Medical Research Foundation Research Articles

Acute myocardial infarction in the Covid-19 era: incidence, clinical characteristics and in-hospital outcomes – a multicenter registry

Abstract Background A reduction in acute myocardial infarction (AMI) hospitalizations during the coronavirus pandemic has been previously documented. We aimed to describe the characteristics and in-hospital outcomes of AMI patients during the Covid-19 era compared to a recent previous registry. Methods We conducted a prospective, multicenter, observational study involving 13 intensive cardiac care units (ICCUs) to evaluate consecutive AMI patients admitted throughout an 8-week period during the Covid-19 outbreak. Data were compared to the corresponding period in 2018 using an acute coronary syndrome survey conducted in all ICCUs in Israel. The primary end-point was defined as a composite of sustained ventricular arrhythmia, pulmonary congestion, and/or in-hospital mortality. Results The study cohort comprised 1466 patients, of whom 774 (53%) were hospitalized during the Covid-19 outbreak. Overall, 841 patients were diagnosed with ST-elevation MI (STEMI): 424 (50.4%) during the Covid-19 era and 417 (49.6%) during the parallel period in 2018. No differences were detected in the admission rate of patients between the two study periods. STEMI patients admitted during the Covid-19 period tended to have fewer co-morbidities, but a higher Killip class (p value = 0.03). The median time from symptom onset to reperfusion was extended from 180 minutes (IQR 122–292) in 2018 to 290 minutes (IQR 161–1080, p<0.001) in 2020. Hospitalization during the Covid-19 era was independently associated with an increased risk of the combined endpoint of heart failure, malignant arrhythmia, or death in the multivariable logistic regression model (OR 1.63, 95% CI 1.02–2.65, p value = 0.05). Conclusion While the admission rate of AMI and STEMI in Israel remained similar during both the Covid-19 era and the corresponding period in 2018, total ischemic time extended significantly during the Covid-19 period, which translated into a more severe disease status upon hospital admission, and a higher rate of in-hospital adverse events. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): This work was supported by a grant from a Fefer foundation for medical research

Low endothelial shear stress, microcalcification activity and high-risk plaque features: merging computational flow modelling, OCT and 18F-NaF PET/CT

Abstract Background Endothelial shear stress (ESS) has a critical role in endothelial function. Abnormal shear stress leads to endothelial dysfunction, which contributes to arterial plaque initiation and development. Four dimensional magnetic resonance can determine shear stress in the larger arteries but cannot resolve the detail needed to calculate shear stress in the coronary arteries and thus methods such as computational fluid dynamics (CFD) are required. Additionally, a key feature of biologically active plaques is microcalcification activity, and this can be detected using 18F-sodium fluoride (18F-NaF) positron emission tomography (PET). Furthermore, using high resolution optical coherence tomography (OCT), the high-risk features plaques can be visualized and quantified. We aimed to merge these three techniques to investigate if low ESS is associated with high-risk plaque features and active microcalcifications in acute coronary syndrome. Methods We began by merging OCT images with CTCA images to obtain detailed 3D reconstructions of the target vessel. We then simulated blood flow and calculated the ESS, from which we extracted the area of low ESS (<0.4 Pa). We quantified plaque features using OCT and measured the maximum 18F-NaF uptake, and compared data at both the coronary segment and whole artery level (Figure 1). Results We investigated 20 arteries from 18 patients which we obtained 38 coronary segments according to the SCCT guidelines. We found that areas of low ESS were were significantly and positively associated with high-risk plaque features: macrophage infiltration (segment, rs=0.33, p=0.043; artery, rs=0.46, p=0.041) and presence of cholesterol crystals (segment, rs=0.45, p=0.005; artery, rs=0.58, p=0.007). Vessel segments with thin-capped fibroatheroma had greater area of low ESS (20 vs 4%). The uptake of 18F-NaF was positively associated with the area of low ESS (segment, rs=0.52, p=0.001; artery, rs=0.64, p=0.002). We found that there were typically more plaque features found in regions of low ESS (Table 1). Conclusion Here we provide the first data associating low ESS with both high-risk plaque features and active microcalcifications in patients with acute coronary syndrome. Although our sample size is small, these data are encouraging and could lead to better understanding of how best to deem a plaque “high risk”. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Royal Perth Hospital Medical Research Foundation Figure 1Table 1

