Study of clinical profile and management of patients with pulmonary embolism – Single center study

Objective

To study the clinical profile, diagnostic methods and management in patients with symptomatic pulmonary embolism (PE).

Methods

Retrospective assessment of clinical features and management of patients presenting with symptomatic pulmonary embolism from January 2005 to March 2012.

Results

35 patients who were newly diagnosed to have pulmonary embolism with a mean age of 52.1 years were included in the study. Dyspnea (91.4%) and syncope (22.8%) were the predominant symptoms. Echocardiography was done in all patients. 30 patients (85.7%) had pulmonary arterial hypertension, 31 patients (88.5%) had evidence of RV dysfunction and 4 patients (16.7%) had evidence of thrombus in PA, RV. Out of 35 patients, 34 patients (97.14%) showed positive d-dimer reports. Among 35 patients, 24 (68.5%) had positive troponin values. V/Q scan was done in 14 patients (40%) and CT pulmonary angiogram (CTPA) was done in 24 patients (68.5%.). Thrombolysis was done is 24 patients (68.5%). All patients received low molecular weight heparin followed by warfarin. Of the 35 patients, 34 (97.1%) were discharged and were under regular follow up for 6 months and one patient died during the hospital stay.

Conclusion

Pulmonary embolism is a common problem and can be easily diagnosed provided it is clinically suspected. Early diagnosis and aggressive management is the key to successful outcome.     

Ameliorative effect of ferulic acid against renal injuries mediated by nuclear factor-kappaB during glycerol-induced nephrotoxicity in Wistar rats

The pathogenesis of glycerol-induced myoglobinuric acute renal failure involves ischemia, vascular congestion and reactive oxygen metabolites. In this study, we have investigated for the first time, the role of ferulic acid in attenuating glycerol-induced nephrotoxicity. Male Wistar rats were injected intramuscularly with 8?mL/kg body weight of 50% glycerol, glycerol?+?ferulic acid at the dose of 5, 10, 15, 20 and 25?mg/kg body weight. After 24?h, the rats were sacrificed and the kidneys were removed for histological and immunohistochemical studies. Furthermore, determinations of lipid peroxidation (LPO) as well as antioxidant enzymes were also analyzed; blood, urine samples were collected in order to quantify renal function and nitric oxide generation, respectively. Glycerol-induced rats showed a significant increase in the level of urinary markers assessed in serum as well as kidney and these were reversed upon ferulic acid treatment. A significant increase in urine nitric oxide, serum as well as kidney LPO, decrease in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione were observed in glycerol-induced rats. Immunohistochemical study in glycerol-induced rats demonstrated an increase in the level of nuclear factor-kappaB (NF-κB). All these effects induced by glycerol were reduced upon treatment with ferulic acid in a dose-dependent manner. To conclude, ferulic acid enhances antioxidants and decreases NF-κB, thereby protecting the cells against stress induced by glycerol.     

Long‐term outcomes in African American kidney transplant recipients under contemporary immunosuppression: a four‐yr analysis of the Mycophenolic acid Observational REnal transplant (MORE) study

Mycophenolic acid Observational REnal transplant (MORE) was a prospective, observational study of de novo kidney transplant patients receiving mycophenolic acid (MPA). Four‐yr data on 904 patients receiving tacrolimus and enteric‐coated mycophenolate sodium (EC‐MPS) or mycophenolate mofetil (MMF) were analyzed to evaluate immunosuppression and graft outcomes in African American (AA, n = 218) vs. non‐AA (n = 686) patients. Mean tacrolimus dose was higher in AA vs. non‐AA patients but mean tacrolimus trough concentration was similar. Use of the recommended MPA dose in AA patients decreased from 78.9% at baseline to 33.1% at year 3. More AA patients received the recommended MPA dose with EC‐MPS than MMF at month 6 (56.2% vs. 35.7%, p = 0.016) and month 36 (46.6% vs. 16.7%, p = 0.029), with no safety penalty. Significantly, more AA patients received corticosteroids than non‐AA patients. Biopsy‐proven acute rejection was higher in AA vs. non‐AA patients (18.9% vs. 10.7%, p = 0.003), as was graft loss (10.9% vs. 4.4%, p = 0.003); differences were confirmed by Cox regression analysis. Patient survival was similar. Estimated GFR was comparable in AA vs. non‐AA patients. Kidney allograft survival remains lower for AA vs. non‐AA recipients even under the current standard of care.     

Effect of gamma-interferon on collagen synthesis by normal and fibrotic human lung fibroblasts.

Increased lung collagen and increased collagen synthesis by lung fibroblasts is well recognized in pulmonary fibrosis. gamma-Interferon has been shown to inhibit collagen synthesis by fibroblasts. To understand its effect on lung fibroblasts we compared how this lymphokine affects the growth and collagen synthesis of normal and fibrotic human lung fibroblasts. The results showed that gamma-IFN inhibited DNA synthesis in all fibroblast strains examined. Both collagen production and type 1 mRNA levels were reduced in three normal and two fibrotic cell strains exposed to gamma-IFN, while they were not affected in one strain from fibrotic lung. Even though an occasional cell was unaffected by the gamma-IFN, collagen mRNA level was reduced in most cells and it remained reduced for 48 h after removing the gamma-IFN. These results show that gamma-IFN inhibits the growth of fibroblast cultures derived from normal and fibrotic human lungs and suppresses collagen synthesis in most of these cells.     

