bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive phenotypic and functional analysis of dominant and recessiveFOXE3alleles in ocular developmental disorders
Authors: Reis Linda M , Sorokina Elena A , Dudakova Lubica , Moravikova Jana , Skalicka Pavlina , Malinka Frantisek , Seese Sarah E , Thompson Samuel , Bardakjian Tanya , Capasso Jenina , Allen William , Glaser Tom , Levin Alex V , Schneider Adele , Khan Ayesha , Liskova Petra , Semina Elena V
Published: May 2021

The forkhead transcription factor FOXE3 is critical for vertebrate eye development. Recessive and dominant variants cause human ocular disease but the full range of phenotypes and mechanisms of action for the two classes of variants are unknown. We identified FOXE3 variants in individuals with congenital eye malformations and carried out in vitro functional analysis on selected alleles. Sixteen new recessive and dominant families, including six novel variants, were identified. Analysis of new and previously reported genetic and clinical data demonstrated a broad phenotypic range with an overlap between recessive and dominant disease. Most families with recessive alleles, composed of truncating and forkhead-domain missense variants, had severe corneal opacity (90%; sclerocornea in 47%), aphakia (83%) and microphthalmia (80%), but some had milder features including isolated cataract. The phenotype was most variable for recessive missense variants, suggesting that the functional consequences may be highly dependent on the type of amino acid substitution and its position. When assessed, aniridia or iris hypoplasia were noted in 89% and optic nerve anomalies in 60% of recessive cases, indicating that these defects are also common and may be underrecognized. In dominant pedigrees, caused by extension variants, normal eye size (96%), cataracts (99%) and variable anterior segment anomalies were seen in most, but some individuals had microphthalmia, aphakia or sclerocornea, more typical of recessive disease. Functional studies identified variable effects on the protein stability, DNA binding, nuclear localization and transcriptional activity for recessive FOXE3 variants, whereas dominant alleles showed severe impairment in all areas and dominant-negative characteristics.
Quinacrine Treatment of Nitroimidazole-Refractory Giardiasis
Authors: Ydsten Karin A , Hellgren Urban , Asgeirsson Hilmir
Published: May 2021

Background

Limited evidence exists on efficacy and tolerability of quinacrine for nitroimidazole-refractory giardiasis.

Methods

Nitroimidazole-refractory giardiasis cases, defined as microbiologically (microscopy and/or PCR) confirmed treatment failure after 2 courses, during 2008–2020, were retrospectively identified.

Results

Of 87 patients, 54 (62%) had visited India. Quinacrine was used in 54 (62%); 51 received monotherapy and 3 combined with metronidazole. Only 3 had positive stool samples with persisting symptoms after quinacrine treatment (94% parasitological efficacy) and all were cured after a second treatment. One (1.9%) had mild adverse effects recorded.

Conclusions

Quinacrine is an effective treatment for nitroimidazole-refractory giardiasis with good tolerability.
Type I, II, and III Interferon Signatures Correspond to Coronavirus Disease 2019 Severity
Authors: Kim Myung-Ho , Salloum Shadi , Wang Jeffrey Y , Wong Lai Ping , Regan James , Lefteri Kristina , Manickas-Hill Zachary , Gao Ce , Li Jonathan Z , Sadreyev Ruslan I , Yu Xu G , Chung Raymond T ,   MGH COVID-19 Collection & Processing Team
Published: May 2021

We analyzed plasma levels of interferons (IFNs) and cytokines, and expression of IFN-stimulated genes in peripheral blood mononuclear cells in patients with coronavirus disease 2019 of varying disease severity. Patients hospitalized with mild disease exhibited transient type I IFN responses, while intensive care unit patients had prolonged type I IFN responses. Type II IFN responses were compromised in intensive care unit patients. Type III IFN responses were induced in the early phase of infection, even in convalescent patients. These results highlight the importance of early type I and III IFN responses in controlling coronavirus disease 2019 progression.
Postpartum Disseminated Herpes Simplex Virus Type 1 Infection With Hemophagocytic Lymphohistiocytosis and Fulminant Neonatal Herpes Infection
Authors: Freytag Mette Ratzer , Jørgensen Sofie Eg , Thomsen Michelle Mølgaard , Al-Mousawi Ali , Hait Alon Schneider , Olagnier David , Bay Jakob T , Helleberg Marie , Mogensen Trine H
Published: May 2021

The present study describes a 19-year-old woman with systemic herpes simplex virus (HSV)-1 infection and hemophagocytic lymphohistiocytosis (HLH) postpartum, and a fatal course of neonatal herpesvirus infection. Functional investigation of cells from the mother demonstrated significantly impaired induction of antiviral interferons and cytokines in the context of normal activation of the transcription factors NF-κB and IRF3. Whole-exome sequencing did not reveal any functionally validated genetic variants. We suggest that the functionally impaired antiviral responses, potentially caused by a variant in CASP8 or other variants in noncoding regions of the genome, contributed to the unusually severe disease course observed in two generations.
The Digestive Diverticula in the Carnivorous Nudibranch, Melibe leonina, Do Not Contain Photosynthetic Symbionts
Authors: Watson W H , Bourque K M F , Sullivan J R , Miller M , Buell A , Kallins M G , Curtis N E , Pierce S K , Blackman E , Urato S , Newcomb J M
Published: May 2021

