The Outcome of Catheter-Directed Thrombolysis in COVID-19-Associated Deep Vein Thrombosis

Introduction Published evidence of venous thrombotic complications of COVID-19 is lacking from India. This case series consists of twenty-nine adult patients who were COVID -19 positive and treated for Deep Vein Thrombosis (DVT) during the second wave of the COVID-19 pandemic, in India. The study was aimed at analyzing patient demographics of patients with DVT and the outcome of Catheter-Directed Thrombolysis (CDT) in COVID positive patients. Material and Methods: Patients who developed DVT while or after being COVID positive were managed between February and April 2021 at the institution of the first two authors and were included in this retrospective study. Demographic, clinical data, laboratory data, and treatment given were analyzed. All patients were followed up for 3 months with a Villalta score. Results: There were a total of 29 patients (12 male and 17 female) included in the study with a mean age of 47 ± 17 years. The average time of presentation from being COVID positive was 17.8 ± 3.6 days and one patient developed DVT after becoming Covid negative. All but one patient had lower limb involvement, with 42.8% having proximal and 57.2% distal DVT. All patients with Iliofemoral and two with Femoropopliteal DVT were treated with catheter-di thrombolysis and the other 15 patients were managed with anticoagulation alone. No re-thrombosis was observed in the thrombolysis group. Overall average Villalta score at 3 months was 10.7 ± 2.1 with a score of 10.58 ± 2.1 in the anticoagulation-only group and 10.85 ± 2.3 in the CDT group. Conclusion: COVID-19 seems to be an additional risk factor in the development of DVT. The outcome of such patients, treated by thrombolysis appears to be similar to non-COVID patients. In this, observational experience of the authors suggests that CDT could be offered to COVID positive patients with symptomatic Iliofemoral DVT with good outcomes and an acceptable post-intervention Villalta score.

Prone Positioning as a Potential Risk Factor for Deep Vein Thrombosis in COVID-19 Patients: A Hypothesis Generating Observation

Aims of the study: Virchow’s triad with stasis, activated coagulation, and endothelial damage is common in SARS-CoV2. Therefore, we sought to retrospectively assess whether the duration of prone position may serve as a risk factor for deep vein thrombosis in critically ill patients. Methods: In this single center retrospective study of a tertiary referral hospital, patients with acute respiratory distress syndrome (ARDS) due to COVID-19 pneumonia admitted to critical care underwent venous ultrasound screening for deep vein thrombosis (DVT). Data on DVT diagnosis, duration of prone positioning, demographic, respiratory, and laboratory parameters were retrospectively collected and compared between DVT and non-DVT patients. Results: 21 patients with ARDS from COVID-19 pneumonia were analyzed. DVT was detected in 11 (52%) patients (76.2% male, median age 64 (58; 68.5) years, median body mass index 31 (27; 33.8) kg/m2). In patients diagnosed with DVT, median prone ventilation had been maintained twice as long as compared to patients without DVT (57 (19; 72) versus 28 (0; 56.3) h, p = 0.227) on ICU day 5 with a trend towards longer prone position time (71 (19; 104) versus 28 (0; 73) h, p = 0.06) on ICU day 7. Conclusions: Prone ventilation and constitutional factors may constitute an additional risk factor for DVT in COVID-19 patients. Since recent studies have shown that therapeutic anticoagulation does not impact the occurrence of thromboembolic events, it may be worthwhile to consider mechanical factors potentially affecting blood flow stasis in this high-risk population. However, due to the limited number of patients, our observations should only be considered as hypothesis-generating. Future studies, sufficiently powered and preferably prospective, will be needed to confirm our hypothesis.

AGEs and sRAGE Variations at Different Timepoints in Patients with Chronic Kidney Disease

Patients with chronic kidney disease (CKD) are affected by enhanced oxidative stress and chronic inflammation, and these factors may contribute to increase advanced glycation end-products (AGEs). In this study we quantified AGEs and soluble receptors for AGE (sRAGE) isoforms and evaluated the association between their variations and eGFR at baseline and after 12 months. We evaluated 64 patients. AGEs were quantified by fluorescence intensity using a fluorescence spectrophotometer, and sRAGE by ELISA. Median age was 81 years, male patients accounted for 70%, 63% were diabetic, and eGFR was 27 ± 10 mL/min/1.73 m2. At follow up, sRAGE isoforms underwent a significant decrement (1679 [1393;2038] vs. 1442 [1117;2102], p < 0.0001), while AGEs/sRAGE ratios were increased (1.77 ± 0.92 vs. 2.24 ± 1.34, p = 0.004). Although AGEs and AGEs/sRAGE ratios were inversely related with eGFR, their basal values as well their variations did not show a significant association with eGFR changes. In a cohort of patients with a stable clinical condition at 1 year follow-up, AGEs/sRAGE was associated with renal function. The lack of association with eGFR suggests that other factors can influence its increase. In conclusion, AGEs/sRAGE can be an additional risk factor for CKD progression over a longer time, but its role as a prognostic tool needs further investigation.

