Effects of chronic iodine excess in a cohort of long-term American workers in West Africa

A cross-sectional survey of 102 Peace Corps volunteers in Niger, West Africa, in 1998 had previously demonstrated a high rate of thyroid dysfunction and goiter attributable to excess iodine from their water filters. The Peace Corps volunteers were followed-up a mean of 30 wk after they ceased using iodine-based water filtration systems. Goiter was present in 44% of subjects during excess iodine ingestion and in 30% after removal of excess iodine. Mean serum iodine decreased from 293 micro g/liter during excess iodine ingestion to 84 micro g/liter after cessation of excess iodine. Mean total serum T(4) values increased from 100.4 to 113.3 nmol/liter (7.8 to 8.8 micro g/dl). Mean serum free T(4) increased from 32.2 to 34.7 pmol/liter (2.5 to 2.7 ng/dl). Mean serum TSH decreased from 4.9 to 1.8 mU/liter. Mean serum thyroid peroxidase antibody levels decreased from 33,000 to 22,000 IU/liter (33 to 22 IU/ml). We found that during prolonged excess iodine exposure there were marked increases in serum total iodine concentrations, and the prevalence of goiter, elevated serum TSH values, and elevated serum thyroid peroxidase antibody values increased. The prevalence of all abnormalities decreased after removal of excess iodine from the drinking water system.     

Flow cytometric analysis of intestinal intraepithelial lymphocytes in the diagnosis of refractory celiac sprue

The etiology of refractory celiac sprue (RCS) is unclear. In a high proportion of cases, the clonal nature of intestinal intraepithelial lymphocytes (IEL) can be demonstrated and a pathogenetic implication of intestinal IEL has been postulated. The prognosis of this subgroup of RCS is poor, with a high risk to develop an overt lymphoma and uncontrolled malabsorption despite steroid/immunosuppressive therapy. Cases with a relatively indolent clinical course, however, exist and their early diagnosis may be difficult. To gain insight into the pathogenic implication of intestinal IEL in refractory celiac sprue, we have performed an extensive phenotypic and functional characterization of clonal intestinal IEL in a patient with an indolent form of refractory celiac sprue, using multiparametric flow cytometry. The abnormal lymphocyte infiltrate lacked surface membrane expression of CD3/T-cell receptor (TCR) complexes (TCR(-), CD4(-), CD8(-), sCD3(-)), but contained intracellular CD3(epsilon) (CyCD3(+)) and surface CD103(+) and CD7(+). In particular, these cells showed a unique spontaneous ex-vivo cytokine secretion profile with an increased percentage of CD3(-) IEL containing TNF-alpha and IL-10, in the absence of IL-2, IL-4 and IFN-gamma. Altogether our results suggest that flow cytometry immunophenotyping of intestinal IEL, in cases suspected of celiac disease and their complicated forms, could be of great help in the correct diagnosis of RCS and the understanding of the immunopathogenic mechanisms of the disease and their clinical and/or therapeutical implications.     

International Impact of COVID-19 on the Diagnosis of Heart Disease

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has adversely affected diagnosis and treatment of noncommunicable diseases. Its effects on delivery of diagnostic care for cardiovascular disease, which remains the leading cause of death worldwide, have not been quantified.ObjectivesThe study sought to assess COVID-19’s impact on global cardiovascular diagnostic procedural volumes and safety practices.MethodsThe International Atomic Energy Agency conducted a worldwide survey assessing alterations in cardiovascular procedure volumes and safety practices resulting from COVID-19. Noninvasive and invasive cardiac testing volumes were obtained from participating sites for March and April 2020 and compared with those from March 2019. Availability of personal protective equipment and pandemic-related testing practice changes were ascertained.ResultsSurveys were submitted from 909 inpatient and outpatient centers performing cardiac diagnostic procedures, in 108 countries. Procedure volumes decreased 42% from March 2019 to March 2020, and 64% from March 2019 to April 2020. Transthoracic echocardiography decreased by 59%, transesophageal echocardiography 76%, and stress tests 78%, which varied between stress modalities. Coronary angiography (invasive or computed tomography) decreased 55% (p < 0.001 for each procedure). In multivariable regression, significantly greater reduction in procedures occurred for centers in countries with lower gross domestic product. Location in a low-income and lower–middle-income country was associated with an additional 22% reduction in cardiac procedures and less availability of personal protective equipment and telehealth.ConclusionsCOVID-19 was associated with a significant and abrupt reduction in cardiovascular diagnostic testing across the globe, especially affecting the world’s economically challenged. Further study of cardiovascular outcomes and COVID-19–related changes in care delivery is warranted.     

