Learning Continuous 2D Diffusion Maps from Particle Trajectories without Data Binning.

Diffusion coefficients often vary across regions, such as cellular membranes, and quantifying their variation can provide valuable insight into local membrane properties such as composition and stiffness. Toward quantifying diffusion coefficient spatial maps and uncertainties from particle tracks, we use a Bayesian method and place Gaussian Process (GP) Priors on the maps. For the sake of computational efficiency, we leverage inducing point methods on GPs arising from the mathematical structure of the data giving rise to non-conjugate likelihood-prior pairs. We analyze both synthetic data, where ground truth is known, as well as data drawn from live-cell single-molecule imaging of membrane proteins. The resulting tool provides an unsupervised method to rigorously map diffusion coefficients continuously across membranes without data binning.

The low loading of metal in metal-organic framework-derived NiNx@NC promotes amide formation through C-N coupling.

The pyrolysis of Ni-substituted zeolitic imidazolate framework-8 produces NiNx@NC with an ultra-low loading of Ni (7.4 × 10-6 mol%). The Ni-N coordination, subnanometer particle size, and uniform distribution of NiNx on the NC support lead to excellent catalytic activity (TON = 2702) and selectivity for the amination of aldehydes to produce amides.

Evaluation of terlipressin-related patient outcomes in hepatorenal syndrome-acute kidney injury using point-of-care echocardiography.

BACKGROUND AND AIMS: Treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI), with terlipressin and albumin, provides survival benefits, but may be associated with cardiopulmonary complications. We analyzed the predictors of terlipressin response and mortality using point-of-care echocardiography (POC-Echo) and cardiac and renal biomarkers. APPROACH: Between December 2021 and January 2023, patients with HRS-AKI were assessed with POC-Echo and lung ultrasound within 6 hours of admission, at the time of starting terlipressin (48 h), and at 72 hours. Volume expansion was done with 20% albumin, followed by terlipressin infusion. Clinical data, POC-Echo data, and serum biomarkers were prospectively collected. Cirrhotic cardiomyopathy (CCM) was defined per 2020 criteria. RESULTS: One hundred and forty patients were enrolled (84% men, 59% alcohol-associated disease, mean MELD-Na 25±SD 5.6). A median daily dose of infused terlipressin was 4.3 (interquartile range: 3.9-4.6) mg/day; mean duration 6.4 ± SD 1.9 days; the complete response was in 62% and partial response in 11%. Overall mortality was 14% and 16% at 30 and 90 days, respectively. Cutoffs for prediction of terlipressin nonresponse were cardiac variables [ratio of early mitral inflow velocity and mitral annular early diastolic tissue doppler velocity > 12.5 (indicating increased left filling pressures, C-statistic: 0.774), tissue doppler mitral velocity < 7 cm/s (indicating impaired relaxation; C-statistic: 0.791), > 20.5% reduction in cardiac index at 72 hours (C-statistic: 0.885); p < 0.001] and pretreatment biomarkers (CysC > 2.2 mg/l, C-statistic: 0.640 and N-terminal proBNP > 350 pg/mL, C-statistic: 0.655; p <0.050). About 6% of all patients with HRS-AKI and 26% of patients with CCM had pulmonary edema. The presence of CCM (adjusted HR 1.9; CI: 1.8-4.5, p = 0.009) and terlipressin nonresponse (adjusted HR 5.2; CI: 2.2-12.2, p <0.001) were predictors of mortality independent of age, sex, obesity, DM-2, etiology, and baseline creatinine. CONCLUSIONS: CCM and reduction in cardiac index, reliably predict terlipressin nonresponse. CCM is independently associated with poor survival in HRS-AKI.

Cirrhotic cardiomyopathy influences clinical outcomes and enhances performance of conventional risk prediction models in acute-on-chronic liver failure with severe sepsis.

