bluuebunny/crossref_metadata_2025 huggingface dataset:
Time in Therapeutic Range for Bivalirudin Among Pediatric Ventricular Assist Device Recipients
Authors: Daugherty Jeremy , Heyrend Caroline , Profsky Michael , Kay Brent , VanderPluym Christina , Griffiths Eric R. , May Lindsay J.
Published: August 2020

Given the adverse event rates involving bleeding and thrombosis among children on ventricular assist devices (VADs), anticoagulant management has become a focal point for quality improvement and innovation. There may be advantages to using direct thrombin inhibitors, such as bivalirudin, though this has not been fully explored. As the percent time in therapeutic range (%TTR) for anticoagulants is classically associated with improved clinical outcomes, we evaluated the %TTR for bivalirudin among pediatric VAD recipients. Using a modification of the Rosendaal method, %TTR was calculated using activated partial thromboplastin time measurements for 11 VAD recipients in the early postoperative period (postoperative days 0–14) and for the duration of VAD support. In the initial 2 weeks after VAD implant, mean %TTR was 68.7 (±13.0). During the entire support course, the mean %TTR improved to 79.6 (±11.0). There was an era effect with improving %TTR in the latter half of the study period. We report very good %TTR for bivalirudin both in the first 2 weeks post implant and this improved over the duration of support. Because %TTR reflects the degree of safety and efficacy in chronic anticoagulation, this relatively high %TTR among a diverse, often critically ill cohort suggests that bivalirudin may be a promising agent. Although this study was underpowered to comprehensively evaluate adverse events on bivalirudin, this represents an important next step for larger scale study.
123I-Ioflupane dopamine transporter imaging (DaTSCAN) appearances in relation to emotional responsiveness, impulsivity and olfaction in suspected Parkinsonian syndrome
Authors: La Torre Guglielmo , Herman Aleksandra Maria , Jessop Maryam , Abdula Nadia , Crawshaw Ania , Begley Patrick , Wroe Emma , Saha Romi Anirban , Duka Theodora , Dizdarevic Sabina
Published: August 2020

Objective

The aim of our study was to ascertain relationships between DaTSCAN, olfactory loss, behavioural and subjective measurements of impulsivity and emotional responsiveness in patients with clinically suspected Parkinsonian syndrome (PS).

Methods

A prospective study of 20 drug-naive patients with parkinsonism, underwent the University of Pennsylvania Smell Identification Test, impulsivity measurements and mood-state-questionnaires before visual and semi-quantitative DaTQUANT analyses. There were two subgroups: nine patients with scans without evidence of dopaminergic deficit (SWEDD – controls) and 11 patients with PS.

Results

The PS group reported lower non-planning impulsivity than the SWEDD group (P = 0.039). A positive correlation was found between the non-planning impulsivity ratings and right anterior putamen/background (bck) ratio in PS group (r = 0.598, P = 0.068). Higher ratings of anger (r = 0.575, P = 0.016), fatigue (r = 0.746, P = 0.001), confusion (r = 0.561, P = 0.019) and depression were positively correlated with putamen/caudate ratios (R > L) on DaTSCAN. Higher self-reported arousal was associated with lower right putamen/caudate ratio (P = −0.581, P = 0.014). Only fatigue was positively correlated with putamen/bck (r = 0.564, P = 0.018). The degree of smell deficit correlated negatively with performance on reflection impulsivity tasks (r = −0.470, P = 0.049).

Conclusion

DaTSCAN appearances correlated with emotional dysfunction and self-reported impulsivity in patients with PS. Olfactory impairment was associated with increased reflection impulsivity and the age of patients. Higher DaTSCAN putamen/caudate ratios were associated with higher emotional responsiveness and higher non-planning impulsivity in PS patients. These preliminary findings may be relevant in clinical practice in differentiating PS from SWEDD and identifying susceptibility to impulse control disorder although larger studies are warranted.
Seronegative Villous Atrophy in Children
Authors: Mandile Roberta , Maglio Mariantonia , Pellino Nicoletta , Russo Marina , Miele Erasmo , Spagnuolo Maria Immacolata , Troncone Riccardo , Auricchio Renata
Published: August 2020

Objectives:

Villous atrophy (VA) is not pathognomonic of celiac disease (CD). We aimed at reporting distribution, clinical, and immunohistochemical features of seronegative VA (SNVA) in a pediatric population.

Methods:

We retrospectively collected data from patients who underwent intestinal biopsies between 2010 and 2017 and showed VA without serum CD‐associated autoantibodies. Marsh‐Oberhuber grading was used. Density of intraepithelial lymphocytes (IELs) expressing CD3 or TCRγδ+ receptor and of lamina propria CD25+ cells was assessed by immunohistochemistry. Intestinal deposits of anti‐tissue tranglutaminase2 (anti‐TG2) were also investigated by double immunofluorescence.

Results:

Over a 7‐year period, 64 out of 1282 patients with VA had negative serum CD serology. Diagnoses were: inflammatory bowel diseases (IBD) (21/64), Gastro‐Esophageal Reflux Disease (GERD) (12/64), food allergy (8/64), infections (7/64, of which 3 HIV infections), immune deficiency (3/64), short bowel syndrome (3/64), congenital diarrhea (2/64), other/inconclusive diagnosis (8/64). Forty‐four, 15, and 5 showed Marsh 3a, 3b, and 3c lesion, respectively. The latter category included 2 patients with Crohn disease, 2 with immunodeficiencies, 1 with lymphohistiocytosis. In 41/46 (89%) patients, mononuclear CD25+ cells were above the cut‐off, indicating mucosal inflammation but only 18/46 (39%) had IELs and TCRγδ + IELs above limits of normality. In 10 of 46 (22%) patients, a positive immunofluorescence indicated the presence of anti‐TG2 mucosal antibodies.

