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Penn Medicine Head and Neck Cancer Service Line COVID-19 Management Guidelines
Head and Neck Editor

Gregory S. Weinstein, M.D.

May 21, 2020
Introduction: The COVID-19 pandemic caused by the SARS-CoV-2 virus has altered the healthcare environment for the management of head and neck cancers.  The purpose of these guidelines is to provide direction during the pandemic for rational Head and Neck Cancer management in order to achieve a medically and ethically appropriate balance of risks and benefits.Methods: Creation of consensus document.Results: The process yielded a consensus statement among a wide range of practitioners involved in the management of head and neck cancer patients in a multi-hospital tertiary care health system. Conclusions: These guidelines support an ethical approach for the management of head and neck cancers during the COVID-19 epidemic consistent with both the local standard of care as well as the head and neck oncological literature. 
Head and neck cancer radiotherapy amid COVID-19 pandemic: Report from Milan, Italy   ...
Head and Neck Editor

Stefania Volpe MD

May 21, 2020
Background: Management of head and neck cancers (HNC) in Radiation Oncology in the COVID-19 era is challenging. Aim of our work is to report organization strategies at a Radiation Therapy (RT) Department in the first European area experiencing the COVID-19 pandemic. Methods: We focused on 1) dedicated procedures for HNC, 2) radiation treatment scheduling and 3) healthcare professionals’ protection applied during the Covid-19 breakdown (from 1st March to 30th April 2020). Results: Applied procedures are reported and discussed. Forty-three pts were treated. Image-guided, Intensity Modulated RT was performed in all cases. Median overall treatment time (OTT) was 50 (IQR: 47-54.25) days. RT was interrupted/delayed in seven pts (16%) for suspected COVID-19 infection. Two health professionals managing HNC pts were proven as COVID-19 positive. Conclusion: Adequate and well-timed organization allowed for the optimization of HNC pts balancing at the best of our possibilities pts’ care and personnel’s safety.
De novo chromosome-level genome assembly of Chinese walnut (Juglans cathayensis Dode)
Feng Yan
Rui-Min Xi

Feng Yan

and 9 more

May 21, 2020
Chinese walnut (Juglans cathayensis Dode), is a diploid, woody species native to China. It has 16 chromosomes (2n =2x= 32), as do all members of its genus and most members of its family (Juglandaceae). Although high-quality sequence data and reference genomes are available for several Juglans species, our goal was to produce a de novo, chromosome-level assembly of the Chinese walnut genome to gain insights into the species’ evolution and biology. Our assembly was based on Nanopore long reads and chromosome conformation capture (Hi-C) data. The final assembly showed a contig N50 size of 6.49 Mb and a scaffold N50 size of 36.1 Mb. The final genome size of Chinese walnut was estimated to be 548 Mb. The sixteen scaffolds of the assembly anchored 99 % of the Chinese walnut genome. The assembly of the gene space (BUSCO) was 92.0 %. We annotated 29,032 protein coding genes with a mean of 6 exons per gene. We detected 2,993 non-coding RNA in the genome. A phylogenetic analysis based on 552 single-copy orthologs indicated that Chinese walnut close relative to Persian walnut (J. regia). The collinearity analysis showed that two whole genome duplication (WGD) events in J. cathayensis and J. regia from a common ancestor. Comparative genome analysis of J. cathayensis versus J. regia showed that 399 and 1,528 gene families were expanded and contracted respectively in the Chinese walnut genome. This J. cathayensis genome should be a useful resource for study of the evolution, breeding, and genetic variation in walnuts (Juglans).
THE ROLE OF THE LEFT ATRIAL STRAIN PARAMETERS ON GRADING OF AORTIC REGURGITATION
Sedat Kalkan
Suleyman Efe