Advance Care Planning Coaching in CKD Clinics: A Pragmatic Randomized Clinical Trial

Although guidelines recommend more and earlier advance care planning (ACP) for patients with chronic kidney disease (CKD), scant evidence exists to guide incorporation of ACP into clinical practice for patients with stages of CKD prior to kidney failure. Involving nephrology team members in addition to primary care providers in this important patient-centered process may increase its accessibility. Our study examined the effect of coaching implemented in CKD clinics on patient engagement with ACP. Multicenter, pragmatic randomized controlled trial. Three CKD clinics in different states participated: 273 patients consented to participate, 254 were included in analysis. Eligible patients were 55 years or older, had stage 3-5 CKD, and were English speaking. Nurses or social workers with experience in nephrology or palliative care delivered individualized in-person ACP sessions. The enhanced control group was given Make Your Wishes About You (MY WAY) education materials and was verbally encouraged to bring their completed advance directives to the clinic. Primary outcome measures were scores on a 45-point ACP engagement scale at 14 weeks and a documented advance directive or portable medical order at 16 weeks after enrollment. Among 254 participants analyzed, 46.5% were 65-74 years of age, and 54% had CKD stage 3. The coached patients scored 1.9 points higher at 14 weeks on the ACP engagement scale (β= 1.87 [95% CI, 0.13-3.64]) adjusted for baseline score and site. Overall, 32.8% of intervention patients (41 of 125) had an advance directive compared with 17.8% (23 of 129) of patients in the control group. In a site-adjusted multivariable model, coached patients were 79% more likely to have a documented advance directive or portable medical order (adjusted risk ratio, 1.79 [95% CI, 1.18-2.72]), with the impact principally evident at only 1 study site. Small number of study sites and possible unrepresentativeness of the broader CKD population by study participants. Individualized coaching may be effective in enhancing ACP, but its impact may be influenced by the health care environment where it is delivered. The Patrick and Catherine Weldon Donaghue Medical Research Foundation, via the Greater Value Portfolio. Registered at ClinicalTrials.gov with study number NCT03506087.

A study of neutrophil lymphocyte ratio (NLR) as a predictor of complicated appendicitis

Introduction: Appendicitis is one of the most common surgical pathologies. It is classified into complicated and uncomplicated appendicitis. Neutrophil Lymphocyte ratio (NLR) is an easily available lab parameter which can be used to differentiate complicated and uncomplicated appendicitis.Aims and objectives: To identify the reliability of NLR as a predictor of complicated appendicitis and to study the association of increased NLR with complicated appendicitis, among the cases of appendicitis who presented to our tertiary care centre.Methodology: This a retrospective study of all the cases operated for appendicitis in surgical department of Dr. Pinnamaneni Siddhartha Institute of Medical Sciences and Research Foundation over a period of 2 years. Clinical details were retrieved from case records and data was analysed using IBM SPSS version 21. Results and conclusion: Total sample size was 250 (Male-193, Female-57), Mean age 30.6 ±15.294 years. The mean value of the NLR for Complicated appendicitis based on ROC analysis is 7.3 ± 2.98 and area under ROC curve was 0.7, with a Sensitivity of 98% and a specificity of 65% for predicting complicated appendicitis. NLR is a reliable preoperative investigation to predict complicated appendicitis.

A clinicopathological study of psoriasiform dermatitis

Background: Psoriasis being an autoimmune disease, affecting almost 3% of the world’s population has been an agonizing problem both to the patient and to the doctor who treat them. It has been confusing to the world since biblical times as to it origin and course. Though not contagious, contrary to the beliefs of our fore fathers, the disease is still associated with social stigma and thus has a negative psychological effect on the patient.Though not completely curable, the modern medicine can help in bringing down the severity of the disease if diagnosed correctly and thus uplift the sufferers.Methodology: This study was conducted on 75 patients who attended the OPD of the Department of Dermatology, Sree Gokulam Medical College and Research Foundation, with an aim to decrease the dilemma of diagnosing psoriasis and differentiating it from psoriasiform dermatitis for a period of one year.Results: The histopathological parameters were compared among the 53 patients who were divided into two groups, psoriasis and psoriasiform dermatitis. The different histopathological parameters were compared among these two groups. Of these parameters, parakeratosis, hypogranulosis, acanthosis, regular elongation of rete ridges, mitosis extending beyond the basal layer of epidermis, pallor in the upper layers of epidermis, suprapapillary thinning, dermal oedema and dilated and tortuous blood vessels in the papillary dermis have been evaluated as significant determinants to the diagnosis of psoriasis even in the absence of Munro microabscess and spongiform pustule of Kogoj.Conclusion: The study proved helpful in assessing the determinants that would favor the diagnosis of psoriasis in the absence of a classical histopathological picture, thus aiding in the treatment of the patient.