Conclusions:

SNVA is not rare representing up to 5% of the cases of VA. Most patients have a Marsh 3a lesion. Immunohistochemical analysis may be helpful in excluding CD, whereas the finding of mucosal anti‐TG2, particularly with a weak staining, shows no absolute specificity for CD.
Method for Removing Thawed Human Milk From a Plastic Storage Bag Impacts Fat Retention
Authors: Friend Linda L. , Gutierrez dos Santos Bruna , El‐Khouri Kristina G. , Perrin Maryanne T.
Published: August 2020

Objectives:

Determine how thaw stage and bag manipulation (folding and squeezing) influence the retention of fat and number of aerobic bacteria colony‐forming units when decanting human milk (HM) from plastic storage bags.

Methods:

Lactating women (n = 40) in the Greensboro, North Carolina area were recruited to provide fresh HM. Samples were equally divided and frozen in storage bags for 2 months. Two thaw stages (ice/liquid) and the use of bag manipulation (yes/no) were assessed. Fat was measured using ether extraction and bacteria were measured using plate enumeration. Paired t tests were used to compare the effects of thaw stage and bag manipulation on post‐thaw fat content. Repeated measures analysis of variance was used to compare the effect of bag manipulation on pre‐ and post‐thaw bacteria.

Results:

Fat retention was not significantly different when thawing to liquid versus ice (mean difference = 0.10 g/dL; n = 17 paired samples; P = 0.07). Decanting with bag manipulation retained more fat than decanting without manipulation, but only when HM was thawed to liquid (mean difference = 0.13 g/dL; n = 11 paired samples; P = 0.005), not when HM was thawed to ice (P = 0.47). Bag manipulation did not increase total aerobic bacteria for either thaw stage (P = 0.49).

Conclusions:

Fat retention is influenced by the method of removing previously frozen HM from plastic storage bags. Folding and squeezing the storage bag when decanting HM thawed to a liquid state increases fat recovery without increasing bacterial contamination.
Expedited surgery in geriatric hip fracture patients taking direct oral anticoagulants is not associated with increased short-term complications or mortality rates
Authors: Brown Alexander , Zmich Zachary , Roberts Aaron , Lipof Jason , Judd Kyle T.
Published: August 2020

Objectives:

The purpose of this study was to evaluate potential differences in time to surgery, bleeding risk, wound complications, length of stay, transfusion rate, and 30-day mortality between patients anticoagulated with direct oral anticoagulants (DOACs) and those not anticoagulated at the time of evaluation for an acute hip fracture.

Design:

Retrospective chart review Level III Study.

Setting:

One university-based hospital in Rochester, NY.

Patients/Intervention

: Patients 65 years and older undergoing operative treatment of a hip fracture over a 5-year period. Chart review identified patients on DOAC therapy at the time of injury as well as an age and sex-matched control group not on anticoagulation.

Main outcome measurements

: Demographics, procedure type, admission/postoperative laboratory work, perioperative metrics, transfusion metrics, discharge course, reoperation, readmission, wound complications, and 30-day mortality were obtained for comparison.

Results:

Thirty-six hip fractures anticoagulated on DOACs were compared to 108 controls. The DOAC group had delays to operative treatment (27.6 h, SD 16.3 h, 95% CL [22.0–33.1]) vs the control group (19.8 h, SD 10.5 h, 95% CL [17.7–21.8], P = .01). No differences were found in estimated blood loss, procedure time, or change in hemoglobin. Transfusion rates were not significantly different between groups (58.3% DOAC vs 47.2% control, P = .25). No difference in reoperation, readmission, wound complication, deep venous thrombosis rates, or 30-day mortality rates were found.

Conclusion:

Patients presenting on DOAC therapy at the time of hip fracture have a delay to surgery compared with age and sex-matched controls, but no increase in short term complications or mortality rates. Expedited surgery (within 48 h) appeared to be safe and effective treatment for hip fracture patients on DOAC therapies.
High-grade Neuroendocrine Carcinomas of the Vulva
Authors: Chen Peter P. , Ramalingam Preetha , Alvarado-Cabrero Isabel , Euscher Elizabeth D. , Nagarajan Priyadharsini , Lawson Barrett C. , Malpica Anais
Published: August 2020

Vulvar high-grade neuroendocrine carcinomas (HGNECs) are rare and primarily thought to represent Merkel cell carcinoma (MCC). We present the clinicopathologic features of 16 such cases, the largest series to date. Patients were most often White, postmenopausal, and symptomatic from a palpable vulvar mass/nodule. Tumors ranged from 0.7 to 6 cm and most commonly involved the labium majus. Majority of the cases were pure HGNECs (15/16) with small cell (SC) morphology (14/16); 2 were large cell neuroendocrine carcinomas, of which 1 was combined with moderately differentiated adenocarcinoma. All tumors expressed synaptophysin. Of the 14 HGNECs with SC morphology, 6 were CK20-positive MCCs with characteristic CAM5.2 and neurofilament (NF) expression. Five of these MCCs were positive for Merkel cell polyoma virus large T-antigen (MCPyVLTAg). In contrast, 6 HGNECs with SC morphology were negative for CK20, NF, and MCPyVLTAg and classified as SCNECs. High-risk human papilloma virus was positive in all SCNECs and negative in all MCCs. One case of HGNEC with SC morphology could not be entirely characterized due to lack of tissue for ancillary testing. Five of 12 (42%) cases had a discrepant diagnosis initially rendered. Most patients (10/15) presented with International Federation of Gynecology and Obstetrics stage III or IV disease. Usual sites of metastasis included inguinal lymph node, liver, bone, and lung. Twelve patients underwent surgery with adjuvant chemotherapy and/or radiation therapy, 1 received adjuvant immunotherapy, and 1 patient received neoadjuvant chemotherapy followed by surgery and adjuvant radiation therapy. Median overall survival was 24 months (range: 7 to 103 mo), and overall 5-year survival was 12% (95% confidence interval: 1% to 39%). In summary, vulvar HGNECs are rare, aggressive neoplasms that can be further subclassified into MCC, SCNEC, and large cell neuroendocrine carcinoma. CK20, CAM5.2, NF, TTF-1, MCPyVLTAg, and high-risk human papilloma virus facilitate the distinction of MCC from SCNEC. Proper identification of vulvar HGNECs is critical for patient management.
Chondroblastoma Expresses RANKL by RNA In Situ Hybridization and May Respond to Denosumab Therapy
Authors: Suster David I. , Kurzawa Pawel , Neyaz Azfar , Jarzembowski Jason A. , Lozano-Calderon Santiago , Raskin Kevin , Schwab Joseph , Choy Edwin , Chebib Ivan , Deshpande Vikram
Published: August 2020

