bluuebunny/crossref_metadata_2025 huggingface dataset:
Early versus late acute kidney injury among patients with COVID-19—a multicenter study from Wuhan, China
Authors: Peng Suyuan , Wang Huai-Yu , Sun Xiaoyu , Li Pengfei , Ye Zhanghui , Li Qing , Wang Jinwei , Shi Xuanyu , Liu Liu , Yao Ying , Zeng Rui , He Fan , Li Junhua , Ge Shuwang , Ke Xianjun , Zhou Zhibin , Dong Erdan , Wang Haibo , Xu Gang , Zhang Luxia , Zhao Ming-Hui
Published: October 2020

Background

Acute kidney injury (AKI) is an important complication of coronavirus disease 2019 (COVID-19), which could be caused by both systematic responses from multi-organ dysfunction and direct virus infection. While advanced evidence is needed regarding its clinical features and mechanisms. We aimed to describe two phenotypes of AKI as well as their risk factors and the association with mortality.

Methods

Consecutive hospitalized patients with COVID-19 in tertiary hospitals in Wuhan, China from 1 January 2020 to 23 March 2020 were included. Patients with AKI were classified as AKI-early and AKI-late according to the sequence of organ dysfunction (kidney as the first dysfunctional organ or not). Demographic and clinical features were compared between two AKI groups. Their risk factors and the associations with in-hospital mortality were analyzed.

Results

A total of 4020 cases with laboratory-confirmed COVID-19 were included and 285 (7.09%) of them were identified as AKI. Compared with patients with AKI-early, patients with AKI-late had significantly higher levels of systemic inflammatory markers. Both AKIs were associated with an increased risk of in-hospital mortality, with similar fully adjusted hazard ratios of 2.46 [95% confidence interval (CI) 1.35–4.49] for AKI-early and 3.09 (95% CI 2.17–4.40) for AKI-late. Only hypertension was independently associated with the risk of AKI-early. While age, history of chronic kidney disease and the levels of inflammatory biomarkers were associated with the risk of AKI-late.

Conclusions

AKI among patients with COVID-19 has two clinical phenotypes, which could be due to different mechanisms. Considering the increased risk for mortality for both phenotypes, monitoring for AKI should be emphasized during COVID-19.
Comorbidities and outcomes in South Asian individuals with chronic kidney disease: an observational primary care cohort
Authors: Major Rupert W , Shepherd David , Medcalf James F , Xu Gang , Gray Laura J , Brunskill Nigel J
Published: October 2020

Background

South Asian (SA) individuals are more likely to develop end-stage renal disease (ESRD), but how chronic kidney disease (CKD) differs in relation to demographics, comorbidities and outcomes has not been studied. We aimed to study differences in SA individuals with CKD compared with White individuals.

Methods

This was an observational CKD cohort comparing SA with White individuals. Inclusion criteria were ≥18 years of age and two or more Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRs <60 mL/min/1.73 m2 >3 months apart. Individuals with ESRD at baseline were excluded. Baseline characteristics, including eGFR formulae [CKD-EPI and CKD-EPI-Pakistan (CKD-EPI-PK)], were compared. Analysis using competing risk regression for cardiovascular (CV) and ESRD events and Cox proportional hazard model for mortality was performed.

Results

From an adult population of 277 248 individuals, 17 248 individuals had CKD, of whom 1990 (11.5%) were of SA ethnicity. Age-adjusted prevalence of CKD was similar between ethnicities. SA individuals were more likely to be male, younger and socioeconomically deprived, and to have diabetes mellitus, CV disease and advanced CKD. Mean CKD-EPI-PK eGFR was 6.5 mL/min/1.73 m2 lower (41.1 versus 47.6, 95% confidence interval for difference 6.47–6.56) than for CKD-EPI. During 5 years of follow-up, 5109 (29.6%) individuals died, 2072 (12.0%) had a CV and 156 (0.90%) an ESRD event. Risk for SA individuals was higher for ESRD, similar to CV events and lower for mortality. Each 1 mL/min/1.73 m2 decrease in CKD-EPI-PK was associated with a 13.1% increased ESRD risk (adjusted subdistribution hazard ratio 0.869, 95% confidence interval 0.841–0.898).

Conclusions

SA individuals with CKD were younger and had more advanced disease than White individuals. Risk of ESRD was higher and CKD-EPI-PK was associated with ESRD risk in SA individuals. Specific CKD interventions, including the use of CKD-EPI-PK, should be considered in SA populations.
Investigating new treatment opportunities for patients with chronic kidney disease in type 2 diabetes: the role of finerenone
Authors: Agarwal Rajiv , Anker Stefan D , Bakris George , Filippatos Gerasimos , Pitt Bertram , Rossing Peter , Ruilope Luis , Gebel Martin , Kolkhof Peter , Nowack Christina , Joseph Amer ,   on behalf of the FIDELIO-DKD and FIGARO-DKD Investigators
Published: October 2020

Despite the standard of care, patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) progress to dialysis, are hospitalized for heart failure and die prematurely. Overactivation of the mineralocorticoid receptor (MR) causes inflammation and fibrosis that damages the kidney and heart. Finerenone, a nonsteroidal, selective MR antagonist, confers kidney and heart protection in both animal models and Phase II clinical studies; the effects on serum potassium and kidney function are minimal. Comprising the largest CKD outcomes program to date, FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) and FIGARO-DKD (FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease) are Phase III trials investigating the efficacy and safety of finerenone on kidney failure and cardiovascular outcomes from early to advanced CKD in T2D. By including echocardiograms and biomarkers, they extend our understanding of pathophysiology; by including quality of life measurements, they provide patient-centered outcomes; and by including understudied yet high-risk cardiorenal subpopulations, they have the potential to widen the scope of therapy in T2D with CKD.

