bluuebunny/crossref_metadata_2025 huggingface dataset:
COMPREHENSIVE MULTIPLATFORM ANALYSIS OF CDKN2A ALTERATIONS IN MENINGIOMAS
Authors: Wang Justin Z , Patil Vikas , Liu Jeff , Dogan Helin , Tabatabai Ghazaleh , Behling Felix , Hoffman Elgin , Bunda Severa , Yakubov Rebecca , Kaloti Ramneet , Brandner Sebastian , Gao Andrew , Gadol Aaron-Cohen , Barnholtz-Sloan Jennifer , Skardelly Marco , Tatagiba Marcos , Raleigh David , Sahm Felix , Boutros Paul C , Aldape Kenneth ,   The International Consortium on Meningiomas (ICOM), Nassiri Farshad , Zadeh Gelareh
Published: July 2023

BTFC travel award recipient

In meningiomas, CDKN2A/B deletions are associated with poor clinical outcomes but are exceeding rare in most cohorts (1-5% of cases). Large molecular datasets are therefore required to explore these deletions and their relationship to other CDKN2A alterations that may be more common, but also prognostic on a transcriptomic, epigenomic, and/or copy number level.

METHODS: We used multidimensional molecular data of 560 meningioma samples from 5 independent cohorts to comprehensively interrogate the spectrum of CDKN2A alterations through DNA methylation, copy number variation, transcriptomics, and proteomics using an integrated molecular approach, and utilized preclinical models to validate our findings. RESULTS: Meningiomas with either CDKN2A/B deletions (partial or homozygous loss) or an intact CDKN2A gene locus but elevated mRNA expression (CDKN2Ahigh) both had poor clinical outcomes. Increased CDKN2A mRNA expression was a poor prognostic factor independent of deletion status. CDKN2A expression and p16 protein also progressively increased with tumor grade and more aggressive molecular and methylation groups. CDKN2Ahigh meningiomas and meningiomas with CDKN2A deletions were enriched for similar cell cycling pathways but dysregulated at different checkpoints (G1/S vs G2/M). p16 immunohistochemistry was unreliable in differentiating between meningiomas with and without CDKN2A deletions, but increased positivity was associated with mRNA expression. CDKN2Ahigh meningiomas were associated with gene hypermethylation, Rb-deficiency, and lack of response to CDK inhibition. CONCLUSIONS: In meningiomas, CDKN2A mRNA expression consistently increases with biological aggressiveness, is prognostic independent of copy number loss, and may be used as an important prognostic biomarker with therapeutic implications for resistance to CDK4/6 inhibitors clinically.
Mismatch repair protein mutations in isocitrate dehydrogenase (IDH)-mutant astrocytoma and IDH-wild-type glioblastoma
Authors: Richardson Timothy E , Yokoda Raquel T , Rashidipour Omid , Vij Meenakshi , Snuderl Matija , Brem Steven , Hatanpaa Kimmo J , McBrayer Samuel K , Abdullah Kalil G , Umphlett Melissa , Walker Jamie M , Tsankova Nadejda M
Published: July 2023

Background

Mutations in mismatch repair (MMR) genes (MSH2, MSH6, MLH1, and PMS2) are associated with microsatellite instability and a hypermutator phenotype in numerous systemic cancers, and germline MMR mutations have been implicated in multi-organ tumor syndromes. In gliomas, MMR mutations can function as an adaptive response to alkylating chemotherapy, although there are well-documented cases of germline and sporadic mutations, with detrimental effects on patient survival.

Methods

The clinical, pathologic, and molecular features of 18 IDH-mutant astrocytomas and 20 IDH-wild-type glioblastomas with MMR mutations in the primary tumor were analyzed in comparison to 361 IDH-mutant and 906 IDH-wild-type tumors without MMR mutations. In addition, 12 IDH-mutant astrocytomas and 18 IDH-wild-type glioblastomas that developed MMR mutations between initial presentation and tumor recurrence were analyzed in comparison to 50 IDH-mutant and 104 IDH-wild-type cases that remained MMR-wild-type at recurrence.

Results

In both IDH-mutant astrocytoma and IDH-wild-type glioblastoma cohorts, the presence of MMR mutation in primary tumors was associated with significantly higher tumor mutation burden (TMB) (P < .0001); however, MMR mutations only resulted in worse overall survival in the IDH-mutant astrocytomas (P = .0069). In addition, gain of MMR mutation between the primary and recurrent surgical specimen occurred more frequently with temozolomide therapy (P = .0073), and resulted in a substantial increase in TMB (P < .0001), higher grade (P = .0119), and worse post-recurrence survival (P = .0022) in the IDH-mutant astrocytoma cohort.

Conclusions

These results suggest that whether present initially or in response to therapy, MMR mutations significantly affect TMB but appear to only influence the clinical outcome in IDH-mutant astrocytoma subsets.
Immune Response Kinetics Following a Third Heterologous BNT162b2 Booster Dose After Primary 2-Dose ChAdOx1 Vaccination in Relation to Omicron Breakthrough Infection: A Prospective Nationwide Cohort Study in South Korea
Authors: Ahn Jin Young , Ko Jae-Hoon , Peck Kyong Ran , Bae Seongman , Kim Sung-Han , Lee Kyoung Hwa , Song Young Goo , Kim Yong Chan , Park Yoon Soo , Song Kyoung-Ho , Kim Eu Suk , Jeong Hye Won , Kim Shin-Woo , Kwon Ki Tae , Choi Won Suk , Choi Jun Yong
Published: July 2023

Background

Immune responses to each vaccine must be investigated to establish effective vaccination strategies for the ongoing coronavirus disease (COVID-19) pandemic. We investigated the long-term kinetics of immune responses after heterologous booster vaccination in relation to Omicron breakthrough infection (BI).

