Diffusion Tensor Imaging in a Large Longitudinal Series of Patients With Cervical Spondylotic Myelopathy Correlated With Long-Term Functional Outcome

BACKGROUND Fractional anisotropy (FA) of the high cervical cord correlates with upper limb function in acute cervical cord injury. We investigated the correlation between preoperative FA at the level of maximal compression and functional recovery in a group of patients after decompressive surgery for cervical spondylotic myelopathy (CSM). OBJECTIVE To determine the usefulness of FA as a biomarker for severity of CSM and as a prognostic biomarker for improvement after surgery. METHODS Patients received diffusion tensor imaging (DTI) scans preoperatively. FA values of the whole cord cross-section at the level of maximal compression and upper cervical cord (C1-2) were calculated. Functional status was measured using the modified Japanese Orthopedic Association (mJOA) scale preoperatively and at follow-up up to 2 yr. Regression analysis between FA and mJOA was performed. DTI at C4-7 was obtained in controls. RESULTS Forty-four CSM patients enrolled prior to decompression were compared with 24 controls. FA at the level of maximal compression correlated positively with preoperative mJOA score. Preoperative FA correlated inversely with recovery throughout the postoperative period. This was statistically significant at 12 mo postoperation and nearly so at 6 and 24 mo. Patients with preoperative FA0.55. CONCLUSION In the largest longitudinal study of this kind, FA promises a valid biomarker for severity of CSM and postoperative improvement. FA is an objective measure of function and could provide a basis for prognosis. FA is particularly useful if preoperative values are less than 0.55

Newly Diagnosed Papillary Craniopharyngioma With BRAF V600E Mutation Treated With Single-Agent Selective BRAF Inhibitor Dabrafenib: A Case Report

We report a case of a patient with newly diagnosed, locally extensive and cystic, suprasellar papillary craniopharyngioma successfully treated with single-agent Dabrafenib. The patient was symptomatic with gait imbalance with falls, lethargic episodes, fatigue and incontinence. Diagnostic imaging demonstrated a cystic suprasellar tumor extending into the third ventricle causing obstructive hydrocephalus. The tumor was partially debulked, and bilateral shunts were placed. NGS sequencing demonstrated BRAF V600E mutation, and the patient was prescribed dual agent Dabrafenib and Trametinib. However, due to insurance denial for Trametinib, he only received single-agent Dabrafenib (150mg BID). The treatment resulted in a major response (over two years), including reduction of the tumor cyst, and improvement of the clinical symptoms. No adverse events have been reported. The patient continues on Dabrafenib (150 mg BID) with a steady reduction in tumor size, and improvement in cognitive function leading to independent living

Serous effusions in Burkitt lymphomas: a report of two paediatric cases with review of literature

The serosal cavity can be involved in many diseases, both benign and malignant. Such involvement is secondary to occurrence of disease at other sites. Lymphoma, although not a very common cause for serous effusion, is one of the most important one. The reason for serosal involvement in lymphomas has not been fully elucidated. These two cases highlight the importance of pleural and peritoneal fluid examination in the diagnosis of lymphoma. There is correlation between fluid examination and subsequent cytological and histopathological studies, with immunohistochemical confirmation. A comprehensive understanding of the mechanism of serosal involvement in lymphomas may lead to early diagnosis, better patient management and also development of newer treatment modalities for the same

Primary Chondrosarcoma in L-shaped Crossed Fused Renal Ectopia Coexisting with Papillary Urothelial Carcinoma in Urinary Bladder – An Enigmatic Entity with Poor Prognosis

Primary renal chondrosarcomas are rare tumors that are high-grade in nature and, unfortunately, have poorly understood pathogenesis and extremely low prognosis. The coexistence of a discrete malignancy in the urinary bladder is even rarer, with the occurrence of distinct papillary urothelial carcinoma in the urinary bladder in this case. The clinical presentation is nonspecific, and the primary radiological investigations have a limited scope in providing specific diagnosis of this entity. The final diagnosis is possible on thorough histopathological examination of the resected specimen, which requires extensive sampling and meticulous reporting. As of now, the only way to achieve a better prognosis is by early diagnosis. It is necessary to keep the possibility of occurrence of sarcomas at rare sites in the differential diagnoses. The cytogenetic and molecular abnormalities associated with this entity need to be elucidated to achieve a more satisfactory outcome concerning the overall management of the patient