Synopsis

A number of nudibranchs, including Melibe engeli and Melibe pilosa, harbor symbiotic photosynthetic zooxanthellae. Melibe leonina spends most of its adult life on seagrass or kelp, capturing planktonic organisms in the water column with a large, tentacle-lined oral hood that brings food to its mouth. M. leonina also has an extensive network of digestive diverticula, located just beneath its translucent integument, that are typically filled with pigmented material likely derived from ingested food. Therefore, the focus of this project was to test the hypothesis that M. leonina accumulates symbiotic photosynthetic dinoflagellates in these diverticula. First, we conducted experiments to determine if M. leonina exhibits a preference for light, which would allow chloroplasts that it might be harboring to carry out photosynthesis. We found that most M. leonina preferred shaded areas and spent less time in direct sunlight. Second, we examined the small green circular structures in cells lining the digestive diverticula. Like chlorophyll, they exhibited autofluorescence when illuminated at 480 nm, and they were also about the same size as chloroplasts and symbiotic zooxanthellae. However, subsequent electron microscopy found no evidence of chloroplasts in the digestive diverticula of M. leonina; the structures exhibiting autofluorescence at 480 nm were most likely heterolysosomes, consistent with normal molluscan digestion. Third, we did not find evidence of altered oxygen consumption or production in M. leonina housed in different light conditions, suggesting the lack of any significant photosynthetic activity in sunlight. Fourth, we examined the contents of the diverticula, using HPLC, thin layer chromatography, and spectroscopy. The results of these studies indicate that the diverticula did not contain any chlorophyll, but rather harbored other pigments, such as astaxanthin, which likely came from crustaceans in their diet. Together, all of these data suggest that M. leonina does sequester pigments from its diet, but not for the purpose of symbiosis with photosynthetic zooxanthellae. Considering the translucent skin of M. leonina, the pigmented diverticula may instead provide camouflage.
Ganciclovir therapeutic drug monitoring in transplant recipients
Authors: Märtson Anne-Grete , Edwina Angela E. , Burgerhof Johannes G. M. , Berger Stefan P. , de Joode Anoek , Damman Kevin , Verschuuren Erik A. M. , Blokzijl Hans , Bakker Martijn , Span Lambert F. , van der Werf Tjip S. , Touw Daan J. , Sturkenboom Marieke G. G. , Knoester Marjolein , Alffenaar Jan W. C.
Published: May 2021

Background

The use of (val)ganciclovir is complicated by toxicity, slow response to treatment and acquired resistance.

Objectives

To evaluate a routine therapeutic drug monitoring (TDM) programme for ganciclovir in a transplant patient population.

Methods

An observational study was performed in transplant recipients from June 2018 to February 2020. Dose adjustments were advised by the TDM pharmacist as part of clinical care. For prophylaxis, a trough concentration (Cmin) of 1–2 mg/L and an AUC24h of >50 mg·h/L were aimed for. For treatment, a Cmin of 2–4 mg/L and an AUC24h of 80–120 mg·h/L were aimed for.

Results

Ninety-five solid organ and stem cell transplant patients were enrolled. Overall, 450 serum concentrations were measured; with a median of 3 (IQR = 2–6) per patient. The median Cmin and AUC24h in the treatment and prophylaxis groups were 2.0 mg/L and 90 mg·h/L and 0.9 mg/L and 67 mg·h/L, respectively. Significant intra- and inter-patient patient variability was observed. The majority of patients with an estimated glomerular filtration rate of more than 120 mL/min/1.73 m2 and patients on continuous veno-venous haemofiltration showed underexposure. The highest Cmin and AUC24h values were associated with the increase in liver function markers and decline in WBC count as compared with baseline.

Conclusions

This study revealed that a standard weight and kidney function-based dosing regimen resulted in highly variable ganciclovir Cmin and under- and over-exposure were observed in patients on dialysis and in patients with increased renal function. Clearly there is a need to explore the impact of concentration-guided dose adjustments in a prospective study.
Chromosome-Level Reference Genome Assembly for the American Pika (Ochotona princeps)
Authors: Sjodin Bryson M F , Galbreath Kurt E , Lanier Hayley C , Russello Michael A
Published: May 2021

The American pika (Ochotona princeps) is an alpine lagomorph found throughout western North America. Primarily inhabiting talus slopes at higher elevations (>2000 m), American pikas are well adapted to cold, montane environments. Warming climates on both historical and contemporary scales have contributed to population declines in American pikas, positioning them as a focal mammalian species for investigating the ecological effects of climate change. To support and expand ongoing research efforts, here, we present a highly contiguous and annotated reference genome assembly for the American pika (OchPri4.0). This assembly was produced using Dovetail de novo proximity ligation methods and annotated through the NCBI Eukaryotic Genome Annotation pipeline. The resulting assembly was chromosome- scale, with a total length of 2.23 Gb across 9350 scaffolds and a scaffold N50 of 75.8 Mb. The vast majority (>97%) of the total assembly length was found within 36 large scaffolds; 33 of these scaffolds correlated to whole autosomes, while the X chromosome was covered by 3 large scaffolds. Additionally, we identified 17 enriched gene ontology terms among American pika-specific genes putatively related to adaptation to high-elevation environments. This high-quality genome assembly will serve as a springboard for exploring the evolutionary underpinnings of behavioral, ecological, and taxonomic diversification in pikas as well as broader-scale eco-evolutionary questions pertaining to cold-adapted species in general.
Submucosal gastric heterotopia presenting as an upper esophageal nodule
Authors: Dawley Jillian C , Gavini Hemanth K , Sun Belinda L
Published: May 2021