Methods

Our study included 373 healthcare workers who received primary ChAdOx1 vaccine doses and a third BNT162b2 vaccine dose. BIs that occurred after the third vaccine were investigated. Blood specimens were collected before and 3 months after the booster dose from participants without BI and 1, 4, and 6 months after BI from participants who experienced BI. Spike-specific binding and neutralizing antibody levels against the wild-type virus, Omicron BA.1, and Omicron BA.5, as well as cellular responses, were analyzed.

Results

A total of 346 participants (82 in the no BI group; 192 in the BI group during the BA.1/BA.2 period; 72 in the BI group during the BA.5 period) were included in the analysis. Participants without BI exhibited the highest binding and neutralizing antibody concentrations and greatest cellular response 1 month after the third vaccination, which reached a nadir by the ninth month. Antibody and cellular responses in participants who experienced BI substantially increased postinfection. Neutralizing antibody titers in individuals who experienced BI during the BA.1/BA.2 period showed more robust increase against wild-type virus than against BA.1 and BA.5.

Conclusions

Our findings provide evidence of antigenic imprinting in participants who received a heterologous booster vaccination, thereby serving as a foundation for further studies on the impact of BIs on immune responses.
Preferred nesting habitat of the slow-breeding Superb Lyrebird is rare and was disproportionately impacted by Australia’s “Black Summer” megafires (2019–2020) within a World Heritage Area
Authors: Hughes Eric J , Austin Victoria I , Backhouse Fiona , Maisey Alex C , Lopez Kelsie A , Mikles Chloe S , Odom Karan J , Welbergen Justin A , Dalziell Anastasia H
Published: July 2023

Understanding nest site selection is critical to developing effective conservation management actions. The Superb Lyrebird (Menura novaehollandiae) is one of many endemic species extensively impacted by Australia’s unprecedented 2019–2020 megafires. Over a period of 5 months, an estimated 43% of the entire range of this slow-breeding species was burnt, with the biggest impact on the central subspecies M. n. novaehollandiae (55%). Four months prior to these megafires, we conducted a field study of nest site habitat selection in the Superb Lyrebird within the Greater Blue Mountains World Heritage Area (15,400 km2): a key stronghold of the central subspecies of the Superb Lyrebird. We found that at the local scale, lyrebird nest sites were more likely to be found in habitats characterized by dense canopy trees and rich in rainforest elements such as vines and treeferns. At the landscape scale, lyrebird nests were most likely to be constructed in rainforest; this fire-sensitive habitat type made up only 1% of the Greater Blue Mountains World Heritage Area. The probability of nest occurrence also increased with slope. We also found that >74% of all nesting habitat within the Greater Blue Mountains World Heritage Area burned in the 2019–2020 megafires, including 80% of areas of high suitability for nesting. These results suggest that the impact of these megafires on Superb Lyrebirds may be greater than currently thought. Given the importance of rainforest as nesting habitat for the ﻿Superb Lyrebird, managers should prioritize its restoration and protect it from future fire events. More broadly, our results illustrate how large-scale catastrophic events—such as megafires—can disproportionately affect habitats critical to specific points within an organism’s life cycle.
How Responsive Are Wages to Firm-Specific Changes in Labour Demand? Evidence from Idiosyncratic Export Demand Shocks
Authors: Garin Andrew , Silvério Filipe
Published: July 2023

Do firms adjust wages in response to changes in their own demand level or to changes in competitive pressure from rival employers? We study how exporters adjust wages in response to unexpected product demand shocks during the 2008–9 Great Recession. Using rich data on Portuguese firms’ pre-recession export shipments, we measure firm-level shocks to export demand during the Recession. We show that shocks constructed at the firm level are not necessarily firm-specific and can be decomposed into a common component affecting all producers in a product market and an idiosyncratic component affecting individual firms within markets based on the locations of their pre-recession customers. We demonstrate that while both components impact firms’ output and their workers’ wages, the common component spills over from firms to their labour market rivals, whereas the idiosyncratic component does not. We find that 10–15% of firms’ idiosyncratic demand passes through to their employees’ wage growth with no effect on retention rates, implying significant dependence of wages on noncompetitive quasi-rents. Moreover, we find that wages respond primarily to shifts in internal labour demand when labour markets are thin, but they respond more to competition from other employers when labour markets are fluid. These results indicate that employers’ ability to set wages hinges on the underlying competitiveness of the labour market.
The onset of large size in Cretaceous marine turtles (Protostegidae) evidenced by new fossil remains from the Valanginian of Colombia
Authors: Cadena Edwin-Alberto , Combita-Romero Diego A
Published: July 2023

The evolution of large size in vertebrates is a fascinating research topic, relevant, for example, for the Cretaceous turtles of the Protostegidae clade, which includes some of the largest turtles to have ever inhabited the Earth. However, there is still limited understanding regarding when and under what conditions large size emerged in this group. Here we describe several limb bones and fossil shell remains from the upper Valanginian, Rosa Blanca Formation of Colombia that, together, shed light on the onset conditions and characteristics of large-size evolution in protostegids. The material, although fragmentary, preserves enough features, such as the sigmoidal curvature of the shaft of the humeri in anterior view and their strong waist, to be attributed to Protostegidae. The fossil turtles described here constitute the largest ever known for the Early Cretaceous worldwide and the oldest record for their group. The ecological and climatic conditions of northern South America during the Late Valanginian are discussed as potential triggers of the emergence of large body size in protostegid turtles.
Mycobiome Analysis of Tall Fescue Grass Under Drought Stress Using the Illumina MiSeq and Oxford Nanopore Technology MinION
Authors: Groben Glen , Clarke Bruce B. , Kerkhof Lee J. , Bonos Stacy A. , Meyer William A. , Qu Yuanshuo , Luo Jing , Walsh Emily , Zhang Ning
Published: July 2023