Trial registration number: FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049)
Herpetological phylogeographic analyses support a Miocene focal point of Himalayan uplift and biological diversification
Authors: Xu Wei , Dong Wen-Jie , Fu Ting-Ting , Gao Wei , Lu Chen-Qi , Yan Fang , Wu Yun-He , Jiang Ke , Jin Jie-Qiong , Chen Hong-Man , Zhang Ya-Ping , Hillis David M , Che Jing
Published: October 2020

The Himalaya are among the youngest and highest mountains in the world, but the exact timing of their uplift and origins of their biodiversity are still in debate. The Himalayan region is a relatively small area but with exceptional diversity and endemism. One common hypothesis to explain the rich montane diversity is uplift-driven diversification—that orogeny creates conditions favoring rapid in situ speciation of resident lineages. We test this hypothesis in the Himalayan region using amphibians and reptiles, two environmentally sensitive vertebrate groups. In addition, analysis of diversification of the herpetofauna provides an independent source of information to test competing geological hypotheses of Himalayan orogenesis. We conclude that the origins of the Himalayan herpetofauna date to the early Paleocene, but that diversification of most groups was concentrated in the Miocene. There was an increase in both rates and modes of diversification during the early to middle Miocene, together with regional interchange (dispersal) between the Himalaya and adjacent regions. Our analyses support a recently proposed stepwise geological model of Himalayan uplift beginning in the Paleocene, with a subsequent rapid increase of uplifting during the Miocene, finally giving rise to the intensification of the modern South Asian Monsoon.
Capital Accumulation, Supply Networks and the Composition of the Roman Senate, 14–235 ce
Authors: Weisweiler John
Published: October 2020

In the first two centuries ce, the Roman senate transformed from an assembly of Italian landowners into a multi-regional group. The admission of thousands of provincials into Rome’s governing elite is often taken as evidence for the successful integration of subject populations. This article challenges such views of the senate as an inclusive institution. It shows that the overwhelming majority of non-Italian senators came from merely four (out of more than thirty) provinces: Baetica (in southern Spain), Narbonensis (Provence), Africa (the coastlines of Algeria, Tunisia and Libya) and Asia (western Anatolia). The elites of these regions entertained close links to Italy since the second century bce. In the first centuries ce, they acquired enormous wealth through predation, through investments in capital-intensive agriculture and through their ability to exploit state supply networks for their own benefit. The steep rise in the number of provincial senators should thus not be read as evidence for the large-scale participation of conquered groups in the imperial administration. Rather, it chiefly was a product of the new opportunities for wealth accumulation and exploitation generated by Roman imperialism.
AAAPT Diagnostic Criteria for Acute Neuropathic Pain
Authors: Doshi Tina L , Dworkin Robert H , Polomano Rosemary C , Carr Daniel B , Edwards Robert R , Finnerup Nanna B , Freeman Roy L , Paice Judith A , Weisman Steven J , Raja Srinivasa N
Published: October 2020

Objective

Acute neuropathic pain is a significant diagnostic challenge, and it is closely related to our understanding of both acute pain and neuropathic pain. Diagnostic criteria for acute neuropathic pain should reflect our mechanistic understanding and provide a framework for research on and treatment of these complex pain conditions.

Methods

The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public–private partnership with the U.S. Food and Drug Administration (FDA), the American Pain Society (APS), and the American Academy of Pain Medicine (AAPM) collaborated to develop the ACTTION-APS-AAPM Pain Taxonomy (AAAPT) for acute pain. A working group of experts in research and clinical management of neuropathic pain was convened. Group members used literature review and expert opinion to develop diagnostic criteria for acute neuropathic pain, as well as three specific examples of acute neuropathic pain conditions, using the five dimensions of the AAAPT classification of acute pain.

Results

AAAPT diagnostic criteria for acute neuropathic pain are presented. Application of these criteria to three specific conditions (pain related to herpes zoster, chemotherapy, and limb amputation) illustrates the spectrum of acute neuropathic pain and highlights unique features of each condition.

Conclusions

The proposed AAAPT diagnostic criteria for acute neuropathic pain can be applied to various acute neuropathic pain conditions. Both the general and condition-specific criteria may guide future research, assessment, and management of acute neuropathic pain.
New species of mammaliaform and the cranium ofBorealestes(Mammaliformes: Docodonta) from the Middle Jurassic of the British Isles
Authors: Panciroli Elsa , Benson Roger B J , Fernandez Vincent , Butler Richard J , Fraser Nicholas C , Luo Zhe-Xi , Walsh Stig
Published: October 2020