Microsurgical Resection of Dorsal Pontine Cavernous Malformation: The Telovelar Approach Augmented by the Tonsillouvular Fissure Exposure: 2-Dimensional Operative Video.

Surgical approaches to lesions of the fourth ventricle (FV) have been modified over the years to reduce the complications associated with splitting the inferior cerebellar vermis (ICV) and disrupting the brainstem and critical surrounding structures.1-4 Two common approaches to lesions of this region include the transvermian approach (TVA) and telovelar approach (TeVA).2 The TVA was initially considered the conventional route of access to lesions of the FV1 but has been associated with significant risks, including possible gait ataxia and dysarthria.3 The TeVA is advantageous, as it involves dissection along natural clefts and division of non-neural tissue and provides good exposure of the superolateral recess with modest exposure of the rostral FV. The TeVA approach can be augmented by opening the tonsilouvular fissures (TUFs). This added dissection allows greater lateral and superior exposure with less need for retraction. In this operative video, we demonstrate a case in which we augmented the TeVA with a TUF dissection to access a dorsal pontine cavernous malformation. We performed a midline suboccipital craniotomy with a C1 posterior laminectomy. TUF dissection was followed by division of the tela choroidea (TC), which allowed for more lateral exposure of the FV and excellent visualization of the cavernous malformation without the need to traverse neural tissue. TeVA augmented by TUF dissection provided adequate access to the dorsal pons for complete resection of the cavernous malformation. The patient consented to the procedure as shown in this operative video and gave informed written consent for use of her images in publication. Anatomic images provided by courtesy of © The Rhoton Collection. http://rhoton.ineurodb.org/. Video © Mayo Foundation for Medical Education and Research, 2021. Used with permission.

Ethical Concerns About Reidentification of Individuals from MRI Neuroimages

Ethical Concerns About Reidentification of Individuals from MRI Neuroimages

Rapid Onset Functional Tic-Like Behaviors in Young Females During the COVID-19 Pandemic.

Rapid Onset Functional Tic-Like Behaviors in Young Females During the COVID-19 Pandemic.

Ageing and chronic disease-related changes in the morphometric characteristics of ovarian follicles in cynomolgus monkeys (Macaca fascicularis).

