bluuebunny/crossref_metadata_2025 huggingface dataset:
Detecting co-selection through excess linkage disequilibrium in bacterial genomes
Authors: Mallawaarachchi Sudaraka , Tonkin-Hill Gerry , Pöntinen Anna K , Calland Jessica K , Gladstone Rebecca A , Arredondo-Alonso Sergio , MacAlasdair Neil , Thorpe Harry A , Top Janetta , Sheppard Samuel K , Balding David , Croucher Nicholas J , Corander Jukka
Published: June 2024

Population genomics has revolutionized our ability to study bacterial evolution by enabling data-driven discovery of the genetic architecture of trait variation. Genome-wide association studies (GWAS) have more recently become accompanied by genome-wide epistasis and co-selection (GWES) analysis, which offers a phenotype-free approach to generating hypotheses about selective processes that simultaneously impact multiple loci across the genome. However, existing GWES methods only consider associations between distant pairs of loci within the genome due to the strong impact of linkage-disequilibrium (LD) over short distances. Based on the general functional organisation of genomes it is nevertheless expected that majority of co-selection and epistasis will act within relatively short genomic proximity, on co-variation occurring within genes and their promoter regions, and within operons. Here, we introduce LDWeaver, which enables an exhaustive GWES across both short- and long-range LD, to disentangle likely neutral co-variation from selection. We demonstrate the ability of LDWeaver to efficiently generate hypotheses about co-selection using large genomic surveys of multiple major human bacterial pathogen species and validate several findings using functional annotation and phenotypic measurements. Our approach will facilitate the study of bacterial evolution in the light of rapidly expanding population genomic data.
NFixDB (Nitrogen Fixation DataBase)—a comprehensive integrated database for robust ‘omics analysis of diazotrophs
Authors: Bellanger Madeline , Figueroa Jose L , Tiemann Lisa , Friesen Maren L , III Richard Allen White
Published: June 2024

Biological nitrogen fixation is a fundamental biogeochemical process that transforms molecular nitrogen into biologically available nitrogen via diazotrophic microbes. Diazotrophs anaerobically fix nitrogen using the nitrogenase enzyme which is arranged in three different gene clusters: (i) molybdenum nitrogenase (nifHDK) is the most abundant, followed by it's alternatives, (ii) vanadium nitrogenase (vnfHDK) and (iii) iron nitrogenase (anfHDK). Multiple databases have been constructed as resources for diazotrophic ‘omics analysis; however, an integrated database based on whole genome references does not exist. Here, we present NFixDB (Nitrogen Fixation DataBase), a comprehensive integrated whole genome based database for diazotrophs, which includes all nitrogenases (nifHDK, vnfHDK, anfHDK) and nitrogenase-like enzymes (e.g. nflHD) linked to ribosomal RNA operons (16S–5S–23S). NFixDB was computed using Hidden Markov Models (HMMs) against the entire whole genome based Genome Taxonomy Database (GTDB R214), providing searchable reference HMMs for all nitrogenase and nitrogenase-like genes, complete ribosomal RNA operons, both GTDB and NCBI/RefSeq taxonomy, and an SQL database for querying matches. We compared NFixDB to nifH databases from Buckley, Zehr, Mise and FunGene finding extensive evidence of nifH, in addition to vnfH and nflH. NFixDB contains >4000 verified nifHDK sequences contained on 50 unique phyla of bacteria and archaea. NFixDB provides the first comprehensive nitrogenase database available to researchers unlocking diazotrophic microbial potential.
Characterization of trans-spliced chimeric RNAs: insights into the mechanism of trans-splicing
Authors: Yokomori Rui , Kusakabe Takehiro G , Nakai Kenta
Published: June 2024

Trans-splicing is a post-transcriptional processing event that joins exons from separate RNAs to produce a chimeric RNA. However, the detailed mechanism of trans-splicing remains poorly understood. Here, we characterize trans-spliced genes and provide insights into the mechanism of trans-splicing in the tunicate Ciona. Tunicates are the closest invertebrates to humans, and their genes frequently undergo trans-splicing. Our analysis revealed that, in genes that give rise to both trans-spliced and non-trans-spliced messenger RNAs, trans-splice acceptor sites were preferentially located at the first functional acceptor site, and their paired donor sites were weak in both Ciona and humans. Additionally, we found that Ciona trans-spliced genes had GU- and AU-rich 5′ transcribed regions. Our data and findings not only are useful for Ciona research community, but may also aid in a better understanding of the trans-splicing mechanism, potentially advancing the development of gene therapy based on trans-splicing.
Multiscale Bayesian simulations reveal functional chromatin condensation of gene loci
Authors: Brandani Giovanni B , Gu Chenyang , Gopi Soundhararajan , Takada Shoji
Published: June 2024