Esophageal gastric heterotopia (GH), the presence of differentiated gastric tissue in the esophagus, is estimated in up to 14% of populations worldwide and has always been reported on the surface of the esophagus, where it is also known as inlet patch. However, submucosal GH, in any tissue, is a rare finding. We report the case of a 50 year-old male presenting with chronic cough, heartburn and raspy vocalizations. Endoscopic examination showed a single 7 mm esophageal nodule, 20 cm from the incisors, interpreted as a submucosal mass. Pathologic examination of the endoscopically excised nodule showed well-differentiated gastric mucosa within the submucosa underneath the overlying squamous mucosa, consistent with submucosal GH. This case raises the awareness of an atypical presentation and location of GH seen as a submucosal mass on endoscopy.
Second wave of COVID-19: emergency situation in India
Authors: Kumar Saurabh
Published: May 2021

The COVID-19 pandemic has so far infected 25 385 043 people and has taken 280 683 lives (18 May 2021). Several infectious variants are circulating in the country, including the B.1.1.7, B.1.351, B.1.617 and B.1.618. Preventive strategies may include a large-scale testing, tracing, treatment approach, imposing Indian Penal Code 144 or lockdown in the hotspot areas and mass vaccination.
Integrated Environmental and Genomic Analysis Reveals the Drivers of Local Adaptation in African Indigenous Chickens
Authors: Gheyas Almas A , Vallejo-Trujillo Adriana , Kebede Adebabay , Lozano-Jaramillo Maria , Dessie Tadelle , Smith Jacqueline , Hanotte Olivier
Published: May 2021

Breeding for climate resilience is currently an important goal for sustainable livestock production. Local adaptations exhibited by indigenous livestock allow investigating the genetic control of this resilience. Ecological niche modeling (ENM) provides a powerful avenue to identify the main environmental drivers of selection. Here, we applied an integrative approach combining ENM with genome-wide selection signature analyses (XPEHH and Fst) and genotype−environment association (redundancy analysis), with the aim of identifying the genomic signatures of adaptation in African village chickens. By dissecting 34 agro-climatic variables from the ecosystems of 25 Ethiopian village chicken populations, ENM identified six key drivers of environmental challenges: One temperature variable—strongly correlated with elevation, three precipitation variables as proxies for water availability, and two soil/land cover variables as proxies of food availability for foraging chickens. Genome analyses based on whole-genome sequencing (n = 245), identified a few strongly supported genomic regions under selection for environmental challenges related to altitude, temperature, water scarcity, and food availability. These regions harbor several gene clusters including regulatory genes, suggesting a predominantly oligogenic control of environmental adaptation. Few candidate genes detected in relation to heat-stress, indicates likely epigenetic regulation of thermo-tolerance for a domestic species originating from a tropical Asian wild ancestor. These results provide possible explanations for the rapid past adaptation of chickens to diverse African agro-ecologies, while also representing new landmarks for sustainable breeding improvement for climate resilience. We show that the pre-identification of key environmental drivers, followed by genomic investigation, provides a powerful new approach for elucidating adaptation in domestic animals.
Robotics in Spine Surgery and Spine Surgery Training
Authors: Liounakos Jason I , Chenin Louis , Theodore Nicholas , Wang Michael Y
Published: May 2021

The increasing interest and advancements in robotic spine surgery parallels a growing emphasis on maximizing patient safety and outcomes. In addition, an increasing interest in minimally invasive spine surgery has further fueled robotic development, as robotic guidance systems are aptly suited for these procedures. This review aims to address 3 of the most critical aspects of robotics in spine surgery today: salient details regarding the current and future development of robotic systems and functionalities, the reported accuracy of implant placement over the years, and how the implementation of robotic systems will impact the training of future generations of spine surgeons. As current systems establish themselves as highly accurate tools for implant placement, the development of novel features, including even robotic-assisted decompression, will likely occur. As spine surgery robots evolve and become increasingly adopted, it is likely that resident and fellow education will follow suit, leading to unique opportunities for both established surgeons and trainees.
Posteromedial Hypothalamic Deep Brain Stimulation for Refractory Aggressiveness in a Patient With Weaver Syndrome: Clinical, Technical Report and Operative Video
Authors: Blasco García de Andoain Guillermo , Navas García Marta , González Aduna Óscar , Bocos Portillo Alvaro , Ezquiaga Terrazas Elena , Ayuso-Mateos José Luis , Pastor Jesús , Vega-Zelaya Lorena , Torres Cristina V
Published: May 2021

BACKGROUND AND IMPORTANCE

Deep brain stimulation of the posteromedial hypothalamus (PMH DBS) appears to be an effective treatment for drug-resistant aggressiveness. Weaver syndrome (WS) is a rare genetic disorder in which patients develop some degree of intellectual disability and rarely severe behavioral alterations that may benefit from this procedure.

CLINICAL PRESENTATION

We present the case of a 26-yr-old man diagnosed with WS presenting with uncontrollable self and heteroaggressiveness and disruptive behavior refractory to pharmacological treatment and under severe physical and mechanical restraining measures. The patient was successfully treated with bilateral PMH DBS resulting in affective improvement, greater tolerance for signs of affection, regularization in his sleep pattern and appetite disturbances at 12-mo follow-up. A detailed description and video of the procedure are presented, and a review of the clinical characteristics of WS and the utility and benefits of PMH DBS for refractory aggressiveness are reviewed.

CONCLUSION

To our knowledge, this is the first case of refractory aggressiveness described in WS as well as the first patient with WS successfully treated with PMH DBS.
A Novel Negative Pressure, Face-Mounted Antechamber to Minimize Aerosolization of Particles During Endoscopic Skull Base Surgery
Authors: Kim Matthew , Lee Mark , Schwarz Justin , Kacker Ashutosh , Schwartz Theodore H
Published: May 2021

BACKGROUND

The COVID-19 pandemic has revealed deficiencies in the adequacy of personal protective equipment (PPE) for healthcare workers. Endoscopic endonasal skull base surgery is thought to be among the highest-risk aerosol-generating procedures for surgeons and operating room personnel.

