Adenylate kinase 5 (AK5) autoimmune encephalitis: Clinical presentations and outcomes in three new patients.

Adenylate kinase 5 (AK5) antibodies are biomarkers of a poorly responsive to immunotherapy, non-paraneoplastic, autoimmune limbic encephalitis. We detected 6 patients (all female, median age: 72 years [49-80]) with identical CSF antibody staining by indirect immunofluorescence on mouse tissues. We identified AK5 as the antigen and confirmed with standardized assays. Three patients with clinical information had limbic encephalitis, inflammatory CSF and mesiotemporal lobe T2 hyperintensities that evolved to atrophy on brain MRI. One patient had burning smell sensation with no evidence of seizures. Despite immunotherapy, minimal improvement was noticed in one patient; all had severe memory deficits remaining.

Medical marijuana knowledge and attitudes amongst internal medicine residents.

BACKGROUND: Mounting evidence suggests the safety and efficacy of medical marijuana (MM) in treating chronic ailments, including chronic pain, epilepsy, and anorexia. Despite incremental use of medical and recreational cannabinoids, current limited evidence shows generalized unpreparedness of medical providers to discuss or recommend these substances to their patients. Herein, the present study aims to examine internal medicine residents' knowledge of marijuana and their attitude towards its medical use. METHODS: This is a descriptive cross-sectional study. A survey with 12 standardized queries was created and distributed among the internal medicine residents from Mount Sinai Morningside-West (MSMW) program from July 2020 to December 2020. Participants included preliminary and categorical residents from post-graduate years one to three. The survey consisted of self-assessment of residents' knowledge on the indication, contraindication, adverse effects of MM. RESULTS: Eighty-six (59%) out of 145 residents completed the questionnaire. Despite most trainees (70%) having considered certifying the use of MM for their patients, over 90% reported none to little knowledge on its use. Approximately 80% of the surveyed residents expressed willingness to receive an appropriate educational curriculum. CONCLUSION: To the best of our knowledge, this is the first study that indicated a critical lack of medical marijuana-related knowledge in surveyed internal medicine residents. In a population with growing cannabis consumption, physician training on the indication, toxicity, and drug interaction of cannabinoids is warranted.

Hepatocellular carcinoma, novel therapies on the horizon.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and is associated with high mortality rate. Incidence remains high due to the persistent prevalence of viral hepatitis, alcoholic cirrhosis, and non-alcoholic fatty liver disease (NFLD). Despite screening efforts, the majority of patients present with advanced disease, add to the high risk of recurrence after curative surgery. Conventional chemotherapy did not alter the nature history of advanced and metastatic HCC. The discovery of multiple tyrosine kinase inhibitors (TKIs) led to the approval of sorafenib as first efficacious therapy. A new era in the treatment paradigm of HCC is evolving. Since the advent of sorafenib as an active treatment option for patients presenting with advanced or metastatic disease, several agents have been examined. This was linked with many failures, and success stories to celebrate. Herein, we describe the historical progress and current advances of systemic therapies post-sorafenib. Lenvatinib, regorafenib, cabozantinib, ramucirumab, pembrolizumab, and nivolumab, are all presently added and available therapeutic options in the advanced setting. The evaluation of novel treatment combinations including anti-angiogenic, TKIs plus checkpoint inhibitors, add to dual checkpoint inhibitors is evolving rapidly starting with the advent of the combination of atezolizumab plus bevacizumab. Combining local and systemic therapies is being actively investigated, as an option for locally advanced disease conventionally treated with locoregional approaches. The horizon remains promising and continues to evolve for HCC a disease long considered with unmet needs.

Admission D-dimer levels, D-dimer trends, and outcomes in COVID-19.

Observational data suggest an acquired prothrombotic state may contribute to the pathophysiology of COVID-19. These data include elevated D-dimers observed among many COVID-19 patients. We present a retrospective analysis of admission D-dimer, and D-dimer trends, among 1065 adult hospitalized COVID-19 patients, across 6 New York Hospitals. The primary outcome was all-cause mortality. Secondary outcomes were intubation and venous thromboembolism (VTE). Three-hundred-thirteen patients (29.4%) died, 319 (30.0%) required intubation, and 30 (2.8%) had diagnosed VTE. Using Cox proportional-hazard modeling, each 1 µg/ml increase in admission D-dimer level was associated with a hazard ratio (HR) of 1.06 (95%CI 1.04-1.08, p < 0.0001) for death, 1.08 (95%CI 1.06-1.10, p < 0.0001) for intubation, and 1.08 (95%CI 1.03-1.13, p = 0.0087) for VTE. Time-dependent receiver-operator-curves for admission D-dimer as a predictor of death, intubation, and VTE yielded areas-under-the-curve of 0.694, 0.621, and 0.565 respectively. Joint-latent-class-modeling identified distinct groups of patients with respect to D-dimer trend. Patients with stable D-dimer trajectories had HRs of 0.29 (95%CI 0.17-0.49, p < 0.0001) and 0.22 (95%CI 0.10-0.45, p = 0.0001) relative to those with increasing D-dimer trajectories, for the outcomes death and intubation respectively. Patients with low-increasing D-dimer trajectories had a multivariable HR for VTE of 0.18 (95%CI 0.05-0.68, p = 0.0117) relative to those with high-decreasing D-dimer trajectories. Time-dependent receiver-operator-curves for D-dimer trend as a predictor of death, intubation, and VTE yielded areas-under-the-curve of 0.678, 0.699, and 0.722 respectively. Although admission D-dimer levels, and D-dimer trends, are associated with outcomes in COVID-19, they have limited performance characteristics as prognostic tests.