How is the localisation of ovarian follicles affected by ageing and chronic diseases? Ovarian follicles shift deeper towards the medulla, due to thickening of the tunica albuginea (TA), with ageing and some major common chronic diseases. The ovary undergoes morphological and functional changes with ageing. The follicular pool follows these changes with alterations in the amount and distribution of residual follicles. Diseases causing a chronic inflammatory process are associated with morphological changes and impaired ovarian function. We conducted a cross-sectional study, examining 90 ovaries from 90 female monkeys. The samples were collected from April 2018 to March 2019 at Tsukuba Primate Research Center in National Institutes of Biomedical Innovation, Health and Nutrition, Japan. Ovarian samples were obtained from cynomolgus monkeys that died from natural causes or were euthanised. Ovarian sections were stained with haematoxylin and eosin (H&E) for histological analyses. In ovarian sections from 64 female macaques aged 0-25 years, a total of 13 743 follicles at different developmental stages (primordial, intermediary, primary, early secondary and late secondary) were assessed to determine the depth of each follicle from the outer surface of the ovarian cortex to the far end of the follicle, by using a digital imaging software. TA thickness was measured as sum of basal membrane and tunica collagen layer for each ovary under H&E staining. To explore the possibility of age-related trends in ovarian morphometric characteristics, samples were divided into four different age groups (0-3 years (pre-menarche), 4-9 years, 10-14 years and 15-20 years). To evaluate the effect of common chronic diseases on ovarian morphometric characteristics, macaques with diabetes mellitus (DM) (n = 10), endometriosis (n = 8) or inflammatory bowel disease (IBD) (n = 8) were compared to age-matched controls without chronic diseases. Ovarian morphometric analysis revealed that the relative location of follicles became deeper in all age groups according to development of follicles (P < 0.05). Total follicle distance from the ovarian surface was increased with ageing (P < 0.05). In a sub-analysis according to developmental stage, only primordial and intermediary follicles were localised deeper with increasing age (P < 0.05). TA thickness was also increased with ageing (P < 0.05). The localisation of the total number of follicles became deeper in ovaries from monkeys with DM, endometriosis or IBD as compared to the control group (P < 0.05). With DM, analysis of follicles distance at almost each developmental stage was significantly deeper compared to controls (P < 0.05) with the exception of early secondary follicles. With endometriosis, follicles at primary and early and late secondary stages were significantly deeper compared to controls (P < 0.05). Also with IBD, follicles at primary and early and late secondary follicles were significantly deeper compared to controls (P < 0.001). The TA was thicker with DM and endometriosis compared to controls (P < 0.05), but not with IBD (P = 0.16). NA. Two-dimensional histology was used to assess follicle localisation. The possibility of minimal variations between the measured distance to the actual distance in a spherical structure cannot be excluded. Additionally, the severity of disease was not assessed. This study is the first step towards enhancing our understanding of how ageing and chronic diseases affect the relative localisation of dormant and developing follicles. These observations, combined with possible future human studies, may have managerial implications in the field of fertility preservation and other conditions involving ovarian tissue cryopreservation. The present work was supported by the Grant-in-Aid for Scientific Research B (19H03801) (to K.K.), Challenging Exploratory Research (18K19624), Japan Agency for Medical Research and Development, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Takeda Science Foundation and Naito Foundation (to K.K.). All authors have no conflicts of interest directly relevant to the content of this article.

Optic Canal Decompression: Concepts and Techniques: 2-Dimensional Operative Video

The optic canal (OC) is a bony channel that transmits the optic nerve (ON) and ophthalmic artery (OphA) as they course through the lesser wing of the sphenoid bone to the orbital apex. The OC is involved in a variety of intracranial and extracranial pathologies,1 and opening of the canal may be necessary in order to achieve adequate exposure, better disease control, and vision preservation.2 Depending on the location of the pathology and its relationship with the optic nerve, the OC may be decompressed through an open transcranial approach or an endoscopic endonasal approach.1,3 OC drilling can be tailored based on the location of the pathology and its extension. Anterior clinoid process and optic strut drilling can be added based on these factors as well.4,5 In this video, we demonstrate the steps of OC drilling in both transcranial microscopic and endoscopic endonasal approaches through a combination of animated illustrations and operative videos. We present 4 cases, including 2 transcranial microscopic and 2 endoscopic endonasal approaches,6 demonstrating OC decompression and its technical nuances. Each case was selected to represent the range of pathologies relevant to OC drilling to allow for a complete understanding of the techniques and concepts required for optimal treatment. An informed written consent has been obtained from each of the patients in this publication. Video © Mayo Foundation for Medical Education and Research. All rights reserved. Copyright information: Bendok BR, Abi-Aad KR, Sattur MG, Welz ME, Hoxworth JM, Lal D. Endoscopic resection of a paraclinoid meningioma extending into the optic canal: 2-dimensional operative video. Operative Neurosurgery. 2018 September 1;15(3):356 by permission of Oxford University Press. Cadaveric images provided by courtesy of: The Rhoton Collection. http://rhoton.ineurodb.org/.