Sedat Kalkan

and 5 more

May 21, 2020
BACKGROUND:Aortic regurgitation(AR) is a clinical status characterized by diastolic blood backflow from aorta to the left ventricle. Grading the severity of AR is very important for clinical follow-up. In spite of numerous parameters, the severity of AR still remains unclear in some patients. In AR, left atrial(LA) mechanics can be affected in time and LA strain variations can be illuminating for the grading of AR. The purpose of this study is to determine whether the LA strain parameters are associated with the severity of aortic regurgitation or not. METHOD:64 consecutive patients with AR were included in this study.After echocardiographic examination according to the aortic regurgitation degree. Patients divided in three groups as mild(n: 22),moderate(n: 15) or severe(n: 27). All patients LA strain measurements performed and results compared between groups. RESULTS:According to echocardiographic measurements; between the groups; LA reservoir in the mild, moderate and severe AR groups were(42.0 ±18.0, 41.4±14.8, 29.2 ±6.0 repectively, p:0.002) and LA conduit in the mild, moderate and severe AR groups were (21.2±8.7, 19.3±7.4 and 13.1 ± 4.4 respectively p <0.001), statistically significant different, while no statistically significant difference was noticed on LA SRs,LA SRe,LA SRa. CONCLUSION:This study showed that LA reservoir and LA conduit parameters of the patients with severe AR significantly decreased compared to those of the mild and moderate AR group. The grading of the LA mechanics in patients with chronic AR might provide a supplementary contribution to the present parameters in the grading of AR. Keywords: Aortic regurtation, graduation, left atrial strain
Notched P-wave related to a conduction disturbance in a thoracic vein as a potential...
Noriyuki Kobayashi
Teppei Yamamoto

Noriyuki Kobayashi

and 5 more

May 21, 2020
A 65-year-old male underwent a second ablation procedure for recurrent paroxysmal atrial fibrillation (AF). Twelve-lead ECG during sinus rhythm exhibited biphasic and split P-wave with a prolonged duration, which called notched P-wave (NPW). Radio-frequency applica-tion in the coronary sinus (CS) resulted AF termination and elimination of triggering ectopy with NPW disappearance. The CS musculature which played a principal role in triggering and maintaining AF formed the NPW. In patients with repetitive recurrent AF after the estab-lishment of the PV isolation who exhibit NPW during sinus rhythm, the CS might be one of the arrhythmogenic sources of AF.
Letter to the Editor regarding the paper “Comparative study of strategies to prevent...
Shailee Shah
Marcela Mercado Montoya

Shailee Shah

and 3 more

May 21, 2020
A document by Shailee Shah. Click on the document to view its contents.
Complete title: Low Voltage Zones as the Atrial Fibrillation Substrates: Relationship...
Zheng Liu
Yuanfeng Gao

Zheng Liu

and 9 more

May 21, 2020
Background: Low voltage Zones (LVZ) were usually targeted for ablation in atrial fibrillation (AF). But its relationship with AF initiation, maintenance, and termination remains to be studied. We tried to explore the relationships. Methods and Results: Consecutive AF patients were enrolled for assessment AF inducibility, AF duration or AF termination before ablation. Inducible AF was defined if induced AF last over 30 seconds. Sustainable AF was defined if it last over 300 seconds. Terminable AF was defined if it could be cardioverted into sinus rhythm within 1-hour after ibutilide administration. Voltage mapping was performed in sinus rhythm for all patients before stimulation or after cardioversion. LVZ was quantified as the percentage of LVZ area(LVZ%)to left atrium (LA) body surface. A total of 86 patients enrolled for AF induction and 36 for AF termination. 32 (37.2%) patients had inducible AF, 24 (27.9%) were sustainable, and 12 (33.3%) were terminable. Inducible AF patients had higher LVZ% in anterior wall (18.6±24.6 vs. 7.0±12.1, P=0.014). Global LVZ% was not different between inducible and uninducible AF patients. Global LVZ% was higher in patients with sustainable AF or interminable AF (LVZ%: sustainable vs unsustainable AF: 10.6±12.1 vs. 0.8±0.8, p=0.001; terminable vs. interminable: 17.1±13.5vs.40.6±24.5, p<0.001). Sustainable AF had larger LVZ% in roof, anterior wall, septum, floor. Interminable AF patients had higher LVZ% in anterior wall, septum, posterior wall and floor. Higher LVZ% was independent risk factor of recurrence (OR=1.015, P=0.042). Conclusion: The association between LVZ with AF initiation, perpetuation and termination were different.
Safety of Inpatient Dofetilide Initiation per Cardiology Services: A Retrospective Re...
Carrie Cicirale

