypsin inhibitors (ATIs) are widely consumed in cereal-based foods and have been implicated in adverse reactions to wheat exposure, such as respiratory and food allergy, and intestinal responses associated with coeliac disease and non-coeliac wheat sensitivity. ATIs occur in multiple isoforms which differ in the amounts present in different types of wheat (including ancient and modern ones). Measuring ATIs and their isoforms is an analytical challenge as is their isolation for use in studies addressing their potential effects on the human body. ATI isoforms differ in their spectrum of bioactive effects in the human gastrointestinal (GI), which may include enzyme inhibition, inflammation and immune responses and of which much is not known. Similarly, although modifications during food processing (exposure to heat, moisture, salt, acid, fermentation) may affect their structure and activity as shown in vitro, it is important to relate these changes to effects that may present in the GI tract. Finally, much of our knowledge of their potential biological effects is based on studies in vitro and in animal models. Validation by human studies using processed foods as commonly consumed is warranted. We conclude that more detailed understanding of these factors may allow the effects of ATIs on human health to be better understood and when possible, to be ameliorated, for example by innovative food processing. We therefore review in short our current knowledge of these proteins, focusing on features which relate to their biological activity and identifying gaps in our knowledge and research priorities

Endomicroscopic and transcriptomic analysis of impaired barrier function and malabsorption in environmental enteropathy

Introduction: Environmental enteropathy (EE) is associated with growth failure, micronutrient malabsorption and impaired responses to oral vaccines. We set out to define cellular mechanisms of impaired barrier function in EE and explore protective mechanisms. Methods: We studied 49 adults with environmental enteropathy in Lusaka, Zambia using confocal laser endomicroscopy (CLE); histology, immunohistochemistry and mRNA sequencing of small intestinal biopsies; and correlated these with plasma lipopolysaccharide (LPS) and a zinc uptake test. Results: CLE images (median 134 for each study) showed virtually ubiquitous small intestinal damage. Epithelial defects, imaged by histology and claudin 4 immunostaining, were predominantly seen at the tips of villi and corresponded with leakage imaged in vivo by CLE. In multivariate analysis, circulating log-transformed LPS was correlated with cell shedding events (β = 0.83; P = 0.035) and with serum glucagon-like peptide-2 (β = -0.13; P = 0.007). Zinc uptake from a test dose of 25mg was attenuated in 30/47 (64%) individuals and in multivariate analysis was reduced by HIV, but positively correlated with GLP-2 (β = 2.72; P = 0.03). There was a U-shaped relationship between circulating LPS and villus surface area. Transcriptomic analysis identified 23 differentially expressed genes in severe enteropathy, including protective peptides and proteins. Conclusions: Confocal endomicroscopy, claudin 4 immunostaining and histology identify epithelial defects which are probably sites of bacterial translocation, in the presence of which increased epithelial surface area increases the burden of translocation. GLP 2 and other protective peptides may play an important role in mucosal protection in EE

Rapid drug susceptibility testing and treatment outcomes for multidrug-resistant tuberculosis in Peru.

SETTING: The detection of multidrug-resistant tuberculosis (MDR-TB) using rapid drug susceptibility testing (DST) has increased steadily in recent years in Peru, from 9216 tests in 2010 to 27 021 tests in 2015. Research examining the impact of rapid DST on treatment outcomes is required. OBJECTIVE: To evaluate the association between rapid DST use (nitrate reductase assay, microscopic observation drug susceptibility assay [MODS] and GenoType® MTBDRplus) and treatment outcomes and mortality in MDR-TB patients in Peru. DESIGN: Retrospective cohort study of patients diagnosed with pulmonary MDR-TB between 2010 and 2013 (with treatment outcomes up to December 2015) using the electronic registry of the Peruvian National TB Programme. RESULTS: A total of 2671 MDR-TB patients were included; the median age was 27 years, 2.8% were co-infected with the human immunodeficiency virus. Use of rapid DST was associated with a 40% increase in the adjusted odds of treatment success (aOR 1.40, 95%CI 1.19-1.64) and a 54% reduction in mortality (aOR 0.46, 95%CI 0.33-0.64). Higher treatment success rates were driven by MODS and GenoType® MTBDRplus testing (aORs for unsuccessful outcomes respectively 0.68 and 0.66). CONCLUSION: The use of rapid DST (MODS and MTBDRplus) to diagnose MDR-TB was associated with a reduction in the odds of death and a substantial increase in the odds of treatment success

Repeated Mechanical Endovascular Thrombectomy for Recurrent Large Vessel Occlusion: A Multicenter Experience

BACKGROUND AND PURPOSE: Mechanical thrombectomy (MT) is now the standard of care for large vessel occlusion (LVO) stroke. However, little is known about the frequency and outcomes of repeat MT (rMT) for patients with recurrent LVO. METHODS: This is a retrospective multicenter cohort of patients who underwent rMT at 6 tertiary institutions in the United States between March 2016 and March 2020. Procedural, imaging, and outcome data were evaluated. Outcome at discharge was evaluated using the modified Rankin Scale. RESULTS: Of 3059 patients treated with MT during the study period, 56 (1.8%) underwent at least 1 rMT. Fifty-four (96%) patients were analyzed; median age was 64 years. The median time interval between index MT and rMT was 2 days; 35 of 54 patients (65%) experienced recurrent LVO during the index hospitalization. The mechanism of stroke was cardioembolism in 30 patients (56%), intracranial atherosclerosis in 4 patients (7%), extracranial atherosclerosis in 2 patients (4%), and other causes in 18 patients (33%). A final TICI recanalization score of 2b or 3 was achieved in all 54 patients during index MT (100%) and in 51 of 54 patients (94%) during rMT. Thirty-two of 54 patients (59%) experienced recurrent LVO of a previously treated artery, mostly the pretreated left MCA (23 patients, 73%). Fifty of the 54 patients (93%) had a documented discharge modified Rankin Scale after rMT: 15 (30%) had minimal or no disability (modified Rankin Scale score ≤2), 25 (50%) had moderate to severe disability (modified Rankin Scale score 3-5), and 10 (20%) died. CONCLUSIONS: Almost 2% of patients treated with MT experience recurrent LVO, usually of a previously treated artery during the same hospitalization. Repeat MT seems to be safe and effective for attaining vessel recanalization, and good outcome can be expected in 30% of patients