BACKGROUND: Point-of-care echocardiography (POC-Echo) is an essential intensive care hemodynamic monitoring tool. AIMS: To assess POC-Echo parameters [i.e., cardiac index (CI), systemic vascular resistance index (SVRI) and cirrhotic cardiomyopathy (CCM) markers] and serum biomarkers in predicting circulatory failure (need for vasopressors) and mortality in patients with acute-on-chronic liver failure (ACLF) having sepsis-induced hypotension. METHODS: We performed serial POC-Echo within 6 hours (h) of presentation and subsequently at 24, 48 and 72 h in patients with ACLF and sepsis-induced hypotension admitted to our liver intensive care unit. Clinical data, POC-Echo data and serum biomarkers were collected prospectively. RESULTS: We enrolled 120 patients [59% men, aged 49 ± 12 years, 56% alcohol-related disease and median MELDNa of 30 (27-32)], of whom 68 (56.6%) had circulatory failure, with overall mortality of 60%. CCM was present in 52.5%. The predictors of circulatory failure were CI (aHR -1.5; p = 0.021), N-terminal brain natriuretic peptide (aHR -1.1; p = 0.007) and CCM markers; e' septal mitral velocity (aHR -0.5; p = 0.039) and E/e' ratio (aHR -1.2; p = 0.045). Reduction in CI by 20% and SVRI by 15% at 72 h predicted mortality with a sensitivity of 84% and 72%, and specificity 76% and 65%, respectively (p < 0.001). The MELD-CCM model and CLIF-CCM model were computed as MELDNa + 1.815 × E/e' (septal) + 0.402 × e' (septal) and CLIF-C ACLF + 1.815 × E/e' (septal) + 0.402 × e' (septal), respectively, based on multivariable logistic regression. Both scores outperformed MELDNa (z-score = -2.073, p = 0.038) and CLIF-C ACLF score (z score = -2.683, p-value = 0.007), respectively, in predicting 90-day mortality. CONCLUSION: POC-Echo measurements such as CCM markers (E/e' and e' velocity) and change in CI reliably predict circulatory failure and mortality in ACLF with severe sepsis. CCM markers significantly enhanced the CLIF-C ACLF and MELDNa predictive performance.

Transcatheter Aortic Valve Replacement Outcomes in End-Stage Renal Disease Patients on Hemodialysis Requiring Midodrine.

Background: Patients with dialysis-dependent end-stage renal disease (ESRD) taking midodrine may be at high risk for poor outcomes following transcatheter aortic valve replacement (TAVR). We evaluated dialysis-dependent ESRD patients taking midodrine. Methods: We conducted a retrospective analysis of non-clinical trial TAVR patients from February 2012 to December 2020 from 11 facilities in a Western US health system. Patient groups included ESRD patients on midodrine before TAVR (ESRD [+M]), ESRD patients without midodrine (ESRD [-M]), and non-ESRD patients. The endpoints of 30-day and 1-year mortality were represented by Kaplan-Meier survival estimator and compared by log-rank test. Results: Forty-five ESRD (+M), 216 ESRD (-M), and 6898 non-ESRD patients were included. ESRD patients had more comorbid conditions, despite no significant difference in predicted Society of Thoracic Surgeons mortality risk between ESRD (+M) and ESRD (-M) (8.7% vs. 9.2%, p = 0.491). Thirty-day mortality was significantly higher for ESRD (+M) patients vs. ESRD (-M) patients (20.1% vs. 5.6%, p = 0.001) and for ESRD (+M) vs. non-ESRD patients (2.5%, p < 0.001). One-year mortality trended higher for ESRD (+M) vs. ESRD (-M) patients (41.9% vs. 29.8%, p = 0.07), and was significantly higher for ESRD (+M) vs. non-ESRD patients (10.7%, p < 0.001). Compared to ESRD (-M), ESRD (+M) patients had a higher incidence of 30-day stroke (6.7% vs. 1.4%, p = 0.033), 30-day vascular complications (6.7% vs. 0.9%, p = 0.011), and a lower rate of discharge to home (62.2% vs. 84.7%, p < 0.001). In contrast, ESRD (-M) patients had no significant differences from non-ESRD patients for these outcomes. Conclusions: Our experience suggests ESRD patients on midodrine are a higher acuity population with worse survival after TAVR, compared to ESRD patients not on midodrine. These findings may help with risk stratification for ESRD patients undergoing TAVR.