The effects that mycobiomes have on physiological traits in turfgrasses are poorly understood. Drought tolerance, an economically and ecologically important trait, can be influenced by symbiotic fungi. In this two-year study, we evaluated the mycobiome associated with tall fescue exposed to prolonged periods of drought stress in a rainout shelter. Twelve plants, comprising six sets of half-sibs (progenies having one parent in common), one exhibiting a drought-tolerant phenotype and the other a drought-susceptible phenotype, were selected for analysis each year. The mycobiomes associated with the shoot, root, and rhizosphere soil were evaluated for each tall fescue half-sib pair using both short-read Illumina MiSeq and long-read Oxford Nanopore Technology (ONT) MinION sequencing pipelines. Both platforms sequenced portions of the fungal nuclear ribosomal RNA genes. The Illumina MiSeq sequenced the internal transcribed spacer region (ITS, 600 bp), while the ONT MinION covered the small subunit, ITS, and partial large subunit (4,600 bp). Both sequencing pipelines revealed that the mycobiomes associated with the roots, shoots, and soil were significantly different. The ONT MinION pipeline identified more diverse fungal lineages and had higher taxonomic resolution than the Illumina pipeline. Our results also indicated that root pathogens may play a more important role than endophytic or mycorrhizal symbionts in tall fescue drought stress tolerance.
Health Status of Ready-to-Plant Grapevine Nursery Material in Canada Regarding Crown Gall and Description of the First Allorhizobium vitis Strain OP-G1 Isolated from British Columbia
Authors: Voegel Tanja M. , McGonigal Portiaa , Nelson Louise M. , Úrbez-Torres José R.
Published: July 2023

Crown gall disease of grapevines caused by Allorhizobium vitis causes significant damage to vineyards in cold-climate viticulture areas such as Canada and the northern United States. Introduction of the disease into vineyards occurs mainly through planting of infected but asymptomatic nursery material. Because A. vitis is not a regulated pest for import into Canada, no information on the health status of nursery material destined for import into Canada has previously been collected. This study evaluated the health status of ready-to-plant nursery material from domestic and international nurseries in regard to crown gall by determining the abundance of A. vitis in different plant sections via Droplet Digital PCR technology. In addition, different rootstocks from one nursery were compared. Results showed that A. vitis was present in planting material from all nurseries tested. The bacteria were nonuniformly distributed in dormant nursery material, and there was no difference in abundance between the rootstocks tested. In addition, the first A. vitis strain OP-G1 isolated from galls in British Columbia is described. Results showed that a minimum of 5,000 bacterial OP-G1 cells were needed for symptom expression, suggesting that the initiation of symptom development is not based on presence of bacteria in nursery material alone; a minimum threshold is needed, and environmental conditions need to be met.
Therapy of autoimmune inflammation in sporadic amyotrophic lateral sclerosis: Dimethyl fumarate and H‐151 downregulate inflammatory cytokines in the cGAS‐STING pathway
Authors: Zamiri Kurosh , Kesari Santosh , Paul Ketema , Hwang Sung Hee , Hammock Bruce , Kaczor‐Urbanowicz Karolina Elżbieta , Urbanowicz Andrzej , Gao Lucy , Whitelegge Julian , Fiala Milan
Published: July 2023

In sporadic amyotrophic lateral sclerosis (sALS), IL‐17A‐ and granzyme‐positive cytotoxic T lymphocytes (CTL), IL‐17A‐positive mast cells, and inflammatory macrophages invade the brain and spinal cord. In some patients, the disease starts following a trauma or a severe infection. We examined cytokines and cytokine regulators over the disease course and found that, since the early stages, peripheral blood mononuclear cells (PBMC) exhibit increased expression of inflammatory cytokines IL‐12A, IFN‐γ, and TNF‐α, as well as granzymes and the transcription factors STAT3 and STAT4. In later stages, PBMCs upregulated the autoimmunity‐associated cytokines IL‐23A and IL‐17B, and the chemokines CXCL9 and CXCL10, which attract CTL and monocytes into the central nervous system. The inflammation is fueled by the downregulation of IL‐10, TGFβ, and the inhibitory T‐cell co‐receptors CTLA4, LAG3, and PD‐1, and, in vitro, by stimulation with the ligand PD‐L1. We investigated in two sALS patients the regulation of the macrophage transcriptome by dimethyl fumarate (DMF), a drug approved against multiple sclerosis and psoriasis, and the cyclic GMP‐AMP synthase/stimulator of interferon genes (cGAS/STING) pathway inhibitor H‐151. Both DMF and H‐151 downregulated the expression of granzymes and the pro‐inflammatory cytokines IL‐1β, IL‐6, IL‐15, IL‐23A, and IFN‐γ, and induced a pro‐resolution macrophage phenotype. The eicosanoid epoxyeicosatrienoic acids (EET) from arachidonic acid was anti‐inflammatory in synergy with DMF. H‐151 and DMF are thus candidate drugs targeting the inflammation and autoimmunity in sALS via modulation of the NFκB and cGAS/STING pathways.
Curiosity, Opportunity, and Luck: Were the 1970s Different?
Authors: Gattinoni Luciano
Published: July 2023

Control of Breathing Using an Extracorporeal Membrane Lung. By T Kolobow, L Gattinoni, TA Tomlinson, JE Pierce. Anesthesiology 1977; 46:138–41. Reprinted with permission.