Chromatin, the complex assembly of DNA and associated proteins, plays a pivotal role in orchestrating various genomic functions. To aid our understanding of the principles underlying chromatin organization, we introduce Hi-C metainference, a Bayesian approach that integrates Hi-C contact frequencies into multiscale prior models of chromatin. This approach combines both bottom-up (the physics-based prior) and top-down (the data-driven posterior) strategies to characterize the 3D organization of a target genomic locus. We first demonstrate the capability of this method to accurately reconstruct the structural ensemble and the dynamics of a system from contact information. We then apply the approach to investigate the Sox2, Pou5f1, and Nanog loci of mouse embryonic stem cells using a bottom-up chromatin model at 1 kb resolution. We observe that the studied loci are conformationally heterogeneous and organized as crumpled globules, favoring contacts between distant enhancers and promoters. Using nucleosome-resolution simulations, we then reveal how the Nanog gene is functionally organized across the multiple scales of chromatin. At the local level, we identify diverse tetranucleosome folding motifs with a characteristic distribution along the genome, predominantly open at cis-regulatory elements and compact in between. At the larger scale, we find that enhancer–promoter contacts are driven by the transient condensation of chromatin into compact domains stabilized by extensive internucleosome interactions. Overall, this work highlights the condensed, but dynamic nature of chromatin in vivo, contributing to a deeper understanding of gene structure–function relationships.
ChatGPT prompts for generating multiple-choice questions in medical education and evidence on their validity: a literature review
Authors: Kıyak Yavuz Selim , Emekli Emre
Published: June 2024

ChatGPT’s role in creating multiple-choice questions (MCQs) is growing but the validity of these artificial-intelligence-generated questions is unclear. This literature review was conducted to address the urgent need for understanding the application of ChatGPT in generating MCQs for medical education. Following the database search and screening of 1920 studies, we found 23 relevant studies. We extracted the prompts for MCQ generation and assessed the validity evidence of MCQs. The findings showed that prompts varied, including referencing specific exam styles and adopting specific personas, which align with recommended prompt engineering tactics. The validity evidence covered various domains, showing mixed accuracy rates, with some studies indicating comparable quality to human-written questions, and others highlighting differences in difficulty and discrimination levels, alongside a significant reduction in question creation time. Despite its efficiency, we highlight the necessity of careful review and suggest a need for further research to optimize the use of ChatGPT in question generation.

Main messages  Ensure high-quality outputs by utilizing well-designed prompts; medical educators should prioritize the use of detailed, clear ChatGPT prompts when generating MCQs. Avoid using ChatGPT-generated MCQs directly in examinations without thorough review to prevent inaccuracies and ensure relevance. Leverage ChatGPT’s potential to streamline the test development process, enhancing efficiency without compromising quality.
Survival analysis of adult visceral leishmaniasis patients admitted to Metema Hospital, Metema, Ethiopia: a hospital-based cross-sectional study
Authors: Wudu Habitamu , Alemu Chekol
Published: June 2024

Background

Visceral leishmaniasis (VL) is a neglected tropical disease that mostly affects the working class and impoverished segments of society, having a significant negative effect on the economic development of the affected nation. While anti-leishmanial medications lower mortality among VL patients, patients may still die or require more time to recover while receiving treatment. In this regard, there are limited studies in Ethiopia. This study aims to determine the time to recovery and its associated predictors among adult VL patients at Metema Hospital, Metema, Ethiopia.

Methods

A hospital-based cross-sectional study was employed and the data were collected from patient's charts from September 2017 to September 2021. Data were entered and analysed using EpiData version 3.1, Stata version 14.2 and R version 3.4.0 statistical software. Kaplan–Meier survival curves and logrank tests were used to compare the survival time. The Cox proportional hazards model assumption and model fitness were checked and used to identify statistical association predictors in VL patients.

Results

The Cox proportional hazards model was fitted. The overall medium recovery time was 7 d (minimum 4, maximum 14). The variables of nasal bleeding (adjusted hazard ratio [aHR] 0.44 [95% confidence interval {CI} 0.19 to 0.89]), no comorbidity (aHR 2.29 [95% CI 1.27 to 4.11]), relapse of VL (aHR 0.33 [95% CI 0.15 to 0.75]), low parasite load (aHR 2.58 [95% CI 1.48 to 4.51]) and ambulatory (aHR 3.26 [95% CI 2.45 to 6.53]) were significantly associated with time to recovery in VL patients.

Conclusions

Patients with comorbidities, nasal bleeding, relapse of VL, bedridden and high parasite load should be treated and monitored carefully to recover quickly from their illness.
Sugammadex and oral contraceptives
Authors: Devoy Tamblyn , Smith Natalie
Published: June 2024

Purpose of review

This review article explores the evidence regarding sugammadex (MSD Australia) and its potential interaction with hormonal contraceptives. The impact of recent clinical trials and review articles is examined.

Recent findings

Recent clinical data suggest that the interaction between sugammadex and estrogen and progesterone concentrations may not be clinically significant and may confer some protection against ovulation. There are no clinical trials reporting interactions between sugammadex and the exogenous hormonal compounds found in oral contraceptive pills. The method of contraception is an important consideration, as sugammadex theoretically affects oral and nonoral, and combined versus single agent methods differently. Two large retrospective database studies have reported two cases of pregnancy postoperatively in patients on hormonal contraceptives whose anesthetic included sugammadex.

Strong clinical evidence to support or refute claims of a significant impact of sugammadex on contraceptive efficacy in women on contraception is lacking. The existing evidence does not suggest a basis for concern regarding the impact of sugammadex on contraception in the perioperative setting.
Racial Disparities in Newborn Drug Testing After Implementation of Question-Based Screening for Prenatal Substance Use
Authors: Soos Alexandra , Plegue Melissa , Darwiche Adam , Oshman Lauren , Frank Christopher J.
Published: June 2024

OBJECTIVE:

To examine the association of universal question-based screening for prenatal substance use on racial inequities in prenatal and newborn drug testing.