OBJECTIVE

To validate the efficacy and clinical feasibility of a novel surgical device.

METHODS

A low-cost, modifiable, and easily producible negative pressure, face-mounted antechamber was developed utilizing 3D printing and silicone molding. Efficacy was evaluated using an optical particle sizer to quantify aerosols generated during both cadaver and intraoperative human use with high-speed drilling.

RESULTS

Particle counts in the cadaver showed that drilling led to a 2.49-fold increase in particles 0.3 to 5 μm (P = .001) and that the chamber was effective at reducing particles to levels not significantly different than baseline. In humans, drilling led to a 37-fold increase in particles 0.3 to 5 μm (P < .001), and the chamber was effective at reducing particles to a level not significantly different than baseline. Use of the antechamber in 6 complex cases did not interfere with the ability to perform surgery. Patients did not report any facial discomfort after surgery related to antechamber use.

CONCLUSION

The use of a negative pressure facial antechamber can effectively reduce aerosolization from endoscopic drilling without disturbing the flow of the operation. The antechamber, in conjunction with appropriate PPE, will be useful during the COVID-19 pandemic, as well as during flu season and any future viral outbreaks.
Perioperative Outcomes After Preoperative Epidural Analgesia in Patients with Hip Fracture Undergoing Surgical Repair: A Systematic Review
Authors: Choi Jonathan V , Cheung Rachel M , Mozel Michelle R , Merchant Richard N , Lee Susan M
Published: May 2021

Objective

To examine the effectiveness and safety of epidural analgesia in the presurgical period in patients with hip fracture undergoing surgical repair.

Design

Systematic review.

Methods

The study protocol was registered with the PROSPERO systematic reviews registry with the (identifier CRD42019140396). Electronic databases were searched for randomized controlled trials comparing preoperative epidural analgesia with other forms of pain management in patients with a hip fracture. The primary outcomes included perioperative cardiac events and death. Pain, noncardiac complications, and adverse effects were also examined as secondary outcomes. The heterogeneity of the included studies was assessed with the I2 statistic, and a random-effects meta-analysis was conducted once sufficient homogeneity was demonstrated.

Results

Four studies, which included a total of 221 patients, met the inclusion criteria. Preoperative epidural analgesia resulted in fewer cardiac events, which was a reported outcome in two included studies (relative risk 0.30; 95% confidence interval 0.14–0.63; I2=0%). Preoperative epidural analgesia was also associated with a decreased perioperative mortality rate in a meta-analysis of two studies (relative risk 0.13; 95% confidence interval 0.02–0.98; I2 = 0%). Pain was not pooled because of variability in assessment methods, but preoperative epidural analgesia was associated with reduced pain in all four studies.

Conclusions

Preoperative epidural analgesia for hip fracture may reduce perioperative cardiac events and deaths, but the number of included studies in this systematic review was low. More research should be done to determine the benefit of early epidural analgesia for patients with hip fracture.
Efficacy and safety of switching from reference adalimumab to CT-P17 (100 mg/ml): 52-week randomized, double-blind study in rheumatoid arthritis
Authors: Furst Daniel E , Jaworski Janusz , Wojciechowski Rafal , Wiland Piotr , Dudek Anna , Krogulec Marek , Jeka Slawomir , Zielinska Agnieszka , Trefler Jakub , Bartnicka-Maslowska Katarzyna , Krajewska-Wlodarczyk Magdalena , Klimiuk Piotr A , Lee Sang Joon , Kim Sung Hyun , Bae Yun Ju , Yang Go Eun , Yoo Jae Kyoung , Kay Jonathan , Keystone Edward
Published: May 2021

Objective

To compare the safety and efficacy of switching from reference adalimumab to adalimumab biosimilar CT-P17 with continuing reference adalimumab/CT-P17 in active RA.

Methods

This double-blind, phase III study randomized (1:1) subjects with active RA to receive 40 mg (100 mg/ml) CT-P17 or European Union-sourced reference adalimumab subcutaneously every 2 weeks (Q2W) until week (W) 24 [treatment period (TP) 1]. Thereafter, subjects receiving reference adalimumab were randomized (1:1) to continue reference adalimumab or switch to CT-P17 from W26 (both Q2W until W48; TP2). Subjects receiving CT-P17 in TP1 continued CT-P17. W0–W24 results were previously reported; we present W26–W52 findings. End points were efficacy (including joint damage progression), pharmacokinetics, safety and immunogenicity.

Results

Of 607 subjects who initiated TP2 treatment, 303 continued CT-P17, 153 continued reference adalimumab and 151 switched to CT-P17. Efficacy improvements up to W24 were maintained during TP2; efficacy was comparable among groups. At W52, 20% improvement in ACR response rates were 80.5% (continued CT-P17), 77.8% (continued reference adalimumab) and 82.2% (switched to CT-P17). Joint damage progression was minimal. Mean trough serum adalimumab concentrations were similar among groups. CT-P17 and reference adalimumab safety profiles were numerically similar and switching did not affect immunogenicity. At W52, 28.4% (continued CT-P17), 27.0% (continued reference adalimumab) and 28.3% (switched to CT-P17) of subjects were anti-drug antibody-positive.

Conclusion

Efficacy, pharmacokinetics, safety and immunogenicity of CT-P17 and reference adalimumab were comparable after 1 year of treatment, including after switching from reference adalimumab to CT-P17.