Genome-Wide Identification and Characterisation of Cytokinin-O-Glucosyltransferase (CGT) Genes of Rice Specific to Potential Pathogens.

Cytokinin glucosyltransferases (CGTs) are key enzymes of plants for regulating the level and function of cytokinins. In a genomic identification of rice CGTs, 41 genes with the plant secondary product glycosyltransferases (PSPG) motif of 44-amino-acid consensus sequence characteristic of plant uridine diphosphate (UDP)-glycosyltransferases (UGTs) were identified. In-silico physicochemical characterisation revealed that, though the CGTs belong to the same subfamily, they display varying molecular weights, ranging from 19.6 kDa to 59.7 kDa. The proteins were primarily acidic (87.8%) and hydrophilic (58.6%) and were observed to be distributed in the plastids (16), plasma membrane (13), mitochondria (5), and cytosol (4). Phylogenetic analysis of the CGTs revealed that their evolutionary relatedness ranged from 70-100%, and they aligned themselves into two major clusters. In a comprehensive analysis of the available transcriptomics data of rice samples representing different growth stages only the CGT, Os04g25440.1 was significantly expressed at the vegetative stage, whereas 16 other genes were highly expressed only at the reproductive growth stage. On the contrary, six genes, LOC_Os07g30610.1, LOC_Os04g25440.1, LOC_Os07g30620.1, LOC_Os04g25490.1, LOC_Os04g37820.1, and LOC_Os04g25800.1, were significantly upregulated in rice plants inoculated with Rhizoctonia solani (RS), Xoo (Xanthomonas oryzae pv. oryzae) and Mor (Magnaporthe oryzae). In a qRT-PCR analysis of rice sheath tissue susceptible to Rhizoctonia solani, Mor, and Xoo pathogens, compared to the sterile distilled water control, at 24 h post-infection only two genes displayed significant upregulation in response to all the three pathogens: LOC_Os07g30620.1 and LOC_Os04g25820.1. On the other hand, the expression of genes LOC_Os07g30610.1, LOC_Os04g25440, LOC_Os04g25490, and LOC_Os04g25800 were observed to be pathogen-specific. These genes were identified as the candidate-responsive CGT genes and could serve as potential susceptibility genes for facilitating pathogen infection.

Identification of novel resources for panicle blast resistance from wild rice accessions and mutants of cv. Nagina 22 by syringe inoculation under field conditions.

Panicle blast is the most severe type of rice blast disease. Screening of rice genotypes for panicle blast resistance at the field level requires an efficient and robust method of inoculation. Here, we standardized a method that can be utilized for both small- and large-scale screening and assessment of panicle blast infection and disease reaction. The method involves inoculation of Magnaporthe oryzae spore culture in the neck of the rice panicle using a syringe and covering the inoculation site with wet cotton wrapped with aluminum foil to provide the required humidity for spore germination. The method was standardized using panicle blast-resistant cv. Tetep and susceptible cv. HP2216 inoculated with Mo-ni-025 isolate of M. oryzae. The method was evaluated at phenotypic as well as molecular level by expression analysis of disease responsive pathogenesis-related (PR) genes. We found this method simple, robust, reliable, and highly efficient for screening of large germplasm sets of rice for panicle blast. This was validated by screening the wild rice germplasm for panicle blast response in the field using three M. oryzae strains and subsequently with the most virulent strain in 45 EMS-induced mutants of Nagina 22 shortlisted based on field screening in a blast hotspot region. We identified five novel blast disease-resistant wild rice genotypes and 15 Nagina 22 mutants that can be used in breeding programmes.

Axillary transvalvular microaxial pump as extended bridge to transcatheter aortic valve replacement in cardiogenic shock with severe aortic stenosis.