Docodonta are one of the earliest diverging groups of mammaliaforms, and their morphology provides key information on the transition between non-mammalian cynodonts and Mammalia. We describe the partial skulls of two docodontans Borealestes serendipitus and Borealestes cuillinensis sp. nov. from the Kilmaluag Formation (Middle Jurassic: Bathonian), Isle of Skye, Scotland. We visualize their cranial anatomy using laboratory and synchrotron X-ray micro-CT. The skulls belong to two partial skeletons, currently comprising the most complete Mesozoic mammal fossils reported from the British Isles. The associated upper and lower dentitions show that the lower dentition of Borealestes is not diagnostic to species level. We establish, B. cuillinensis, based on upper molar characters, and re-identify upper molars previously assigned to ‘Borealestes’ mussettae as belonging to B. cuillinensis. ‘Borealestes’ mussettae, based on distinctive lower molars, is found to be morphologically and phylogenetically distinct from Borealestes, necessitating assignment to a new genus, Dobunnodon gen. nov. The skulls of Borealestes retain many plesiomorphic features seen in Morganucodon but absent in more crownward mammaliaforms. Our study highlights that generic and species taxonomy of docodontans are more reliable when based on both upper and lower teeth, while lower molar morphology may underrepresent the true diversity of Mesozoic mammaliaforms.
Effects of Water Temperature, Inoculum Concentration and Age, and Sanitizers on Infection of Ceratocystis fimbriata, Causal Agent of Black Rot in Sweetpotato
Authors: Stahr Madison N. , Quesada-Ocampo Lina M.
Published: October 2020

Black rot, caused by Ceratocystis fimbriata, is a devastating postharvest disease of sweetpotato that recently re-emerged in 2014. Although the disease is known to develop in storage and during export to overseas markets, little is known as to how pathogen dispersal occurs. This study was designed to investigate dump tank water as a means of dispersal through four different types of water treatments: inoculum concentration (0, 5, 5 × 101, 5 × 102, and 5 × 103 spores/ml), inoculum age (0, 24, 48, 96, and 144 h), water temperature (10°C, 23°C, 35°C, and 45°C), and presence of a water sanitizer (DryTec, SaniDate, FruitGard, and Selectrocide). Wounded and nonwounded sweetpotato storage roots were soaked in each water treatment for 20 min, stored at 29°C for a 14-day period, and rated for disease incidence every other day. Disease was observed in sweetpotato storage roots in all water treatments tested, except in the negative controls. Disease incidence decreased with both inoculum concentration and inoculum age, yet values of 16.26% and up to 50% were observed for roots exposed to 5 spores/ml and 144-h water treatments, respectively. Sanitizer products that contained a form of chlorine as the active ingredient significantly reduced disease incidence in storage roots when compared with control roots and roots exposed to a hydrogen-peroxide based product. Finally, no significant differences in final incidence were detected in wounded sweetpotato storage roots exposed to water treatments of any temperature, but a significant reduction in disease progression was observed in the 45°C treatment. These findings indicate that if packing line dump tanks are improperly managed, they can aid C. fimbriata dispersal through the build-up of inoculum as infected roots are unknowingly washed after storage. Chlorine-based sanitizers can reduce infection when applied after root washing and not in the presence of high organic matter typically found in dump tanks.
Nail Versus Plate: A Biomechanical Comparison of a Locking Plate Versus an Intramedullary Nail With an Angular Stable Locking System in a Shoulder Simulator With Active Muscle Forces Using a Two-Part Fracture Model
Authors: Strasser Susanne , Kralinger Franz , Blauth Michael , Schmoelz Werner
Published: October 2020

Objectives:

To compare a locking compression plate versus an intramedullary nail with an angular stable locking system (ASLS) using a 2-part fracture model in a shoulder test bench.

Methods:

Twelve fresh frozen humeri were used for biomechanical testing in a shoulder simulator. A 2-part fracture model, with and without medial cortical support, was used to compare the locking plate and a nail with an ASLS. The varus impaction, varus per cycle motion, tilt, and tilt per cycle were analyzed.

Results:

No significant differences for the resulting forces in the glenoid fossa were evaluated. The stable fracture model showed no significant differences for the 2 groups. The median varus impaction was −0.96 degrees (range −0.55 to −4.26 degrees) in the plate group and 0.5 degrees (range −3.06 to 0.98 degrees) in the nail group, after 500 cycles of cyclic loading in the unstable fracture model. The plate group showed a significantly higher median varus impaction per cycle motion and median varus impaction at the 200th, 300th, and 400th cycle of physiological loading.

Conclusions:

The intramedullary nail with the ASLS could be an alternative for patients suffering from osteoporosis and comorbidities.
The “Double Washer” Technique Is an Effective Strategy for Bicortical Fixation in Periprosthetic Fractures About a Femoral Stem: A Technical Trick and Case Series
Authors: Goch Abraham M. , Tarpada Sandip , Loloi Jeremy , Sen Milan K. , Harbacheuski Ryhor , Dimitroulias Apostolos
Published: October 2020

Periprosthetic fractures about the hip and knee are challenging injuries to treat for the orthopaedic surgeon. The pre-existing femoral implant and poor bone quality provide for difficulties in achieving stable fixation. We present a surgical technique and clinical series of 5 patients describing the use and outcomes of a 3.5 screw with a “double washer” technique to achieve bicortical fixation around a femoral prosthesis.
Are Arthroplasty Procedures Really Better in the Treatment of Complex Proximal Humerus Fractures? A Comprehensive Meta-Analysis and Systematic Review
Authors: Pizzo Richard A. , Gianakos Arianna L. , Haring Richard Sterling , Gage Mark J. , Stevens Nicole M. , Liporace Frank A. , Yoon Richard S.
Published: October 2020

Objective:

A meta-analysis and systematic review was performed to compare outcomes of open reduction and internal fixation (ORIF), hemiarthroplasty (HA), and reverse total shoulder arthroplasty (rTSA) for complex proximal humerus fractures. Data sources: MEDLINE, Embase, and Cochrane Library databases were screened. Search terms included reverse total shoulder arthroplasty, open reduction internal fixation, hemiarthroplasty, and proximal humerus fracture.