Trial registration

ClinicalTrials.gov, http://clinicaltrials.gov, NCT03789292.
Immunohistological Examination of AKT Isoforms in the Brain: Cell-Type Specificity That May Underlie AKT’s Role in Complex Brain Disorders and Neurological Disease
Authors: Levenga Josien , Wong Helen , Milstead Ryan , LaPlante Lauren , Hoeffer Charles A
Published: May 2021

Protein kinase B (PKB/AKT) is a central kinase involved in many neurobiological processes. AKT is expressed in the brain as three isoforms, AKT1, AKT2, and AKT3. Previous studies suggest isoform-specific roles in neural function, but very few studies have examined AKT isoform expression at the cellular level. In this study, we use a combination of histology, immunostaining, and genetics to characterize cell-type-specific expression of AKT isoforms in human and mouse brains. In mice, we find that AKT1 is the most broadly expressed isoform, with expression in excitatory neurons and the sole detectable AKT isoform in gamma-aminobutyric acid ergic interneurons and microglia. By contrast, we find that AKT2 is the sole isoform expressed in astroglia and is not detected in other neural cell types. We find that AKT3 is expressed in excitatory neurons with AKT1 but shows greater expression levels in dendritic compartments than AKT1. We extend our analysis to human brain tissues and find similar results. Using genetic deletion approaches, we also find that the cellular determinants restricting AKT isoform expression to specific cell types remain intact under Akt deficiency conditions. Because AKT signaling is linked to numerous neurological disorders, a greater understanding of cell-specific isoform expression could improve treatment strategies involving AKT.
Optimal use of intranasal corticosteroids and intranasal saline, is there a clear answer?
Authors: Freeman Catherine M. , Rank Matthew A.
Published: May 2021

Purpose of review

Chronic rhinosinusitis (CRS) is a prevalent condition that poses a significant burden on both quality of life and healthcare utilization. Notwithstanding the heterogenous nature of CRS endotypes and phenotypes, isotonic saline and corticosteroids are recommended as first line medical therapy by recent clinical guidelines. We provide an overview of recent studies of topical saline and corticosteroids for people with CRS and emphasize areas of unmet needs.

Recent findings

Recent trials suggest exhalation delivery systems of corticosteroid are effective and well tolerated but did not involve comparison with another active treatment. Recent comparative efficacy studies show no clear differences in doses of topical corticosteroid, method of topical corticosteroid delivery, advantage over macrolide antibiotic, or method or type of saline irrigation.

The preeminent formulation, dosage, and delivery of topical corticosteroid and saline for people with CRS represents an area of ongoing research need.
Readmissions After Guillain–Barre Syndrome: Nationally Representative Data
Authors: Roberts Mallory , Jin Peter , Shin Susan , Dhamoon Mandip
Published: May 2021

Objectives:

We aimed to obtain nationally representative data on hospital readmission rates after Guillain–Barre syndrome (GBS).

Methods:

International Classification of Disease, Ninth Revision codes from the 2013 National Readmissions Database identified adult GBS admissions, comorbidities, and readmission diagnoses. Logistic regression estimated odds ratios (ORs) for readmission.

Results:

Of 2109 GBS admissions identified, 20.8% were readmitted within 1 year and 12.2% within 30 days. Age did not predict readmission. Plasmapheresis use showed a nonsignificant trend toward readmission versus intravenous immunoglobulin use [OR 1.43, 95% confidence interval (CI) 1.00–2.051, P = 0.050]. Respiratory failure (OR 1.70, 95% CI 1.23–2.35, P = 0.0014), heart failure (OR 2.14, 95% CI 1.25–3.66, P = 0.0057), and renal failure (OR 2.00, 95% CI 1.20–3.32, P = 0.0078) predicted readmission. Top readmission diagnoses included GBS or chronic inflammatory demyelinating polyneuropathy (42.0%) and sepsis (3.5%).

Conclusions:

One-fifth of GBS patients were readmitted within 1 year. Comorbid illnesses and respiratory complications increased a readmission risk but age did not.
I Want to Row Across the Atlantic. But You Have Amyotrophic Lateral Sclerosis!
Authors: Alderman Alan , Hayes Heather , Gibson Summer , Bromberg Mark B.
Published: May 2021

We describe an individual with slowly progressive amyotrophic lateral sclerosis who decided to enter the Talisker Whisky Atlantic Challenge, a rowing event across the Atlantic Ocean, and completes it in 51 days in a 5-man boat.
Psychosocial Adjustment in Emerging Adults With and Without Spina Bifida: A 14-Year Follow-up Study
Authors: Holmbeck Grayson N. , Kritikos Tessa K.
Published: May 2021

Objective:

A 14-year follow-up of youth with spina bifida (SB), as compared to a matched comparison sample without a chronic health condition, focused on psychosocial adjustment during emerging adulthood (ages 22–23).

Methods:

The initial cohort at time 1 consisted of 68 families with an 8-year-old or 9-year-old child with SB and a matched comparison sample of 68 typically developing children and their families. At the final assessment (time 7), participants included 56 emerging adults with SB (82% of those who participated at time 1) and 62 comparison youth (91% of those who participated at time 1) who completed a set of self-report measures.

Results:

Emerging adults with SB continue to lag behind across several important developmental milestones, including decision-making responsibility, involvement in social and romantic relationships, sexual intimacy, educational and vocational achievement, financial independence, and engagement in health-related behaviors. However, from a resilience perspective, these individuals also exhibited a number of strengths across the following areas: identity development, quality of social supports, and fewer problem behaviors (e.g., alcohol and other substance use). Most findings were still significant after controlling for a verbal intelligence quotient proxy.