METHODS:

We conducted a retrospective cohort study of 32,802 live births of patients receiving prenatal care at an academic medical center in the midwestern United States from 2014 to 2022, before and after implementation of question-based screening in 2018. Primary outcomes included prenatal and newborn drug test orders. Logistic regression models using a generalized estimating equation framework assessed associations with question-based screening and results, birthing parent age, race, ethnicity, marital status, and insurance type. Charts of patients who indicated difficulties stopping substance use were audited for guideline-directed care.

RESULTS:

A total of 12,725 of 14,992 pregnant people (85.3%) received question-based screening. Implementation of question-based screening was associated with a decrease in prenatal urine test orders (5.0% [95% CI, 4.6–5.3%] before implementation, 3.1% [95% CI, 2.8–3.4%] after implementation; P<.001), with Black birthing parents having the largest reduction in prenatal urine drug testing (10.3% [95% CI, 9.0–11.7%] before implementation, 4.9% [95% CI, 3.9–5.9%] after implementation). However, rates of newborn drug testing did not change (4.7% [95% CI, 4.4–5.0%] before implementation, 4.5% [95% CI, 4.2–4.8%] after implementation; P=.46), and clinicians continued to order significantly more newborn drug tests for newborns of Black birthing parents compared with other race and ethnicity groups.

CONCLUSION:

Implementation of question-based screening for substance use in pregnancy was associated with decreased prenatal urine drug testing but no change in overall newborn drug testing or racial inequities in newborn drug testing for Black birthing people. Further policy efforts are warranted to improve substance use treatment and to eliminate racial inequities in punitive policies such as newborn drug testing and subsequent child protective services reporting.
Causal relationship between sex hormones and cutaneous melanoma: a two-sample Mendelian randomized study
Authors: Luo Pan , Guo Rui , Gao Dejin , Zhang Qingguo
Published: June 2024

This study aimed to elucidate the genetic aspects of the relationship between sex hormones and cutaneous melanoma risk, providing valuable insights into this complex association. In this study, we used estradiol, bioavailable testosterone, sex hormone-binding globulin, and total testosterone as the exposure and melanoma as the outcome for two-sample Mendelian randomization analysis. In this study, a random-effects inverse-variance weighting (IVW) model was used as the main analysis model, and the corresponding weighted median, simple mode, weighted mode, and Mendelian randomization‒Egger methods were used as supplementary methods. We assessed both heterogeneity and horizontal pleiotropy in our study, scrutinizing whether the analysis results were affected by any individual single nucleotide polymorphism. The random-effects IVW method indicated that estradiol [odds ratio (OR), 1.000; 95% confidence interval (CI), 0.998–1.003; P = 0.658], bioavailable testosterone (OR = 1.001, 95% CI, 0.999–1.003; P = 0.294), sex hormone-binding globulin (IVW: OR, 1.000; 95% CI, 0.998–1.003; P = 0.658), and total testosterone (IVW: OR, 1.002; 95% CI, 0.999–1.005; P = 0.135) were not genetically linked to cutaneous melanoma. No analyses exhibited heterogeneity, horizontal pleiotropy, or deviations. We were unable to find genetic evidence for a causal relationship between sex hormones and the occurrence of cutaneous melanoma in this study. These results are limited by sample size and population, so the causal relationship between sex hormones and cutaneous melanoma needs to be further studied.
Two Cases of Cutaneous Sarcomatoid Squamous Cell Carcinoma Resembling Cutaneous Giant Cell Tumor of Soft Tissue
Authors: McAlpine Sarah G. , Carrasquillo Osward Y. , Miedema Jayson , Googe Paul B.
Published: June 2024

Cutaneous sarcomatoid squamous cell carcinoma is well-described with histology resembling pleomorphic undifferentiated sarcoma featuring collagenous or myxoid stroma with or without elements of keratinizing squamous carcinoma. This report presents 2 cases of dedifferentiated squamous cell carcinoma (SCC) composed of sheets of malignant mononuclear cells with malignant osteoclast–like multinucleated giant cells, extravasated blood, and hemosiderin resembling cutaneous giant cell tumor (cGCT). In the first case, an exophytic facial mass of a 96-year-old woman removed by shave showing extensive cGCT-like tumor but with microscopic elements of SCC in situ and positivity for cytokeratin 5/6 in the malignant spindle cells and SCC. The second case involved a 32-year-old man with a pedunculated penile mass removed by shave biopsy, displaying malignant cytology resembling cGCT, focal staining for cytokeratin AE1/AE3 and p63, and CD68 highlighting the osteoclast-like giant cells. Molecular analysis revealed CDKN2A, TP53, and TERT. Upon reexcision, case 2 showed focally invasive keratinizing SCC associated with differentiated penile intraepithelial neoplasia and lichen sclerosus. Skin specimens with an exophytic mass histologically resembling cGCT but with malignant cytology should be meticulously evaluated for elements of SCC. Molecular analysis, detecting mutations like H3F3 or HMGA2-NCOR2 fusion, can aid in distinguishing cutaneous sarcomatoid squamous cell carcinoma from GCT bone or GCT soft tissue.
Pseudolymphomatous Cutaneous Angiosarcoma Presenting With Persistent Firm Facial Edema in a Patient With Systemic Sclerosis
Authors: Méndez-Flores Silvia , Saeb-Lima Marcela , Fragoso-Loyo Hilda Esther
Published: June 2024