Lesions of bone featuring osteoclast-like giant cells comprise a diverse group of entities, including giant cell tumor (GCT) of bone, chondroblastoma, and aneurysmal bone cyst, among others. The receptor activator of nuclear factor-κB ligand (RANKL) has been implicated in the pathogenesis of GCT of bone and may play a role in the pathogenesis of other giant cell–rich lesions as well. In addition, RANKL inhibitors (denosumab) have also been shown to have some efficacy in treating some giant cell–rich lesions. Herein, we examine RANKL expression by RNA in situ hybridization in a total of 84 osseous lesions with a focus on chondroblastoma, GCT, fibrous dysplasia, and aneurysmal bone cyst. The lesions were tested for RANKL expression using a chromogenic RNA in situ hybridization assay. RANKL expression was identified in 24/25 (96%) GCT, 24/26 (92%) chondroblastomas, 6/7 (86%) aneurysmal bone cysts, and 3/16 (19%) patients with fibrous dysplasia. RANKL expression was statistically lower in chondroblastoma and aneurysmal bone cyst compared with GCT. RANKL reactivity in fibrous dysplasia was exclusively seen in the 3 cases with osteoclast-type giant cells. Our results indicate a high proportion of chondroblastomas, GCTs, and aneurysmal bone cysts express RANKL while reactivity in fibrous dysplasia is dependent on the presence of osteoclast-type giant cells. On the basis of the success of denosumab therapy for GCTs, our results indicate that it may be a potential therapeutic option in other primary osseous tumors.
Impact of Infant Positioning on Cardiopulmonary Resuscitation Performance During Simulated Pediatric Cardiac Arrest: A Randomized Crossover Study
Authors: Mühlbacher Jakob , Pröbstl Cordula , Granegger Marcus , Schiefer Judith , Duma Andreas , Hüpfl Michael , Herkner Harald , Röhrich Michael , Schebesta Karl
Published: August 2020

Objectives:

The primary objective was to determine the impact of infant positioning on cardiopulmonary resuscitation performance during simulated pediatric cardiac arrest.

Design:

A single-center, prospective, randomized, unblinded manikin study.

Setting:

Medical university-affiliated simulation facility.

Subjects:

Fifty-two first-line professional rescuers (n = 52).

Interventions:

Performance of cardiopulmonary resuscitation was determined using an infant manikin model in three different positions (on a table [T], on the provider’s forearm with the manikin’s head close to the provider’s elbow [P], and on the provider’s forearm with the manikin’s head close to the provider’s palm [D]). For the measurement of important cardiopulmonary resuscitation performance variables, a commercially available infant simulator was modified. In a randomized sequence, healthcare professionals performed single-rescuer cardiopulmonary resuscitation for 3 minutes in each position. Performances of chest compression (primary outcome), ventilation, and hands-off time were analyzed using a multilevel regression model.

Measurements and Main Results:

Mean (± sd) compression depth significantly differed between table and the other two manikin positions (31 ± 2 [T], 29 ± 3 [P], and 29 ± 3 mm [D]; overall p < 0.001; repeated measures design adjusted difference: T vs P, –2 mm [95% CI, –2 to –1 mm]; T vs D, –1 mm [95% CI, –2 to –1 mm]). Secondary outcome variables showed no significant differences.

Conclusions:

Compressions were significantly deeper in the table group compared to positions on the forearm during cardiopulmonary resuscitation, yet the differences were small and perhaps not clinically important.
Preventing HIV outbreaks among people who inject drugs in the United States: plus ça change, plus ça même chose
Authors: Strathdee Steffanie A. , Kuo Irene , El-Bassel Nabila , Hodder Sally , Smith Laramie R. , Springer Sandra A.
Published: August 2020

This editorial review covers current trends in the epidemiology of HIV among people who inject drugs (PWID) in the United States, including four recent HIV outbreaks. We discuss gaps in the prevention and treatment cascades for HIV and medications for opioid disorder and propose lessons learned to prevent future HIV outbreaks. Over the last decade, North America has been in the throes of a major opioid epidemic, due in part to over-prescribing of prescription opiates, followed by increasing availability of cheap heroin, synthetic opioids (e.g. fentanyl), and stimulants (e.g. methamphetamine). Historically, HIV infection among PWID in the US had predominantly affected communities who were older, urban and Black. More recently, the majority of these infections are among younger, rural or suburban and Caucasian PWID. All four HIV outbreaks were characterized by a high proportion of women who inject drugs and underlying socioeconomic drivers such as homelessness and poverty. We contend that the US response to the HIV epidemic among PWID has been fractured. A crucial lesson is that when evidence-based responses to HIV prevention are undermined or abandoned because of moral objections, untold humanitarian and financial costs on public health will ensue. Restructuring a path forward requires that evidence-based interventions be integrated and brought to scale while simultaneously addressing underlying structural drivers of HIV and related syndemics. Failing to do so will mean that HIV outbreaks among PWID and the communities they live in will continue to occur in a tragic and relentless cycle.
Pain and Fatigue in Patients With Ankylosing Spondylitis Treated With Tumor Necrosis Factor Inhibitors
Authors: Strand Vibeke , Deodhar Atul , Alten Rieke , Sullivan Emma , Blackburn Stuart , Tian Haijun , Gandhi Kunal K. , Jugl Steffen M. , Conaghan Philip G.
Published: August 2020