Body Position Changes Redistribute Lung Computed-Tomographic Density in Patients with Acute Respiratory Failure. By L Gattinoni, P Pelosi, G Vitale, A Pesenti, L D’Andrea, D Mascheroni. Anesthesiology 1991; 74:15–23. Reprinted with permission.

Dr. Gattinoni’s scientific career was primarily driven by curiosity. His generation was not formally trained, but he was part of a community of young and enthusiastic colleagues who were forging a new discipline: intensive care medicine. The most significant opportunity of Dr. Gattinoni’s career was becoming the research fellow of a visionary genius, Dr. Theodor Kolobow, who focused on extracorporeal carbon dioxide removal after the failure of the first trial on extracorporeal membrane oxygenation. CO2 removal, by allowing control over the intensity of mechanical ventilation, opened the path to “lung rest” to prevent ventilator-induced lung injury. A unique opportunity for research was the spontaneous birth of a network of scientists who became friends in the European Group of Research in Intensive Care Medicine. In this environment, it was possible to develop core concepts such as the “baby lung” and to understand the mechanisms underlying computed tomography–density redistribution in the prone position. Physiology guided us in the 1970s, and understanding mechanisms remains of paramount importance today.
Reconstruction of the Exenterated Orbit with an Island Pericranial Flap: A New Surgical Approach
Authors: Kuehnel Sophia , Grimm András , Bohr Christopher , Hosemann Werner , Weber Rainer , Ettl Tobias , Kuehnel Thomas
Published: July 2023

Background:

Reconstruction of the bony socket after orbital exenteration is a matter of much debate. Prompt defect closure with a microvascular flap is desirable but involves a major surgical procedure and hence, places considerable burden on the patient. The new surgical technique presented here permits a technically simpler wound closure with fewer complications after orbital exenteration.

Methods:

Between May 2014 and June 2022 in the ENT department of Regensburg University, nine patients underwent exenteration and reconstruction with a pericranial flap. The flap was raised via a broken line incision in the forehead or endoscopically, incised in a roughly croissant-like shape, then introduced into the orbit through a tunnel in the eyebrow. A retrospective analysis of the patients and considerations about determining the size, shape, and vascular supply of the flap are presented.

Results:

Flap healing was uncomplicated in all cases. Only 6 weeks after surgery, the flap was stable, making it possible to start adjuvant therapy and prosthetic rehabilitation swiftly. The flap is adapted to the near cone-shape of the orbit. The mean (± standard deviation) surface area of the measured orbits is (39.58 ± 3.32) cm2. The territory of the angular artery provides the periosteal flap arterial blood supply. Venous drainage is via venous networks surrounding the artery.

Conclusions:

Use of the pericranial flap makes it possible to close the orbital cavity promptly with minimal donor site defect and a short operating time, thereby minimizing the surgical risk and speeding up physical and psychological recovery.
The Pedicled Anterolateral Thigh Flap for Donor Site Closure after a Large Superficial Circumflex Iliac Artery Perforator Flap Harvest
Authors: Onuma Haruka , Fuse Yuma , Karakawa Ryo , Yano Tomoyuki , Yoshimatsu Hidehiko
Published: July 2023

The superficial circumflex iliac artery perforator (SCIP) flap is useful for covering defects in the extremities because its pedicle size can match many recipient options. However, when harvesting a large flap, skin grafting of the donor site is not highly recommended because of the mobility of the hip joint and occasional lymphorrhea. Here, we present a case of a successful reconstruction of a defect in the lower leg after sarcoma resection, using a large SCIP flap. A 58-year-old man underwent resection of a large soft tissue tumor in the lower leg, resulting in a 16 × 14 cm defect. A 25 × 14 cm SCIP flap was harvested from the groin, and the superficial circumflex iliac artery and the superficial circumflex iliac vein were anastomosed to the saphenous artery and the great saphenous vein, respectively, in an end-to-end fashion. For coverage of the groin donor site, a 25 × 8 cm pedicled anterolateral thigh (ALT) flap was harvested from the ipsilateral lateral thigh and was pulled through a subcutaneous tunnel to the groin. The additional operative time for pedicled ALT flap elevation and transfer was approximately 15 minutes. With this pedicled ALT flap, the donor site of the SCIP flap could be closed directly over a drain. The follow-up at 3 months showed complete survival of both flaps, and the patient was able to walk with a cane. The pedicled ALT flap allows for direct closure of the donor site after a large SCIP flap harvest.
Successful Treatment of Wounds from Nonuremic Calciphylaxis with Acellular Piscine Dermis
Authors: Shahriari Shawhin , Ensign Eric , Huang Samantha , Harrison Joshua , Whisonant Cees , Aubin-Lemay Camille
Published: July 2023

In this report, we present a 57-year-old man with chronic bilateral lower extremity wounds from nonuremic calciphylaxis, which were successfully reconstructed using a piscine-derived acellular dermal matrix. The acellular dermal matrix incorporated quickly, providing a wound bed that was amenable to skin grafting. We demonstrate that this is an effective off-the-shelf solution for these chronic wounds, resulting in pain reduction and complete closure of the wounds, allowing the patient to return to his previous baseline activities, and improving his quality of life.
Sex hormone-binding globulin levels and development of hypertension in middle-aged men and women
Authors: Watz Michel E.S. , Tivesten Åsa , Ottarsdottir Kristin , Li Ying , Hellgren Margareta I. , Lindblad Ulf , Daka Bledar
Published: July 2023

Objective:

To investigate the association between sex hormone-binding globulin (SHBG) levels, change in blood pressure and development of hypertension.