Study Selection:

English-language studies published within the past 15 years evaluating outcomes of ORIF, rTSA, or HA for complex proximal humerus fractures with minimum of 1-year follow-up were included, resulting in 51 studies with 3064 total patients. Review articles, basic science studies, biomechanical studies, and cadaveric studies were excluded.

Data Extraction:

The methodological quality of evidence was assessed using the Jadad scale and methodological index for nonrandomized studies.

Data Synthesis:

Demographic data were compared using the χ2 test. Mean data were weighted by study size and used to calculate composite mean values and confidence intervals. Continuous data were compared using the Metan module with fixed effects. Count data were compared using the Kruskal–Wallis test. Alpha was set at 0.05 for all tests.

Conclusions:

Patients undergoing rTSA had lower risks of complication (relative risk 0.41) and reoperation (relative risk 0.28) than HA patients. rTSA resulted in higher Constant scores (standard mean difference 0.63) and improved active forward flexion when compared with HA (standard mean difference 0.76). Pooled mean data demonstrated better outcome scores and active forward flexion of ORIF versus HA and rTSA, although the patients were younger and had more simple fracture patterns.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Clinical Correlation of the Orthopaedic Trauma Association Open Fracture Classification With Wound Closure and Soft-Tissue Complications in Open Upper Extremity Fractures
Authors: Putnam Sara M. , Dunahoe Jacquelyn , Agel Julie , Garner Matthew R.
Published: October 2020

Objectives:

To correlate domains of the Orthopaedic Trauma Association Open Fracture Classification (OTA-OFC) in open upper extremity injuries with type of definitive soft-tissue closure, complication rates, and unanticipated return to the operating room for complication.

Design:

Retrospective review of prospectively collected data.

Setting:

Level I trauma center.

Patients:

Two hundred thirty-four consecutive open upper extremity fractures.

Intervention:

Operative management of open upper extremity fractures.

Main outcome measurements:

Type of definitive closure, 90-day wound complication, and wound complication necessitating return to the operating room.

Results:

Two hundred eighty injuries were identified, and 234 had sufficient data for analysis. Eighty-four percent (196/234) of open wounds were closed primarily, 7% (16/234) required a skin graft, and 4% (9/234) required rotational or free flap. Thirteen percent (22/166) of those followed for 90 days had a wound complication, and 50% of those with complication required a return to the OR. All OTA-OFC classifications statistically significantly correlated with type of closure (P < 0.001), with skin having a high correlation (r = 0.79), muscle (r = 0.49) and contamination (r = 0.47) moderate correlations, and arterial (r = 0.32) and bone loss (r = 0.33) low correlations. OTA-OFC muscle classification was predictive of 90-day wound complication (OR 0.31, 95% confidence interval 0.07–0.21). OTA-OFC domains correlated variably with return to the OR.

Conclusion:

OTA-OFC clinically correlates with definitive wound management and 90-day wound complication in open upper extremity fractures. OTA-OFC skin classification has a high correlation with the type of definitive wound closure. OTA-OFC muscle was the only domain that correlated with 90-day wound complication and was predictive of 90-day wound complication.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Systematic review and meta-analysis: risks of postoperative complications with preoperative use of anti-tumor necrosis factor-alpha biologics in inflammatory bowel disease patients
Authors: Moosvi Zain , Duong Jacqueline , Bechtold Matthew L. , Nguyen Douglas L.
Published: October 2020

Objective

The preoperative use of anti-tumor necrosis factor-alpha (anti-TNF) in inflammatory bowel disease (IBD) patients undergoing surgery has been controversial due to concern for increased risks of postoperative complications. We aimed to determine the effect of preoperative anti-TNF therapy on postoperative complications in IBD patients undergoing abdominal surgery.

Methods

A literature search of Google Scholar, PubMed, The Cochrane Library, EMBASE, and CINAHL was performed through October 2019. Studies reporting postoperative complication rates of Crohn’s disease (CD), ulcerative colitis (UC), and IBD-unspecified patients with preoperative anti-TNF treatment undergoing abdominal surgery compared to controls without preoperative anti-TNF treatment were included. The main outcomes measured were overall, infectious, and noninfectious postoperative complications.

Results

Forty-one studies totaling 20 274 patients were included. There was a significant increase in overall complications in all patients treated with anti-TNF vs. controls [odds ratio (OR) = 1.13, 95% confidence interval (CI), 1.01–1.25, P = 0.03, I2 = 6%] with an absolute risk increase (ARI) of 5.5% and a number needed to harm (NNH) of 18. There was also a significant increase in infectious complications in CD patients (OR = 1.44; 95% CI 1.02–2.03, P = 0.04, I2 = 49%, ARI = 5.5%, NNH = 20) only. Contrastingly, there was a significant increase in noninfectious complications in all patients (OR = 1.44, 95% CI 1.13–1.85, P = 0.003, I2 = 8%, ARI = 6.4%, NNH = 16) and UC patients (OR = 1.57, 95% CI 1.15–2.14, P = 0.005, I2 = 25%, ARI = 8.5%, NNH = 12) only.

Conclusion

Preoperative use of anti-TNF agents in IBD patients undergoing abdominal surgery is associated with increases in overall postoperative complications in all patients, infectious postoperative complications in CD patients, and noninfectious postoperative complications in UC patients.
Estimation of CARE Dose 4D quality reference mAs conversion factors for child to adult reference patient in child protocols on Siemens Symbia SPECT-CT systems
Authors: Hansen Sofie L. , Bebbington Natalie A.
Published: October 2020

Objectives

CARE Dose 4D modulates mAs through several mechanisms according to patient size and shape, whilst maintaining user-defined reference image quality on Siemens Symbia single-photon emission computed tomography (SPECT)-computed tomography (CT) systems. A 20 kg child reference was used in child protocols prior to software version VB10 and a 75 kg adult thereafter. Quality reference mAs conversion factors are estimated for delivering equivalent mAs to children between two comparable SPECT-CT systems using adult and child references for topogram-based patient-size-related dose level adaptations.