Background/Objective

Patients with ankylosing spondylitis (AS) experience symptoms and comorbidities that impact their health-related quality of life (HRQoL) and ability to work. This real-world, global survey was conducted among AS patients receiving tumor necrosis factor inhibitors (TNFis) to evaluate both the frequency and severity of persistent symptoms, and the impact of pain and fatigue on HRQoL, employment status, and work activity.

Methods

Patients with AS and their treating physicians from 13 countries across 5 continents completed questionnaires capturing demographics, patient symptoms, current disease status, HRQoL, current therapy, employment status, and Work Productivity and Activity Impairment.

Results

Seven hundred five patients who had been receiving a TNFi for 3 months or more and completed both Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) pain and fatigue domains were included in the analysis; of these, 37.6% reported high BASDAI pain scores and 41.3% high BASDAI fatigue scores. Medical Outcomes Study–Short Form, 36-item version 2 domain, 5-dimensional EuroQoL Questionnaire, and 5-dimensional EuroQoL visual analog scale scores were significantly lower (p < 0.0001), and Work Productivity and Activity Impairment scores significantly higher (p < 0.0001), in patients with high levels of pain or fatigue than low levels.

Conclusions

Globally, levels of pain and fatigue remained high in AS patients receiving TNFi treatment, which were significantly associated with reduced HRQoL and work productivity. Such persistent symptoms in usual care suggest a substantial unmet need in AS pharmacologic and nonpharmacologic therapeutic pathways.
Ultradelayed Arterial Thrombosis
Authors: Smith Jesse R. , Teven Chad M. , Choudry Umar , Gottlieb Lawrence J.
Published: August 2020

Background and Objectives

Delayed arterial thrombus causing loss of a cutaneous free flap at or beyond 6 months is a rare phenomenon. The purpose of this report is to describe 2 cases of arterial compromise requiring medical and surgical intervention at or beyond 6 months after radial forearm free flap (RFFF) phalloplasty and to define the phenomenon of ultradelayed arterial thrombosis.

Methods

Patient 1 is a 44-year-old transmale who presented with pulselessness, pallor, and hypersensitivity of his neophallus 10 years status post-RFFF phalloplasty using a saphenous vein interposition graft (SVIG) between the superficial femoral artery (SFA) and radial artery (RA). Patient 2 is a 35-year-old transmale who presented with similar complaints 6 months status post-RFFF phalloplasty with the same vascular connections as above.

Results

Patient 1 was found to have an arterial thrombus distal to the SFA-SVIG anastomosis requiring catheter-directed thrombolysis with tissue plasminogen activator, resulting in partial loss limited to the distal three fourths of the shaft. Patient 2 was also found to have an arterial thrombus distal to the SFA-SVIG anastomosis requiring catheter-directed thrombolysis with tissue plasminogen activator and common femoral artery CFA-RA bypass, resulting in partial loss limited to the neoglans.

Conclusions

Ultradelayed arterial thrombosis is a rare phenomenon requiring urgent intervention. The exact causes of this phenomenon, whether mechanical or physiological or both, have yet to be fully elucidated but it is hypothesized that the original anastomosis may continue to serve as the critical blood supply to its flap as far as 10 years after surgery.
Perforator-Based Pedicled Cross-Leg Flaps in Pediatric Patients
Authors: Abdelmegeed Ahmed Gaber , Abulezz Tarek Abdelhameed , Abo-Saeda Mohamed Abdel-al , Allam Karam Ahmed
Published: August 2020

Background

Distal lower limb reconstruction is one of the most difficult and challenging tasks in plastic surgery. Despite the continuous advances in microsurgical techniques, pedicled cross-leg flaps still have a major role particularly in pediatric patients. Many techniques have been described to maximize the potential of the cross-leg flaps. The introduction of fasciocutaneous flaps has provided more potentials and made lower leg reconstruction easier and more successful. The description of perforator system in the leg has also made a revolution in the regional reconstruction. In this report, we present a new modification that increases the reach and facilitates the inset of the flaps.

Methods

The flap is taken from the posteromedial skin of the middle third of the leg. The design is determined by the location, size, and shape of the defect. The base of the flap should contain at least 2 perforators located by Doppler device. After elevation of the fasciocutaneous flap, 2 back cuts are performed in the upper and lower edge of the flap base preserving the 2 previously located perforators.

Results

Fifty patients, 32 males and 18 females, were reviewed and presented. Age of the patients ranged from 4 to 13 years and the defect size ranged from 20 to 130 cm. All flaps survived with 3 flaps had mild marginal ischemia, 2 flaps had mild infection, and 1 flap had partial dehiscence.

