What We Know (and Do not Know) Regarding the Pathogenesis of Pulmonary Thrombosis in COVID-19

The clinical course of coronavirus disease 2019 (COVID-19) is often complicated by the onset of venous thrombosis and thromboembolism (VTE), encompassing also pulmonary thrombosis. Recent statistics attests that the cumulative frequency of VTE can be as high as 30% in COVID-19 hospitalized patients, increasing to nearly 40 to 70% (depending on systematic screening) in those with severe illness, mechanical ventilation, or intensive care unit admission. The risk of venous thrombosis seems mostly limited to the active phase of disease, and is directly associated with some genetic (i.e., inherited prothrombotic predisposition) and demographical factors (male sex, overweight/obesity), disease severity (risk increasing progressively from hospitalization to development of severe illness, being the highest in patients needing mechanical ventilation and/or intensive care), presence and extent of pulmonary disease, coexistence of multiple risk factors (immobilization, mechanical ventilation, co- or superinfections), along with increased values of inflammatory and thrombotic biomarkers. At least three different phenotypes of pulmonary thrombosis may develop in COVID-19 patients, one caused by typical embolization from peripheral venous thrombosis (e.g., deep vein thrombosis), a second type triggered by local inflammation of nearby pulmonary tissue, and a third one mostly attributable to the prothrombotic state consequent to the pronounced systemic inflammatory response (i.e., the so-called cytokine storm) that is frequently observed in COVID-19. Although the pathogenesis of these three conditions has different features, their discrimination is essential for diagnostic and therapeutic purposes. The prognosis of COVID-19 patients who develop pulmonary thrombosis is also considerably worse than those who do not, thus probably needing frequent monitoring and more aggressive therapeutic management.

Upper extremity deep vein thrombosis in COVID-19: Incidence and correlated risk factors in a cohort of non-ICU patients

Background Venous thromboembolism is a frequent complication of COVID-19 infection. Less than 50% of pulmonary embolism (PE) is associated with the evidence of deep venous thrombosis (DVT) of the lower extremities. DVT may also occur in the venous system of the upper limbs especially if provoking conditions are present such as continuous positive airway pressure (CPAP). The aim of this study was to evaluate the incidence of UEDVT in patients affected by moderate-severe COVID-19 infection and to identify potential associated risk factors for its occurrence. Methods We performed a retrospective analysis of all patients affected by moderate-severe COVID-19 infection admitted to our unit. In accordance with the local protocol, all patients had undergone a systematic screening for the diagnosis of UEDVT, by vein compression ultrasonography (CUS). All the patients were receiving pharmacological thromboprophylaxis according to international guidelines recommendations. Univariate and multivariate analyses were used to identify risk factors associated with UEDVT. Results 257 patients were included in the study, 28 patients were affected by UEDVT with an incidence of 10.9% (95% CI, 7.1–14.7). At univariate analysis UEDVT appeared to be significantly associated (p< 0.05) with pneumonia, ARDS, PaO2/FiO2, D-dimer value higher than the age adjusted cut off value and need for CPAP ventilation. Multivariate analysis showed a significant association between UEDVT and the need for CPAP ventilation (OR 5.95; 95% IC 1.33–26.58). Increased mortality was found in patients affected by UEDVT compared to those who were not (OR 3.71; 95% CI, 1.41–9.78). Conclusions UEDVT can occur in COVID-19 patients despite adequate prophylaxis especially in patients undergoing helmet CPAP ventilation. Further studies are needed to identify the correct strategy to prevent DVT in these patients.

Integration of Systematic Screening for Tuberculosis in Outpatient Departments of Urban Primary Health-Care Facilities in Zambia: A Case Study of Kitwe District

Background Tuberculosis (TB) is the leading cause of death from a single infectious agent globally, yet 3 million cases are missed every year. The World Health Organization recommends systematic screening of suspected active TB patients among those visiting the healthcare facilities. While many countries have scaled-up systematic screening of TB, there has been limited assessment of the extent of its integration into the health system. This study sought to explore factors that shaped the integration of systematic screening of TB in outpatient departments of primary healthcare facilities in Kitwe district, Zambia. Methods This was a qualitative case study with health providers including district managers, TB focal point persons and laboratory personnel working in six purposively selected primary healthcare facilities. Data was collected through key informant (n=8) and in-depth (n=15) interviews. Data analysis was conducted using QDA Miner software and guided by Atun’s Integration framework. Results Integration was facilitated by perceptions of the magnitude of the TB burden, alignment of the intervention with national TB aspirations, knowledge of stakeholder interests, power and values, regular performance management and intra-facility collaboration. Constraining factors included external partners’ influence in the TB screening program, unbalanced incentivization mechanisms, donor-driven financing and social determinants of health such as gender and stigma including the COVID-19 pandemic. Conclusion Systematic screening of TB is not well integrated into the primary healthcare facilities to capture all those suspected with active TB that make contact with the health system. Finding the missing TB cases will, therefore, require contextual adaptation of the systematic screening for TB and strengthening the health system.