Methods

A child phantom was scanned using child protocols on a Siemens Symbia T16 (child reference) and a Siemens Symbia Intevo Bold (adult reference). On each system, scans of the thorax, abdomen and pelvis were acquired with arms up and down, at 80 and 110 kVp. Quality reference mAs settings of 10–50 were used on the Symbia T16 and 40–200 on the Symbia Intevo Bold. These data were used to propose quality reference mAs (adult/child reference) conversion factors according to scan range, arm position and tube voltage.

Results

Quality reference mAs for child protocols using the adult reference should multiply the child quality reference mAs by the following factors, to give comparable delivered mAs: arms up 80 kV: 3.8 (thorax), 3.8 (abdomen), 4.3 (pelvis); arms up at 110 kV: 3.8 (thorax), 4.1 (abdomen), 4.6 (pelvis); arms down at 80 kV: 4.0 (thorax), 3.7 (abdomen), 3.9 (pelvis); arms down at 110 kV: 4.3 (thorax), 4.0 (abdomen), 4.2 (pelvis).

Conclusion

Conversion factors for child to adult dose modulation references are proposed, allowing comparable delivered mAs to a child.

Video abstract: http://links.lww.com/NMC/A178
Hemodynamic Response to Fluid Boluses for Hypotension in Children in a Cardiac ICU
Authors: Gelbart Ben , Harrois Anatole , Gardiner Lauren , Mcgregor Cherie , Bitker Laurent , Van Zanten Eva , Beel Emma , Bellomo Rinaldo , Duke Trevor , Butt Warwick
Published: October 2020

Objectives:

To describe the hemodynamic response to fluid boluses for hypotension in children in a cardiac ICU.

Design:

A prospective, observational study.

Setting:

Single-centered cardiac ICU.

Patients:

Children in a cardiac ICU with hypotension.

Interventions:

Clinician prescribed fluid bolus.

Measurements and Main Results:

Sixty-four fluid boluses were administered to 52 children. Fluid composition was 4% albumin in 36/64 (56%), 0.9% saline in 18/64 (28%), and cardiopulmonary bypass pump blood in 10/64 (16%). The median volume and duration were 5.0 mL/kg (interquartile range, 4.8–5.4) and 8 minutes (interquartile range, 4–19), respectively. Hypovolemia/low filling pressures was the most common additional indication (25/102 [25%]). Mean arterial pressure response, defined as a 10% increase from baseline, occurred in 42/64 (66%) of all fluid boluses at a median time of 6 minutes (interquartile range, 4–11). Mean arterial pressure responders had a median peak increase in the mean arterial pressure of 15 mm Hg (43 mm Hg [interquartile range, 29–50 mm Hg] to 58 mm Hg [interquartile range, 49–65 mm Hg]) at 17 minutes (interquartile range, 14–24 min) compared with 4 mm Hg (48 mm Hg [interquartile range, 40–51 mm Hg] to 52 mm Hg [interquartile range, 45–56 mm Hg]) at 10 minutes (interquartile range, 3–18 min) in nonresponders. Dissipation of mean arterial pressure response, when defined as a subsequent decrement in mean arterial pressure below 10%, 5%, and 2% increases from baseline, occurred in 28/42 (67%), 18/42 (43%), and 13/42 (31%) of mean arterial pressure responders, respectively. Cardiopulmonary bypass pump blood was strongly associated with peak change in mean arterial pressure from baseline (coefficient 11.0 [95% CI, 4.3–17.7]; p = 0.02). Fifty out of 64 (78%) were receiving a vasoactive agent. However, change in vasoactive inotrope score was not associated with change in mean arterial pressure (coefficient 2.3 [95% CI, –2.5 to –7.2]; p = 0.35). Timing from admission, nor fluid bolus duration, influenced mean arterial pressure response.

Conclusions:

In children with hypotension in a cardiac ICU, the median dose and duration of fluid boluses were 5 mL/kg and 8 minutes. Peak response occurred shortly following administration and commonly returned to baseline.
Development of a Smartphone-Based Skin Simulation Model for Medical Education
Authors: Dsouza Roshan , Spillman Darold R. , Barrows Scott , Golemon Thomas , Boppart Stephen A.
Published: October 2020

Introduction

Teaching dermatology to medical students entails a series of lectures, pictures, and hands-on skin examinations to convey a sense of skin features and textures, often by use of simulated skin models. However, such methods can often lack accurate visual and tactile texture representation of skin lesions. To facilitate learning, we have developed a smartphone-based skin simulation model, which provides a configurable visual and tactile sense of a lesion by using the ubiquitous availability of smartphone-based mobile platforms.

Methods

A polydimethylsiloxane (PDMS) overlay was used as a configurable translucent elastomer material to model the stiffness and texture of skin. A novel custom smartphone-based app was developed to capture images of various skin lesions, which were subsequently displayed on a tablet or second smartphone, over which the PDMS model skin elastomer was placed. Using the local Bluetooth connection between mobile devices, an iterative feedback algorithm corrected the visual distortion caused by the optical scattering of the translucent elastomer, enabling better virtual visualization of the lesion.

Results

The developed smartphone-based app corrected the distortion of images projected through the simulated skin elastomer. Surface topography of the developed PDMS elastomer provided a more accurate representation of skin texture.