Pseudolymphomatous cutaneous angiosarcoma (cAS) is a rare subtype characterized by a prominent lymphocytic infiltrate, posing diagnostic challenges due to its resemblance to lymphoid neoplastic processes. We present a novel case highlighting the clinical and histopathological features, notably its association with persistent firm facial edema in a patient with systemic sclerosis (SSc). A 47-year-old woman with a 21-year history of SSc presented with firm palpebral edema evolving to involve the entire face and cervical region over six months. Diagnostic imaging revealed inflammatory changes in orbital regions, supradiaphragmatic lymphadenopathies, and lytic lesions. Skin biopsy demonstrated a diffuse neoplasm with vascular channels and solid areas, accompanied by dense lymphocytic proliferation. Pseudolymphomatous cutaneous angiosarcoma, a rare malignant neoplasm, exhibits variable clinical presentations and rapid progression. Histologically, it manifests as irregularly shaped vascular channels lined by prominent endothelial cells. Immunohistochemistry, particularly markers such as v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG), aids in diagnosis. Notably, this case marks the first presentation of cAS with persistent facial edema in SSc, highlighting the association between SSc and cancer risk. This case underscores the diagnostic challenges posed by cAS and emphasizes the importance of early detection for optimal patient outcomes. Further understanding of its association with autoimmune disorders such as SSc is crucial for comprehensive management strategies.
Navigating Diagnostic and Therapeutic Challenges in Primary Cutaneous Gamma/Delta T-Cell Lymphoma: A Case Study of Fatal Outcomes Within Two Months
Authors: Shaker Nada , Blankenship Heath , Masatkar Vaishali , Niu Shuo , Sangueza Omar P.
Published: June 2024

Primary cutaneous gamma/delta T-cell lymphoma (PCGD-TCL) is a rare yet highly aggressive subtype of primary cutaneous lymphoma. Characterized by its challenging diagnosis and poor prognosis, PCGD-TCL presents unique clinical and histopathological features that distinguish it from other primary cutaneous lymphoma subtypes. Here, we report the case of a 75-year-old man who initially presented with multiple erythematous indurated plaques over his back and bilateral lower extremities. The initial biopsy suggested primary cutaneous T-cell lymphoma (PCTCL) with a CD30-negative phenotype. However, within a 2-month interval, the disease progressed rapidly, manifesting as extensive skin involvement across the chest and upper extremities. A repeat skin biopsy was performed, revealing dermal atypical lymphocytes without epidermotropism. Immunohistochemical analysis demonstrated positivity for CD3, CD5, and CD4, as well as T-cell receptor delta (TCR delta) expression, along with the loss of CD8 and CD30 expression. These findings were consistent with a diagnosis of PCGD-TCL. Despite therapeutic interventions, including systemic treatments, the patient's condition deteriorated rapidly, ultimately leading to his demise within a month of receiving the PCGD-TCL diagnosis. This case highlights the diagnostic complexities associated with PCGD-TCL, emphasizing the importance of careful histopathological examination and immunophenotypic characterization. Given its aggressive nature and propensity for rapid dissemination, early recognition of PCGD-TCL is paramount for initiating appropriate therapeutic interventions. However, effective treatment options for PCGD-TCL remain limited, and the disease typically carries an unfavorable prognosis. Further research is needed to elucidate the underlying molecular mechanisms driving the pathogenesis of PCGD-TCL, to identify novel therapeutic targets, and to improve patient outcomes. In addition, increased awareness among clinicians and pathologists regarding the clinical presentation and diagnostic criteria of PCGD-TCL is crucial for facilitating timely diagnosis and management of this challenging malignancy.
Superficial Atypical Lipomatous Tumor With Pleomorphic Features: Case Report and Discussion of the Literature
Authors: Adeuyan Oluwaseyi , Gordon Emily R. , Lapolla Brigit A. , Schreidah Celine M. , Jobanputra Vaidehi , Gru Alejandro A. , Geskin Larisa J.
Published: June 2024

Among liposarcomas, well-differentiated liposarcoma and dedifferentiated liposarcoma are the most common. The majority of these tumors are found in deep retroperitoneum or extremities. When found outside the retroperitoneum, these adipose-derived tumors are known as atypical lipomatous tumors (ALT). Superficial ALT are particularly rare; thus, little is known about their clinical presentation, genomic status, and management. Here, we present the case of a 54-year-old man with an intermittently bothersome, slowly growing mass on his left upper back for over 2 years, which was incidentally diagnosed as ALT. This patient's ALT, however, showed a profound degree of pleomorphism with MDM2 and control centromere 12 (CEP12) coamplification and negative CD34 and S100 and RB1 expression, unlike most other ALT described in the literature. This case report details the diagnostic workup and histopathological findings for adipose tumors and summarizes the different subtypes, including atypical spindle cell/pleomorphic lipomatous tumor, pleomorphic liposarcoma, and spindle cell/pleomorphic lipoma, with brief discussion on management.
Schwannian and Perineuriomatous Differentiation in a Series of Giant Congenital Melanocytic Nevi
Authors: Kletskaya Irina , Belousova Irena , Makarova Olga , Narbutov Anton , Oganesyan Raisa , Donati Michele , Říčař Jan , Salgado Claudia M. , Reyes-Múgica Miguel , Kazakov Dmitry V.
Published: June 2024