Drinking water contaminants as risk factors for the health of the Ulyanovsk region population

The main goal of health risk analysis is to obtain and generalize information about the possible influence of environmental factors on human health. As a result of hydrochemical analysis of drinking water supply sources in the Ulyanovsk region, a list of main contaminants has been established. It includes ammonium, iron, copper, phosphates, sulfates, chlorides, nitrates, zinc, manganese and chromium. Among them three pollutants - iron, manganese and sulfates – had surpassed maximum permissible concentration. The concentration of iron at the level of threshold chronic effects was found in drinking water of Baryshsky (0.13), Melekessky (0.16), Sengileevsky (0.13) districts. Severe chronic effects can be caused by the concentration of iron and manganese in the drinking water of the Staromainsky (0.4 and 0.3) and Cherdaklinsky (0.9 and 0.27) districts. Assessment of health risks led us to the conclusion that drinking water can serve as an additional risk factor and provoke disease development. Key words: risk factors, morbidity, maximum permissible concentration, pollutants, relative conditional risk, average daily dose.

Hematogenous thrombophilia as an additional risk factor for cerebral circulation disorders

Введение. Гематогенная тромбофилия служит дополнительным фактором риска нарушений мозгового кровообращения (НМК). Цель исследования: изучить влияние повышенного уровня фактора VIII и нарушений в системе фибринолиза на НМК у пациентов с сочетанной патологией системы свертывания крови. Материалы и методы. Обследовано 20 пациентов с перенесенными ишемическими инсультами в возрасте от 36 до 56 лет. Определяли показатели плазменного, тромбоцитарного звеньев гемостаза, системы фибринолиза, а также генетические полиморфизмы системы гемостаза. Результаты. У всех пациентов выявлены различные сочетания генетических полиморфизмов, связанных с изменениями антикоагулянтного звена гемостаза, а также дефекты системы фибринолиза и коагуляционного звена гемостаза, что является дополнительным фактором риска НМК. Заключение. У пациентов молодого и среднего возраста, перенесших острое НМК по ишемическому типу, необходимо исследование системы свертывания крови, включающее определение содержания фактора VIII в крови, показателей системы фибринолиза и уровня гомоцистеина. Background. Hematogenous thrombophilia is an additional risk factor for cerebral circulatory disorders (ССD). Objectives: to study the impact of increased factor VIII level and disturbances of fibrinolysis system on ССD in patients with combined pathology of blood coagulation. Patients/Methods. We examined 20 patients with ischemic strokes aged from 36 to 56 years. The parameters of plasma hemostasis, platelet function, fibrinolysis system, as well as the genetic polymorphisms of hemostasis system were determined. Results. All patients had different combinations of genetic polymorphisms associated with anticoagulant hemostasis changes, as well as defects in fibrinolysis system and coagulation hemostasis that is an additional risk factor for ischemic stroke. Conclusions. In young and middle-aged patients with history of acute ischemic ССD, it is necessary to study blood coagulation, including the determination of blood factor VIII level, fibrinolysis system parameters and homocysteine content.