Conclusions

Back cuts made at the edges of the base of a cross-leg flap, preserving the feeding perforators, can increase the flap reach without jeopardizing its viability. It is also an easy to do technique and does not require any extra equipment or time.
ISAPS International Aesthetic Facial Plastic Surgery Fellowship in Rotterdam
Authors: Sanchez Balado Adrian
Published: August 2020

Facial plastic surgery and esthetic surgery are among the most challenging parts of the residency training. As a former fellow at Velthuis Kliniek Rotterdam with Dr. Van Der Meulen and Dr. Stevens, the author hereby present his unique 3-month experience offering actively participation in surgeries and consultation, academical education and research, and personal development for junior plastic surgeons who want to aspire to make facial and esthetic surgery their area of expertise.
Clinical Course of 195 Critically Ill COVID-19 Patients: A Retrospective Multicenter Study
Authors: Zhou Shuliang , Yang Yadong , Zhang Xingguo , Li Zhifeng , Liu Xing , Hu Chang , Chen Chunxi , Wang Dawei , Peng Zhiyong
Published: August 2020

Introduction:

Coronavirus disease-2019 (COVID-19) outbreak has spread around the world. However, the dynamic course of critically ill COVID-19 has not been described thoroughly.

Patients and Methods:

We retrospectively analyzed 195 critically ill COVID-19 patients in Hubei province, China, between January 5, 2020 and April 3, 2020. Epidemiologic data, clinical features, treatments, and outcomes were collected and analyzed.

Results:

Most critically ill patients were older with higher Acute Physiology and Chronic Health Evaluation II scores. After critical illness onset, a total of 181 (92.8%) patients received ventilation support, of which 84 (43.1%) received noninvasive and 97 (49.7%) received invasive mechanic ventilation (IMV). Among the 97 patients with IMV, 28 (28.9%) received prone ventilation, 57 (58.8%) received neuromuscular blocked therapy, and 22 (11.3%) received tracheostomy due to prolonged ventilator use. Early hypoxemia, subsequent hypercapnia, pulmonary hypertension, and finally pulmonary fibrosis were notable in the clinical course of acute respiratory distress syndrome (ARDS). Eighty-nine (45.6%) patients presented with shock. Acute kidney injury (29.7%) and secondary infection (28.2%) were also notable. The overall mortality of critically ill patients at day 28 was 42.1%. Intensive care unit (ICU) mortality was around 33%, as 16 patients died prior to ICU admission. A low PaO2/FiO2 ratio was an independent risk factor for death. High viral load was observed in most non-survivors.

Conclusion:

ARDS and shock were notable in the critical illness of COVID-19. Ventilation support and hemodynamic support were the cornerstones for critical care. High viral load was associated with death of critically ill COVID-19 patients.
End-Tidal Carbon Dioxide Impacts Brain and Kidney Injury in Experimental Extracorporeal Cardiopulmonary Resuscitation (ECPR)
Authors: Ölander Carl-Henrik , Vikholm Per , Schiller Petter , Hellgren Laila
Published: August 2020

Purpose:

Extracorporeal membrane oxygenation-assisted cardiopulmonary resuscitation (ECPR) is proposed for cardiac resuscitation in selected cases. End-tidal carbon dioxide (ETCO2) is easily obtained during conventional cardiopulmonary resuscitation (CPR). We hypothesized that the level of ETCO2 during CPR would reflect the degree of brain and kidney damage following ECPR in experimental refractory cardiac arrest.

Methods:

Ventricular fibrillation was induced in 10 pigs, followed by mechanical CPR for 45 min and thereafter ECPR for 180 min. Blood- and urine-samples, physiologic parameters, and histopathology of brain and kidney were analyzed. Animals were divided into Group High (GHigh) and Group Low (GLow) according to value of ETCO2 (10 mm Hg) at the end of CPR.

Results:

Carotid blood pressure and blood flow declined over time in both groups during CPR but was higher in GHigh. Coefficient of determination for ETCO2 and carotid blood flow was substantial (r2 = 0.62). The oxygen delivery index was higher for GHigh 444 (396–485) L/min/m2 as compared with GLow
at 343 (327–384) L/min/m2 (P = 0.02) at the end of ECPR. Also, P-S100B were lower in GHigh, (P < 0.05) and GLow demonstrated worse histopathological injury in central parts of the brain (P < 0.01). During ECPR, urinary output was higher in GHigh (P < 0.05). Kidney injury marker Plasma Neutrophil Gelatinae-associated Lipocalin increased in both groups during ECPR but was more pronounced in GLow (P = 0.03). Renal histopathology revealed no difference between groups.

Conclusions:

ETCO2 at the end of mechanical CPR is inversely associated with extent of brainstem and renal injury following ECPR.
Initial Report From a Swedish High-volume Transplant Center After the First Wave of the COVID-19 Pandemic
Authors: Felldin Marie , Søfteland John Mackay , Magnusson Jesper , Ekberg Jana , Karason Kristjan , Schult Andreas , Larsson Hillevi , Oltean Mihai , Friman Vanda
Published: August 2020

Background.

Solid organ transplant (SOT) recipients may be more vulnerable to coronavirus disease 2019 (COVID-19). Data on the clinical course of COVID-19 in immunosuppressed patients are limited, and the optimal management strategy for these patients is yet unclear.

Methods.

We present 53 SOT recipients (31 kidney transplant recipients, 8 liver transplant recipients, 5 heart transplant recipients, 5 lung transplant recipients, 3 liver-kidney transplant recipients, and 1 kidney-after-heart transplant recipient), transplanted at a Swedish high-volume transplant center and each diagnosed with COVID-19 between February 21, 2020 and June 22, 2020. Demographic, clinical, and treatment data were extracted from the electronic patient files.

Results.