Close relationship between melanocytes and neural cells is accepted to reflect their common derivation from the neural crest and tumors combining both elements. We present a series of 10 patients with giant congenital melanocytic nevi (CMN) in which a secondary proliferation (11 lesions) with schwannian and/or perineuriomatous differentiation developed in the course of the disease. The age of the patients (4 male and 6 female) at the time of surgery and histological assessment varied from 3 months to 57 years. Histopathologically, the following subgroups were delineated: (1) nodular/tumoriform “neurotization” in CMN, (2) diffuse neurofibroma–like proliferation within CMN, (3) plexiform neurofibroma–like proliferation within CMN, and (4) diffuse perineuriomatous (hybrid schwannomatous–perineuriomatous) differentiation in CMN. We review the pertinent literature, including the role of recently identified Schwann cell precursors which are believed to represent the nerve-associated state of neural crest-like cells that persists into later developmental stages.
Primary Cutaneous Cryptococcosis in an Elderly Patient: A Case Report and Review of Literature
Authors: Zhang Yuyan , Jiang Faxing , Zhang Siping , Liu Jinli
Published: June 2024

This article reports an elderly male patient with nodules and ulcers on the face and behind the left ear after trauma. Primary cutaneous cryptococcosis was confirmed using pathological biopsy, special staining, tissue culture, and fungal sequencing. The patient received a therapeutic intervention involving the administration of the antifungal agent itraconazole. Substantial amelioration of cutaneous manifestations was observed after a 3-month course of treatment. After an elapsed interval, the patient was diagnosed with esophageal tumor. Moreover, the literature on 33 patients with primary cutaneous cryptococcosis published in the past 10 years was also reviewed.
Coma Blister After Trazodone Misuse: A Case Report
Authors: Yang Seanna , Chen Vivien , Bitar Carole
Published: June 2024

Coma blisters are epidermal and subepidermal bullous lesions that can arise throughout the body after a prolonged impairment of consciousness. Coma blister-like lesions have been well-documented in adults after barbiturate-induced intoxication. More recently, other drugs and substances have been associated with the development of these bullae, which has broadened the scope of medications that put patients at risk of developing coma blister-like lesions. We present a unique case of a noncomatose patient who developed coma blister-like lesions after trazodone misuse. This case illustrates the need to further investigate the mechanism behind drug-induced coma bullae-like lesions so that clinicians can better identify and discontinue drugs that precipitate such lesions.
Three-dimensional Hemifacial Microsomia Classification with New Subtypes Based on the Pruzansky and Kaban Classification
Authors: Shibazaki-Yorozuya Reiko , Yamada Akira , Sasaki Ryo , Watanabe Yorikatsu
Published: June 2024

Background:

Various classifications of hemifacial microsomia (HFM) have been described previously. Although some of these classifications are used widely, others use external outlines of reference organs, even in three-dimensional (3D) images. The purpose of this study was to investigate the 3D characteristics of the mandibular condyle in HFM and to update the Pruzansky and Kaban classification as a 3D classification.

Methods:

Fifty-three patients with HFM were classified according to the Pruzansky and Kaban classification (type I, IIA, IIB, and III) using computed tomographic scan images. 3D images of the mandible were isolated, and the 3D characteristics were observed; furthermore, the angle of inclination of the mandibular condyle was measured in 3D.

Results:

Subtypes of retroflexed mandibular condyle in 3D were observed in the Pruzansky and Kaban classification type IIA and IIB, termed as type IIAβ (33.3% in type IIA) and type IIBβ (100% in type IIB). Although some differences were observed in the inclination of the mandibular condyle between the control and the affected sides in type I and IIAα, multiple differences were observed in type IIAβ and IIBβ.

Conclusions:

To the best of our knowledge, this is the first report that identified the retroflexed mandibular condyle as subtypes type IIAβ and IIBβ. Notably, this could not be identified in the two-dimensional images (lateral cephalogram) yet. We proposed to update the Pruzansky and Kaban classification as a 3D classification with a new 3D subtype. The angle of the retroflexed mandibular condyle may predict mandibular growth in HFM.
Incidental Diagnosis of Four Lid Orbital Lymphoma during a Blepharoplasty
Authors: Anderson Daniella L. , Gruizinga Brandt A. , Dean Hannah C. , Hassan Adam S.
Published: June 2024

Chronic lymphocytic leukemia is characterized by the accumulation of mature CD5-positive B-cells in the lymphoid organs.1 Extranodal involvement occurs in up to 10% of cases and can arise in various tissues, including the orbit. Less than 400 cases of orbital lymphoma are diagnosed per year in the United States, typically manifesting as a form of B-cell non-Hodgkin lymphoma, with extranodal marginal zone B-cell lymphoma being the most common subtype. Orbital lymphoma typically presents with proptosis and a palpable mass; however, patients may also have a relatively benign examination. Here, we present a 76-year-old man with symmetric dermatochalasis and marked fat prolapse of all four lids, who was incidentally diagnosed with secondary orbital lymphoma in all four eyelids during a cosmetic four lid blepharoplasty. His history was significant for RAI Stage 0 chronic lymphocytic leukemia diagnosed 15 years before consultation. Orbital lymphoma presenting as orbital fat prolapse has only been reported a few times in the literature. To our knowledge, this is the first case of secondary orbital lymphoma in all four eyelids found incidentally during an aesthetic four lid blepharoplasty.
A Shaped Pectoralis Major Muscle Flap under Indocyanine Green Fluorescence Angiography for Sternal Wound Infection
Authors: Sato Hideyoshi , Nakai Yosuke , Suda Hisao , Tsunekawa Yukiyo , Koyama Chisato , Fujioka Urara , Toriyama Kazuhiro
Published: June 2024