Cisd2 Plays an Essential Role in Corneal Epithelial Regeneration

Age-related changes affecting the cornea and ocular surface cause vision loss in the elderly. We investigated the role of Cisd2 in corneal health and disease. Five major discoveries were made. Firstly, in patients with corneal epithelial disease, CISD2 is down-regulated in their corneal epithelial cells. Secondly, using mouse cornea, Cisd2 deficiency causes a cycle of chronic injury and persistent repair resulting in exhaustion of the limbal progenitor cells. Thirdly, in human corneal epithelial cells, Cisd2 deficiency disrupts intracellular Ca2+ homeostasis, impairing mitochondrial function, thereby retarding corneal repair. Fourthly, cyclosporine A and EDTA facilitate corneal epithelial wound healing in Cisd2 knockout mice. Finally, cyclosporine A treatment restores corneal epithelial erosion in patients with dry eye disease, which affects the ocular surface. These findings reveal that Cisd2 plays an essential role in the cornea and that Ca2+ signaling pathways are potential targets for developing therapeutics of corneal epithelial disease. Keywords: corneal wound healing; Cisd2; calcium homeostasis; limbal stem cell deficiency; EDTA; cyclosporine A. Funding: We acknowledge the support provided by grants from the Ministry of Science and Technology (MOST104-2314-B-182-070, MOST105-2314-B-182-066-MY3, and MOST108-2314-B-182-049- MY3 to CCS; MOST 109-2327-B-010-002, MOST 109-2320-B-010-043 and MOST 107-2320-B-010- 037-MY3 to TFT), and from Chang Gung Medical Research Foundation (CORPG2L0011 to CCS). Declaration of Interest: None to declare. Ethical Approval: This study has been approved by the Institutional Review Board (#201509558B0, #201900646B0, #20200799B0, #202001685B0) at Chang Gung Memorial Hospital, Taiwan. The animal protocols were approved by the Institutional Animal Care and Use Committee of Chang Gung Memorial Hospital (approval no. 2015121606, 2020092211)and National Yang-Ming University (approval no. 1021218).

4-Phenylbutyrate Restores Localization and Membrane Repair to Human Dysferlin Mutation

Dysferlinopathies are muscular dystrophies caused by recessive loss-of-function mutations in dysferlin ( DYSF), a membrane protein involved in skeletal muscle membrane repair. We describe a cell-based assay in which human DYSF proteins bearing missense mutations are quantitatively assayed for membrane-localization by flow cytometry, and identified 64 localization-defective DYSF mutations. Using this platform, we show that the clinically approved drug 4-phenylbutryric acid (4-PBA) partially restores membrane-localization to 25 mutations, as well as membrane repair to cultured myotubes expressing two different mutations. Two-day oral administration of 4-PBA to mice homozygous for one of these mutations restored myofiber membrane repair. 4-PBA may hold therapeutic potential for treating a subset of humans with muscular dystrophy due to dysferlin deficiency. Funding Information: The Glenn Foundation for Medical Research, The Jain Foundation, National Institutes of Health R21 Grant 1-R21AR068477-01 (MV, EOW), Grant-in-Aid from Japan Society for the Promotion of Science JSPS 16J40231 (KT), Uehara Memorial Foundation, Japan (KT), Kanzawa Medical Research Foundation Grant-in-Aid (NT), Japan Society for the Promotion of Science Overseas Research Fellowships No. 363 (NT), National Cancer Institute Grant P30-CA14051 Koch Institute. Declaration of Interests: LG is a founder of Elysium Health and Galilei Biosciences.

A Computational Tumor-Infiltrating Lymphocyte Assessment Method Comparable with Visual Reporting Guidelines for Triple-Negative Breast Cancer.

BackgroundTumor-infiltrating lymphocytes (TILs) are clinically significant in triple-negative breast cancer (TNBC). Although a standardized methodology for visual TILs assessment (VTA) exists, it has several inherent limitations. We established a deep learning-based computational TIL assessment (CTA) method broadly following VTA guideline and compared it with VTA for TNBC to determine the prognostic value of the CTA and a reasonable CTA workflow for clinical practice.MethodsWe trained three deep neural networks for nuclei segmentation, nuclei classification and necrosis classification to establish a CTA workflow. The automatic TIL (aTIL) score generated was compared with manual TIL (mTIL) scores provided by three pathologists in an Asian (n = 184) and a Caucasian (n = 117) TNBC cohort to evaluate scoring concordance and prognostic value.FindingsThe intraclass correlations (ICCs) between aTILs and mTILs varied from 0.40 to 0.70 in two cohorts. Multivariate Cox proportional hazards analysis revealed that the aTIL score was associated with disease free survival (DFS) in both cohorts, as either a continuous [hazard ratio (HR)=0.96, 95% CI 0.94–0.99] or dichotomous variable (HR=0.29, 95% CI 0.12–0.72). A higher C-index was observed in a composite mTIL/aTIL three-tier stratification model than in the dichotomous model, using either mTILs or aTILs alone.InterpretationThe current study provides a useful tool for stromal TIL assessment and prognosis evaluation for patients with TNBC. A workflow integrating both VTA and CTA may aid pathologists in performing risk management and decision-making tasks.