Patients reported fever (61%), cough (43%), diarrhea (31%), and upper respiratory symptoms (29%). The median age was 56 years, and 57% were male. According to severity, 55% had mild, 13% had moderate, 19% had severe, and 13% had critical disease. Thirty-seven patients (70%) were hospitalized, with 8 requiring intensive care. Thirteen of the 37 patients were initially managed as outpatients but later hospitalized. One patient received hydroxychloroquine, and no patients received antivirals. Antimetabolites and calcineurin inhibitors were held or reduced in two-thirds. Twenty-seven of 37 hospitalized patients (73%) received low-molecular-weight heparin. Five (13.5%) hospitalized patients died. Overall survival for the entire cohort was 90.5%. No rejection episodes were noted.

Conclusions.

Hospitalization, lowering of immunosuppression, and prophylactic anticoagulation were the most common therapeutic interventions for SOT recipients with COVID-19. A significant proportion of patients could be managed on an outpatient basis, while keeping a low threshold for admission. Mild and moderate disease forms seem to have a good outcome.
Total Charge Required to Induce a Seizure in a Retrospective Cohort of Patients Undergoing Dose Titration of Right Unilateral Ultrabrief Pulse Electroconvulsive Therapy
Authors: Luccarelli James , McCoy Thomas H. , Seiner Stephen J. , Henry Michael E.
Published: August 2020

Objectives

The use of ultrabrief pulse (UBP) stimuli and individual seizure threshold determination have been proposed as ways of minimizing the cognitive side effects of electroconvulsive therapy (ECT), but large samples of patients receiving UBP ECT are lacking. This study reports a retrospective cohort of patients receiving an index course of right unilateral UBP ECT and characterizes the amount of charge required to induce a seizure.

Methods

A single-center retrospective chart review was conducted of adult patients receiving a first lifetime course of ECT using an UBP titration from 2005 to 2017.

Results

There were 2328 patients that received a dose titration during the study period, with a mean dose of 21.82 ± 21.61 mC applied to induce a seizure. During the early part of the study period, a mean dose of 18.73 ± 8.99 mC was used, with 28% of patients seizing at a dose of less than 19.2 mC. In the later period, the initial step of dose titration was standardized at 19.2 mC, yielding a mean initial dose to induce a seizure of 22.72 ± 24.00 mC.

Conclusions

Mean seizure thresholds may be lower than reported in previous studies, and a significant proportion of patients may have a seizure threshold lower than the first step of many existing dose titration protocols.
Pseudomonas karstica sp. nov. and Pseudomonas spelaei sp. nov., isolated from calcite moonmilk deposits from caves
Authors: Švec Pavel , Kosina Marcel , Zeman Michal , Holochová Pavla , Králová Stanislava , Němcová Eva , Micenková Lenka , Urvashi  , Gupta Vipin , Sood Utkarsh , Lal Rup , Korpole Suresh , Sedláček Ivo
Published: August 2020

A taxonomic study of two fluorescent

Pseudomonas

strains (HJ/4T and SJ/9/1T) isolated from calcite moonmilk samples obtained from two caves in the Moravian Karst in the Czech Republic was carried out. Results of initial 16S rRNA gene sequence analysis assigned both strains into the genus

Pseudomonas

and showed

Pseudomonas yamanorum

8H1T as their closest neighbour with 99.8 and 99.7 % 16S rRNA gene similarities to strains HJ/4T and SJ/9/1T, respectively. Subsequent sequence analysis of rpoD, rpoB and gyrB housekeeping genes confirmed the highest similarity of both isolates to

P. yamanorum

8H1T, but phylogeny and sequences similarities implied that they are representatives of two novel species within the genus

Pseudomonas

. Further study comprising whole-genome sequencing followed by average nucleotide identity and digital DNA–DNA hybridization calculations, repetitive sequence-based PCR fingerprinting with the REP and ERIC primers, automated ribotyping with the EcoRI restriction endonuclease, cellular fatty acid analysis, quinone and polar lipid characterization, and extensive biotyping confirmed clear separation of both analysed strains from the remaining

Pseudomonas

species and showed that they represent two novel species within the genus

Pseudomonas

for which the names Pseudomonas karstica sp. nov. (type strain HJ/4T=CCM 7891T=LMG 27930T) and Pseudomonas spelaei sp. nov. (type strain SJ/9/1T=CCM 7893T=LMG 27931T) are suggested.
Real-time spatial health surveillance: mapping the UK COVID-19 epidemic
Authors: Fry Richard , Hollinghurst Joe , R Stagg Helen , A Thompson Daniel , Fronterre Claudio , Orton Chris , A Lyons Ronan , V Ford David , Sheikh Aziz , J Diggle Peter
Published: August 2020

The COVID-19 pandemic has highlighted the need for robust data linkage systems and methods for identifying outbreaks of disease in near real-time. Using self-reported app data and the Secure Anonymised Information Linkage (SAIL) Databank, we demonstrate the use of sophisticated spatial modelling for near-real-time prediction of COVID-19 prevalence at small-area resolution to inform strategic government policy areas. A pre-requisite to an effective control strategy is that predictions need to be accompanied by estimates of their precision, to guard against over-reaction to potentially spurious features of ‘best guess’ predictions. In the UK, important emerging risk-factors such as social deprivation or ethnicity vary over small distances, hence risk needs to be modelled at fine spatial resolution to avoid aggregation bias. We demonstrate that existing geospatial statistical methods originally developed for global health applications are well-suited to this task and can be used in an anonymised databank environment, thus preserving the privacy of the individuals who contribute their data.
On COVID-19-safety ranking of seats in intercontinental commercial aircrafts: A preliminary multiphysics computational perspective
Authors: Desai Prathamesh S. , Sawant Nihar , Keene Andrew
Published: August 2020