The treatment of a sternal wound infection is challenging because it requires radical debridement and reconstruction with a well-vascularized flap. The defects after debridement are three-dimensionally complex, especially if synthetic grafts are involved. Although the pectoralis major muscle (PMM) flap is useful for reconstruction, it is difficult to fill up the complex dead space surrounding the vascular prosthesis when using a conventional PMM flap. Herein, we describe a new technique of splitting and shaping the PMM flap to fit the complex defect. Intraoperative indocyanine green fluorescence angiography was used to assess dynamic blood flow of the PMM supplied by internal mammary artery perforators. This technique allows the PMM flap to be split and shaped to securely fit the dead space, which may improve the healing rate.
Enhanced Recovery after Surgery Protocol Decreases Length of Stay and Postoperative Narcotic Use in Tissue Expander-based Breast Reconstruction
Authors: Taylor Jeremiah M. , Moman Precious D. , Chevalier Jose M. , Tseng Charles Y. , Festekjian Jaco H. , Delong Michael R.
Published: June 2024

Background:

Enhanced recovery after surgery (ERAS) protocols have demonstrated success in reducing hospital stay and opioid consumption, but are less well studied in patients undergoing tissue expander-based breast reconstruction (TEBR). This study evaluates the effectiveness of an ERAS postoperative protocol for TEBR at a high-volume center.

Methods:

All patients undergoing immediate tissue expander reconstruction after the introduction of ERAS were prospectively included from April 2019 to June 2023. An equivalent number of similar patients were retrospectively reviewed before this date as the non-ERAS control. Data included demographics, operative details, postoperative length of stay, inpatient and discharge narcotic quantities, inpatient pain assessments, postoperative radiation, and complications within 90 days.

Results:

There were 201 patients in each cohort with statistically similar demographics. Patients in the ERAS cohort were more likely to undergo prepectoral reconstruction (83.1% versus 4.5%, P < 0.001), be discharged by day 1 (96.5% versus 70.2%, P < 0.001) and consume lower inpatient milligram morphine equivalent (MME) median (79.8 versus 151.8, P < 0.001). Seroma rates (17.4% versus 3.5%, P < 0.001) and hematoma incidence (4.5% versus 0%, P = 0.004) were higher in the ERAS cohort. Adjusting for implant location, ERAS was associated with a 60.7 MME reduction (β=-60.7, P < 0.001) and a shorter inpatient duration by 0.4 days (β =-0.4, P < 0.001). Additionally, prepectoral reconstruction significantly decreased MME (β=-30.9, P = 0.015) and was the sole predictor of seroma development (odds ratio = 5.2, P = 0.009).

Conclusions:

ERAS protocols significantly reduce opioid use and hospital stay after TEBR.
Superficial Thoracic Artery Perforator Flap for Volume Replacement Oncoplastic Breast-conserving Surgery
Authors: Hayakawa Masashi , Nakao Junichi , Tadokoro Yukiko , Nakamura Shogo , Suzuki Shinya , Matsubara Ken , Mori Hiroaki , Araki Jun , Nishimura Seiichiro , Yasunaga Yoshichika
Published: June 2024

Lateral chest wall perforator flaps, such as the lateral intercostal artery perforator flap, lateral thoracic artery perforator flap, and thoracodorsal artery perforator flap, have been used for volume replacement oncoplastic breast-conserving surgery (VR-OPBCS) in the lateral and central breast. However, there are cases in which these perforators are missing or too thin, making it difficult to raise a flap for partial breast reconstruction. A 58-year-old woman underwent VR-OPBCS for breast cancer in the lower quadrant of the right breast. Preoperative imaging studies did not identify lateral thoracic artery perforator or thoracodorsal artery perforator but identified a well-developed superficial thoracic artery perforator (STAP). A flap based on the STAP was dissected, and partial breast reconstruction was performed. The flap survived with no complications. No deformity of the lower breast or displacement of the nipple–areola complex was observed 8 months after the completion of postoperative radiotherapy. The STAP flap can be used as an alternative to VR-OPBCS when other lateral chest wall perforator flaps are unavailable.
Identification of fluid overload in critically ill children: fluid status, the missing vital sign
Authors: Starr Michelle C. , Arrowood Haley , Weston Eliza , Chmielewski Jennifer , Hopwood Andrew , Liberio Brianna , Selewski David T. , Soranno Danielle E.
Published: June 2024

Fluid overload, defined as a state of pathologic fluid excess or positive fluid balance, is increasingly recognized as a deleterious state in critically ill infants and children. Fluid overload is common, and mounting evidence shows that it is associated with increased mortality, organ dysfunction, and prolonged need for mechanical ventilation. Despite studies showing adverse outcomes associated with fluid overload, awareness of fluid overload remains limited, especially in small children and infants. Fluid overload as a biomarker and vital sign in the clinical setting has also not been routinely adopted despite its link with morbidity and mortality, and it remains underrecognized by providers. In this review, we first discuss the definition of fluid balance and fluid overload, then briefly review existing data on associations of fluid overload with outcomes in critically ill infants and children. We then consider existing and new data on recognition of fluid overload in critically ill children and infants before closing with the need for better awareness of fluid overload, and a discussion of future research directions and gaps in the field.
Measuring Access to Mental Health Services Among Primary Care Patients
Authors: Hargraves J. Lee , Cosenza Carol , Cleary Paul D.
Published: June 2024

Background:

The lifetime risk of mental health disorders is almost 50% and, in any year, about 25% of the population have a psychiatric disorder. Many of those people are cared for in primary care settings.

Research Objective:

Measure access to mental health services, such as getting counselling or prescription mental health medications, using new patient survey questions that can be added to Consumer Assessment of Healthcare Providers and Systems (CAHPS) surveys.