Systemic Lupus Erythematosus Research: A Bibliometric Analysis over a 50-Year Period.

Bibliometric analysis is a well-established approach to quantitatively assess scholarly productivity. However, there have been few assessments of research productivity on systemic lupus erythematosus (SLE) to date. The aim of this study was to analyze global research productivity through original articles published in journals indexed by the Web of Science from 1971 to 2020. Bibliometric data was obtained from the Science Citation Index Expanded in the Web of Science Core Collection database. Only original articles published between 1971 and 2020 on SLE were included in the analysis. Over the 50-year period, publication production in SLE research has steadily increased with a mean annual growth rate of 8.0%. A total of 44,967 articles published in 3435 different journals were identified. The journal Lupus published the largest number of articles (n = 3371; 8.0%). A total of 148 countries and regions contributed to the articles. The global productivity ranking was led by the United States (n = 11,244, 25.0%), followed by China (n = 4893, 10.9%). A three-field plot showed that the Oklahoma Medical Research Foundation and the Johns Hopkins University together contributed 18.5% of all articles from the United States. A co-occurrence network analysis revealed five highly connected clusters of SLE research. In conclusion, this bibliometric analysis provided a comprehensive overview of the status of SLE research, which could enable a better understanding of the development in this field in the past 50 years.

Predictive Factors of Overall Survival and the Completion of Four Cycles of Azacitidine: An MDS-CAN Study

Predictive Factors of Overall Survival and the Completion of Four Cycles of Azacitidine: An MDS-CAN Study

An MDS Specific Frailty Index Based on Cumulative Deficits Adds Independent Prognostic Value to Established Clinical Prognostic Scoring Systems

An MDS Specific Frailty Index Based on Cumulative Deficits Adds Independent Prognostic Value to Established Clinical Prognostic Scoring Systems

Cannabinoid treatment of opiate addiction

RC is funded by the Ainsworth Medical Research Innovation Fund and the Rebecca Cooper Medical Research Foundation.

Strategies to Minimize Heterogeneity and Optimize Clinical Trials in Acute Respiratory Distress Syndrome (ARDS): Insights from Mathematical Modeling

Background: Mathematical deconvolution of multiple biologic pathways simultaneously active in critical illness may aid in the interpretation of clinical data.Methods: Using a systems biology model of COVID-19, we analyze the effect of immunomodulation on diverse patient phenotypes. We define optimal treatment and optimal treatment initiation time, identify biologic programs which determine heterogeneous clinical responses and predict biomarkers of those programs. Finally, we evaluate the utility of model biomarkers for identifying high-risk patients in a clinical database of COVID-19 patients.Findings: We predict patient phenotypes with disparate clinical responses to the same therapy. Older and hyperinflammed patients respond better to immunomodulation than obese and diabetic patients. Optimal treatment initiation time is driven by neutrophil recruitment dynamics, extra-pulmonary cytokine expression, systemic microthrombosis and the renin-angiotensin system (RAS) in older patients, and by RAS, systemic microthrombosis and trans IL6 signaling for hyperinflamed patients. For older and hyperinflamed patients, IL6 modulating therapy is optimal when initiated very early (th day of infection) and broad immunosuppression therapy (corticosteroids) is better later in the disease (between 7th– 9thday of infection). We show that biologic programs identified by the model correspond to clinically identified markers of disease severity,Interpretation: Modeling of COVID-19 pathobiology suggests combinations of patient phenotypes which may lead to disparate outcome when included in a trial with a single intervention protocol. Systems biology modeling thus has potential for suggesting refinements to clinical trial design by aiding in the identification of biologic mechanisms underlying clinical heterogeneity and predicting markers of those mechanisms.Funding: Jain’s research is supported by NIH grants R35-CA197743, U01-CA224348, R01-CA259253, R01-CA208205 R01-NS118929, National Foundation for Cancer Research, Ludwig Cancer Center at Harvard; Advanced Medical Research Foundation and Jane's Trust Foundation. Lance Munn’s research is supported by R01-CA2044949. No other funding to declare. Declaration of Interest: LLM owns equity in Bayer AG and consultant for SimBiosys. Jain received an Honorarium from Amgen; Consultant fees from Chugai, Elpis, Pfizer, SPARC, SynDevRx; Owns equity in Accurius, Enlight, SynDevRx; Board of Trustees of Tekla Healthcare Investors, Tekla Life Sciences Investors, Tekla Healthcare Opportunities Fund, Tekla World Healthcare Fund and received a research Grant from Boehringer Ingelheim. All others have nothing to declare. Ethical Approval: This analysis was approved by the MGB Institutional Review Board (IRB protocol #2020P000964).