Carrie Cicirale

May 21, 2020
Background Dofetilide is an antiarrhythmic medication that has the potential to cause life threatening arrhythmias, such as Torsade de pointes. The 2014 ACC/AHA/HRS guidelines for the management of patients with atrial fibrillation state that patients need to meet certain criteria to be initiated on dofetilide. Patients who are not initiated on this therapy according to the guideline criteria are likely to be at higher risk of adverse reactions. Methods This is a single center, retrospective chart review of patients who were initiated on dofetilide from July 2016-December 2019. Patients included in the study were initiated on dofetilide as a new antiarrhythmic and monitored inpatient for three days. The primary outcome was a composite of incidence of cardiac arrhythmias, cardiac arrest, cardiac death, and cardiac related hospital readmission. Results There were 224 patients included in the analysis: 190 patients who were initiated on dofetilide inappropriately and 34 that were initiated appropriately. The primary outcome (composite of cardiac arrhythmia, cardiac arrest, cardiac death, and hospital readmission) was statistically significant with more patients experiencing an outcome in the group initiated inappropriately. Discussion Patients are placed at a higher risk of adverse reactions when this potentially dangerous antiarrhythmic medication is not used according to the protocol set forth by the guidelines. Conclusion Practitioners should use caution when prescribing dofetilide. Other antiarrhythmic medications or non-pharmacologic options should be considered due to the incidence of these dangerous adverse reactions.
Risk Factors for Development of Complications by Untreated Common Bile Duct Stones: A...
Dong jun Oh
Ji Hyung  Nam

Dong jun Oh

and 3 more

May 21, 2020
Background It is recommended by the latest guidelines that common bile duct stones (CBDSs) should be removed, preferentially endoscopically, regardless of the presence of symptoms or complications. However, it may not be feasible due to very-old age and/or co-morbidities or rejected by patients. Aim We aimed to identify factors for development of complications after diagnosis of CBDSs to select vulnerable patients for whom removal of CBDSs should be performed despite of risks. Methods Medical records of patients with radiologically-confirmed CBDSs between October 2005 and September 2019 were retrospectively analyzed. Results Among a total of 634 consecutive patients, complications, defined as obstructive jaundice, biliary pancreatitis, or acute cholangitis, were already present in 416 (65.6%) at the time of diagnosis of CBDSs and developed in 95 (15.0%) afterwards. Forty four (6.9%) patients remained silent with the median follow-up periods of 31.5 months. With multivariate analyses, untreatment within 1 month and the size of CBDSs > 5 mm turned out to be independent risk factors for development of complications. Spontaneous passage of CBDSs was confirmed radiologically in 9 (11.1%) out of 81 patients untreated within 1 month. Conclusions CBDSs should be removed within 1 month from the diagnosis, even in unsuitable patients, especially if the size exceeds 5 mm.
Sharing Experience in the Application of Distributed Map of Intractable Epistaxis in...
Hui-Yi Deng
Huijun Qiu