Conclusion:

This study highlighted vulnerabilities and strengths of individuals with SB as they enter emerging adulthood, with considerable continuity across childhood, adolescence, and emerging adulthood.
Assessing Ease of Delivering Emergency Care for Patients with Autism Spectrum Disorders
Authors: Kouo Theodore , Bharadwaj Neha , Kouo Jennifer , Tackett Sean , Ryan Leticia
Published: May 2021

Objective:

The aim of this study was to develop a method for objectively assessing the delivery of care to children with autism spectrum disorder (ASD) in the emergency department (ED).

Methods:

A case-control study of patients ages 2 to 18 years admitted to the hospital from January 2016 to January 2018. Cases were defined as patients with an International Classification of Diseases, Tenth Revision diagnosis of ASD or other pervasive developmental disorder (F84) in their medical record and were matched 1:1 with neurotypical controls. The primary outcome was ability to complete several core tasks clinically necessary within an ED visit and summarized into a Task Completion Index (TCI).

Results:

Overall, children with ASD had higher median TCIs of 0.25 (interquartile range [IQR] 0–0.45) versus 0 (IQR 0–0.25) when compared with children without ASD (p < 0.01). Children with ASD were 5 times more likely to have difficulty with triage vitals, 3 times more likely to require additional staff for peripheral intravenous placement, and 4 times more likely to experience delays or disruptions to their plan of care. The TCI was also associated with 8-fold increased odds of receiving pharmacologic or physical restraint.

Conclusions:

The TCI reflects difficulty accomplishing core tasks necessary to complete an ED visit. Children with ASD have higher TCIs than neurotypical controls, which puts them at higher risk for care disruptions. Evaluation of initiatives to improve quality of care for children with ASD should focus not only on metrics of overall experience and satisfaction but also how these initiatives affect the ability to effectively administer care.
Unraveling the Role of 12- and 20- HETE in Cardiac Pathophysiology: G-Protein–Coupled Receptors, Pharmacological Inhibitors, and Transgenic Approaches
Authors: Pascale Jonathan V. , Lucchesi Pamela A. , Garcia Victor
Published: May 2021

Arachidonic acid–derived lipid mediators play crucial roles in the development and progression of cardiovascular diseases. Eicosanoid metabolites generated by lipoxygenases and cytochrome P450 enzymes produce several classes of molecules, including the epoxyeicosatrienoic acid (EET) and hydroxyeicosatetraenoic acids (HETE) family of bioactive lipids. In general, the cardioprotective effects of EETs have been documented across a number of cardiac diseases. In contrast, members of the HETE family have been shown to contribute to the pathogenesis of ischemic cardiac disease, maladaptive cardiac hypertrophy, and heart failure. The net effect of 12(S)- and 20-HETE depends upon the relative amounts generated, ratio of HETEs:EETs produced, timing of synthesis, as well as cellular and subcellular mechanisms activated by each respective metabolite. HETEs are synthesized by and affect multiple cell types within the myocardium. Moreover, cytochrome P450–derived and lipoxygenase- derived metabolites have been shown to directly influence cardiac myocyte growth and the regulation of cardiac fibroblasts. The mechanistic data uncovered thus far have employed the use of enzyme inhibitors, HETE antagonists, and the genetic manipulation of lipid-producing enzymes and their respective receptors, all of which influence a complex network of outcomes that complicate data interpretation. This review will summarize and integrate recent findings on the role of 12(S)-/20-HETE in cardiac diseases.
MiR-340 Promotes the Proliferation of Vascular Smooth Muscle Cells by Targeting von Hippel–Lindau Tumor Suppressor Gene
Authors: Chen Sheng , Zhao Wei , Min Hongye , Xu Yawei
Published: May 2021

MiRNAs play key roles in the proliferation of vascular smooth muscle cells (VSMCs). However, the roles and underlying mechanism of miRNAs in VSMCs are not fully understood. The aim of this study was to evaluate the role of miR-340 in the proliferation of VSMCs. The expression levels of miR-340 and von Hippel–Lindau tumor suppressor (VHL) in VSMCs induced by platelet-derived growth factor-BB or fetal bovine serum were measured by q-polymerase chain reaction. The effects of miR-340 and VHL on cell proliferation and invasion were evaluated by CCK-8 assay. Target gene prediction and screening as well as luciferase reporter assay were performed to verify the downstream target genes of miR-340. Western blotting was used to detect the protein expression levels of vascular endothelial growth factor and VHL. Our results showed that the miR-340 was upregulated in platelet-derived growth factor-BBor fetal bovine serum–induced VSMCs. In addition, overexpression of miR-340 promoted VSMCs proliferation and invasion. Moreover, VHL was found to be a potential target for miR-340 and upregulation of VHL-inhibited VSMCs proliferation. MiR-340 plays a critical role in VSMC proliferation and neointimal hyperplasia in rats' carotid balloon injury model. Reduced expression levels of miR-340 promoted VHL-inhibited VSMCs proliferation. In conclusion, miR-340 may play a role in the regulation of proliferation of VSMCs by inhibition of VHL.
In Vivo Perforasome Perfusion in Hemi-DIEP Flaps Evaluated with Indocyanine-green Fluorescence Angiography and Infrared Thermography
Authors: Chaudhry Muiz A. , Mercer James B. , de Weerd Louis
Published: May 2021

Background:

There are no in vivo studies that evaluate the effect of perforator dissection on the perfusion territory of a perforator (perforasome). In this study, indocyanine green fluorescence angiography (ICG-FA) and infrared thermography (IRT) were used intraoperatively to evaluate perforasome perfusion in hemi-DIEP flaps.