Conclusions

In this investigation, we developed a smartphone-based skin lesion visualization app with a simulated skin elastomer for training/education in not only dermatology but also all general medical specialties that examine the skin. This technique has the potential to advance the educational experience by giving students the ability to see, touch, and feel pragmatic skin textures and lesions.
Helicobacter monodelphidis sp. nov. and Helicobacter didelphidarum sp. nov., isolated from grey short-tailed opossums (Monodelphis domestica) with endemic cloacal prolapses
Authors: Shen Zeli , Mannion Anthony , Lin Maggie , Esmail Michael , Bakthavatchalu Vasudevan , Yang Stephanie , Ho Calvin , Feng Yan , Smith Briony , Elliott James , Gresham Vince , VandeBerg John L. , Samollow Paul B. , Fox James G.
Published: October 2020

In a search for potential causes of increased prolapse incidence in grey short-tailed opossum colonies, samples from the gastrointestinal tracts of 94 clinically normal opossums with rectal prolapses were screened forHelicobacterspecies by culture and PCR. Forty strains of two novelHelicobacterspecies which differed from the establishedHelicobactertaxa were isolated from opossums with and without prolapses. One of theHelicobacterspecies was spiral-shaped and urease-negative whereas the otherHelicobacterstrain had fusiform morphology with periplasmic fibres and was urease-positive. 16S rRNA gene sequence analysis revealed that all the isolates had over 99 % sequence identity with each other, and were most closely related toHelicobacter canadensis. Strains from the two novelHelicobacterspecies were subjected togyrBandhsp60gene and whole genome sequence analyses. These two novelHelicobacterspecies formed separate phylogenetic clades, divergent from other knownHelicobacterspecies. The bacteria were confirmed as novelHelicobacterspecies based on digital DNA–DNA hybridization and average nucleotide identity analysis of their genomes, for which we propose the namesHelicobacter monodelphidissp. nov. with the type strain MIT 15-1451T(=LMG 29780T=NCTC 14189T) andHelicobacter didelphidarumsp. nov with type strain MIT 17-337T(=LMG 31024T=NCTC 14188T)
Clinical, neuroimaging and molecular spectrum of TECPR2-associated hereditary sensory and autonomic neuropathy with intellectual disability
Authors: Neuser Sonja , Brechmann Barbara , Heimer Gali , Brösse Ines , Schubert Susanna , O’Grady Lauren , Zech Michael , Srivastava Siddharth , Sweetser David A. , Dincer Yasemin , Mall Volker , Winkelmann Juliane , Behrends Christian , Darras Basil T , Graham Robert J , Jayakar Parul , Byrne Barry , El Bar-Aluma Bat , Haberman Yael , Szeinberg Amir , Aldhalaan Hesham Mohamed , Hashem Mais , Al Tenaiji Amal , Ismayl Omar , Al Nuaimi Asma E. , Maher Karima , Ibrahim Shahnaz , Khan Fatima , Houlden Henry , Ramakumaran Vijayalakshmi Salem , Pagnamenta Alistair T , Posey Jennifer E , Lupski James R , Tan Wen-Hann , ElGhazali Gehad , Herman Isabella , Muñoz Tatiana , Repetto Gabriela M. , Seitz Angelika , Krumbiegel Mandy , Poli M. Cecilia , Kini Usha , Efthymiou Stephanie , Meiler Jens , Maroofian Reza , Alkuraya Fowzan S. , Jamra Rami Abou , Popp Bernt , Ben-Zeev Bruria , Ebrahimi-Fakhari Darius
Published: October 2020

PURPOSE

Bi-allelic TECPR2 variants have been associated with a complex syndrome with features of both a neurodevelopmental and neurodegenerative disorder. Here, we provide a comprehensive clinical description and variant interpretation framework for this genetic locus.

METHODS

Through an international collaboration, we identified 17 individuals from 15 families with bi-allelic TECPR2-variants. We systemically reviewed clinical and molecular data from this cohort and 11 cases previously reported. Phenotypes were standardized using Human Phenotype Ontology terms.

RESULTS

A cross-sectional analysis revealed global developmental delay/intellectual disability, muscular hypotonia, ataxia, hyporeflexia, respiratory infections and central/nocturnal hypopnea as core manifestations. A review of brain MRI scans demonstrated a thin corpus callosum in 52%. We evaluated 17 distinct variants. Missense variants in TECPR2 are predominantly located in the N- and C-terminal regions containing β-propeller repeats. Despite constituting nearly half of disease associated TECPR2 variants, classifying missense variants as (likely) pathogenic according to ACMG criteria remains challenging. We estimate a pathogenic variant carrier frequency of 1/1,221 in the general and 1/155 in the Jewish Ashkenazi populations.

CONCLUSION

Based on clinical, neuroimaging and genetic data, we provide recommendations for variant reporting, clinical assessment, and surveillance/treatment of individuals with TECPR2-associated disorder. This sets the stage for future prospective natural history studies.