Hui-Yi Deng

and 3 more

May 21, 2020
Sharing Experience in the Application ofDistributed Map of Intractable Epistaxis in Concealed SitesHuiyi. Deng1, #, Huijun. Qiu1, #, Weihao Wang1, Qintai. Yang1,2, *1 Department of Otolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China2 Department of Allergy, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China# The authors contributed equally to this work.* Corresponding authorQintai Yang, MD, PhDDepartment of Otolaryngology-Head and Neck SurgeryDepartment of AllergyThe Third Affiliated Hospital, Sun Yat-sen UniversityNo. 600 Tianhe Road, Guangzhou 510630, ChinaPhone: 020-85252239E-mail: yang.qt@163.com
Effects of clitoral reconstruction for female genital mutilation on perinatal outcome...
Sebastien Madzou
Chloe Reau-Guisti

Sebastien Madzou

and 11 more

May 21, 2020
Objectives: To investigate the perinatal outcomes of women with a history of female genital mutilation (FGM) who underwent clitoral reconstruction (CR) compared with women with FGM who did not undergo CR. Design: Retrospective case-control study Setting: Angers University Hospital, between 2005 and 2017 Methods: Inclusion criteria: pregnant women >18 years who underwent CR after FGM. Only the first subsequent delivery after CR was included. Each woman with CR was matched for age, ethnicity, FGM type, parity, and gestational age at the time of delivery with two women with FGM who did not undergo CR during the same period of time. Main outcome measures: at birth: need for episiotomy and intact perineum Results: 84 women were included (28 in the CR group; 56 in the control group). In the CR group, patients required significantly fewer episiotomies (5/17[29.4%]) compared to the control group (28/44[63.6%], p=0.02), even after excluding operative vaginal deliveries (2/13[15.4%] vs 21/36[58.3], p<0.01). CR reduces the risk of episiotomy (aOR=0.15, 95%CI [0.04-0.56]; p<0.01) after adjusting on the infant weight and the need for instrumental delivery. In the CR group, 47% of the patients had an intact perineum after delivery, compared to 20.4% in the control group (p=0.04). CR increases the odds of having an intact perineum at birth by 3.46 times (CI95%[1.04-11.49]; p=0.04). Conclusion: CR after FGM increases the chances of having an intact perineum after delivery by 3.46 times and reduces the risk of episiotomy by 0.15 times compared to women with FGM who did not underwent CR.
Telepsychiatry and other cutting edge technologies in Covid-19 pandemic: bridging the...
Francesco Di Carlo
Antonella Sociali

Francesco Di Carlo

and 7 more

May 21, 2020
BACKGROUND: Initially identified in December 2019 in China, the 2019 Coronavirus disease (COVID-19) is now affecting more than 200 countries and territories around the world. Given the current unavailability of an effective medical cure for COVID-19, a public health strategy of reduced social contact and shelter in place has been adopted worldwide. Nonetheless, social distancing and isolation could also represent risk factors for mental disorders, determining loneliness, reduced social support and under-detection of mental health needs. Along with this, social distancing determines an insurmountable obstacle for direct access to psychiatric care services. The pandemic generates the urgent need for integrating technology into innovative models of mental healthcare. AIMS: In this paper we discuss the potential role of telepsychiatry and other cutting-edge technologies in the management of mental health assistance. We narratively review the literature to examine advantages and risks related to the massive application of these new therapeutic settings, along with the possible limitations and ethical concerns. RESULTS: Telemental health services are particularly feasible and appropriate for the support of patients, family members and health-care providers during this COVID-19 pandemic. The integration of telepsychiatry with other technological innovations (e.g., mobile apps, virtual reality, big data and artificial intelligence) opens up interesting future perspectives for the improvement of mental health assistance. CONCLUSION: The COVID-19 pandemic situation shows us how vast the amount of untreated mental illnesses can be. The pandemic crisis can contribute to spread, among numerous mental health professionals, the knowledge of the possibilities offered by the digital era.
The efficacy of DNA barcoding in the classification, biodiversity and environmental a...
Yihao Ge
Chengxin Xia