The evolution of coronavirus disease (COVID-19) into a pandemic has severely hampered the usage of public transit systems. In a post-COVID-19 world, we may see an increased reliance on autonomous cars and personal rapid transit (PRT) systems, with inherent physical distancing, over buses, trains and aircraft for intracity, intercity, and interstate travel. However, air travel would continue to be the dominant mode of intercontinental transportation for humans. In this study, we perform a comprehensive computational analysis of typical intercontinental aircraft ventilation systems to determine the seat where environmental factors are most conducive to human comfort with regards to air quality, protection from orally or nasally released pollutants such as CO2 and coronavirus, and thermal comfort levels. Air velocity, temperature, and air pollutant concentration emitted from the nose/mouth of fellow travelers are considered for both Boeing and Airbus planes. In each plane, first class, business class, and economy class sections were analyzed. We present conclusions as to which is the optimum seat in each section of each plane and provide the data of the environmental conditions to support our inferences. The findings may be used by the general public to decide which seat to occupy for their next intercontinental flight. Alternatively, the commercial airliners can use such a model to plan the occupancy of the aircraft on long-duration intercontinental flights (viz., Airbus A380 and Boeing B747).
The Mental Health of Healthcare Staff during the COVID-19 Pandemic: It Depends on How Much They Work and Their Age
Authors: Xu Xingzi , Zhang Stephen X. , Jahanshahi Asghar Afshar , Li Jizhen , Bagheri Afsaneh , Nawaser Khaled
Published: August 2020

Background

Healthcare staff are the forefront of fight against COVID-19 and they are under enormous pressure due to the fast growth in the number and severity of infected cases. This creates their mental issues such as distress, depression and anxiety. Exploring healthcare staff’s mental health during the pandemic contributes to improving their persistence in the growing challenges created by COVID-19 and enabling effective management of their mental health.

Methods

An online survey of 280 healthcare staff in all the 31 provinces of Iran was conducted during April 5–20, 2020. The survey assessed staff’s distress, depression and anxiety in the COVID-19 pandemic.

Results

Nearly a third of healthcare staff suffered from distress, depression and anxiety. Females and more educated healthcare staff were more likely to experience distress. Compared to personnel who did not have COVID-19, those who were unsure whether they had COVID-19 were more likely to experience distress and depression. The number of COVID-19 cases among the staff’s colleagues or friends positively predicted their anxiety. Compared to radio technologists, doctors were less likely to experience distress and anxiety. Technicians and obstetrics experienced less anxiety. Analysis the interaction between weekly working days and age of the staff indicated the chance of experiencing distress and depression varied greatly by working days among younger but not older healthcare staff.

Conclusion

The predictors of mental health issues assists healthcare organizations to identify healthcare staff with mental health issues in sever crises such as the COVID-19 pandemic. Our research highlight the need to identify more working characteristics as predictors for healthcare staff at different ages.

Funding

This work was supported by Tsinghua University-INDITEX Sustainable Development Fund (No. TISD201904).
Cancer in HIV-positive and HIV-negative adolescents and young adults in South Africa: a cross-sectional study
Authors: Dhokotera Tafadzwa , Bohlius Julia , Egger Matthias , Spoerri Adrian , Ncayiyana Jabulani , Naidu Gita , Olago Victor , Zwahlen Marcel , Singh Elvira , Muchengeti Mazvita
Published: August 2020

Objective

To determine the spectrum of cancers in AYAs living with HIV in South Africa compared to their HIV negative peers.

Design

Cross sectional study with cancer data provided by the National Cancer Registry and HIV data from the National Health Laboratory Service.

Setting and participants

The NHLS is the largest provider of pathology services in the South African public sector with an estimated coverage of 80%. The NCR is a division of the NHLS. We included AYAs (aged 10-24 years) diagnosed with cancer by public health sector laboratories between 2004 and 2014 (n=8 479). We included 3 672 in the complete case analysis.

Primary and secondary outcomes

We used linked NCR and NHLS data to determine the spectrum of cancers by HIV status in AYAs. We also used multivariable logistic regression to describe the association of cancer in AYAs with HIV, adjusting for age, sex (as appropriate), ethnicity, and calendar period. Due to the large proportion of unknown HIV status we also imputed (post-hoc) the missing HIV status.

Results

From 2004-2014, 8 479 AYAs were diagnosed with cancer, HIV status was known for only 45% (n=3812); of those whose status was known, about half were HIV positive (n=1853). AYAs living with HIV were more likely to have Kaposi’s sarcoma (adjusted odds ratio (aOR) 218, 95% CI 89.9-530), cervical cancer (aOR 2.18, 95% CI 1.23-3.89), non-Hodgkin’s lymphoma (aOR 2.12, 95% CI 1.69-2.66), and anogenital cancers other than cervix (aOR 2.73, 95% CI 1.27-5.86). About 44% (n=1 062) of AYAs with HIV related cancers had not been tested for HIV, though they were very likely to have the disease.

Conclusions

Cancer burden in AYAs living with HIV in South Africa could be reduced by screening young women for cervical cancer and vaccinating them against human papilloma virus (HPV) infection.

Strength and limitations

This is the first nationwide study in South Africa to compare the distribution of cancers in adolescents and young adults (AYAs) by HIV status.

The record linkage and the additional results determined from the text mining process ensured that we extracted the maximum available HIV results.