Methods:

In a community-based study, we examined 2816 middle-aged participants with focus on cardiometabolic risk factors in 2002–2005. A representative sample of 1954 men and women was invited to follow-up in 2012–2014 and 1327 were included in a second study visit. Mean follow-up time was 9.7 years. Blood pressure was measured according to the guidelines from the seventh Joint National Committee of Hypertension, and new cases of hypertension were recorded. SHBG was measured at baseline. The association between SHBG, blood pressure and new cases of hypertension was investigated using linear regression analyses and logistic regression analyses after excluding individuals treated with blood pressure-lowering drugs.

Results:

Mean SBP and DBP at follow-up was 123 and 72 mmHg, respectively, and mean increase from baseline was 5.8 and 2.9 mmHg. During the follow-up time, 167 new cases of hypertension (16.1%) were identified. One standard deviation (SD) increase in SHBG at baseline was inversely associated with the risk to develop hypertension at follow-up (OR = 0.74, 95% CI 0.58–0.95) in the fully adjusted model. Moreover, one SD increase in SHBG was associated with a decrease in mean SBP (delta = −1.5 mmHg, 95% CI − 2.2 to −0.8) and DBP (delta = − 1.0 mmHg, 95% CI − 1.5 to −0.4), after adjusting for covariates.

Conclusion:

SHBG levels are inversely associated with development of hypertension and change in blood pressure levels independent of major risk factors.
Status of Type II vs. Type I Bipolar Disorder: Systematic Review with Meta-Analyses
Authors: Hernandorena Carolina V. , Baldessarini Ross J. , Tondo Leonardo , Vázquez Gustavo H.
Published: July 2023

Learning Objectives: After participating in this CME activity, the psychiatrist should be better able to

• Analyze and compare the different bipolar disorder (BD) types.

• Identify markers that distinguish BD types and explain how the DSM-IV defines the disorder.

Since the status of type II bipolar disorder (BD2) as a separate and distinct form of bipolar disorder (BD) remains controversial, we reviewed studies that directly compare BD2 to type I bipolar disorder (BD1). Systematic literature searching yielded 36 reports with head-to-head comparisons involving 52,631 BD1 and 37,363 BD2 patients (total N = 89,994) observed for 14.6 years, regarding 21 factors (with 12 reports/factor). BD2 subjects had significantly more additional psychiatric diagnoses, depressions/year, rapid cycling, family psychiatric history, female sex, and antidepressant treatment, but less treatment with lithium or antipsychotics, fewer hospitalizations or psychotic features, and lower unemployment rates than BD1 subjects. However, the diagnostic groups did not differ significantly in education, onset age, marital status, [hypo]manias/year, risk of suicide attempts, substance use disorders, medical comorbidities, or access to psychotherapy. Heterogeneity in reported comparisons of BD2 and BD1 limits the firmness of some observations, but study findings indicate that the BD types differ substantially by several descriptive and clinical measures and that BD2 remains diagnostically stable over many years. We conclude that BD2 requires better clinical recognition and significantly more research aimed at optimizing its treatment.
Pathophysiology of Slow-Flow Vascular Malformations: Current Understanding and Unanswered Questions
Authors: Clapp Averill , Shawber Carrie J. , Wu June K.
Published: July 2023

Background:

Slow-flow vascular malformations include venous, lymphatic, and lymphaticovenous malformations. Recent studies have linked genetic variants hyperactivating either the PI3K/AKT/mTOR and/or RAS/RAF/MAPK signaling pathways with slow-flow vascular malformation development, leading to the use of pharmacotherapies such as sirolimus and alpelisib. It is important that clinicians understand basic and translational research advances in slow-flow vascular malformations.

Methods:

A literature review of basic science publications in slow-flow vascular malformations was performed on Pubmed, using search terms “venous malformation,” “lymphatic malformation,” “lymphaticovenous malformation,” “genetic variant,” “genetic mutation,” “endothelial cells,” and “animal model.” Relevant publications were reviewed and summarized.

Results:

The study of patient tissues and the use of primary pathogenic endothelial cells from vascular malformations shed light on their pathological behaviors, such as endothelial cell hyperproliferation and disruptions in vessel architecture. The use of xenograft and transgenic animal models confirmed the pathogenicity of genetic variants and allowed for preclinical testing of potential therapies. These discoveries underscore the importance of basic and translational research in understanding the pathophysiology of vascular malformations, which will allow for the development of improved biologically targeted treatments.

Conclusion:

Despite basic and translation advances, a cure for slow-flow vascular malformations remains elusive. Many questions remain unanswered, including how genotype variants result in phenotypes, and genotype-phenotype heterogeneity. Continued research into venous and lymphatic malformation pathobiology is critical in understanding the mechanisms by which genetic variants contribute to vascular malformation phenotypic features.
Esophageal Lichen Planus
Authors: Aby Elizabeth S. , Eckmann Jason D. , Abimansour Jad , Katzka David A. , Beveridge Claire , Triggs Joseph R. , Dbouk Mohamad , Abdi Tsion , Turner Kevin O. , Antunes Catiele , Zhuo Justin , Kamal Afrin N. , Patel Parth , Gyawali C. Prakash , Sloan Joshua A.
Published: July 2023

Goals:

To better understand the characteristics, treatment approaches, and outcomes of patients with esophageal lichen planus (ELP).

Background:

ELP is a rare, often unrecognized and misdiagnosed disorder. Data on this unique patient population are currently limited to small, single-center series.