Cardiogenic shock in the setting of severe aortic stenosis is associated with poor outcomes. We describe 5 patients with cardiogenic shock and severe aortic stenosis who received an axillary microaxial pump (Impella) as an extended bridge to transcatheter aortic valve replacement. The median (range) age was 65 (61-87) years old, 80% were male, and 80% presented with stage D or E cardiogenic shock. In most cases, balloon aortic valvuloplasty was performed prior to pump insertion. Stabilization by Impella allowed for heart team evaluation and additional interventions, including percutaneous coronary intervention, MitraClip, and cardioversion. After a median (range) of 7 (5-14) days of Impella support, semi-elective transcatheter aortic valve replacement was successfully performed. All patients survived to discharge. Four patients (80%) were alive beyond 1 year. In these high-risk patients, prolonged support with a microaxial pump allowed for stabilization, ancillary interventions, and multi-disciplinary heart team evaluation prior to transcatheter aortic valve replacement.

Comparable Outcomes for Transcarotid and Transfemoral Transcatheter Aortic Valve Replacement at a High Volume US Center.

With continued growth of transcatheter aortic valve replacement (TAVR), safe alternative access remains important for patients without adequate transfemoral (TF) access. Registry-based outcomes with transcarotid (TC) TAVR are favorable compared to transapical or transaxillary/subclavian, but TC vs TF comparisons have not been made. Our objective was to compare outcomes between TF and TC access routes for TAVR at a high-volume United States center. Methods: We retrospectively evaluated all TF and TC TAVR procedures from June 11, 2014 (first TC case) through December 31, 2019. The primary outcomes were 30-day stroke and 30-day mortality. Secondary outcomes were 1-year stroke, 1-year survival, and 30-day and 1-year life-threatening/major bleeding, vascular complications, and myocardial infarction. Propensity score weighted (PSW) models were used to compare risk-adjusted TF and TC outcomes. Of 1,465 TAVR procedures, 1319 (90%) were TF and 146 (10%) were TC. Procedure time and length of stay did not differ between groups. Unadjusted 30-day stroke (TF = 2.0%, TC = 2.7%, P = 0.536) and mortality (TF = 2.1%, TC = 2.7%, P = 0.629) were similar between groups. PSW 30-day stroke (odds ratio (OR) (95% confidence interval (CI)) = 0.8 (0.2-2.8)) and mortality (OR (95% CI) = 0.8 (0.2-3.0)) were similar between groups. Unadjusted and PSW 30-day major/life threatening bleeding, major vascular complications, and myocardial infarction did not differ between groups. Survival at one year was 90% (88%-92%) for TF patients and 87% (81%-93%) for TC patients (unadjusted P = 0.28, PSW hazard ratio = 1.0 (0.6-1.7)). Transcarotid TAVR is associated with similar outcomes compared to transfemoral TAVR at an experienced, high-volume center.

Understanding Rice-Magnaporthe Oryzae Interaction in Resistant and Susceptible Cultivars of Rice under Panicle Blast Infection Using a Time-Course Transcriptome Analysis.

Rice blast is a global threat to food security with up to 50% yield losses. Panicle blast is a more severe form of rice blast and the response of rice plant to leaf and panicle blast is distinct in different genotypes. To understand the specific response of rice in panicle blast, transcriptome analysis of blast resistant cultivar Tetep, and susceptible cultivar HP2216 was carried out using RNA-Seq approach after 48, 72 and 96 h of infection with Magnaporthe oryzae along with mock inoculation. Transcriptome data analysis of infected panicle tissues revealed that 3553 genes differentially expressed in HP2216 and 2491 genes in Tetep, which must be the responsible factor behind the differential disease response. The defense responsive genes are involved mainly in defense pathways namely, hormonal regulation, synthesis of reactive oxygen species, secondary metabolites and cell wall modification. The common differentially expressed genes in both the cultivars were defense responsive transcription factors, NBS-LRR genes, kinases, pathogenesis related genes and peroxidases. In Tetep, cell wall strengthening pathway represented by PMR5, dirigent, tubulin, cell wall proteins, chitinases, and proteases was found to be specifically enriched. Additionally, many novel genes having DOMON, VWF, and PCaP1 domains which are specific to cell membrane were highly expressed only in Tetep post infection, suggesting their role in panicle blast resistance. Thus, our study shows that panicle blast resistance is a complex phenomenon contributed by early defense response through ROS production and detoxification, MAPK and LRR signaling, accumulation of antimicrobial compounds and secondary metabolites, and cell wall strengthening to prevent the entry and spread of the fungi. The present investigation provided valuable candidate genes that can unravel the mechanisms of panicle blast resistance and help in the rice blast breeding program.