We assumed a CD4 count test indicates being HIV positive but CD4 testing maybe performed for other reasons

Since this was a population of only AYAs diagnosed with cancer, the odds ratios could be overestimated or underestimated depending on the frequency of the cancer
A Human-Immune-System (HIS) humanized mouse model (DRAGA: HLA-A2. HLA-DR4. Rag1 KO.IL-2Rγc KO. NOD) for COVID-19
Authors: Brumeanu Teodor-D. , Vir Pooja , Karim Ahmad Faisal , Kar Swagata , Benetiene Dalia , Lok Megan , Greenhouse Jack , Putmon-Taylor Tammy , Kitajewski Christopher , Chung Kevin K. , Pratt Kathleen P. , Casares Sofia A.
Published: August 2020

We report the first Human Immune System (HIS)-humanized mouse model (“DRAGA”: HLA-A2.HLA-DR4.Rag1KO.IL-2RγcKO.NOD) for COVID-19 research. This mouse is reconstituted with human cord blood-derived, HLA-matched hematopoietic stem cells. It engrafts human epi/endothelial cells expressing the human ACE2 receptor for SARS-CoV-2 and TMPRSS2 serine protease co-localized on lung epithelia. HIS-DRAGA mice sustained SARS-CoV-2 infection, showing deteriorated clinical condition, replicating virus in the lungs, and human-like lung immunopathology including T-cell infiltrates, microthrombi and pulmonary sequelae. Among T-cell infiltrates, lung-resident (CD103+) CD8+T cells were sequestered in epithelial (CD326+) lung niches and secreted granzyme B and perforin, indicating cytotoxic potential. Infected mice also developed antibodies against the SARS-CoV-2 viral proteins. Hence, HIS-DRAGA mice showed unique advantages as a surrogatein vivohuman model for studying SARS-CoV-2 immunopathology and for testing the safety and efficacy of candidate vaccines and therapeutics.
Latent dynamical variables produce signatures of spatiotemporal criticality in large biological systems
Authors: Morrell Mia C. , Sederberg Audrey J. , Nemenman Ilya
Published: August 2020

Understanding the activity of large populations of neurons is difficult due to the combinatorial complexity of possible cell-cell interactions. To reduce the complexity, coarse-graining had been previously applied to experimental neural recordings, which showed over two decades of scaling in free energy, activity variance, eigenvalue spectra, and correlation time, hinting that the mouse hippocampus operates in a critical regime. We model the experiment by simulating conditionally independent binary neurons coupled to a small number of long-timescale stochastic fields and then replicating the coarse-graining procedure and analysis. This reproduces the experimentally-observed scalings, suggesting that they may arise from coupling the neural population activity to latent dynamic stimuli. Further, parameter sweeps for our model suggest that emergence of scaling requires most of the cells in a population to couple to the latent stimuli, predicting that even the celebrated place cells must also respond to non-place stimuli.
A fresh look at an old concept: Home-range estimation in a tidy world
Authors: Signer Johannes , Fieberg John
Published: August 2020

A rich set of statistical techniques have been developed over the last several decades to estimate the spatial extent of animal home ranges from telemetry data, and new methods to estimate home ranges continue to be developed.

Here we investigate home-range estimation from a computational point of view and aim to provide a general framework for computing home ranges, independent of specific estimators.

We show how such a workflow can help make home-range estimation easier and more intuitive, and we provide a series of examples illustrating how different estimators can be compared easily, so that one can perform a sensitivity analysis to determine the degree to which the choice of estimator influences qualitative and quantitative conclusions.

By providing a standardized, tidy implementation of home-range estimators, we hope to equip analysts with the tools needed to explore how estimator choice influences answers to biologically meaningful questions.
Protein interaction probability landscapes for yeast replicative aging
Authors: Guo Hao-Bo , Ghafari Mehran , Dang Weiwei , Qin Hong
Published: August 2020

We proposed a novel probability landscape approach to map the systems-level profile changes of gene networks during replicative aging inSaccharomyces cerevisiae. This approach enabled us to apply quasi-potentials, the negative logarithm of the probabilities, to calibrate the elevation of the landscapes with young cells as a reference state. Our approach detected opposite landscape changes based on protein abundances from transcript levels, especially for intra-essential gene interactions. We showed that essential proteins play different roles from hub proteins on the age-dependent landscapes. We verified that hub proteins tend to avoid other hub proteins, but essential proteins are attractive to other essential proteins. Overall, we showed that the probability landscape is promising for inferring network profile change during aging and that the essential hub proteins may play an important role in the uncoupling between protein and transcript levels during replicative aging.
Exploring G and C-quadruplex structures as potential targets against the severe acute respiratory syndrome coronavirus 2
Authors: Belmonte-Reche Efres , Serrano-Chacón Israel , Gonzalez Carlos , Gallo Juan , Bañobre-López Manuel
Published: August 2020

In this paper we report the analysis of the 2019-nCoV genome and related viruses using an upgraded version of the open-source algorithm G4-iM Grinder. This version improves the functionality of the software, including an easy way to determine the potential biological features affected by the candidates found. The quadruplex definitions of the algorithm were optimized for 2019-nCoV. Using a lax quadruplex definition ruleset, which accepts amongst other parameters two residue G- and C-tracks, hundreds of potential quadruplex candidates were discovered. These sequences were evaluated by theirin vitroformation probability, their position in the viral RNA, their uniqueness and their conservation rates (calculated in over three thousand different COVID-19 clinical cases and sequenced at different times and locations during the ongoing pandemic). These results were compared sequentially to otherCoronaviridaemembers, other Group IV (+)ssRNA viruses and the entire realm. Sequences found in common with other species were further analyzed and characterized. Sequences with high scores unique to the 2019-nCoV were studied to investigate the variations amongst similar species. Quadruplex formation of the best candidates was then confirmed experimentally. Using NMR and CD spectroscopy, we found several highly stable RNA quadruplexes that may be suitable theranostic targets against the 2019-nCoV.

GRAPHICAL ABSTRACT
Rice Tolerance to Drought is Complex Both Physiologically and Genetically
Authors: Jernigan Paula , Nies Luca , Fernandes George , Quesada Roberto
Published: August 2020

This paper has been withdrawn by bioRxiv because its content, including the author names, was fabricated and fraudulently submitted in what may have been an attempt to game citation statistics or other metrics.