Pregnancy in Women With Monogenic Diabetes due to Pathogenic Variants of the Glucokinase Gene: Lessons and Challenges

Heterozygous loss-of-function variants of the glucokinase (GCK) gene are responsible for a subtype of maturity-onset diabetes of the young (MODY). GCK-MODY is characterized by a mild hyperglycemia, mainly due to a higher blood glucose threshold for insulin secretion, and an up-regulated glucose counterregulation. GCK-MODY patients are asymptomatic, are not exposed to diabetes long-term complications, and do not require treatment. The diagnosis of GCK-MODY is made on the discovery of hyperglycemia by systematic screening, or by family screening. The situation is peculiar in GCK-MODY women during pregnancy for three reasons: 1. the degree of maternal hyperglycemia is sufficient to induce pregnancy adverse outcomes, as in pregestational or gestational diabetes; 2. the probability that a fetus inherits the maternal mutation is 50% and; 3. fetal insulin secretion is a major stimulus of fetal growth. Consequently, when the fetus has not inherited the maternal mutation, maternal hyperglycemia will trigger increased fetal insulin secretion and growth, with a high risk of macrosomia. By contrast, when the fetus has inherited the maternal mutation, its insulin secretion is set at the same threshold as the mother’s, and no fetal growth excess will occur. Thus, treatment of maternal hyperglycemia is necessary only in the former situation, and will lead to a risk of fetal growth restriction in the latter. It has been recommended that the management of diabetes in GCK-MODY pregnant women should be guided by assessment of fetal growth by serial ultrasounds, and institution of insulin therapy when the abdominal circumference is ≥ 75th percentile, considered as a surrogate for the fetal genotype. This strategy has not been validated in women with in GCK-MODY. Recently, the feasibility of non-invasive fetal genotyping has been demonstrated, that will improve the care of these women. Several challenges persist, including the identification of women with GCK-MODY before or early in pregnancy, and the modalities of insulin therapy. Yet, retrospective observational studies have shown that fetal genotype, not maternal treatment with insulin, is the main determinant of fetal growth and of the risk of macrosomia. Thus, further studies are needed to specify the management of GCK-MODY pregnant women during pregnancy.

How much does TB screening cost? A systematic review of economic evaluations

BACKGROUND: Systematic screening for TB has been recommended as a method to control TB on a global level; however, this involves significant costs that place a burden on the health system.METHODS: We conducted a systematic review of the existing economic literature on systematic screening for TB to summarise costs, cost-effectiveness and affordability, and the key factors that influence costs and cost-effectiveness. Specific populations of interest included the general population, children and close contacts of TB patients.RESULTS: We identified 21 studies that provided both cost and outcome data on TB screening among the populations of interest. All were from low- and middle-income settings. Studies were heterogenous in the intervention, and included costs and reported outcomes. The incremental cost-effectiveness ratio (ICER) estimates ranged from USD281 to USD698 per disability-adjusted life-year (DALY) averted among the general population, USD619/DALY averted among children and USD372–3,718/DALY averted among close contacts.CONCLUSION: Prevalence of TB among targeted high-risk groups was identified across the majority of studies as a driver of cost-effectiveness. The heterogeneity of the included costs and outcomes across the economic literature for systematic screening suggests a need for standardisation of included cost components and key economic evaluation methods to improve comparability and generalisability of results.