Yihao Ge

and 5 more

May 21, 2020
Macroinvertebrates have been recognized as key ecological indicators of environmental and biodiversity assessment in aquatic ecosystems. However, species identification of macroinvertebrates (especially aquatic insects) proves to be very difficult due to lack of expertise. In this study, we evaluated the feasibility of DNA barcoding for the classification of benthic macroinvertebrates and investigated the genetic differentiation in nine taxonomic groups (Ephemeroptera, Plecoptera, Trichoptera, Diptera, Hemiptera, Coleoptera, Odonata, Mollusca and Annelida) from four large transboundary rivers of northwest China, and further explored its potential application to environment and biodiversity assessment. A total of 1227 COI sequences, belonging to 189 species, 122 genera and 59 families were obtained. The barcode gap analysis supported species status using the barcode gap approach. Meanwhile, NJ phylogenetic trees showed that all species group into single-species representing clusters whether from the same population or not, except two species (Polypedilum. laetum and Polypedilum. bullum). The ABGD analysis divided into 190 OTUs (P = 0.0599) and BIN analysis generated 201 different BINs. Phylogenetic diversity (PD) metrics can reflect environmental stress and serve as a metrics of Index of Biotic Integrity (IBI) to reflect the degree of disturbance in river systems.
Improving glutarate production in Escherichia coli by enhancing the CoA precursors
Mei Zhao
Yu Zhou

Mei Zhao

and 4 more

May 21, 2020
Glutarate is an attractive C5 platform chemical having wide application in nylon and plasticizer. However, microbial glutarate is mainly accumulated in the degradation of lysine and other methods were rarely explored for producing the glutarate from glucose directly. Here, we utilized a reversed adipic acid degradation pathway (RADP) and improved the glutarate production by increasing the precursors (malonyl-CoA and acetyl-CoA) based on the previously studied strain Bgl4146. Specifically, the conversion system of intracellular acetyl-CoA to malonyl-CoA was firstly constructed and optimized to balance acetyl-CoA synthase and acetyl-CoA carboxylase under different dissolved oxygen, enhancing the glutarate production from 0.09 g/L to 0.49 g/L. Then, modulating CoA balance by monitoring the expression of acetate kinase and pyruvate dehydrogenase resulting in a rise in glutarate titer up to 0.70 g/L. Finally, the optimized strain Bgl51464 was able to produce 7.97 g/L glutarate in a 5-L bioreactor. This strategy was described here, which could lay a certain foundation for the development of effective CoA balance to produce industrially high value-added chemicals.
PARP-inhibitors in a non‐oncological indication as COVID-19: are we aware about its p...
Ettore Capoluongo

Ettore Capoluongo

May 21, 2020
Capoluongo E.
Agent Orange-Induced Primary Cutaneous Anaplastic Large Cell Lymphoma (PC-ALCL) of th...
Morgan Lorio
Brandon Lewis

Morgan Lorio

and 3 more

May 21, 2020
Primary cutaneous anaplastic large cell lymphoma (PC‐ALCL) is a CD30+ lymphoproliferative disorder of the skin. There are currently no case reports involving the presentation of Agent Orange-induced PC-ALCL of the hand, surgical excision, and follow-up treatment. We present a case of Agent Orange-induced PC-ALCL and the subsequent surgical management.
Structural and Dynamic Analysis of Phyllosphere Fungal Community of Walnut Leaves Inf...
yu Tan
Tian hui Zhu

Yu Tan

and 2 more

May 21, 2020
High-throughput sequencing technology was used to analyse the species diversity, richness and dynamics of fungal communities in healthy and infected walnut leaves. The dominant phyla included Ascomycota, Basidiomycota, and Glomeromycota; the dominant classes were Tremellomycetes, Dothideomycetes, and Leotiomycetes; the dominant orders were Tremelellas, Capnodiales, and Erysiphales; the dominant families were Bulleribasidiaceae, Mycosphaerellaceae, and Erysiphaceae; the dominant genera were Vishniacozyma, Cercospora, and Ramularia; and the dominant species were Vishniacozyma heimaeyensis, Cercospora asparagi, and Cladosporium chasmanthicola. The results of this study also provided a new understanding of the succession of the walnut phyllosphere fungal community, filling a void in the knowledge of the microbial diversity associated with walnut leaf spot disease. At the same time, these results provide a scientific basis for early intervention and micro-ecological regulation of walnut phyllosphere fungal communities to prevent and control leaf spot or anthracnose.
Cardioprotective natural compound pinocembrin prevents acute ischemic myocardial inju...
Jingrong Lin
Yanjun Zheng