Progressive Myelopathy After Spine Surgery

A 69-year-old man with a progressive myelopathy for 2 years was referred for evaluation of suspected transverse myelitis. His medical history included discectomies, a severe episode of herpes simplex virus type 1 meningoencephalitis, and development of insidiously progressive numbness and weakness of his hands. Cervical spine magnetic resonance imaging showed 2 small, dural-based, gadolinium-enhancing lesions. Biopsy of these lesions showed only normal neural tissue. Subsequently, the dura was stripped away surgically from the lower cervical region, in an effort to remove these lesions. During the next year, a sensory level developed at about the level of the nipples (T4), along with a squeezing sensation on his trunk below. Imbalance and bilateral lower extremity weakness and numbness then developed. Magnetic resonance imaging showed a longitudinally extensive cord signal abnormality. The cause of the patient’s initial subjective hand numbness and weakness was indeterminate. The onset of severely progressive symptoms after surgical removal of those lesions and the reported stripping of dura made it likely that the progressive cord edema was due to chronic adhesive arachnoiditis. His prior meningoencephalitis was a potential additional risk factor for arachnoiditis. Computed tomography myelography showed a markedly abnormal spinal canal with scalloping of the cord contour, with delayed flow of contrast above C6-C7, consistent with arachnoid adhesions causing obstruction of normal cerebrospinal fluid flow. The patient was diagnosed with chronic adhesive arachnoiditis. A C4-C7 laminectomy and surgical lysis of the cord meningeal adhesions was performed, with subsequent intensive neurorehabilitation. Follow-up spinal cord magnetic resonance imaging 6 months after surgery showed improvement of the T2-signal abnormality but persistent myelomalacia and spinal cord atrophy. Adhesive arachnoiditis is an uncommon cause of progressive myelopathy resulting from an insult to the arachnoid meningeal layer, followed by inflammation and fibrosis. This process renders the arachnoid abnormally thick and adherent to the pia and dura mater. Abnormal adhesion of nerve roots or spinal cord to the dura produces neurologic impairment. Typical symptoms include back pain, paresthesias, lower limb weakness, and sensory loss. It is diagnosed clinically with supportive magnetic resonance imaging and computed tomography myelography findings.

494. Characteristics and Outcomes of COVID-19 in Hospitalized Native American Patients: A Single-Site Retrospective Analysis

Background COVID-19 continues to threaten public health, particularly in Native American (NA) communities, which experienced some of the highest rates of COVID-19 infection and mortality in the US. Although the risk factors and clinical characteristics of COVID-19 are well documented in the general population, there has been little research on NA patients. Methods We present descriptive data based on chart reviews of COVID-19 patients hospitalized between April 1 and July 31, 2020 at the Whiteriver Service Unit (WRSU), an Indian Health Service site on the Fort Apache Reservation. Results Of the 2,262 COVID-19 cases during the observation period, 490 (22%) were hospitalized and 35 (1.6%) died within 28 days. Compared to previous reports, hospitalized patients at WRSU were younger (median age 54), more likely to be female (55% female), and more likely to have comorbidities (92% at least 1, median 2). Patients under 50 (n=200) often had a history of alcohol abuse (51%) or polysubstance abuse (20%). One third of hospitalized patients (34%) were monitored at home and referred for treatment through a high-risk outreach program. Patients were admitted much earlier at WRSU than in other locations, with a median interval of 4 days from symptom onset to hospitalization compared to 7 days reported elsewhere, but over half were still transferred to higher care. Although WRSU patients had higher rates of comorbidities, the 28-day hospital mortality rate from COVID-19 was nearly half of what has been previously reported (35/490, 7% vs 15-20% reported elsewhere, p &lt; 0.001). This trend persisted after controlling for age. Multivariate logistic regression showed that increasing age, male sex, and high BMI were significantly associated with higher risk of death from COVID-19 (overall model p &lt; 0.001). Characteristics and outcomes of hospitalized COVID-19 patients at WRSU Conclusion Hospitalized patients at WRSU tended to be younger but with more comorbidities than previous studies. This may reflect the fact that NAs tend to acquire comorbidities at younger ages than the general population. This may also reflect the high rates of substance abuse in younger patients, which could be an additional risk factor for severe COVID-19. We believe that the low mortality rates at WRSU are a result of our outreach program, which likely decreased the interval between symptom onset and medical treatment. Disclosures All Authors: No reported disclosures

Benefits of Icosapent Ethyl Across the Range of Kidney Function in Patients with Established Cardiovascular Disease or Diabetes: REDUCE-IT RENAL