Use of autologous interposition vein graft in management of lymphedema: preliminary experimental and clinical observations

We report preliminary experimental studies in rats and rabbits together with clinical observations in 39 patients with chronic lymphedema undergoing interposition autologous lymphatic-venous-lymphatic (LVL) anastomoses. This microsurgical operative technique is an alternative to other lymphatic shunting methods particularly where venous disease coexists in the same limb and where direct lymphatic-venous bypass is accordingly inappropriate. Preoperative diagnostic evaluation including lymphatic and venous isotopic scintigraphy, Doppler venous flow metrics and pressure manometry play an essential role in delineating the status of both the lymphatic and venous systems and in determining which microsurgical procedure, if any, is indicated. Our microsurgical method consists of inserting suitably large and lengthy autologous venous grafts between lymphatic collectors above and below the site of blockage to lymph flow. The data demonstrate the feasibility of the LVL technique experimentally and in 39 patients with obstructive lymphedema (either arm or leg). Using LVL shunt, improvement was seen in both limb function and edema, and in some, edema regression was permanent for as long as 5 years.     

Echocardiographic assessment of left ventricular midwall mechanics in spontaneously hypertensive rats.

AIMS: The present study was attempted to determine whether LV midwall mechanics yielded different conclusions about LV systolic function than the assessment of endocardial LV mechanics by echocardiography in spontaneously hypertensive rats (SHR). METHODS AND RESULTS: Thirty-six (18 Wistar normotensive (W), 18 [SHR]) anesthetized rats were studied with two-dimensional directed M-mode echocardiogram to analyze LV structure (LV diameter, left ventricular wall thickness and LV mass [LVM]) and LV function (endocardial shortening [ES] and midwall shortening [MS]). Measurements were made from three consecutive cardiac cycles on the M-mode tracings. There was no significant difference in LV dimension. LVM was higher in SHR (SHR: 595 +/- 111 mg, W: 413 +/- 83 mg--p < 0.01). ES was higher in SHR (SHR: 64.1 +/- 6%, w: 58.2 +/- 4%--p < 0.01), whereas no significant difference was found in MS (SHR: 24 +/- 4%, W: 27.6 +/- 4%--ns). Twelve of 18 (66%) SHR showed endocardial shortening higher than normally predicted, compared with 3/18 (16%) with observed enhanced MS (p < 0.01). CONCLUSION: These results suggest that the analysis of midwall mechanics by echo allows us to better understand the LV performance in SHR and that the exaggerated endocardial motion could not represent a really supernormal systolic performance.     

An altered composition of the microbiome in microscopic colitis is driven towards the composition in healthy controls by treatment with budesonide

Background and aim: Microscopic colitis (MC) is an inflammatory disease of the bowel, hypothetically induced by an immunologic response to a luminal microbial agent. We aimed to characterize the microbiome composition in MC and subtypes collagenous colitis (CC) and lymphocytic colitis (LC) and to identify a possible microbial effect of treatment.

Method: Stool samples were collected from MC patients prior to treatment, at 8 weeks (during treatment) and at 16 weeks (after treatment), and from healthy controls, not receiving treatment, at matched time-points. Microbiome composition was analyzed by sequencing of the 16S and 18S genes. Differences between patients and controls were analyzed by Shannon’s diversity index (mean, standard deviation (SD)) and principal coordinate analysis (PCoA) complemented with a permanova test of UniFrac distances.