Methods:

Patients selected for DIEP breast reconstruction were prospectively included in the study. Preoperative perforator mapping was performed with CTA and handheld Doppler ultrasound. In general anesthesia, perforasome perfusion was evaluated with ICG-FA and IRT both before surgery and after flap dissection with preserved dominant perforators.

Results:

Thirty hemi-DIEP flaps were dissected in 15 patients (average BMI 26.6 kg/m2), of which 40% had been operated on in the lower abdomen. Fluorescence spots from ICG were associated with infrared radiation hotspots on IRT and these corresponded with the locations of the selected perforators. IRT and ICG-FA demonstrated similar patterns in perforasome perfusion before and after perforator dissection. Perforator dissection changed the perforasome perfusion. IRT made it possible to continuously monitor the perforator activity during surgery. ICG-FA easily identified areas with impaired flap perfusion due to previous surgery.

Conclusions:

Perforasome perfusion is a dynamic process that changes with perforator dissection. ICG-FA and IRT are reproducible techniques for in vivo evaluation of perforasome perfusion and produce comparable results.
Patient-reported Outcomes and 3-dimensional Surface Imaging after Risk-reducing Mastectomy and Immediate Breast Reconstruction
Authors: Bai Lucy , Sandelin Kerstin , Wickman Marie , Arver Brita , Lundström Ola , Johansson Hemming , Brandberg Yvonne
Published: May 2021

Background:

The cosmetic results after risk-reducing mastectomy (RRM) and immediate breast reconstruction (IBR) are intended to be long-lasting. Long-term follow-up of the cosmetic outcome can be evaluated subjectively by the women themselves through patient-reported outcome measures such as questionnaires, or by using data from three-dimensional surface imaging (3D-SI) to calculate the volume, shape, and symmetry of the reconstructed breasts as a more objective cosmetic evaluation. The study aim was to evaluate the correspondence between patient-reported measures and 3D-SI measurements.

Methods:

Questionnaires (EORTC QLQ-BRECON23 and BIS) were sent to women on average 13 [7–20] years after RRM and IBR. Items were preselected for comparison with 3D measurements of women imaged using the VECTRA XT 3D-imaging system at the long-term follow-up.

Results:

Questionnaire responses and 3D images of 58 women, 36 without and 22 with previous breast cancer (where 15 also received radiotherapy) before RRM and IBR, were analyzed. Median age at follow-up was 57 [41–73] years. Patient-reported satisfaction with the cosmetic outcome was positive for both groups. 3D measurements indicated more symmetrical cosmetic results for women without previous breast cancer. No statistically significant associations between patient-reported satisfaction and 3D measurements were found.

Conclusions:

Satisfaction with the long-term cosmetic outcome after RRM and IBR was, in general, positive when evaluated by the women. 3D-SI could be used as a more objective approach to assess the cosmetic outcome in terms of volume and shape-symmetry; however, it does not directly translate to the patient-reported satisfaction.
Chronic Nerve Injuries and Delays in Surgical Treatment Negatively Impact Patient-reported Quality of Life
Authors: Felder John M. , Ducic Ivica
Published: May 2021

Background:

Little emphasis has been paid to characterize quality of life (QoL) burdens experienced by patients seeking surgical treatment for nerve injuries and neuropathic pain.

Methods:

A cross-sectional survey was distributed to all patients (N = 767) from a single nerve surgeon’s practice between 2014 and 2019. Data collected included demographics, specifics of the injury and symptoms, time to referral, and effects of the injury, surgery, and timing of surgery on QoL.

Results:

Of the 767 patients, 209 (27.2%) completed the survey. Average age was 48.8 years; 68.9% of patients were women and 31.1% men. At presentation, 68% had experienced symptoms for more than 1 year; 86.1% reported severity as being profound; 97.6% reported QoL was at least moderately negatively impacted by nerve injury; 70% felt they should have been referred earlier for surgical evaluation; 51.2% were not told that nerve surgery was an option for their problem; 83.1% felt that earlier referral would have improved their QoL. After surgery, symptoms were significantly mitigated in 55.5% of the patients, moderately mitigated in 21.5%. Patients reported QoL was significantly (59.8%) or at least moderately (76.6%) improved by nerve surgery.

Conclusions:

The majority of patients reported that nerve injuries imparted a moderate to severe impact on QoL, and that surgical treatment improved QoL. Most patients felt that earlier referral for surgical intervention would have led to better outcome and positively impacted QoL. Interdisciplinary treatment algorithms, including a role for surgical intervention, may be helpful in facilitating timely diagnosis, referral, and thus improved outcomes.
Facial Trauma 8 years after a Face Transplantation
Authors: Goutard Marion , Lellouch Alexandre G. , Dussol Bertrand , Lantieri Laurent A.
Published: May 2021

Over the past 20 years, vascularized composite allografts (VCAs) have emerged as a realistic option in reconstructive surgery. Long-term follow-up reports indicate that face transplant patients have gained in quality of life and social integration. However, they require close monitoring of their immunosuppressive therapy because they are at high-risk for acute rejection episodes, leading eventually to chronic rejection and allograft loss. Reported acute rejection episodes in VCA recipients occur due to low immunosuppressive therapy (mainly due to lack of patient compliance or decreased doses of immunosuppressants to counter side-effects). Repeated mechanical traumas have recently been shown to trigger acute rejection episodes, especially in hand transplant patients. This article reports our experience of a 10-year follow-up of a 57-year-old face transplant patient and the management of his accidental facial trauma. To our knowledge, our patient is the first to undergo a major trauma on his VCA endangering his graft function and vitality. This report discusses the management of an acute surgical situation in those particular patients, and the challenges that arise to avoid acute rejection of the allograft. Ten years into his face transplant and at 18 months follow-up after his facial trauma, our patient shows great aesthetic and functional outcomes and remains rejection-free; a very encouraging result for all VCA candidates.
Severe Craniofacial Morbidity from a Bean Bag Projectile
Authors: Gonzalez Santiago R. , Loomba Vishalli , Obi-Osuagwu Osita , Al-Nowaylati Abdl-Rawf , Rahgozar Paymon
Published: May 2021