Background: Chronic kidney disease is associated with adverse outcomes among patients with established cardiovascular disease (CVD) or diabetes. Commonly used medications to treat CVD are less effective among patients with reduced kidney function. Methods: The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) was a multicenter, double-blind, placebo-controlled trial that randomized statin-treated patients with elevated triglycerides (135-499 mg/dL) who had CVD or diabetes and one additional risk factor to treatment with icosapent ethyl (4 grams daily) or placebo. Patients from REDUCE-IT were categorized by prespecified eGFR categories to analyze the effect of icosapent ethyl on the primary endpoint (composite of cardiovascular [CV] death, nonfatal myocardial infarction nonfatal stroke, coronary revascularization, or unstable angina) and key secondary endpoint (a composite of CV death, nonfatal myocardial infarction, or nonfatal stroke). Results: Among the 8179 REDUCE-IT patients, median baseline eGFR was 75 mL/min/1.73m 2 (range: 17 to 123 mL/min/1.73m 2 ). There were no meaningful changes in median eGFR for icosapent ethyl versus placebo across study visits. Treatment with icosapent ethyl led to consistent reduction in both the primary and secondary composite endpoints across baseline eGFR categories. Patients with eGFR<60 mL/min/1.73m 2 treated with icosapent ethyl had the largest absolute and similar relative risk reduction for the primary composite endpoint (icosapent ethyl versus placebo, 21.8% versus 28.9%, hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.59-0.85, P=0.0002) and key secondary composite endpoints (16.8% versus 22.5%, HR 0.71, 95% CI 0.57-0.88, p=0.001). The numerical reduction in CV death was greatest in the eGFR <60 mL/min/1.73m 2 group (icosapent ethyl: 7.6%; placebo: 10.6%; HR 0.70, 95% CI 0.51-0.95, P=0.02). While patients with eGFR <60 mL/min/1.73m 2 treated with icosapent ethyl had the highest numerical rates of atrial fibrillation/flutter (icosapent ethyl: 4.2%; placebo 3.0%; HR 1.42, 95% CI 0.86-2.32, P=0.17) and serious bleeding (icosapent ethyl: 5.4%; placebo 3.6%; HR 1.40, 95% CI 0.90-2.18, P=0.13), hazard ratios for atrial fibrillation/flutter and serious bleeding were similar across eGFR categories (P-interaction for atrial fibrillation/flutter = 0.92; P-interaction for serious bleeding = 0.76). Conclusions: In REDUCE-IT, icosapent ethyl reduced fatal and nonfatal ischemic events across the broad range of baseline eGFR categories. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT01492361

Environment and chronic kidney disease in farmers

The prevalence of chronic kidney disease (CKD) has been on the rise worldwide. Epidemiological studies performed primarily in Central America and South Asia have reported high prevalence of CKD among young and middle-aged men working in agricultural communities. The clinical features do not appear linked to any classical CKD risk factors, such as hypertension, diabetes, or chronic nephritis. The disease develops and progresses as interstitial nephritis, without showing noticeable symptoms or high levels of proteinuria. Pathologically, the disease essentially represents chronic interstitial nephritis and is termed chronic interstitial nephritis in agricultural communities (CINAC). The potential causes of CINAC include: (1) heat stress-related factors associated with increased ambient temperatures resulting from global warming; and (2) factors connected with exposure to agrochemicals and/or pesticides. Global warming and environmental pollution will undoubtedly pose a significant health risk to farmers, and heat stress during farm work could easily result in the development and progression of CKD. Japanese agricultural regions evidently will not be spared from global environmental changes. For future epidemiological studies, researchers should establish a more comprehensive analytical method that can incorporate additional risk-factor variables, such as occupational history (including agricultural work) and ambient temperature.

Insulin resistance and risk of vascular events, interventions and mortality in type 1 diabetes

Objective: To identify determinants associated with insulin resistance and to assess the association between insulin resistance and cardiovascular events, vascular interventions and mortality in people with type 1 diabetes at high risk of cardiovascular disease . Design: Prospective cohort study. Methods: 195 people with type 1 diabetes from the Secondary Manifestations of ARTerial disease (SMART) cohort were included. Insulin resistance was quantified by the estimated glucose disposal rate (eGDR) with higher eGDR levels indicating higher insulin sensitivity (i.e. lower eGDR levels indicating higher insulin resistance). Linear regression models were used to evaluate determinants associated with eGDR. The effect of eGDR on cardiovascular events, cardiovascular events or vascular interventions (combined endpoint) and on all-cause mortality was analysed using Cox proportional hazards models adjusted for confounders. Results: In 195 individuals (median follow-up 12.9 years, IQR 6.7-17.0), a total of 25 cardiovascular events, 26 vascular interventions and 27 deaths were observed. High eGDR as a marker for preserved insulin sensitivity was independently associated with a lower risk of cardiovascular events (HR 0.75; 95%CI 0.61-0.91), a lower risk of cardiovascular events and vascular interventions (HR 0.74; 95%CI 0.63-0.87), and a lower risk of all-cause mortality (HR 0.81; 95%CI 0.67-0.98). Conclusions: Insulin resistance as measured by eGDR is an additional risk factor for cardiovascular disease in individuals with type 1 diabetes. Modification of insulin resistance by lifestyle interventions or pharmacological treatment could be a viable therapeutic target to lower the risk of cardiovascular disease.