Study Design:

Surveys were conducted with a stratified probability sample of patients receiving primary care services in a single state in 2018–2019. Medicaid and privately insured patients were surveyed by mail or telephone, respectively.

Results:

Approximately 14% of sampled patients responded to a survey. More than 10% of privately insured respondents and about 20% of Medicaid respondents got or tried to get appointments for mental health care. About 15% of privately insured respondents and 11% of Medicaid respondents reported problems getting appointments with counselors. Only 8%–9% of respondents seeking mental health medicines reported problems getting appointments for prescriptions. A composite measure combining access to counselors and prescribers of mental health medicines evidenced adequate internal consistency reliability. Group level reliability estimates were low.

Conclusions:

Many respondents got or tried to get mental health services and a substantial number reported problems getting appointments or getting mental health prescriptions. The tested questions can be combined into an Access to Mental Health Care measure, which can be included in patient experience surveys for ambulatory care to monitor access to behavioral health care.
Current and future microbiome-based therapies in inflammatory bowel disease
Authors: Montrose Jonathan A. , Kurada Satya , Fischer Monika
Published: June 2024

Purpose of review

The role of the microbiome and dysbiosis is increasingly recognized in the pathogenesis of inflammatory bowel disease (IBD). Intestinal microbiota transplant (IMT), previously termed fecal microbiota transplant has demonstrated efficacy in restoring a healthy microbiome and promoting gut health in recurrent Clostridioides difficile infection. Several randomized trials (RCTs) highlighted IMT's potential in treating ulcerative colitis, while smaller studies reported on its application in managing Crohn's disease and pouchitis.

Recent findings

This review delves into the current understanding of dysbiosis in IBD, highlighting the distinctions in the microbiota of patients with IBD compared to healthy controls. It explores the mechanisms by which IMT can restore a healthy microbiome and provides a focused analysis of recent RCTs using IMT for inducing and maintaining remission in IBD. Lastly, we discuss the current knowledge gaps that limit its widespread use.

The body of evidence supporting the use of IMT in IBD is growing. The lack of a standardized protocol impedes its application beyond clinical trials. Further research is needed to identify patient profile and disease phenotypes that benefit from IMT, to delineate key donor characteristics, optimize the delivery route, dosage, and frequency.
Pancreatic and cardiometabolic complications of severe hypertriglyceridaemia
Authors: Bashir Bilal , Ferdousi Maryam , Durrington Paul , Soran Handrean
Published: June 2024

Purpose of review

This review endeavours to explore the aetiopathogenesis and impact of severe hypertriglyceridemia (SHTG) and chylomicronaemia on cardiovascular, and pancreatic complications and summarizes the novel pharmacological options for management.

Recent findings

SHTG, although rare, presents significant diagnostic and therapeutic challenges. Familial chylomicronaemia syndrome (FCS), is the rare monogenic form of SHTG, associated with increased acute pancreatitis (AP) risk, whereas relatively common multifactorial chylomicronaemia syndrome (MCS) leans more towards cardiovascular complications. Despite the introduction and validation of the FCS Score, FCS continues to be underdiagnosed and diagnosis is often delayed. Longitudinal data on disease progression remains scant. SHTG-induced AP remains a life-threatening concern, with conservative treatment as the cornerstone while blood purification techniques offer limited additional benefit. Conventional lipid-lowering medications exhibit minimal efficacy, underscoring the growing interest in novel therapeutic avenues, that is, antisense oligonucleotides (ASO) and short interfering RNA (siRNA) targeting apolipoprotein C3 (ApoC3) and angiopoietin-like protein 3 and/or 8 (ANGPTL3/8).

Despite advancements in understanding the genetic basis and pathogenesis of SHTG, diagnostic and therapeutic challenges persist. The rarity of FCS and the heterogenous phenotype of MCS underscore the need for the development of predictive models for complications and tailored personalized treatment strategies. The establishment of national and international registries is advocated to augment disease comprehension and identify high-risk individuals.
Climate change and resilience for antimicrobial stewardship and infection prevention
Authors: Abeles Shira R. , Kline Ahnika , Lee Pamela
Published: June 2024

Purpose of review

This review covers recent research regarding the challenges posed by climate change within the areas of antimicrobial stewardship and infection prevention, and ways to build resiliency in these fields.

Recent findings

Infectious disease patterns are changing as microbes adapt to climate change and changing environmental factors. Capacity for testing and treating infectious diseases is challenged by newly emerging diseases, which exacerbate challenges to antimicrobial stewardship and infection prevention.

Antimicrobial resistance is accelerated due to environmental factors including air pollution, plastic pollution, and chemicals used in food systems, which are all impacted by climate change.

Climate change places infection prevention practices at risk in many ways including from major weather events, increased risk of epidemics, and societal disruptions causing conditions that can overwhelm health systems. Researchers are building resilience by advancing rapid diagnostics and disease modeling, and identifying highly reliable versus low efficiency interventions.

Climate change and associated major weather and socioeconomic events will place significant strain on healthcare facilities. Work being done to advance rapid diagnostics, build supply chain resilience, improve predictive disease modeling and surveillance, and identify high reliability versus low yield interventions will help build resiliency in antimicrobial stewardship and infection prevention for escalating challenges due to climate change.
Genomic Landscape of Adenocarcinomas Across the Gastroesophageal Junction
Authors: Nakauchi Masaya , Walch Henry S. , Nussenzweig Samuel , Carr Rebecca , Vos Elvira , Berger Michael F. , Schultz Nikolaus , Janjigian Yelena , Wu Abraham , Tang Laura , Shah Pari , Jones David R. , Coit Dan , Strong Vivian E. , Molena Daniela , Sihag Smita
Published: June 2024

Objective:

To investigate how the Siewert classification of gastroesophageal junction adenocarcinomas correlates with genomic profiles.