Dietary Intake of Vitamin K and Its Association With All-Cause, Cardiovascular Disease and Cancer Mortality in the Danish Diet, Cancer, and Health Cohort

ObjectivesOur objective was to examine whether dietary intakes of vitamin K1 and vitamin K2 were associated with all-cause, cardiovascular disease (CVD)-related and cancer-related mortality and to identify subpopulations that may benefit the most from higher vitamin K intakes. MethodsParticipants from the Danish Diet, Cancer, and Health Study cohort, between 50–65 years of age at recruitment, completed a food-frequency questionnaire (FFQ) at baseline and were followed up for cancer-related, CVD-related, and all-cause mortality using nationwide registries. Intakes of vitamin K1 (phylloquinone) and vitamin K2 (menaquinones 4–10) were estimated from FFQs, and their relationship with mortality outcomes was determined using Cox proportional hazards models. ResultsIn total, 56 048 Danish residents, with a median [interquartile range] age of 56 [52–60] years at entry, were followed up for 21 [20–22] years. During follow-up, 14 083 individuals died from any cause; 5015 deaths were CVD-related; and 6342 deaths were cancer-related. Intakes of vitamin K1, but not vitamin K2, were non-linearly inversely associated with both all-cause and cause-specific mortality, after adjusting for demographic and lifestyle confounders. Compared to individuals with the lowest vitamin K1 intakes, individuals with the highest intakes had a 24% [HR (95% CI): 0.76 (0.72, 0.79)] lower risk of all-cause mortality, a 28% [0.72 (0.66, 0.79)] lower risk of CVD-related mortality, and a 20% [0.80 (0.75, 0.86)] lower risk of cancer-related mortality. Furthermore, the association between vitamin K1 intake and cancer mortality appeared to be stronger in smokers than in non-smokers (p for interaction = 0.002). ConclusionsModerate to high intakes of vitamin K1, but not K2, were associated with a lower risk of all-cause, CVD-related and cancer-related, mortality. Promoting adequate intakes of vitamin K1, particularly in smokers, may help to reduce all-cause, CVD-related and cancer-related mortality at the population level. Funding SourcesThe Danish Diet, Cancer, and Health Study was funded by the Danish Cancer Society, Denmark. This study was supported by the Raine Medical Research Foundation and the Healy Medical Research Foundation.

Clinical epidemiology and treatment outcome of Hexaconazole poisoning – A prospective six year study

Background: Hexaconazole is a category 3/4 of poison as per the W.H.O Expert Group on Pesticide Residues. Hexaconazole is used to control infection by fungi in paddy and other crops. Apart from destroying the target species, it can also cause damage to humans. There have been discrete reports of instances of human poisoning due to hexaconazole. Methodology: A patient record-based cross-sectional study was carried out in Konaseema Institute of Medical Science & Research Foundation, Amalapuram, Andhra Pradesh, India during a period from March 2014 to April 2020 on 26 confirmed cases of hexaconazole poisoning. The clinic-demographic data, hematological, and biochemical parameters at the time of admission and at 72 hrs as well as the outcome were recorded and analyzed using descriptive statistics and paired t test. Result: The prevalence of hexaconazole poisoning was 4.79% of all poisoning cases. The major clinical presentation was gastrointestinal symptoms with vomiting being commonest. There was no significant change in the biochemical and hematological parameters. The mean duration of hospitalization was 4.93+1.39 days. The recovery rate was 100% without any major sequel. Conclusion: Poisoning due to hexaconazole is uncommon in comparison to poisoning by other pesticides in the agricultural community. The clinical manifestations of hexaconazole poisoning indicated that it is of non-serious nature and its recovery was without any sequel.