CONFLICTS OF INTEREST

All authors involved in the study declare no conflicts of interest relevant to this study.
Epidemiology and Genetics of Preserved Ratio Impaired SpiroMetry (PRISm): An Analysis of UK Biobank
Authors: Higbee Daniel , Granell Raquel , Davey-Smith George , Dodd James W
Published: October 2020

The authors have withdrawn this manuscript version because the FEV1 percent predicted variable (UK biobank data field 20154) that was used was to determine spirometric pattern was constructed in only “healthy never smokers” or heavy smokers. This means the paper is affected by selection bias and is not generalizable. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Antibody Immunological Imprinting on COVID-19 Patients
Authors: Aydillo T , Rombauts Alexander , Stadlbauer Daniel , Aslam Sadaf , Abelenda-Alonso Gabriela , Escalera Alba , Amanat Fatima , Jiang Kaijun , Krammer Florian , Carratala Jordi , García-Sastre Adolfo
Published: October 2020

While the current pandemic remains a thread to human health, the polyclonal nature of the antibody response against SARS-CoV-2 is not fully understood. Other than SARS-CoV-2, humans are susceptible to six different coronaviruses, and previous exposure to antigenically related and divergent seasonal coronaviruses is frequent. We longitudinally profiled the early humoral immune response against SARS-CoV-2 on hospitalized COVID-19 patients, and quantify levels of pre-existing immunity to OC43, HKU1 and 223E seasonal coronaviruses. A strong back-boosting effect to conserved, but not variable regions of OC43 and HKU1 betacoronaviruses spike protein was observed. All patients developed antibodies against SARS-CoV-2 spike and nucleoprotein, with peak induction at day 7 post hospitalization. However a negative correlation was found between antibody memory boost to human coronaviruses and induction of IgG and IgM against SARS-CoV-2 spike. Our findings provide evidence of immunological imprinting that determine the antibody profile to COVID-19 patients in an original antigenic sin fashion.
Robust Discovery of Mild Cognitive impairment subtypes and their Risk of Alzheimer’s Disease conversion using unsupervised machine learning and Gaussian Mixture Modeling
Authors: Nezhadmoghadam Fahimeh , Martinez-Torteya Antonio , Treviño Victor , Martínez Emmanuel , Santos Alejandro , Tamez-Peña Jose ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: October 2020

Background

Alzheimer’s disease (AD) is an irreversible, progressive brain disorder that slowly destroys memory and thinking skills. The ability to correctly predict the diagnosis of Alzheimer’s disease in its earliest stages can help physicians make more informed clinical decisions on therapy plans.

Objective

To determine whether the unsupervised discovering of latent classes of subjects with mild cognitive impairment (MCI) may be useful in finding different prodromal AD stages and/or subjects that have a low MCI to AD conversion risk.

Methods

18 features relevant with the MCI to AD conversion process described 681 subjects with early MCI. Subjects were split into training (70%) and validation (30%) sets. Subjects from the training set were analyzed using consensus clustering and Gaussian mixture models (GMM) were used to describe the shape of the discovered latent classes. The discovered GMM predicted the latent class of the validation set. Finally, descriptive statistics, rates of conversion, and odds ratios (OR) were computed for each discovered class.

Results

Through consensus clustering we discovered three different clusters among MCI subjects. The three clusters were associated with low-risk (OR = 0.12, 95%CI = 0.04 to 0.3|), medium-risk (OR = 1.33, 95%CI = 0.75 to 2.37), and high-risk (OR = 3.02, 95%CI = 1.64 to 5.57) of converting from MCI to AD, with the high-risk and low-risk groups highly contrasting. Hence, prodromal AD subjects were present on only two clusters.

Conclusion

We successfully discovered three different latent classes among MCI subjects with varied risk of MCI-to-AD conversion through consensus clustering. Two of the discovered classes may represent two different prodromal presentations of the Alzheimer’s disease.
Intravenous Mesenchymal Stem Cells in Extracorporeal Oxygenation Patients with Severe COVID-19 Acute Respiratory Distress Syndrome
Authors: Kaushal Sunjay , Khan Aisha , Deatrick Kristopher , Ng Derek K. , Snyder Abigail , Shah Aakash , Caceres Lina V. , Bacallao Ketty , Bembea Melania , Everett Allen , Zhu Jie , Kaczorowski David , Madathil Ronson , Tabatabai Ali , Rosenthal Geoffrey , Brooks Adriana , Longsomboon Bangon , Mishra Rachana , Saha Progyaparamita , Desire Yvenie , Saltzman Russell , G.Hankey Kim , Arias Sixto A. , Ayoade Folusakin , Tovar Jairo A. , Lamazares Rejane , Gershengorn Hayley B. , Fontaine Magali J. , Klein Matt , Mullins Kristin , Gunasekaran Muthukumar , Loebe Matthias , Karakeshishyan Vela , Jayaweera Dushyantha T. , Atala Anthony , Ghodsizad Ali , Hare Joshua M.
Published: October 2020

Background

There is an ongoing critical need to improve therapeutic strategies for COVID-19 pneumonia, particularly in the most severely affected patients. Adult mesenchymal stem cell (MSC) infusions have the potential to benefit critically ill patients with acute respiratory syndrome SARS-COV-2 infection, but clinical data supporting efficacy are lacking.

Methods

We conducted a case-control study of critically ill patients with laboratory-confirmed COVID-19, severe acute respiratory distress syndrome (ARDS). To evaluate clinical responsiveness in the most critically ill patient we examined outcomes in a sub-group of those requiring extracorporeal membrane oxygenation (ECMO) support. Patients (n=9) were administered with up to 3 infusions of intravenous (IV) MSCs and compared to a local ECMO control group (n=31). The primary outcome was safety, and the secondary outcomes were all-cause mortality (or rate of hospital discharge), cytokine levels, and viral clearance.