Jingrong Lin

and 3 more

May 21, 2020
Background and Purpose: Emerging evidence has shown that pinocembrin protects myocardial from ischemic injury in animals. However, it is unknown whether it has cardioprotection when given at the onset of reperfusion. Also, mechanisms mediating the cardioprotective actions of pinocembrin were largely unknown. Thus, this study aimed to investigate the effects of pinocembrin postconditioning on ischemia-reperfusion (I/R) injury and the underlying mechanisms. Experimental Approach: In vivo mouse model of myocardial I/R injury, ex vivo isolated rat heart with global I/R and in vitro hypoxia/reoxygenation (H/R) injury model for primary cardiomyocytes were used. Key Results: We found that pinocembrin postconditioning significantly reduced the infarct size and improved cardiac contractile function after acute myocardial I/R. Mechanically, in primary cardiomyocytes we found that pinocembrin may confer protection in part via direct stimulation of cardiac glycolysis via promoting the expression of glycolytic enzyme, PFKFB3. Besides, PFKFB3 inhibition abolished pinocembrin-induced glycolysis and protection in cardiomyocytes. More importantly, PFKFB3 knockdown via cardiotropic adeno-associated virus (AAV) abrogated cardioprotective effects of pinocembrin. Conclusions and Implications: In conclusion, these results established that the acute cardioprotective benefits of pinocembrin are mediated in part via glycolytic stimulation through PFKFB3, which may provide a new therapeutic target to impede the progression of myocardial I/R injury.
Vocal cord paralysis secondary to vincristine treatment in children -- A case series...
Joanna Godbehere
Jeanette Payne

Joanna Godbehere

and 2 more

May 21, 2020
IntroductionVincristine is a vinca alkaloid chemotherapy agent used in the treatment haematological malignancies including acute lymphoblastic leukaemia (ALL) and some lymphomas. Common toxicity includes neuropathy which can be peripheral, autonomic or less commonly central1. Vincristine remains an essential chemotherapy agent in modern ALL protocols1,2,3. It’s mechanism of action is by inhibiting the M phase of mitosis by binding with the protein component of microtubules. Axonal degeneration takes place when axonal transport and secretory functions are impaired thus leading to apoptosis and toxicity in neural tissue. This is typically seen within the extra-ocular muscles and larynx in cranial neuropathy1.Recurrent laryngeal nerve palsy resulting in vocal cord paralysis (vcp) in children has been documented in the literature in multiple case reports and small number of case series4.We present the largest case series to date of seven children who sustained vcp secondary to vincristine chemotherapy for ALL and review the literature.
The impact that intense ‘fetal-physiology’ training has on inter-observer agreement i...
Juan de Dios Gutierrez Henares
David Diaz Gomez