Bean bag munitions, less-lethal weapons primarily used by law enforcement, can cause severe morbidity. Although bean bag munitions are less likely to cause severe injury when compared with regular gunshot rounds, it is crucial to understand that bean bag munitions may be life-threatening. In this case, we describe our experience with a patient who suffered a zygomaticomaxillary complex fracture, facial nerve injury, and retained munition round in his maxillary sinus from a bean bag projectile shot during an altercation with the police. The patient was urgently transferred to the operating room for extraction of the bean bag munition, and although fracture repair was successful, the patient sustained significant damage to facial nerves, leading to lagophthalmos. To our knowledge, this is the first case report describing a penetrating injury from a bean bag munition that was retained within a facial structure. We will discuss the surgical intervention used for this patient and the review of the current literature on these less-lethal munitions.
An Argument for the Safety of Immediate Device Reconstruction following Mastectomy during the COVID-19 Crisis
Authors: Huang Hao , Fu Rose H. , Vartanian Emma , Du Jerry Y. , Otterburn David M.
Published: May 2021

Background:

Although oncologic surgery is deemed urgent during the COVID-19 pandemic, clinical guidelines in reconstructive surgery have been unclear. Utilizing propensity-matched pre-pandemic data and our institutional experience during the crisis, we aimed to assess the safety of immediate device reconstruction following mastectomy to aid in decision-making during the pandemic.

Methods:

Women undergoing mastectomy only and mastectomy with immediate breast reconstruction (IBR) with tissue expander or permanent implant from the 2007–2013 ACS-NSQIP datasets were included. Multivariate analysis of independent variables was used to form propensity-matched cohorts. Incidence of 30-day major postoperative bleeding and hospital length of stay were compared.

Results:

In total, 13,580 mastectomy only patients and 11,636 IBR patients were identified. Factors that were found to be associated with IBR included age (P = 0.022), BMI (P < 0.001), race (P = 0.010), diabetes (P = 0.007), chronic steroid use (P = 0.003), pulmonary disease (P = 0.004), cardiovascular disease (P < 0.001), disseminated cancer (P = 0.001), chemotherapy before surgery (P = 0.016), low hematocrit (P < 0.001), and total operative time (P < 0.001). After propensity matching, immediate device reconstruction following mastectomy was not found to be associated with greater risk of postoperative bleeding (1.4% versus 1.0%, P = 0.334) or increased length of stay (1.5 ± 2.9 versus 1.5 ± 3.5 days, P = 0.576).

Conclusions:

Immediate device reconstruction does not elevate morbidity in terms of postoperative bleeding or does not increase the length of hospital exposure. Tissue expander or implant reconstruction can be safely performed immediately following mastectomy during the COVID-19 pandemic. Further, our institutional experience during the pandemic indicates that select patients can continue to safely undergo ambulatory mastectomy with device placement.
Myocardial infarction with nonobstructive coronary artery disease (MINOCA): a review of pathophysiology and management
Authors: Cheema Asim N. , Yanagawa Bobby , Verma Subodh , Bagai Akshay , Liu Shuangbo
Published: May 2021

Purpose of review

Myocardial infarction with nonobstructive coronary artery disease (MINOCA) (≥ 50% stenosis) accounts for 5–8% of acute coronary syndrome (ACS) presentations. The demographic characteristics, risk factors, and management of patients with MINOCA differ from those with atherosclerotic ACS. The objective of this review is to provide a contemporary understanding of the epidemiology, pathophysiology, clinical presentation, and management of MINOCA.

Recent findings

MINOCA is increasingly being recognized as an important and distinct cause of myocardial infarction among patients presenting with ACS. The predominant pathophysiologic mechanisms of MINOCA include both coronary (epicardial vasospasm, coronary microvascular disorder, spontaneous coronary artery dissection, coronary thrombus/embolism) and noncoronary (Takotsubo cardiomyopathy, myocarditis) pathologies. Coronary imaging with intravascular ultrasound and optical coherent tomography, coronary physiology testing, and cardiac magnetic resonance imaging offers important investigative modalities to facilitate diagnosis for appropriate management of MINOCA patients.

MINOCA is an important cause of ACS observed in certain patients with unique challenges for diagnosis and management. A high index of suspicion and a comprehensive diagnostic evaluation are critical for early recognition and successful management.
One Affectionate Puppy: A Case of Septic Arthritis Due to Staphylococcus Pseudintermedius
Authors: Bowen Stephen , DeMarco Arielle , Villasis Lorillaine , Barsi James , Handel Andrew S.
Published: May 2021

We describe a case of septic arthritis caused by Staphylococcus pseudintermedius, a common colonizer of dogs that has emerged as a rare human pathogen. Our patient presented with ankle pain and swelling and was treated adequately with cefazolin/cephalexin and arthrotomy. S. pseudintermedius is often misidentified as other coagulase-positive staphylococcal species and has high rates of methicillin and nonpenicillin antibiotic resistance.