Results: Ten LC patients, 10?CC patients and 10 controls were included. By PCoA, the bacterial composition in MC patients differed from controls at baseline (p?=?.02), but not during and after treatment (p?=?.09 and p?=?.33, respectively). At baseline, bacterial diversity was lower in MC patients compared to controls (2.5, SD: 0.5 vs 3.5, SD: 0.3, p?<?.05). Diversity in MC patients increased during (3.0, SD: 0.6) and after treatment and (2.9, SD: 0.5) compared with baseline (p?<?.01). Eukaryotes were detected in fewer samples from MC patients compared with controls (11/20 (55%) vs. 9/10 (90%), p?=?.06) with no effect of treatment.

Conclusion: Microbiome composition is altered in MC patients. During and after treatment with budesonide the microbiome composition in MC patients was driven towards the composition in healthy controls.     

Isotope Ratio Mass Spectrometry (IRMS) Versus Laser-Assisted Ratio Analyzer (LARA)

This study was carried out to compare the measurements and the diagnostic accuracy of the traditional expensive IRMS and the new economical LARA system using two doses of [¹³C]urea + two different test meals in patients undergoing upper gastrointestinal endoscopy, both before and after anti-Helicobacter treatment. A total of 354 dyspeptic patients underwent endoscopy with gastric biopsies to diagnose H. pylori infection by CLO-test and histology. No patients had taken antibiotics, bismuth, or antisecretory drugs in the 4 weeks before testing. After overnight fasting, breath samples were collected simultaneously in both plastic and glass tubes at baseline and at 30 and 60 min after urea ingestion. In 237 patients 100 mg [¹³C]urea + Ensure and in 117 patients 75 mg [¹³C]urea + citric acid were given. The test was also performed with the two urea dosages and meals in 67 and 64 infected patients, respectively, four weeks after anti-Helicobacter therapy. H. pylori was considered eradicated when both biopsy-based tests were negative. A value >5 was considered positive. Breath samples with insufficient CO₂ levels at both 30 and 60 min were excluded from final analysis (N = 37 in pre- and N = 8 in posttreatment). There was excellent agreement between overall values of the two machines with both [¹³C]urea 100 mg + Ensure and [¹³C]urea 75 mg + citric acid. The 95% CI of the difference against the mean was wider with the former (mean –1.3, +6.3, and –9.4) than with the latter urea dosage and test meal (mean –1.2, +5.2 and –8.1). LARA and IRMS were equally effective (P = NS) in distinguishing infected from uninfected patients before therapy using both doses of [¹³C]urea and test meals (sensitivity ranged from 95% to 99% and specificity from 95% to 97%). This good performance was maintained in the posttreatment phase (sensitivity ranged from 90% to 100% and specificity from 90% to 97%), without any statistical difference among the various combinations (P = NS). The LARA system is a valid alternative to IRMS in the diagnosis of H. pylori infection. Both machines provide highly reliable results after 30 min, so that the 60 min sample can be avoided. The dose of 75 mg + citric acid suffices to ensure an accurate UBT. The test performed with both devices and [¹³C]urea dosages is very effective also for posttherapy evaluation of H. pylori status.     

Lessons Learned about Implementing Research Evidence into Clinical Practice

The mission of the Veterans Health Administration's (VHA) quality enhancement research initiative (QUERI) is to enhance the quality of VHA health care by implementing clinical research findings into routine care. This paper presents lessons that QUERI investigators have learned through their initial attempts to pursue the QUERI mission. The lessons in this paper represent those that were common across multiple QUERI projects and were mutually agreed on as having substantial impact on the success of implementation. While the lessons are consistent with commonly recognized ingredients of successful implementation efforts, the examples highlight the fact that, even with a thorough knowledge of the literature and thoughtful planning, unexpected circumstances arise during implementation efforts that require flexibility and adaptability. The findings stress the importance of utilizing formative evaluation techniques to identify barriers to successful implementation and strategies to address these barriers.