Study:

A multicenter, retrospective descriptive study was conducted of adults diagnosed with ELP over a 5-year period, between January 1, 2015, and October 10, 2020, from 7 centers across the United States.

Results:

Seventy-eight patients (average age 65 y, 86% female, 90% Caucasian) were included. Over half had at least 1 extraesophageal manifestation. Esophageal strictures (54%) and abnormal mucosa (50%) were frequent endoscopic findings, with the proximal esophagus the most common site of stricture. Approximately 20% had normal endoscopic findings. Topical steroids (64%) and/or proton pump inhibitors (74%) dominated management; endoscopic response favored steroids (43% vs. 29% respectively). Almost half of the patients required switching treatment modalities during the study period. Adjunctive therapies varied significantly between centers.

Conclusions:

Given its at times subtle clinical and endoscopic signs, a high index of suspicion and biopsy will improve ELP diagnosis, especially in those with extraesophageal manifestations. Effective therapies are lacking and vary significantly. Prospective investigations into optimal treatment regimens are necessary.
Improving Adherence to Clinical Practice Guidelines for Managing Gastric Intestinal Metaplasia Among Gastroenterologists at a US Academic Institution
Authors: Jacob Jake , Millien Valentine , Berger Scott , Hernaez Ruben , Ketwaroo Gyanprakash A. , Flores Avegail G. , Hou Jason K. , Jarbrink-Sehgal Maria E. , Khalaf Natalia I. , Rosen Daniel G. , El-Serag Hashem B. , Tan Mimi C.
Published: July 2023

Background:

Clinical guidelines reserve endoscopic surveillance after a gastric intestinal metaplasia (GIM) diagnosis for high-risk patients. However, it is unclear how closely guidelines are followed in clinical practice. We examined the effectiveness of a standardized protocol for the management of GIM among gastroenterologists at a US hospital.

Methods:

This was a preintervention and postintervention study, which included developing a protocol and education of gastroenterologists on GIM management. For the preintervention study, 50 patients with GIM were randomly selected from a histopathology database at the Houston VA Hospital between January 2016 and December 2019. For the postintervention study, we assessed change in GIM management in a cohort of 50 patients with GIM between April 2020 and January 2021 and surveyed 10 gastroenterologists. The durability of the intervention was assessed in a cohort of 50 GIM patients diagnosed between April 2021 and July 2021.

Results:

In the preintervention cohort, GIM location was specified (antrum and corpus separated) in 11 patients (22%), and Helicobacter pylori testing was recommended in 11 of 26 patients (42%) without previous testing. Gastric mapping biopsies were recommended in 14% and surveillance endoscopy in 2%. In the postintervention cohort, gastric biopsy location was specified in 45 patients (90%, P<0.001) and H. pylori testing was recommended in 26 of 27 patients without prior testing (96%, P<0.001). Because gastric biopsy location was known in 90% of patients (P<0.001), gastric mapping was not necessary, and surveillance endoscopy was recommended in 42% (P<0.001). One year after the intervention, all metrics remained elevated compared with the preintervention cohort.

Conclusions:

GIM management guidelines are not consistently followed. A protocol for GIM management and education of gastroenterologists increased adherence to H. pylori testing and GIM surveillance recommendations.
Myositis-associated interstitial lung disease
Authors: Vu Trang T.T. , Brown Kevin K. , Solomon Joshua J.
Published: July 2023

Purpose of review

In idiopathic inflammatory myopathies (IIMs), interstitial lung disease (ILD) is common and the autoantibody profile, made up of myositis-specific and myositis-associated (MSA and MAA) antibodies, can predict the clinical phenotype and progression over time. This review will focus on the characteristics and management of antisynthetase syndrome related ILD and anti-MDA5 positive ILD, which are the most clinically relevant subtypes.

Recent findings

The prevalence of ILD in IIM has been estimated in Asia, North America and Europe at 50, 23 and 26%, respectively, and is increasing. In antisynthetase syndrome related ILD, the clinical presentation, progression and prognosis varies among anti-ARS antibodies. ILD is more common and severe in patients with anti-PL-7/anti-PL-12 antibodies when compared with anti Jo-1 patients. The prevalence of anti-MDA5 antibodies is higher in Asians (11–60%) than in whites (7–16%). Sixty-six percent of antisynthetase syndrome patients had ‘chronic ILD’ compared with the more rapidly progressive ILD (RP-ILD) seen in 69% of patients with anti-MDA5 antibodies.

ILD is most common in the antisynthetase subtype of IIM and can be a chronic indolent or RP- ILD. The MSA and MAAs are associated with different clinical phenotypes of ILD. Treatments typically involve combinations of corticosteroids and other immunosuppressants.
Impact of Sleep Disturbance on Fatigue, Nausea, and Pain: Mediating Role of Depressive Symptoms Among Youth With Disorders of Gut-Brain Interaction
Authors: Bedree Helen , Tran Susan T. , Koven Marissa L. , Wershil Sarah J. , Fortunato John E. , Essner Bonnie S.
Published: July 2023

Objectives:

A high degree of sleep disturbance is reported among youth with disorders of gut-brain interaction (DGBIs). Given that sleep quality impacts a range of pediatric health outcomes including somatic sensations (eg, pain) and depressive mood occurs relatively frequently among youth with DGBIs, there is a dire need to disentangle the unique contributions of sleep and depressive mood on the somatic sensations experienced by youth with DGBIs. We aimed to examine whether depressive mood mediates the relations among sleep disturbance and pain intensity, nausea, and fatigue among youth with DGBIs.