Ki67 and P53 in Relation to Disease Progression in Metastatic Pancreatic Cancer: a Single Institution Analysis.

We investigated the expression patterns of Ki67 and p53 in metastatic pancreatic adenocarcinomas and analyzed their relationship with disease progression-free survival (PFS) and overall survival (OS) in the overall study population and in patients treated with a gemcitabine-containing chemotherapy versus FOLFIRINOX chemotherapy. Patients with histologically confirmed stage IV adenocarcinoma of the pancreas treated at AUBMC were included after obtaining institutional review board approval (IRB ID: IM.ST.05). The ROC was plotted to identify the threshold Ki-67, p53 and CA19-9 value for disease progression, the identified value was further used in Kaplan Meier curves to compare PFS for both groups (gemcitabine versus FOLFIRINOX). A value of p < 0.05 was considered significant in all analyses. On univariate analysis, patients who had a Ki-67 > 12.5% or a p53 > 15% had significantly shorter PFS (p = 0.034 and p = 0.016, respectively). This effect was restricted to Gemcitabine or gemcitabine-combination treated patients. A decrease in CA19-9 levels 6-8 weeks after chemotherapy of >58% had significantly longer PFS (p = 0.027). On multivariate analysis after controlling for grade, age and P53, Ki-67 remained significant, for every one unit increase in Ki-67 the progression risk increases by 1.017 times. Our study highlights the negative impact of high P53 expression and Ki67 proliferation index on PFS in patients with metastatic pancreatic cancer.

Cancer-Related Pain: Prevalence, Severity and Management in a Tertiary Care Center in the Middle East

Background: Despite pain awareness and the development of treatment guidelines, cancer-related pain assessment and management remain suboptimal. Our objectives were to estimate the prevalence and severity of pain and its interference with daily activities, and evaluate adequacy of treatment in cancer patients in Lebanon. Methods: A total of 400 cancer patients aged 18 and above were interviewed at the American University of Beirut Medical Center surgical and medical oncology floors, outpatient clinics and chemotherapy units from March 2016-February 2017. The subjects covered were socio-demographics, clinical data, and presence of pain in the past month with use of the Brief Pain Inventory questionnaire. Descriptive statistics were conducted using t-test, chi-square and Fischer's exact tests. Pearson's correlation coefficients were used to examine relationships between pain severity and pain interference. Logistic regression was employed to determine risk factors for pain. Results: The majority of participants were Lebanese (76.0%), females (62.7%), married (80.2%), of Muslim faith (64.2%), of urban residence (85.8%), and with insurance plans (81.3%). Most had breast cancer (38.8%), were stage 4 (52.7%) and underwent a combination of surgery and systemic therapy (55.1%). The prevalence of pain in the past month was 29.8%. Among patients with pain, the highest proportion had moderate pain (37.8%) and around 46% received inadequate treatment. Conclusion: More awareness about cancer-related pain is needed to improve pain management and encourage referral to palliative care and pain specialists early-on in diagnosis of disease.

Neuroproteomics and microRNAs studies in multiple sclerosis: transforming research and clinical knowledge in biomarker research.

Multiple sclerosis (MS) is a complex disease characterized by extensive phenotypic variability. Biomarkers to capture the different aspects of MS heterogeneity, and to help make a diagnosis and monitor disease progression, while providing insights into etiopathogenesis and response to treatment, are urgently needed. Omics technologies and research efforts with microRNAs have provide unparalleled opportunities for exploring altered protein profiles associated with molecular mechanisms of disease, substantially expanding the list of candidate biomarkers for MS. This review presents evidence from proteomic studies that have focused on identification of biomarkers released in biofluids as a result of the different pathophysiological processes of MS. Also discussed is the emerging role of miRNAs as complementary biomarkers related to cellular processes occurring in MS patients. Also provided is an overview of candidate biomarkers that have been proposed for elucidating pathophysiological processes and disease activity and for guiding clinical diagnosis and/or therapeutic interventions in MS.