Intrapleural Fibrinolysis with Urokinase versus Alteplase in Complicated Pleural Effusions and Empyema: A Prospective Randomized Controlled Trial.

BACKGROUND: Intrapleural fibrinolytic therapy (IPFT) has been used as an effective agent since 1949 for managing complicated pleural effusion and empyema. Several agents, such as streptokinase, urokinase (UK), and recombinant tissue plasminogen activator (rt-PA), have been found to be effective with variable effectiveness. However, a head-tohead controlled trial comparing the efficacy of the most frequently used agents, i.e., UK and rt-PA (alteplase) for managing complicated pleural effusion has rarely been reported. METHODS: A total of 50 patients were randomized in two intervention groups, i.e., UK and rt-PA. The dose of rt-PA was 10 mg, and that of UK was 1.0 lac units. UK was given thrice daily for 2 days, followed by clamping to allow the retainment of drugs in the pleural space for 2 hours. rt-PA was instilled into the pleural space twice daily for 2 days, and intercostal drainage was clamped for 1 hour. RESULTS: A total of 50 patients were enrolled into the study, of which 84% (n=42) were males and 16% (n=8) were females. Among them, 30 (60%) patients received UK, and 20 (40%) patients received alteplase as IPFT agents. The percentage of mean± standard deviation changes in pleural opacity was -33.0%±9.9% in the UK group and -41.0%±14.9% in the alteplase group, respectively (p=0.014). Pain was the most common adverse side effect, occurring in 60% (n=18) of the patients in the UK group and in 40% (n=8) of the patients in the alteplase group (p=0.24), while fever was the second most common side effect. Patients who reported early (within 6 weeks of onset of symptoms) showed a greater response than those who reported late for the intervention. CONCLUSION: IPFT is a safe and effective option for managing complicated pleural effusion or empyema, and newer agents, such as alteplase, have greater efficacy and a similar adverse effect profile when compared with conventional agents, such as UK.

The Use of Enteric Contrast in the Emergency Setting.

Historically, computed tomography of the abdomen and pelvis had been performed routinely with enteric contrast to help improve diagnostic accuracy. However, the utility of enteric contrast has been called into question recently, particularly in the high-patient-volume setting of the emergency department. This article reviews the role of enteric contrast in the emergency setting. Particular emphasis is given to specific clinical scenarios in which enteric contrast provides value. These include the identification of abdominal postsurgical complications such as anastomotic leaks and fistulas, detection of penetrating bowel injuries, evaluation of acute appendicitis, and assessment of small-bowel obstructions.

Seroconversion among COVID-19 patients admitted in a dedicated COVID hospital: A longitudinal prospective study of 1000 patients.

BACKGROUND: The immune response after SARS-CoV-2 is complex and may be affected by severity of the disease, race, etc. The present study was conducted to assess the serial antibody response among the COVID-19 patients admitted in the hospital. METHODS: The study was conducted between July and October 2020 in a dedicated COVID-19 hospital. All consented patients underwent serial testing of antibodies using a rapid chromatographic immunoassay-based qualitative IgG/IgM kit every third day until their discharge or death. The data about age, sex, severity of disease, length of stay, onset of symptoms, date of molecular testing were also collected. Appropriate statistical tests were used. RESULTS: The mean age of 1000 COVID-19 patients was 47.5 ± 17.9 years. Out of the total, 687 (68.7%) were males. With respect to severity, 682 (68.2%) were asymptomatic/mild, 200 (20%) were moderate and 118 (11.8%) were severe cases. The seroconversion percentage increased from 12.8% to 97.9% and 16.3% to 80.9% for IgG and IgM respectively in 21 days. The median time for seroconversion was 10 days (IQR:6-12 days) for IgG and eight days (IQR: 6-11 days) for IgM. At the time of discharge (median nine days), detectable IgG and IgM antibodies were present in 502 (52.46%) and 414 (43.26%) participants respectively. Seroconversion was associated with days after the symptoms, increasing severity of the disease and the presence of co-morbidity. CONCLUSION: Seroconversion increased during the period of observation. The severe/moderate cases of COVID-19 tend to have an early seroconversion as compared to the asymptomatic/mild cases. Only half of the patients were seroconverted at discharge.

Has National Medical Commission Short-Changed the Subject of Community Medicine in Its Latest Minimum Requirements for Indian Medical Graduates? A Systems Review.

System analysis is examination of various elements of a system with a view to ascertain whether the proposed solution to a problem will fit the system and in turn effect an overall improvement in the system. The National Medical Commission (NMC) which was constituted by the act of the Parliament, has brought out minimum requirements for annual MBBS admissions regulations, 2020, which replace minimum requirements published by erstwhile Medical Council of India. The NMC also published new competency-based medical education syllabus for MBBS students with an aim to focus on practical skills. This study brings out the scope of the community medicine (CM) in the present context and as envisaged by the NMC. It also analyzes the infrastructure and workforce required in the department of CM and gives recommendations to improve the system.

A series of dual-reporter vectors for ratiometric analysis of protein abundance in plants.