Methods:

One hundred eighteen patients aged 8–17 years (M
age = 14.05, SD = 2.88; 70.34% female), 83.05% White/non-Hispanic recruited at a pediatric neurogastroenterology clinic completed measures of sleep disturbance, nausea, fatigue, pain intensity, and depressive mood. Three mediation models examined the effect of sleep disturbance on nausea, fatigue, and pain, with depressive mood as a mediator.

Results:

Participants reported moderate sleep disturbance. Depressive mood partially mediated the significant, respective relations between greater sleep disturbance and more severe nausea and fatigue. Sleep disturbance was significantly associated with higher pain intensity; however, depressive mood was not a significant mediator of this relation.

Conclusions:

Sleep quality is a major concern among youth with DGBIs. Low sleep quality may worsen nausea and fatigue via co-occurring increases in depressive mood symptoms. In contrast, sleep disturbance may directly increase pain, regardless of youths’ depressive mood symptoms. Future research should explore these relations through prospective studies leveraging a combination of subjective and objective assessment approaches.
Predictors of Sustained Physical Activity During the COVID-19 Pandemic in People With Parkinson Disease in Sweden
Authors: Moulaee Conradsson David , Leavy Breiffni , Hagströmer Maria , Franzén Erika
Published: July 2023

Background and Purpose:

During the first wave of the COVID-19 pandemic, people with Parkinson disease (PwPD) reported deterioration in health and physical activity. The aim of this study was to describe 1-year changes in physical activity and perceived health in PwPD during the COVID-19 pandemic and to identify predictors of sustained physical activity.

Methods:

This study compared perceived health and sensor-derived physical activity (Actigraph GT3x) in PwPD between the first (June to July 2020) and third waves (June to July 2021) of the pandemic. Multiple logistic regression analyses were used to predict sustained physical activity across the study period using personal factors, disease severity, and functioning as independent variables.

Results:

Sixty-three PwPD (mean age 71.0 years, 41% females) completed both baseline and 1-year follow-up (26 lost to follow-up). PwPD showed a decrease in average number of steps per day (Δ415 steps, P = 0.048), moderate-to-vigorous-physical activity (Δ7 minutes, P = 0.007) and increase in sedentary time (Δ36 minutes, P<.001) between baseline and 1-year follow-up. While self-perceived walking impairments and depressive symptoms increased significantly, balance confidence decreased between baseline and 1-year follow-up, no significant changes occurred for self-rated health, quality of life, or anxiety. Significant predictors of sustained physical activity levels were 15 years or more of education (odds ratio [OR] = 7.38, P = 0.013) and higher perceived walking ability (OR = 0.18, P = 0.041).

Discussion and Conclusion:

Among PwPD with mild to moderate disease severity living in Sweden, factors associated with reduced physical activity levels during the COVID-19 pandemic included older age, lower education levels, and greater perceived walking difficulties.
At the Intersection of Intersectionality
Authors: Iwai Yoshiko , Yu Alice Yunzi L. , Thomas Samantha M. , Downs-Canner Stephanie , Beasley Georgia M. , Sudan Ranjan , Fayanju Oluwadamilola M.
Published: July 2023

Objective:

We sought to compare representation of intersectional (i.e., racial/ethnic and gender) identities among surgical faculty versus medical students.

Summary Background Data:

Health disparities are pervasive in medicine, but diverse physicians may help the medical profession achieve health equity.

Methods:

Data from the AAMC for 140 programs (2011/2012-2019/2020) were analyzed for students and full-time surgical faculty. Underrepresented in medicine (URiM) was defined as Black/African American; American Indian/Alaskan Native; Hispanic/Latino/Spanish Origin; or Native Hawaiian/Other Pacific Islander. Non-White included URiM plus Asian, multiracial, and non-citizen permanent residents. Linear regression was used to estimate the association of year and proportions of URiM and non-White female and male faculty with proportions of URiM and non-White students.

Results:

Medical students were comprised of more White (25.2% vs. 14.4%), non-White (18.8% vs. 6.6%), and URiM (9.6% vs. 2.8%) women and concomitantly fewer men across all groups versus faculty (all P<0.01). While the proportion of White and non-White female faculty increased over time (both p≤0.001), there was no significant change among non-White URiM female faculty, nor among non-White male faculty, regardless of whether they were URiM or not. Having more URiM male faculty was associated with having more non-White female students (estimate =+14.5% students/100% increase in faculty, 95% CI 1.0-28.1%, P=0.04), and this association was especially pronounced for URiM female students (estimate =+46.6% students/100% increase in faculty, 95% CI 36.9-56.3%, P<0.001).

Conclusion:

URiM faculty representation has not improved despite a positive association between having more URiM male faculty and having more diverse students.
Novel Application of a Dynamic, In-Room Survey Platform to Measure Surgical Team Satisfaction
Authors: Witmer Hunter D. D. , Morris-Levenson Joshua A. , Keçeli Çağla , Godley Frederick A. , Dhiman Ankit , Adelman Daniel , Turaga Kiran K.
Published: July 2023

Objective:

This study aims to elucidate the potential usage of continuous feedback regarding team satisfaction and correlations with operative performance and patient outcomes.

Background:

Continuous, actionable assessment of teamwork quality in the operating room (OR) is challenging. This work introduces a novel, data-driven approach to prospectively and dynamically assess healthcare provider (HCP) satisfaction with teamwork in the OR.

Methods:

Satisfaction with teamwork quality for each case was assessed utilizing a validated prompt displayed on HappyOrNot® Terminals™ placed in all ORs, with separate panels for circulators, scrub nurses, surgeons, and anesthesia providers. Responses were cross-referenced with OR log data, team familiarity indicators, efficiency parameters and patient safety indicator events through continuous, semi-automated data marts. De-identified responses were analyzed via logistic regression modeling.