Sight-threatening intraocular infection in patients with COVID-19 in India

Purpose:Intraocular infection in patients with COVID-19 could be different in the presence of treatment with systemic corticosteroid and immunosuppressive agents. We describe the epidemiology and microbiological profile of intraocular infection in COVID-19 patients after their release from the hospital.Methods:We analyzed the clinical and microbiological data of laboratory-confirmed COVID-19 patients from April 2020 to January 2021 presenting with features of endogenous endophthalmitis within 12 weeks of their discharge from the hospital in two neighboring states in South India. The data included demography, systemic comorbidities, COVID-19 treatment details, time interval to visual symptoms, the microbiology of systemic and ocular findings, ophthalmic management, and outcomes.Results:The mean age of 24 patients (33 eyes) was 53.6 ± 13.5 (range: 5–72) years; 17 (70.83%) patients were male. Twenty-two (91.6%) patients had systemic comorbidities, and the median period of hospitalization for COVID-19 treatment was 14.5 ± 0.7 (range: 7–63) days. Infection was bilateral in nine patients. COVID-19 treatment included broad-spectrum systemic antibiotics (all), antiviral drugs (22, 91.66% of patients), systemic corticosteroid (21, 87.5% of patients), supplemental oxygen (18, 75% of patients), low molecular weight heparin (17, 70.8% of patients), admission in intensive care units (16, 66.6% of patients), and interleukin-6 inhibitor (tocilizumab) (14, 58.3% of patients). Five (20.8%) patients died of COVID-19-related complications during treatment for endophthalmitis; one eye progressed to pan ophthalmitis and orbital cellulitis; eight eyes regained vision >20/400. Fourteen of 19 (73.7%) vitreous biopsies were microbiologically positive (culture, PCR, and microscopy), and the majority (11 patients, 78.5%) were fungi.Conclusion:Intraocular infection in COVID-19 patients is predominantly caused by fungi. We suggest a routine eye examination be included as a standard of care of COVID-19.     

Pegylated interferon alfa-2b plus ribavirin for treatment of chronic hepatitis C

AIM: To study the safety and efficacy of pegylated interferon alfa-2b, indigenously developed in India, plus ribavirin in treatment of hepatitis C virus(HCV). METHODS: One-hundred HCV patients were enrolled in an open-label, multicenter trial. Patients were treated with pegylated interferon alfa-2b 1.5 μg/kg per week subcutaneously plus oral ribavirin 800 mg/d for patients with genotypes 2 and 3 for 24 wk. The same dose of peginterferon plus weight-based ribavirin(800 mg/d for ≤ 65 kg; 1000 mg/d for 65-85 kg; 1200 mg/d for 85-105 kg; 1400 mg/d for 105 kg body weight) was administered for 48 wk for patients with genotypes 1 and 4. Serological and biochemical responses of patients were assessed.RESULTS: Eighty-two patients(35 in genotypes 1 and 4 and 47 in 2 and 3), completed the study. In genotype 1, 25.9% of patients achieved rapid virologic response(RVR): while the figures were 74.1% for early virologic response(EVR) and 44.4% for sustained virologic response(SVR). For genotypes 2 and 3, all patients bar one belonged to genotype 3, and of those, 71.4%, 87.5%, and 64.3% achieved RVR, EVR, and SVR, respectively. In genotype 4, 58.8%, 88.2%, and 52.9% of patients achieved RVR, EVR, and SVR, respectively. The majority of patients attained normal levels of alanine aminotransferase by 4-12 wk of therapy. Most patients showed a good tolerance for the treatment, although mild-to-moderate adverse events were exhibited; only two patients discontinued the study medication due to serious adverse events(SAEs). Eleven SAEs were observed in nine patients; however, only four SAEs were related to study medication.CONCLUSION: Peginterferon alfa-2b, which was developed in India, in combination with ribavirin, is a safe and effective drug in the treatment of HCV.     