ДЕКОМПЕНСОВАНИЙ ВИПАДОК ГІПОТИРЕОЗА З УРАЖЕННЯМ СЕРЦЕВО-СУДИННОЇ СИСТЕМИ

We present a clinical case that demonstrates a lack of compliance in a patient with hypothyroidism, which led to severe complications of the cardiovascular system. The clinical feature of this case is the development of severe complications of hypothyroidism due to the patient’s low adherence to therapy and untimely treatment. The patient had all characteristic signs of severe hypothyroidism with heart and skin lesions (total alopecia, edema, dryness and peeling of the skin). Fully available diagnostic criteria were as follows: critical disorders of thyroid hormone levels in the blood, hyperenzymemia, hypothyroidism, fluid in the pleural cavity, increased heart shadow, fluid in the pericardial cavity, left ventricular dilatation, decreased ejection fraction, arrhythmia. The predominant lesion of the cardiovascular system is characteristic of such cases and prevailed in the clinical presentation of the disease and was the direct reason for seeking medical help. Under the influence of treatment, the patient's sinus rhythm was restored, myocardial contractility improved, there was no fluid in the pericardial cavity and pleural cavity, edema decreased, mental activity and emotional state improved. However, the patient flatly refused further observation and treatment. As a result, hypothyroidism is underdiagnosed. Initiation of treatment in the early stages of the disease and prevention of complications relies on early diagnosis through systematic screening according to the recommendations. Heart disease, associated with hypothyroidism is a condition that can be prevented if it is detected and treated by family doctors in a timely manner in an outpatient setting. Timely detection of the disease and hospitalization will allow avoiding serious complications of hypothyroidism, timely diagnosing this pathology and prescribing adequate therapy according to the stage of the disease.

Performing cardiac surgery during COVID-19 pandemic in Surabaya, Indonesia: A single-center retrospective observational study

Background Healthcare workers are still the front liners in health care services, and have major roles during the COVID-19 pandemic. In a resource-limited country like Indonesia, it is necessary to provide safe screening and management both for patients and healthcare workers to minimize the transmission. We report our experience in the cardiac surgery department on how to provide safe management during the COVID-19 pandemic. Methods A retrospective observational study was performed in a single-tertiary-center cardiac surgery department in Surabaya and included all patients who underwent cardiac surgery during the first year of the COVID-19 pandemic. We also collected the patients from a 1-year period before the pandemic as the comparison data. Analysis of the patient characteristics, operative data, and postoperative outcome, was performed. This study also provides our experience in changes of admission in the cardiac surgery preoperative system that can be utilized for others. Results A total of 179 patients were admitted to and had cardiac surgery. Of these, 3.80% ( n = 7) were COVID-19 confirmed by a real-time polymerase chain reaction. Five patients were delayed to have cardiac surgery with no mortality or morbidity reported in these patients. During the period after changes of admission procedural in cardiac surgery patients, there were no healthcare workers infected by COVID-19 by patient transmission in our center (0%). Conclusion Our study reported a systematic screening and that possible delay in cardiac surgery appears to be feasible and safe, both for patients and for healthcare workers during the COVID-19 pandemic.

A method for campus-wide SARS-CoV-2 surveillance at a large public university

The systematic screening of asymptomatic and pre-symptomatic individuals is a powerful tool for controlling community transmission of infectious disease on college campuses. Faced with a paucity of testing in the beginning of the COVID-19 pandemic, many universities developed molecular diagnostic laboratories focused on SARS-CoV-2 diagnostic testing on campus and in their broader communities. We established the UC Santa Cruz Molecular Diagnostic Lab in early April 2020 and began testing clinical samples just five weeks later. Using a clinically-validated laboratory developed test (LDT) that avoided supply chain constraints, an automated sample pooling and processing workflow, and a custom laboratory information management system (LIMS), we expanded testing from a handful of clinical samples per day to thousands per day with the testing capacity to screen our entire campus population twice per week. In this report we describe the technical, logistical, and regulatory processes that enabled our pop-up lab to scale testing and reporting capacity to thousands of tests per day.

Developmental Effects of (Pre-)Gestational Diabetes on Offspring: Systematic Screening Using Omics Approaches

Worldwide, gestational diabetes affects 2–25% of pregnancies. Due to related disturbances of the maternal metabolism during the periconceptional period and pregnancy, children bear an increased risk for future diseases. It is well known that an aberrant intrauterine environment caused by elevated maternal glucose levels is related to elevated risks for increased birth weights and metabolic disorders in later life, such as obesity or type 2 diabetes. The complexity of disturbances induced by maternal diabetes, with multiple underlying mechanisms, makes early diagnosis or prevention a challenging task. Omics technologies allowing holistic quantification of several classes of molecules from biological fluids, cells, or tissues are powerful tools to systematically investigate the effects of maternal diabetes on the offspring in an unbiased manner. Differentially abundant molecules or distinct molecular profiles may serve as diagnostic biomarkers, which may also support the development of preventive and therapeutic strategies. In this review, we summarize key findings from state-of-the-art Omics studies addressing the impact of maternal diabetes on offspring health.

Lessons Learned from Implementation of an Interferon Gamma Release Assay to Screen for Latent Tuberculosis Infection in a Large Multicenter Observational Cohort Study in Brazil

The IGRA has emerged as a useful tool for identifying persons with LTBI. Although the implementation of IGRAs is of utmost importance, to our knowledge there is scarce information on the identification of logistical and technical challenges for systematic screening for LTBI on a large scale.