Juan de Dios Gutierrez Henares

and 2 more

May 21, 2020
Abstract Objective: To explore the level of agreement as well as the contribution of human-factors on CTG interpretation in a hospital where a high intense, ‘fetal physiology-based’ training on CTG-interpretation was implemented by a dedicated CTG-Team. Design: Prospective observational study Setting: Tertiary Hospital, UK Population: A total of 25 midwives and 7 doctors (≈10% of staff) Method: interpretation of 5 anonymised colour-printed copies of 5 different CTGs using a questionnaire (160 CTG interpretations) using local CTG-guidelines (pattern-recognition approach) and Types of hypoxia (fetal-physiology). Results: Interpretation of CTG by type of hypoxia compared against CTG-guidelines presented better Proportion of concordance (PC=76.1% vs 61.2%, P=0.006) and slightly better reliability (K= 0.37 (0.35–0.39) vs 0.33 (0.32–0.36)). Doctors rely most in fetal-physiology than midwives who rely most in guidelines. Overall, 68% of the staff felt confident or very confident in CTG interpretation. In general, Self-reported confidence on CTG interpretation and fetal-physiology knowledge increased with the level of seniority. Conclusions: ‘Fetal-physiology-based’ training increases level of self-reported confidence and level of fetal-physiology knowledge leading to better inter-observer agreement and reliability in CTG interpretation especially when considering type of hypoxia in CTG-classification. Funding: JG collected the data as part of a Self-funded university MSc program. A secondary analysis of the data was performed to elaborate this manuscript. There is no source of funding to declare by the rest of co-authors in this paper. Keywords: Fetal-physiology, Cardiotocography Interpretation, Intrapartum fetal monitoring, Inter-observer agreement,
First case of COVID 19 associated with CML at time of presentation
Khaldun Obeidat
mohamed yassin

Khaldun Obeidat

and 2 more

May 21, 2020
COVID-19 outbreak has been a serious threat and it has been reported with different presentations and complications, here we report a 39 year old healthy male who presented with respiratory symptoms and investigation revealed that he is positive for SARS-CoV-2 and work up for Leukocytosis confirmed the diagnosis of CML.
Approaches Towards Fighting COVID-19 in Taiwan
Shih-Chang Tsai
Da-Tian Bau

Shih-Chang Tsai

and 10 more

May 21, 2020
A document by Shih-Chang Tsai. Click on the document to view its contents.
Immunotherapy Using Histobulin in Atopic Dermatitis
Geunwoong Noh

Geunwoong Noh

May 21, 2020
Immunotherapy using Histobulin was attempted in four cases of atopic dermatitis. The patients improved considerably, and one patient showed remission. The patients showed considerable improvement with a lower frequency of upper respiratory infections during immunotherapy.
Vitamin D metabolites and binding protein predict preeclampsia in women with Type 1 d...
Clare Kelly
Carol  Wagner

Clare Kelly

and 12 more

May 21, 2020
Objective: Preeclampsia (PE) occurs about four times more frequently in women with than without diabetes. Vitamin D is essential for healthy pregnancy. We investigated detailed measures of maternal plasma 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), and vitamin D binding protein (VDBP) to define associations with PE in women with Type 1 diabetes (T1DM). Design and setting: A multicentre prospective study in women at ~12, ~22 and ~32 weeks’ gestation (‘Visits’ (V) 1, 2, and 3, respectively). Population: We studied 23 T1DM women who subsequently developed PE, 24 who remained normotensive, and 19 non-diabetic, normotensive women (reference controls). Diabetic women were complication-free at V1, and all study visits preceded PE onset. Main Outcome Measures: Total, bioavailable, and free concentrations of 25(OH)D and 1,25(OH)2D; and VDBP. Results: 25(OH)D deficiency was more frequent in diabetic than non-diabetic women (69% vs 22%, p<0.05), but no measure of 25(OH)D predicted PE. In contrast, higher 1,25(OH)2D concentrations at V2 (total and bioavailable: p<0.01; free: p<0.05) and V3 (bioavailable: p<0.05; free: p<0.01) were associated with subsequent PE in T1DM women, as were lower concentrations of VDBP at V3 (p<0.05) and elevated ratios of 1,25(OH)2D/VDBP (V2, V3: p<0.01) and 1,25(OH)2D/25(OH)D (V3, p<0.05). Significance persisted after adjustment for covariates. Conclusions:In women with T1DM, concentrations of active vitamin D were higher, and VDBP lower, in the second and third trimesters in those who developed PE than in those who did not. Active vitamin D may serve as a new marker for PE risk, and could be implicated in pathogenesis.
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