RiceMetaSysB: a database of blast and bacterial blight responsive genes in rice and its utilization in identifying key blast-resistant WRKY genes.

Nearly two decades of revolution in the area of genomics serves as the basis of present-day molecular breeding in major food crops such as rice. Here we report an open source database on two major biotic stresses of rice, named RiceMetaSysB, which provides detailed information about rice blast and bacterial blight (BB) responsive genes (RGs). Meta-analysis of microarray data from different blast- and BB-related experiments across 241 and 186 samples identified 15135 unique genes for blast and 7475 for BB. A total of 9365 and 5375 simple sequence repeats (SSRs) in blast and BB RGs were identified for marker development. Retrieval of candidate genes using different search options like genotypes, tissue, developmental stage of the host, strain, hours/days post-inoculation, physical position and SSR marker information is facilitated in the database. Search options like 'common genes among varieties' and 'strains' have been enabled to identify robust candidate genes. A 2D representation of the data can be used to compare expression profiles across genes, genotypes and strains. To demonstrate the utility of this database, we queried for blast-responsive WRKY genes (fold change ≥5) using their gene IDs. The structural variations in the 12 WRKY genes so identified and their promoter regions were explored in two rice genotypes contrasting for their reaction to blast infection. Expression analysis of these genes in panicle tissue infected with a virulent and an avirulent strain of Magnaporthe oryzae could identify WRKY7, WRKY58, WRKY62, WRKY64 and WRKY76 as potential candidate genes for resistance to panicle blast, as they showed higher expression only in the resistant genotype against the virulent strain. Thus, we demonstrated that RiceMetaSysB can play an important role in providing robust candidate genes for rice blast and BB.

Single Coronary Artery Arising from the Right Sinus of Valsalva and the Role of Coronary Computed Tomography Angiography.

There are many variations of coronary anatomy encountered during coronary angiogram. Anatomy demonstrating a single coronary artery is a rare congenital coronary artery anomaly. The entire heart is supplied solely by a coronary artery with single coronary ostium. We present a rare case of single coronary artery arising from the right sinus of Valsalva. The patient had presented with atypical chest pain and a stress test was performed, which was abnormal. We proceeded with coronary angiography which showed a common ostium of the right and left coronary artery coming from the right coronary cusp. The coronary computed tomography angiography revealed the left main had a pre-pulmonic course, crossing the base of the heart and passing anterior to the pulmonary artery and then branching into the left anterior descending artery and left circumflex artery. Patients with single coronary artery usually has benign prognosis; however, a specific coronary anomaly may result in myocardial ischemia and sudden cardiac death if the anomalous coronary artery takes an intra-arterial course, running between the aorta and the pulmonary artery. Coronary computed tomography angiography is a useful imaging modality to identify anatomical course of coronary anomaly.

Patterns of in-hospital mortality and bleeding complications following PCI for very elderly patients: insights from the Dartmouth Dynamic Registry.