Optimization of sub 100 nm Γ-gate Si-MOSFETs for RF applications

This paper presents characterization and simulation studies on the RF performance of the Γ (Gamma) gate MOSFETs. The Γ-gate MOSFET offers the advantage of reduced gate resistance, a critical parameter in high frequency circuits. The aim of this study is to identify the optimum Γ-gate extension length from the gate and drain resistance point of view in aggressively scaled CMOS

Statistical analysis of the Indus script using nn-grams

The Indus script is one of the major undeciphered scripts of the ancient world. The small size of the corpus, the absence of bilingual texts, and the lack of definite knowledge of the underlying language has frustrated efforts at decipherment since the discovery of the remains of the Indus civilisation. Recently, some researchers have questioned the premise that the Indus script encodes spoken language. Building on previous statistical approaches, we apply the tools of statistical language processing, specifically $n$-gram Markov chains, to analyse the Indus script for syntax. Our main results are that the script has well-defined signs which begin and end texts, that there is directionality and strong correlations in the sign order, and that there are groups of signs which appear to have identical syntactic function. All these require no {\it a priori} suppositions regarding the syntactic or semantic content of the signs, but follow directly from the statistical analysis. Using information theoretic measures, we find the information in the script to be intermediate between that of a completely random and a completely fixed ordering of signs. Our study reveals that the Indus script is a structured sign system showing features of a formal language, but, at present, cannot conclusively establish that it encodes {\it natural} language. Our $n$-gram Markov model is useful for predicting signs which are missing or illegible in a corpus of Indus texts. This work forms the basis for the development of a stochastic grammar which can be used to explore the syntax of the Indus script in greater detail

Views and attitudes of healthcare professionals on do-not-attempt-cardiopulmonary-resuscitation in low-and-lower-middle-income countries: a systematic review

Background Healthcare Professionals (HCPs) are important stakeholders and gatekeepers in resuscitation decision-making. This systematic review explored the views and attitudes of HCPs on do-not-attempt-cardiopulmonary resuscitation (DNAR) in low-and-lower-middle-income countries (LLMICs). Methods PubMed, EMBASE, PsycInfo, CINAHL, Cochrane library, Scopus, and Web of Science were searched from 01-Jan-1990 to 24-February-2023. Empirical peer-reviewed literature exploring views and attitudes of HCPs on DNAR for adult patients (aged ≽18 years) in LLMIC were included. No restriction on empirical study designs was imposed. Two independent reviewers performed screening, data extraction and critical appraisal. Hawker’s tool and Popay’s narrative synthesis were used for critical appraisal and data synthesis respectively. Review findings were interpreted using Cognitive Dissonance theory (CDT). Results Of the 5132 records identified, 44 studies encompassing 7490 HCPs were included. The median Hawker score was 28 with 27% studies having low risk of bias. Three themes emerged. 1: Meaning-Making of DNAR construct. Most HCPs agreed that DNAR avoided inappropriate resuscitations, needless suffering and allowed fair allocation of resources. However, there was a lack of consensus on DNAR timing. 2: Barriers and Facilitators. Sociocultural norms, lack of legal clarity, organisational policies, societal and family views, religious and ethical beliefs, and healthcare providers’ presuppositions often hindered DNAR practice. HCPs had inconsistent religious and ethical beliefs about DNAR. 3: Tensions and complexities of contemporary practice. HCPs expressed fears, concerns, guilt and distress while recommending DNAR. HCPs differed on involving patients. The DNAR practice was arbitrary and suboptimal like informal DNAR orders, pretended and symbolic CPRs. Conclusion Most HCPs in LLMICs viewed DNAR as essential However, they faced barriers to DNAR implementation at macro-(law, sociocultural norms), meso-(organization) and micro-(HCP- and family views) levels. These barriers contributed to HCPs’ fears, concerns and distress concerning DNAR. The CDT provided the lens to link HCPs cognitions, affect and behaviour into a chain of events that explained suboptimal resuscitation practices