Results:

Over a 24-week period, 4,123 responses from 2,107 cases were recorded. The overall response rate per-case was 32.5%. Greater scrub nurse specialty experience was strongly associated with satisfaction (odds ratio 2.15, 95% CI 1.53—3.03, P<0.001). Worse satisfaction was associated with longer than expected procedure time (odds ratio 0.91, 95% CI 0.82—1.00, P=0.047), nighttime (0.67, 95% CI 0.55—0.82, P<0.001) and add-on cases (0.72, 95% CI 0.60—0.86, P<0.001). Higher material costs (22%, 95% CI 6—37%, P=0.006) were associated with greater team satisfaction. Cases with superior teamwork ratings were associated with a 15% shorter length of hospital stay (95% CI 4—25%, P=0.006).

Conclusions:

This study demonstrates for the feasibility of a dynamic survey platform to report actionable HCP satisfaction metrics in real-time. Team satisfaction is associated with modifiable team variables and some key operational outcomes. Leveraging qualitative measurements of teamwork as operational indicators may augment staff engagement and measures of performance.
Ondansetron for Low Anterior Resection Syndrome (LARS)
Authors: Popeskou Sotirios Georgios , Roesel Raffaello , Faes Seraina , Vanoni Alice , Galafassi Jacopo , di Tor Vajana Antonjacopo Ferrario , Piotet Laure-Meline , Christoforidis Dimitri
Published: July 2023

Objective:

This study examines the efficacity and safety of Ondansetron, a serotonin receptor antagonist, to treat patients with LARS.

Background:

Low Anterior Resection Syndrome (LARS) after rectal resection is common and debilitating. Current management strategies include behavioural and dietary modifications, physiotherapy, antidiarrheal drugs, enemas and neuromodulation, but results are not always satisfactory.

Methods:

This is a randomized, multi-centric, double-blinded, placebo-controlled, cross-over study. Patients with LARS (LARS score >20) no longer than 2 years after rectal resection were randomised to receive either 4 weeks of Ondansetron followed by 4 weeks of placebo (O-P group) or 4 weeks of placebo followed by 4 weeks of Ondansetron (P-O group). The primary endpoint was LARS severity measured using the LARS score; secondary endpoints were incontinence (Vaizey score) and quality of life (IBS-QoL questionnaire). Patients’ scores and questionnaires were completed at baseline and after each 4-week treatment period.

Results:

Out of 46 randomized patients, 38 were included in the analysis. From baseline to the end of the first period, in the O-P group, the mean (SD) LARS score decreased by 25% (from 36.6 (5.6) to 27.3 (11.5)) and the proportion of patients with major LARS (score >30) went from 15/17 (88%) to 7/17 (41%), (P=0.001). In the P-O group, the mean (SD) LARS score decreased by 12% (from 37 (4.8) to 32.6 (9.1)), and the proportion of major LARS went from 19/21 (90%) to 16/21 (76%). After cross over, LARS scores deteriorated again in the O-P group receiving placebo, but further improved in the P-O group receiving Ondansetron. Mean Vaizey scores and IBS QoL scores followed a similar pattern.

Conclusion:

Ondansetron is a safe and simple treatment that appears to improve both symptoms and quality of life in LARS patients.
The Association of ACGME Milestones with Performance on American Board of Surgery Assessments
Authors: Weaver M. Libby , Carter Taylor , Yamazaki Kenji , Hamstra Stanley J. , Holmboe Eric , Chaer Rabih , Park Yoon Soo , Smith Brigitte K.
Published: July 2023

Objective:

To determine the relationship between, and predictive utility of, Milestone ratings and subsequent American Board of Surgery(ABS) vascular in-training(VSITE), qualifying(VQE), and certifying examination(VCE) performance in a national cohort of vascular surgery trainees.

Summary Background Data:

Specialty board certification is an important indicator of physician competence. However, predicting future board certification examination performance during training continues to be challenging.

Methods:

This is a national longitudinal cohort study examining relational and predictive associations between ACGME Milestone ratings and performance on VSITE, VQE, and VCE for all vascular surgery trainees from 2015 through 2021. Predictive associations between Milestone ratings and VSITE were conducted using cross-classified random-effects regression. Cross-classified random-effects logistic regression was utilized to identify predictive associations between Milestone ratings and VQE and VCE.

Results:

Milestone ratings were obtained for all residents and fellows(n=1,118) from 164 programs during the study period(July 2015-June 2021), including 145,959 total trainee assessments. Medical Knowledge(MK) and Patient Care(PC) Milestone ratings were strongly predictive of VSITE performance across all post-graduate years(PGYs) of training, with MK ratings demonstrating a slightly stronger predictive association overall(MK Coefficient 17.26-35.76,β = 0.15- 0.23). All core competency ratings were predictive of VSITE performance in PGYs 4 and 5. PGY 5 MK were highly predictive of VQE performance(OR 4.73,[95% CI: 3.87-5.78],P<0.001). PC subcompetencies were also highly predictive of VQE performance in the final year of training(OR 4.14,[95% CI: 3.17-5.41],P<0.001). All other competencies were also significantly predictive of first-attempt VQE pass with ORs of 1.53 and higher. PGY 4 ICS ratings(OR 4.0,[95% CI: 3.06-5.21],P<0.001) emerged as the strongest predictor of VCE first-attempt pass. Again, all subcompetency ratings remained significant predictors of first-attempt pass on CE with ORs of 1.48 and higher.

Conclusions:

ACGME Milestone ratings are highly predictive of future VSITE performance, and first-attempt pass achievement on VQE and VCE in a national cohort of surgical trainees.