Comparison of ATP-dependent calcium transport and calcium-activated ATPase activities of cardiac sarcoplasmic reticulum and sarcolemma from rats of various ages

Age-associated decline in the Ca2+ pump function of cardiac sarcoplasmic reticulum (SR), and increase in the Ca2+ pump activity of sarcolemma (SL) were suggested by my previous study which compared the ATP-energized in vitro Ca2+ transport activities of these membranes from young (3-4-month-old) and aged (24-25-month-old) rat myocardium (Biochim. Biophys. Acta, 678 (1981) 442-459). In the present study, ATP-dependent Ca2+ transport and Ca2+ sensitive ATPase activities of SR and SL derived from the myocardium of rats aged 3 (young), 6 (young adult), 12 (adult), 18 (aging) and 24 (aged) months were determined so as to further characterize age-related changes in the Ca2+ transport function of these membranes. The rates of ATP-dependent Ca2+ accumulation by SR from 3- and 6-month-old rats were virtually similar whereas the rates of Ca2+ accumulation by this membrane from 12-, 18- and 24-month-old rats were significantly lower when compared to 3- or 6-month-old rats; the magnitude of this age-related decline amounted to approx. 18, 45 and 50%, respectively, for SR from 12-, 18- and 24-month-old animals. In contrast to the above findings with SR, SL from 18- and 24-month-old rats displayed substantially higher rates (approx. 45 and 80% increase, respectively, at 18 and 24 months of age) of ATP-dependent Ca2+ accumulation than SL preparations from 3-, 6- and 12-month-old rats; no significant age-related difference was evident between the latter three age groups. The divergent age-related changes in the Ca2+ accumulating activities of SR and SL were seen at varying Ca2+ concentrations (0.54-25.2 microM). With either membrane, kinetic analysis showed that the velocity of Ca2+ transport, but not the apparent affinity of the transport system for Ca2+ underwent age-related changes. The Ca2+-stimulated ATPase activities of SR and SL were not altered significantly with increasing age from 3 to 24 months. Comparison of the 'combined Ca2+ transport activity' of SR and SL from rats of various ages showed a significant overall age-related decline in the rates of Ca2+ transport via the ATP-driven membrane Ca2+ pumps; this decrement in membrane function was moderate at 12 months of age (approx. 16%) and became pronounced with advancing age thereafter (approx. 35 and 38%, respectively, at 18 and 24 months of age). Similar progressive age-related decline was observed in the ATP-dependent Ca2+ sequestering activity of cardiac homogenates.(ABSTRACT TRUNCATED AT 400 WORDS)     

ProKinO: A Unified Resource for Mining the Cancer Kinome

Protein kinases represent a large and diverse family of evolutionarily related proteins that are abnormally regulated in human cancers. Although genome sequencing studies have revealed thousands of variants in protein kinases, translating “big” genomic data into biological knowledge remains a challenge. Here, we describe an ontological framework for integrating and conceptualizing diverse forms of information related to kinase activation and regulatory mechanisms in a machine readable, human understandable form. We demonstrate the utility of this framework in analyzing the cancer kinome, and in generating testable hypotheses for experimental studies. Through the iterative process of aggregate ontology querying, hypothesis generation and experimental validation, we identify a novel mutational hotspot in the αC‐β4 loop of the kinase domain and demonstrate the functional impact of the identified variants in epidermal growth factor receptor (EGFR) constitutive activity and inhibitor sensitivity. We provide a unified resource for the kinase and cancer community, ProKinO, housed at http://vulcan.cs.uga.edu/prokino .     

Improved detection of intraventricular cysticercal cysts with the use of three-dimensional constructive interference in steady state MR sequences

BACKGROUND AND PURPOSE: Before the advent of MR imaging, intraventricular cysts were difficult to diagnose noninvasively. Among the invasive procedures used were contrast ventriculography and CT ventriculography. MR imaging, with its multiplanar imaging capabilities, excellent depiction of tissue contrast, and versatile parameters, is an important tool in the assessment of intraventricular cystic lesions. We investigated the role of three-dimensional constructive interference in steady state (3D-CISS) MR sequences in the evaluation of intraventricular cysticercal cysts. METHODS: The study group comprised 11 patients with intraventricular cysticercal cysts. MR studies included spin-echo (SE) T1-weighted, turbo-SE T2-weighted, and 3D-CISS sequences. All images were obtained on a superconducting 1.5-T MR unit. The routine and 3D-CISS sequences were reviewed and interpreted separately by two neuroradiologists. RESULTS: All patients underwent surgery for excision of intraventricular cysticercal cysts. Eight patients had cysts in the fourth ventricle, two in the lateral ventricle, and one in the third ventricle. SE T1-weighted images showed the cystic wall in nine cases, the scolex in four, and the cystic fluid in two. Turbo-SE T2-weighted images showed the cystic wall and scolex in three and four cases, respectively. The routine sequences did not show the scolex, cystic wall, or cystic fluid together in any of the 11 patients. 3D-CISS images showed the scolex in all 11 patients and the cystic wall and cystic fluid in eight patients each. In seven of the 11 patients, 3D-CISS images showed the scolex, cystic wall, and fluid together. CONCLUSION: The 3D-CISS sequence is more sensitive and specific than routine SE sequences in the diagnosis of intraventricular cysticercal cysts.     

Single-Center Comparison of Overall Survival and Toxicities in Patients with Infiltrative Hepatocellular Carcinoma Treated with Yttrium-90 Radioembolization or Drug-Eluting Embolic Transarterial Chemoembolization

Purpose

To compare overall survival and toxicities after yttrium-90 (⁹⁰Y) radioembolization and chemoembolization with drug-eluting embolics (DEE) in patients with infiltrative hepatocellular carcinoma (HCC).