BACKGROUND: Very elderly patients (age ≥ 85 years) are a rapidly increasing segment of the population. As a group, they experience high rates of in-hospital mortality and bleeding complications following percutaneous coronary intervention (PCI). However, the relationship between bleeding and mortality in the very elderly is unknown. METHODS: Retrospective review was performed on 17,378 consecutive PCI procedures from 2000 to 2015 at Dartmouth-Hitchcock Medical Center. Incidence of bleeding during the index PCI admission (bleeding requiring transfusion, access site hematoma > 5 cm, pseudoaneurysm, and retroperitoneal bleed) and in-hospital mortality were reported for four age groups (< 65 years, 65-74 years, 75-84 years, and ≥ 85 years). The mortality of patients who suffered bleeding complications and those who did not was calculated and multivariate analysis was performed for in-hospital mortality. Lastly, known predictors of bleeding were compared between patients age < 85 years and age ≥ 85 years. RESULTS: Of 17,378 patients studied, 1019 (5.9%) experienced bleeding and 369 (2.1%) died in-hospital following PCI. Incidence of bleeding and in-hospital mortality increased monotonically with increasing age (mortality: 0.94%, 2.27%, 4.24% and 4.58%; bleeding: 3.96%, 6.62%, 10.68% and 13.99% for ages < 65, 65-74, 75-84 and ≥ 85 years, respectively). On multivariate analysis, bleeding was associated with increased mortality for all age groups except patients age ≥ 85 years [odds ratio (95% CI): age < 65 years, 3.65 (1.99-6.74); age 65-74 years, 2.83 (1.62-4.94); age 75-84 years, 3.86 (2.56-5.82), age ≥ 85 years: 1.39 (0.49-3.95)]. CONCLUSIONS: Bleeding and mortality following PCI increase with increasing age. For the very elderly, despite high rates of bleeding, bleeding is no longer predictive of in-hospital mortality following PCI.

AngioVac System Used as an Adjunct Treatment for Intra-Cardiac Lead and Valvular Vegetations.

Infections are known complications of cardiovascular implantable electronic devices (CIEDs). We describe a case of a 62-year-old male who presented with pulseless electrical activity (PEA) cardiac arrest and respiratory failure. He had a history of cardiac resynchronization device and defibrillator (CRT-D) implantation for nonischemic cardiomyopathy. After resuscitation, he was found to have methicillin sensitive Staphylococcus aureus (MSSA) bacteremia on blood culture and large vegetations on the CRT-D lead and tricuspid valve found on echocardiography. The patient underwent extraction of the leads, but several large vegetations were present adherent to the tricuspid valve on intra-cardiac ultrasound (ICE). Due to comorbidities, the patient was not a candidate for surgical removal of these vegetations. Thus, he underwent percutaneous extraction of tricuspid and right atrial vegetations with the AngioVac device.

Clinical factors associated with physician choice of femoral versus radial access: A real-world experience from a single academic center.

OBJECTIVES: To analyze clinical factors associated with operator's preference in selection of femoral versus radial access for angiography and percutaneous intervention (PCI) procedures. BACKGROUND: There has been an increase in radial access in cardiac catheterization and PCI in the last few decades. METHODS: Data from 11 226 consecutive cardiac catheterization procedures were collected from Sanford University Medical Center (University of South Dakota, Sanford School of Medicine) from 2011 to 2015. RESULTS: In the overall cases, clinical factors that favored upfront femoral access include patients presenting as ST-elevation myocardial infarction (STEMI) or emergent, coronary artery bypass graft, body mass index (BMI) <30 kg/m2 and age ≥70 years, whereas morbidly obese patients (BMI ≥35) and age <70 favored upfront radial access. Radial access in the overall group had lower fluoroscopy time (6.5 vs 8.4 min, P < 0.0001) and lower contrast use (68.8 vs 80.6 cc, P < 0.0001). In the PCI group, efficacy of upfront radial access is less evident with radial fluoroscopy time (10.1 vs 11.0 min, P < 0.0028) and contrast use being higher in radial group (113.8 vs 108.2 cc, P < 0.037). Interventional cardiologists were more efficient in diagnostic cases than non-interventional cardiologists. CONCLUSION: STEMI or emergent cases and elderly patients favor upfront femoral access. As BMI increases and age decreases, radial access is progressively favored. In diagnostic cases, radial access appears to be superior to femoral access in efficacy, but the distinction is less obvious in PCI and STEMI or emergent cases.