Summary/Background Data:

Current staging and treatment guidelines recommend that tumors with an epicenter less than 2 cm into the gastric cardia be treated as esophageal cancers, while tumors with epicenter greater than 2 cm into the cardia be staged and treated as gastric cancers. To date, however, few studies have compared the genomic profiles of the 3 Siewert classification groups to validate this distinction.

Methods:

Using targeted tumor sequencing data on patients with adenocarcinoma of the gastroesophageal junction previously treated with surgery at our institution, we compared genomic features across Siewert classification groups.

Results:

A total of 350 patients were included: 121 had Siewert type I, 170 type II, and 59 type III. Comparisons by Siewert location revealed that Siewert type I and II were primarily characterized as the chromosomal instability (CIN) molecular subtype and displayed Barrett’s metaplasia and p53 and cell cycle pathway dysregulation. Siewert type III tumors, by contrast, were more heterogeneous, including higher proportions of microsatellite instability (MSI) and genomically stable (GS) tumors and more frequently displayed ARID1A and somatic CDH1 alterations, signet ring cell features, and poor differentiation. Overall, Siewert type I and II tumors demonstrated greater genomic overlap with lower esophageal tumors, while Siewert type III tumors shared genomic features with gastric tumors.

Conclusions:

Overall, our results support recent updates in treatment and staging guidelines. Ultimately, however, molecular rather than anatomic classification may prove more valuable in determining staging, treatment, and prognosis.
Graft Inflow Modulation by Splenic Artery Ligation for Portal Hyper Perfusion does not Decrease Rates of Early Allograft Dysfunction in Adult Live Donor Liver Transplantation
Authors: Pamecha Viniyendra , Tharun Gattu , Patil Nilesh , Mohapatra Nihar , Kumar Anubhav , Thapar Shalini , Sindwani Gaurav , Dhingra Udit , Yadav Anil
Published: June 2024

Objective:

The primary objective was to compare the rates of early allograft dysfunction (EAD) in patients undergoing elective adult live donor liver transplantation (ALDLT) with and without graft portal inflow modulation (GIM) for portal hyper-perfusion. The secondary objectives were to compare time to normalization of bilirubin and International Normalized Ratio (INR), day 14 ascitic output more than 1liter, small-for-size syndrome (SFSS), intensive care unit / high dependency unit and total hospital stay, and 90 day morbidity and mortality.

Background:

GIM can prevent EAD in ALDLT patients with portal hyper-perfusion.

Methods:

A single-center randomized trial with and without GIM for portal hyper-perfusion by splenic artery ligation (SAL) in ALDLT was performed. After reperfusion, patients with portal venous pressure (PVP)>15 mm Hg with a gradient (PVP - central venous pressure) of ≥ 7 mm Hg and/or portal venous flow (PVF)>250 mL/min/100 grams of liver were randomized into two groups: GIM and No GIM.

Results:

75 of 209 patients satisfied the inclusion criteria, and 38 underwent GIM. Baseline PVF and PVP were comparable between the GIM and no GIM groups. SAL significantly reduced the PVF and PVP (P<0.001). There were no differences in the primary and secondary outcomes between the two groups. In the subgroup analysis, with a Graft to Recipient Weight Ratio (GRWR)≤0.8, there were no significant differences in the primary and secondary outcomes.

Conclusion:

SAL significantly decreased PVP and PVF, but did not decrease rates of EAD in adult LDLT.
The Effect of Intersectionality on Attrition among US General Surgery Trainees
Authors: Mesiti Andrea , Johnson Josh , Brouwer Julianna , Shui Amy M. , Yeo Heather , Sosa Julie Ann
Published: June 2024

Objective:

To examine the association between intersectionality of race, ethnicity, and sex on retention of U.S. general surgery residents.

Summary Background Data:

There are limited data on the role that intersectionality plays on the US general surgery resident experience.

Methods:

Analysis was performed using Association of American Medical Colleges (AAMC) data for general surgery residents who started their training between 2005-2015 (followed through completion). Regression analyses were used to assess demographic associations with time to attrition or successful completion of residency training. Associations between faculty and resident demographics were assessed.

Results:

25,029 residents were included. Over the decade-long study period, the number of underrepresented in medicine (UIM) residents as a percentage of all residents remained similar from 17% to 19% (P=0.24). The percent of UIM males starting training in 2005 was 11% and 12% in 2015 (P-value=0.38). UIM females comprised 5.5% of trainees in 2005 and increased to 6.9% (P-value=0.003) in 2015; and female non-UIM residents increased from 23 to 28% (P-value<0.001). The overall rate of resident attrition was 15%. UIM females had the highest yearly attrition rate at 21% compared to non-UIM males at 13% (HR 1.7, P<0.001). UIM females were more likely to leave residency compared to UIM males (HR: 1.5; P<0.001). The percent of UIM faculty was positively correlated with percent of UIM residents (r=0.64, P<0.001).

Conclusions:

Increasing intersectionality is positively associated with attrition during surgery residency. The diversity of faculty appears to be associated with resident diversity.