Ratiometric reporter systems enable comparisons of the abundance of a protein of interest, or "target," relative to a reference protein. Both proteins are encoded on a single transcript but are separated during translation. This arrangement bypasses the potential for discordant expression that can arise when the target and reference proteins are encoded by separate genes. We generated a set of 18 Gateway-compatible vectors termed pRATIO that combine a variety of promoters, fluorescent, and bioluminescent reporters, and 2A "self-cleaving" peptides. These constructs are easily modified to produce additional combinations or introduce new reporter proteins. We found that mScarlet-I provides the best signal-to-noise ratio among several fluorescent reporter proteins during transient expression experiments in Nicotiana benthamiana. Firefly and Gaussia luciferase also produce high signal-to-noise in N. benthamiana. As proof of concept, we used this system to investigate whether degradation of the receptor KAI2 after karrikin treatment is influenced by its subcellular localization. KAI2 is normally found in the cytoplasm and the nucleus of plant cells. In N. benthamiana, karrikin-induced degradation of KAI2 was only observed when it was retained in the nucleus. These vectors are tools to easily monitor in vivo the abundance of a protein that is transiently expressed in plants, and will be particularly useful for investigating protein turnover in response to different stimuli.

Education Level Predicts Appropriate Follow-Up of Incidental Findings From Lung Cancer Screening.

PURPOSE: The aim of this study was to identify predictors of appropriate follow-up for clinically significant incidental findings (IFs) detected with low-dose CT during lung cancer screening. METHODS: Charts of 1,458 prospectively enrolled lung screening patients from January 1, 2015, to October 31, 2018, were reviewed. IFs, other than coronary artery calcification and emphysema, were identified. ACR practice guidelines defined appropriate patient follow-up. Patient demographic and social characteristics were obtained from the initial shared decision-making visit and the electronic medical record. Factors of interest included age, gender, race, education level, and insurance status. Education level was reported as high school graduate or less or education past high school. A multivariate logistic regression was estimated to assess patient factors associated with appropriate follow-up. RESULTS: One hundred thirty-eight participants (9%) with 141 actionable IFs were identified. The overall appropriate follow-up rate was 82%. The most common IFs were renal lesions (16%), dilated thoracic aorta (10%), and pulmonary fibrosis (10%). Univariate analysis of appropriate patient follow-up revealed a significant difference for education level (P = .02). A greater than high school education remained strongly associated with appropriate follow-up after controlling for other demographic factors. CONCLUSIONS: Appropriate patient follow-up of clinically significant IFs from lung cancer screening is a well-recognized avenue to improve population health. Education level is a significant independent predictor of appropriate follow-up of IFs, whether as a surrogate for low socioeconomic status or as an indication of health literacy. To address these realities, lung screening shared decision making should adapt to consider health care access and health literacy.

1,2-Propanediol Dehydration in Roseburia inulinivorans: STRUCTURAL BASIS FOR SUBSTRATE AND ENANTIOMER SELECTIVITY.

Glycyl radical enzymes (GREs) represent a diverse superfamily of enzymes that utilize a radical mechanism to catalyze difficult, but often essential, chemical reactions. In this work we present the first biochemical and structural data for a GRE-type diol dehydratase from the organism Roseburia inulinivorans (RiDD). Despite high sequence (48% identity) and structural similarity to the GRE-type glycerol dehydratase from Clostridium butyricum, we demonstrate that the RiDD is in fact a diol dehydratase. In addition, the RiDD will utilize both (S)-1,2-propanediol and (R)-1,2-propanediol as a substrate, with an observed preference for the S enantiomer. Based on the new structural information we developed and successfully tested a hypothesis that explains the functional differences we observe.

Foxo3a transcriptionally upregulates AQP4 and induces cerebral edema following traumatic brain injury.

Increased cranial pressure due to development of edema contributes significantly to the pathology of traumatic brain injury (TBI). Induction of an astrocytic water channel protein, Aquaporin 4 (AQP4), is known to predominantly contribute to cytotoxic edema following TBI. However, the mechanism for the increase in AQP4 following 24 h of TBI is poorly understood. Here we show that transcriptional activation of a ubiquitously expressed mammalian forkhead transcription factor, Foxo3a, induces cerebral edema by increasing the AQP4 level in the controlled cortical impact model of TBI in mice. TBI stimulates nuclear translocation of Foxo3a in astrocytes and subsequently augments its binding to AQP4 promoter in pericontusional cortex. Nuclear accumulation of Foxo3a is augmented by a decrease in phosphorylation at its Ser256 residue due to inactivation of Akt after TBI. Depletion of Foxo3a in mice rescues cytotoxic edema by preventing induction of AQP4 as well as attenuates memory impairment after TBI in mice.

Recurrent adult choroid plexus carcinoma treated with high-dose chemotherapy and syngeneic stem cell (bone marrow) transplant.

Choroid plexus carcinomas (CPCs) are rare epithelial central nervous system tumors. CPC occurs mainly in infants and young children, comprising ≈ 1 to 4% of all pediatric brain neoplasms. There is very limited information available regarding tumor biology and CPC treatment due to its rarity. There have been various case reports and meta-analyses of reported cases with CPC. Surgical resection is often challenging but remains a well-established treatment option. Chemotherapy is often reserved for recurrent or refractory cases, but the goal of treatment is usually palliative. We present a case of recurrent, adult CPC with disseminated leptomeningeal involvement treated with salvage chemotherapy including high-dose ifosfamide, carboplatin, and etoposide; once a remission was achieved, this response was consolidated with a syngeneic stem cell (bone marrow) transplant after a preparative regimen of high-dose chemotherapy with carboplatin, etoposide, and thiotepa. Although the patient tolerated the transplant well and remained disease-free for 12 months, she subsequently succumbed to relapsed disease 18 months posttransplant. We believe that this is the first report of using syngeneic stem cell transplant in CPC to consolidate a remission achieved by salvage chemotherapy.