A Case of an Acute Myocardial Infarction Post Thrombolytic Treatment of Ischemic Stroke - A Management Dilemma.

Acute ischemic stroke and myocardial infarction are emergency clinical events that require prompt intervention. Concurrent occurrence of both events magnifies the complexity of the clinical management. We present a case of a patient who presented with acute ischemic stroke, complicated by acute myocardial infarction shortly after thrombolytic was administered. This case highlights the importance of individualization of management especially in complex cases where there are no clear specific guidelines to follow.

Simultaneous Onset of Deep Vein Thrombosis, Pulmonary Embolism, Cerebral Infarction, and Myocardial Infarction in a Patient with Patent Foramen Ovale.

Paradoxical embolism is a known complication with intra-cardiac shunts. It should be considered in the differential as the pathophysiologic mechanism of simultaneous thromboembolism in the venous and systemic vasculature. We present a case of simultaneous deep venous thrombosis, pulmonary embolism and myocardial infarction in the presence of a confirmed patent foramen ovale on echocardiography. Thrombolytic therapy was administered. Subsequent concerns of intracranial hemorrhage on imaging of the brain complicated the management and added to the challenge of co-managing the clot burden in our patient. This rare presentation highlights the importance of multisystem evaluation in making the best medical decision for the patient.

End-of-Life Care: Consensus Statement by Indian Academy of Pediatrics.

JUSTIFICATION: The right to life has been accepted as one of the fundamental rights in our constitution. Resuscitation is a procedure performed for all patients suffering from cardiac or respiratory arrest irrespective of the clinical condition. There are no legal guidelines defining process to be adopted in situations where resuscitation is unlikely to be useful. There are no guidelines on withdrawal of care or end of life (EOL) decisions, accepted by the Government, judiciary, professionals, academicians or the community. PROCESS: A National Consultative meet was organized by Indian Medico-Legal and Ethics Association and the Medico-legal group of Indian Academy of Pediatrics (IAP) to formulate the guidelines on 'Do Not Resuscitate' (DNR), and 'End of Life Support'. The meeting was organized on 30th May, 2014 at Ram Manohar Lohia Hospital, New Delhi. The meeting involved professionals from legal and various medical fields as well as administrators, and members from Medical Council of India. OBJECTIVES: To frame the guidelines related to EOL care issues and withdrawal or with-holding treatment in situations where outcome of continued treatment is expected to be poor in terms of ultimate survival or quality of life. RECOMMENDATIONS: (i) DNR or end of life care should not be activated till consensus is achieved between treating team and the next of kin; (ii) Consensus within health care team (including nurses) needs to be achieved before discussion with family members; (iii) Discussion should involve the family members - next of kin and other persons who can influence decisions; (iv) If family members want to include their family physician or a prominent person from the community, it should be encouraged. Similarly if family members want a particular member of treating team, he/she should be included; (v) Treating doctors should have all the facts of the case including investigations available with them before discussion; (vi) Unit in-charge or treating doctor should be responsible for achieving consensus and should initiate the discussion; (vii) After presenting the facts of the cases, family members should be encouraged to ask questions and clear doubts (if any); (viii) At the end of discussion, a summary of the discussion should be prepared and signed by the next of kin and the unit in-charge or treating doctors; (ix) DNR orders should be reviewed in the event of unexpected improvement or on request of next of kin. Same should be documented; (x) DNR orders remain valid during transport.

Mechanical Valve Thrombosis on Rivaroxaban: Are Novel Anticoagulants Really an Option?

This is a case of a 54-year-old female with a history of mechanical aortic valve replacement who presented in cardiogenic shock. Her primary care provider started her on rivaroxaban for anticoagulation therapy. An urgent transesophageal echocardiogram revealed a significant gradient and thrombosis on one leaflet of the valve that was immobile. Given that she was not a surgical candidate, she underwent thrombolysis. However, she later died due to complications from the thrombotic valve. The utility of target-specific oral anticoagulants has yet to be established in clinical practice.