Findings

MSC infusions (12 patients) were well tolerated and no side effects occurred. Of ECMO patients receiving MSC infusions, 2 out of 9 died (22.2%; 95%CI: 2.8%, 60.0%) compared with a mortality of 15 of 31 (48.4%; 95%CI: 30.2%, 66.9%; p = 0.25) in the ECMO control group. Isolated plasma exosomes containing the SARS-COV-2 Spike protein decreased after MSC infusions between day 14 or 21 after administration (p=0.003 and p=0.005, respectively) and was associated with a decrease in COVID-19 IgG Spike protein titer at same time points (p = 0.006 and p=0.007, respectively). Control ECMO patients receiving convalescent plasma did not clear COVID-19 IgG over the same time frame.

Interpretation

Together these findings suggest that MSC IV infusion is well tolerated in patients with a broad range of severity including the most severe COVID-19 ARDS requiring ECMO. These data also raise the possibility that MSCs, in addition to exerting an immunomodulatory effect, contribute to viral clearance and strongly support the conduct of randomized placebo-controlled trial.
Assessment of authors understanding of the STROBE-nut reporting guidelines
Authors: Hawwash Dana , Seck Michelle , Quaranta Elisa , Kolsteren Patrick , Lachat Carl
Published: October 2020

Objectives

To test authors’ experience of applying the STrengthening the Reporting of Observational Studies in Epidemiology-nutritional epidemiology (STROBE-nut) on a recently published paper. Correct understanding of the items on the reporting guidelines could lead to appropriate use.

Design

a cross sectional study, with a convenient sample.

Setting

Participants were asked to return the STROBE-nut data collection template filled on recently published papers. Next, an interview was organised to collect feedback on the process of applying the guidelines. Two researchers involved in the development of STROBE-nut completed the template using the participant’s respective published papers. The filled templates were then compared to assess the measure of agreement of the STROBE-nut items as a proxy of understanding.

Participants

Authors who recently published papers reporting dietary assessment or food intake data.

Results

We recruited 12 participants between May 2018 and June 2019. Five participants never used reporting guidelines before, while ten reported intention of future use. Half of the participants reported that the use of filling STROBE nut was useful, but some modifications are needed. Agreement between participants and experts on items reporting was generally low. Only two items had moderate weighted kappa agreement nut 1 (Kappa= 0.4, P 0.02) and nut 22.1 (Kappa= 0.47, P 0.01).

Conclusions

There is need to ensure correct understanding of STROBE-nut by authors. Revisions of STROBE-nut that make the items shorter and simpler can increase understanding. Training researchers at early stage on the aim of reporting guidelines could potentially increase proper use and decrease subjective interpretation.
AUTISM SPECTRUM DISORDER: A POSSIBLE LINK WITH CHONDROITIN SULFATE
Authors: Listik Eduardo , Listik Marcia , Listik Clarice , Toma Leny
Published: October 2020

This study aimed to determine discrepancies in the urinary glycosaminoglycan profiles of autism spectrum disorder (ASD) patients (n=9) when compared with those from healthy volunteers (HVs, n=3). The guardians and/or educators for each participant also returned a validated Autism Behavior Checklist (ABC). The urinary chondroitin sulfate (CS) concentration was 46.1% lower in the ASD group than in the HV group. The ABC score and the urinary CS concentration were negatively correlated (Spearman’s ρ=– 0.2635), indicating that as the severity of the clinical aspect of this disorder increased, the urinary CS concentration decreased. These results suggest that low CS concentrations in the urine may be associated with ASD, and could be measured using a fast and low-cost method for diagnostics.
Systematic review on chronic non-communicable disease in disaster settings
Authors: Ngaruiya Christine , Bernstein Robyn , Leff Rebecca , Wallace Lydia , Agrawal Pooja , Selvam Anand , Hersey Denise , Hayward Alison
Published: October 2020

Background

Non-communicable diseases (NCDs) constitute the leading cause of mortality globally. Low and middle-income countries (LMICs) not only experience the largest burden of humanitarian emergencies but are also disproportionately affected by NCDs, yet primary focus on the topic is lagging. We conducted a systematic review on the effect of humanitarian disasters on NCDs in LMICs assessing epidemiology, interventions, and treatment.

Methods

A systematic search in MEDLINE, MEDLINE (PubMed, for in-process and non-indexed citations), Social Science Citation Index, and Global Health (EBSCO) for indexed articles published before December 11, 2017 was conducted, and publications reporting on NCDs and humanitarian emergencies in LMICs were included. We extracted and synthesized results using a thematic analysis approach and present the results by disease type. The study is registered at PROSPERO (CRD42018088769).

Results

Of the 85 included publications, most reported on observational research studies and almost half (48.9%) reported on studies in the Eastern Mediterranean Region (EMRO), with scant studies reporting on the African and Americas regions. NCDs represented a significant burden for populations affected by humanitarian crises in our findings, despite a dearth of data from particular regions and disease categories. The majority of studies included in our review presented epidemiologic evidence for the burden of disease, while few studies addressed clinical management or intervention delivery. Commonly cited barriers to healthcare access in all phases of disaster and major disease diagnoses studied included: low levels of education, financial difficulties, displacement, illiteracy, lack of access to medications, affordability of treatment and monitoring devices, and centralized healthcare infrastructure for NCDs. Screening and prevention for NCDs in disaster-prone settings was supported. Refugee status was independently identified both as a risk factor for diagnosis with an NCD and conferred worse morbidity.

Conclusions

An increased focus on the effects of, and mitigating factors for, NCDs occurring in disaster-afflicted LMICs is needed. While the majority of studies included in our review presented epidemiologic evidence for the burden of disease, research is needed to address contributing factors, interventions, and means of managing disease during humanitarian emergencies in LMICs.