Phase 1 Trial of TPI 287, a Microtubule Stabilizing Agent, in Combination With Bevacizumab in Adults With Recurrent Glioblastoma

BACKGROUND: Recurrent glioblastoma (rGBM) has limited treatment options. This phase 1 protocol was designed to study the safety and preliminary efficacy of TPI 287, a central nervous system penetrant microtubule stabilizer, in combination with bevacizumab (BEV) for the treatment of rGBM. METHODS: GBM patients with up to 2 prior relapses without prior exposure to anti-angiogenic therapy were eligible. A standard 3 + 3 design was utilized to determine the maximum tolerated dose (MTD) of TPI 287. Cohorts received TPI 287 at 140-220 mg/m RESULTS: Twenty-four patients were enrolled at 6 centers. Treatment was generally well tolerated. Fatigue, myelosuppression, and peripheral neuropathy were the most common treatment emergent adverse events. Dose-limiting toxicity was not observed, thus the MTD was not determined. Twenty-three patients were evaluable for median and 6-month progression-free survival, which were 5.5 months (mo) and 40%, respectively. Median and 12-month overall survival were 13.4 mo and 64%, respectively. The optimal phase 2 dose was determined to be 200 mg/m CONCLUSIONS: TPI 287 can be safely combined with BEV for the treatment of rGBM and preliminary efficacy supports further investigation of this combination

Prediction of Incident Heart Failure in CKD: The CRIC Study.

INTRODUCTION: Heart failure (HF) is common in chronic kidney disease (CKD); identifying patients with CKD at high risk for HF may guide clinical care. We assessed the prognostic value of cardiac biomarkers and echocardiographic variables for 10-year HF prediction compared with a published clinical HF prediction equation in a cohort of participants with CKD. METHODS: We studied 2147 Chronic Renal Insufficiency Cohort (CRIC) participants without prior HF with complete clinical, cardiac biomarker (N-terminal brain natriuretic peptide [NT-proBNP] and high sensitivity troponin-T [hsTnT]), and echocardiographic data (left ventricular mass [LVM] and left ventricular ejection fraction [LVEF] data). We compared the discrimination of the 11-variable Atherosclerosis Risk in Communities (ARIC) HF prediction equation with LVM, LVEF, hsTnT, and NT-proBNP to predict 10-year risk of hospitalization for HF using a Fine and Gray modeling approach. We separately evaluated prediction of HF with preserved and reduced LVEF (LVEF ≥50% and <50%, respectively). We assessed discrimination with internally valid C-indices using 10-fold cross-validation. RESULTS: Participants mean (SD) age was 59 (11) years, 53% were men, 43% were Black, and mean (SD) estimated glomerular filtration rate (eGFR) was 44 (16) ml/min per 1.73 m2. A total of 324 incident HF hospitalizations occurred during median (interquartile range) 10.0 (5.7-10.0) years of follow-up. The ARIC HF model with clinical variables had a C-index of 0.68. Echocardiographic variables predicted HF (C-index 0.70) comparably to the published ARIC HF model, while NT-proBNP and hsTnT together (C-index 0.73) had significantly better discrimination (P = 0.004). A model including cardiac biomarkers, echocardiographic variables, and clinical variables had a C-index of 0.77. Discrimination of HF with preserved LVEF was lower than for HF with reduced LVEF for most models. CONCLUSION: The ARIC HF prediction model for 10-year HF risk had modest discrimination among adults with CKD. NT-proBNP and hsTnT discriminated better than the ARIC HF model and at least as well as a model with echocardiographic variables. HF clinical prediction models tailored to adults with CKD are needed. Until then, measurement of NT-proBNP and hsTnT may be a low-burden approach to predicting HF in this population, as they offer moderate discrimination

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning