bluuebunny/crossref_metadata_2025 huggingface dataset:
Human papillomavirus, tobacco, and poor oral hygiene can act synergetically, modulate the expression of the nuclear factor kappa B signaling pathway for the development and progression of head and neck cancer in the Pakistani population
Authors: Sarwar Sumaira , Mulla Mushir , Mulla Munaz , Tanveer Rida , Sabir Maimoona , Sultan Aneesa , Malik Salman A.
Published: July 2022

Background:

Head and neck cancers (HNCs) are a heterogeneous group of tumors that progress owing to varied enviromental and genetic risk factors. Viral infections are threatening and adept at altering the expression of cellular transcription factors such as nuclear factor kappa B (NF-κB) and deregulation of other cellular proteins like NF kappa B inhibitor alpha (IκBα). The present study was conducted to detect high-risk genotypes of human papillomavirus (HPV) and protein expression of NF-κB signaling pathway in HNC patients with HPV infection.

Methods:

For HPV detection, genomic DNA from 152 HNC tumors was extracted formalin-fixed paraffin-embedded tissue DNA kit. For genotyping, polymerase chain reaction (PCR) using a general primer, HPV type-specific primers and agarose gel electrophoresis were performed. Immunohistochemistry (IHC) was also performed on 4-μm thick tissue sections using HPV E6 monoclonal antibody. Protein expression analysis of NF-κB signaling pathway including p50, p65, and IκBα was performed using IHC.

Results:

PCR analysis showed that 24.3% (37/152) of HNC cases were HPV positive. Among HPV positive, 86.5% (32/37) were tobacco users, while among HPV negative, 66.9% (77/115) were tobacco users. A significant association of HPV positivity and tobacco user was observed by univariate analysis [P 
< 0.01; odds ratio (OR): 0.310, 95% confidence interval (CI): 0.110 to 0.870]. More HPV positive patients were with poor oral hygiene (78.3%) when compared with patients with good oral hygiene (21.6%) [P < 0.03, OR: 2.440, 95% CI: 1.650 to 3.600]. The results of the logistic regression analysis showed that age, tobacco use and oral hygiene are significant predictors (P < 0.02). PCR and IHC staining results confirmed that HPV16 was predominant among HNC cases (64.8%) when compared with HPV18 (35.2%). Expression of NF-κB proteins (p50, p65, and IκBα inhibitor) were also observed in HPV and non-HPV infected HNC tissues. IHC expression of p50, and p65 showed nuclear staining, while IκBα inhibitor showed cytoplasmic staining. Protein expression in HPV cases was higher as compared to HPV naive cases (P < 0.05).

Conclusions:

From the study, it can be established that the use of tobacco, oral hygiene, and HPV infection may be synergistically involved in modulating the expression of NF-κB signaling pathway for the development and progression of HNC in the Pakistani population.
Do methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 polymorphisms modify changes in intelligence of school-age children in areas of endemic fluorosis?
Authors: Feng Zichen , An Ning , Yu Fangfang , Ma Jun , Li Na , Du Yuhui , Guo Meng , Xu Kaihong , Hou Xiangbo , Li Zhiyuan , Zhou Guoyu , Ba Yue
Published: July 2022

Background:

Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 (MTHFD1) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with children's intelligence changes in endemic fluorosis areas has been rarely explored.

Methods:

A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April to May in 2017. A total of 694 children aged 8 to 12 years were included in the study with the recruitment by the cluster sampling method. Urinary fluoride (UF) and urinary creatinine were separately determined using the fluoride ion-selective electrode and creatinine assay kit. Children were classified as the high fluoride group and control group according to the median of urinary creatinine-adjusted urinary fluoride (UFCr) level. Four loci of MTHFD1 were genotyped, and the Combined Raven's Test was used to evaluate children's intelligence quotient (IQ). Generalized linear model and multinomial logistic regression model were performed to analyze the associations between children's UFCr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence.

Results:

In the high fluoride group, children's IQ scores decreased by 2.502 when the UFCr level increased by 1.0 mg/L (β = −2.502, 95% confidence interval [CI]:−4.411, −0.593), and the possibility for having “excellent” intelligence decreased by 46.3% (odds ratio = 0.537, 95% CI: 0.290, 0.994). Children with the GG genotype showed increased IQ scores than those with the AA genotype of rs11627387 locus in the high fluoride group (P 
< 0.05). Interactions between fluoride exposure and MTHFD1 polymorphisms on intelligence were observed (Pinteraction < 0.05).

Conclusion:

Our findings suggest that excessive fluoride exposure may have adverse effects on children's intelligence, and changes in children's intelligence may be associated with the interaction between fluoride and MTHFD1 polymorphisms.
Tumor microenvironment in lung cancer-derived brain metastasis
Authors: Liu Wenwen , Powell Charles A , Wang Qi
Published: July 2022

Brain metastasis (BM) is the leading cause of mortality in lung cancer patients. The process of BM (from initial primary tumor development, migration and intravasation, dissemination and survival in the bloodstream, extravasation, to colonization and growth to metastases) is a complex process for which few tumor cells complete the entire process. Recent research on BM of lung cancer has recently stressed the essential role of tumor microenvironment (TME) in assisting tumor cells in the completion of each BM step. This review summarizes recent studies regarding the effects of TME on tumor cells in the entire process of BM derived from lung cancer. The identification of vulnerable targets in the TME and their prospects to provide novel therapeutic opportunities are also discussed.
A Systematic Review of Conversion to Resectability in Unresectable Metastatic Colorectal Cancer Chemotherapy Trials
Authors: Chrabaszcz Sarah , Rajeev Rahul , Witmer Hunter D.D. , Dhiman Ankit , Klooster Brittany , Gamblin T. Clark , Banerjee Anjishnu , Johnston Fabian M. , Turaga Kiran K.
Published: July 2022

Objectives:

Metastasectomy in patients with metastatic colorectal cancer (mCRC) confers a significant survival benefit. We hypothesized that conversion to resectability (C2R) correlates with superior overall survival (OS) in patients with unresectable mCRC.

Methods:

A prospectively registered systematic review (PROSPERO CRD42015024104) of randomized clinical trials published after 2003 was conducted. Exposure of interest was C2R with a primary outcome of OS. Clinical trials were classified based on difference in C2R between study arms (<2%, 2% to 2.9%, ≥3%). Generalized estimating equations were used to measure associations while adjusting for multiple observations from the same trial.

Results:

Of 2902 studies reviewed, 30 satisfied selection criteria (n=13,618 patients). Median C2R was 7.3% (interquartile range [IQR]: 5% to 12.9%), with maximum C2R in the FOLFOX/FOLFIRI+cetuximab arm (28.6%). The median difference in C2R between 2 arms of the same study was 2.3% (IQR: 1.3% to 3.4%) with a maximum difference of 15.4% seen in FOLFOX/FOLFIRI+cetuximab versus FOLFOX/FOLFIRI. Median OS for the entire patient cohort was 20.7 months (IQR: 18.9 to 22.7 mo), with a between group difference of 1.3 months (IQR: −1.2 to 3.6 mo). The median survival difference between the 2 study arms with <2% C2R difference was 0.8 months versus 1.6 months with ≥3% C2R rates . Increasing C2R had an incremental dose-effect response on OS (P=0.021), and higher response rates correlated with C2R rates (P=0.003).

Conclusions:

C2R occurs infrequently and variably in clinical trials enrolling patients with unresectable mCRC. Prioritization of chemotherapeutic agents that enhance C2R might improve OS of patients.
Factors Associated With Participation Rate and Predictive of Improvement After Cardiac Rehabilitation in Patients With Heart Failure
Authors: Wu Li-Hua , Wang Chao-Hung , Liu Min-Hui , Hsu Chih-Chin , Yuan Pei-Hsun , Fu Tieh-Cheng
Published: July 2022

Purpose:

Patients with heart failure (HF) are often limited in their ability to perform exercise. Cardiac rehabilitation (CR) improves aerobic capacity and quality of life (QOL) and is recommended for patients with clinically stable HF; however, it is underutilized. The aim of this study was to investigate the factors associated with participation and completion rates and predictive of improvement after phase II CR in patients with HF.

Methods:

Participation and completion rates were calculated for all patients with HF enrolled in a multidisciplinary management program from October 2008 to December 2018. Functional capacity and QOL were estimated. In patients undergoing CR, changes in peak oxygen uptake (V˙ o2peak) were measured.

Results:

Of 662 patients enrolled, 448 (68%) completed the cardiopulmonary exercise test (CPX). Phase II CR was recommended in 411 patients, of whom 291 (71%) participated in CR. Participation was significantly related to sex and the time interval in days between hospital discharge and the CPX. Overall, 171 patients completed 36 sessions of CR (with a completion rate of 59%). During CR, there were 18 (6%) adverse events. Cardiac rehabilitation was associated with improvement in V˙ o2peak from 1153 ± 393 to 1342 ± 470 mL/min (a 16% improvement; P < .001) and in QOL. The independent predictors of increase in V˙ o2peak included sex, age, diabetes mellitus, and entry V˙ o2peak.

Conclusions:

In patients with HF, factors associated with CR participation rate included sex and days between hospital discharge and the CPX. Participation in CR improved V˙ o2peak and QOL. The improvement was related to male sex, younger age, no diabetes mellitus, and higher entry V˙ o2peak.
Contractual considerations in the private equity era
Authors: Patel Veshesh , Nijm Lisa M.
Published: July 2022

Private equity (PE) has grown rapidly in medicine. The reintroduction of PE in ophthalmology has necessitated a greater understanding of the potential contractual relationships with PE firms from both a practice owner and an employee physician perspective. There are contractual obligations that need to be met as PE agreements are designed to ensure clear investment patterns and abide by legal mandates. A practice owner entering into a PE contract needs to consider how the practice is being valued, what their obligations are to the PE entity after the sale has been completed to attain full compensation and understand their new role at the practice. On the other hand, employee ophthalmologists must carefully evaluate the compensation package being offered in terms of the type of equity, vesting of shares, obligations to the PE firm under the agreement such as a noncompete clause, and what occurs under a subsequent sale of the practice. Overall, contractual considerations in the private equity era need to be carefully evaluated in order to ensure the agreement is in the best interest for the clinician, practice, and their patients.
Outcomes on the Utilization of Lipodermoid Skin for Anterior Lamella Reconstruction in Severe Lipodermoids With Eyelid Coloboma: A Case Series
Authors: Islam Meriam , Morrison Danny , Hamada Samer , Katowitz James , Malhotra Raman
Published: July 2022

Two young children with upper lid colobomas and associated lipodermoids underwent eyelid reconstruction using lipodermoid skin as an autograft with good cosmesis. We describe their presentation, surgical management, and clinical progress following reconstruction, demonstrating the suitability of this skin as an adequate graft avoiding the need for further skin graft harvesting in such cases.
Bacterial overgrowth and lactose intolerance: how to best assess
Authors: Ghafoor Adil , Karunaratne Tennekoon , Rao Satish S.C.
Published: July 2022

Purpose of review

To provide an up-to-date review on the clinical assessment of two important gastrointestinal problems with overlapping symptomatology but diverse cause and testing methods. Small intestinal bacterial overgrowth (SIBO) is characterized by the presence of excess bacteria in the small intestine associated with bloating, distention, gas, and diarrhea. Lactose intolerance is caused by lactase enzyme deficiency in the small bowel mucosa leading to lactose malabsorption and symptoms of bloating, gas, and diarrhea.

Recent findings

SIBO is assessed by hydrogen/methane breath test using glucose as a substrate and/or small bowel aspirate and culture but these tests have shortcomings. Consequently, several new diagnostic techniques, including novel capsule technologies and other approaches are being evaluated. Lactose intolerance can be assessed by hydrogen/methane breath test using lactose as a substrate, or small bowel mucosal lactase assay, genetic testing and lactose tolerance test, although the efficacy and practicality of these diagnostic modalities are not equal.

In clinical practice, gas, bloating, distention, pain, and diarrhea are common gastrointestinal symptoms that often remain unexplained when routine gastrointestinal endoscopy, imaging, and stool tests are negative. These patients should be evaluated for SIBO and/or food intolerances including lactose intolerance.
Emerging phenotypes of pulmonary hypertension associated with COPD: a field guide
Authors: García Agustín Roberto , Piccari Lucilla
Published: July 2022

Purpose of review

Pulmonary hypertension (PH) is a common complication of chronic obstructive lung disease (COPD), but clinical presentation is variable and not always ’proportional’ to the severity of the obstructive disease. This review aims to analyze heterogeneity in clinical features of PH-COPD, providing a guide for diagnosis and management according to phenotypes.

Recent findings

Recent works have focused on severe PH in COPD, providing insights into the characteristics of patients with predominantly vascular disease. The recently recognized ’pulmonary vascular phenotype’, characterized by severe PH and mild airflow obstruction with severe hypoxemia, has markedly worse prognosis and may be a candidate for large trials with pulmonary vasodilators. In severe PH, which might be best described by a pulmonary vascular resistance threshold, there may also be a need to distinguish patients with mild COPD (pulmonary vascular phenotype) from those with severe COPD ('Severe COPD-Severe PH’ phenotype).

Correct phenotyping is key to appropriate management of PH associated with COPD. The lack of evidence regarding the use of pulmonary vasodilators in PH-COPD may be due to the existence of previously unrecognized phenotypes with different responses to therapy. This review offers the clinician caring for patients with COPD and PH a phenotype-focused approach to diagnosis and management, aimed at personalized care.
Design, Implementation, and Evolution of the Medicaid Outcomes Distributed Research Network (MODRN)
Authors: Zivin Kara , Allen Lindsay , Barnes Andrew J. , Junker Stefanie , Kim Joo Yeon , Tang Lu , Kennedy Susan , Ahrens Katherine A. , Burns Marguerite , Clark Sarah , Cole Evan , Crane Dushka , Idala David , Lanier Paul , Mohamoud Shamis , Jarlenski Marian , McDuffie Mary Joan , Talbert Jeffery , Gordon Adam J. , Donohue Julie M.
Published: July 2022

Background:

In the US, Medicaid covers over 80 million Americans. Comparing access, quality, and costs across Medicaid programs can provide policymakers with much-needed information. As each Medicaid agency collects its member data, multiple barriers prevent sharing Medicaid data between states. To address this gap, the Medicaid Outcomes Distributed Research Network (MODRN) developed a research network of states to conduct rapid multi-state analyses without sharing individual-level data across states.

Objective:

To describe goals, design, implementation, and evolution of MODRN to inform other research networks.

Methods:

MODRN implemented a distributed research network using a common data model, with each state analyzing its own data; developed standardized measure specifications and statistical software code to conduct analyses; and disseminated findings to state and federal Medicaid policymakers. Based on feedback on Medicaid agency priorities, MODRN first sought to inform Medicaid policy to improve opioid use disorder treatment, particularly medication treatment.

Results:

Since its 2017 inception, MODRN created 21 opioid use disorder quality measures in 13 states. MODRN modified its common data model over time to include additional elements. Initial barriers included harmonizing utilization data from Medicaid billing codes across states and adapting statistical methods to combine state-level results. The network demonstrated its utility and addressed barriers to conducting multi-state analyses of Medicaid administrative data.

Conclusions:

MODRN created a new, scalable, successful model for conducting policy research while complying with federal and state regulations to protect beneficiary health information. Platforms like MODRN may prove useful for emerging health challenges to facilitate evidence-based policymaking in Medicaid programs.
Photodermatoses: what's new
Authors: Scollan Margaret E. , Lauren Christine T.
Published: July 2022

Purpose of review

The purpose of this review is to summarize and highlight the recent literature in photodermatoses. In the past year, there have been many developments in this heterogeneous group of conditions.

Recent findings

This review is divided by photodermatoses type, which include idiopathic photodermatoses, photodermatoses secondary to exogenous agents, photodermatoses secondary to endogenous agents (the porphyrias), and genodermatoses. The idiopathic photodermatoses section focuses on case series and reports highlighting new disease presentations or further disease characterization and new treatment strategies for these disorders. The second section discusses a unique case and has a brief update on photoallergens. Clinical, diagnostic, and treatment updates for porphyrias are discussed in Section 3. For genodermatoses, we discuss complications and neoplastic risk of xeroderma pigmentosum and a few highlights from other rare disorders. Finally, we conclude with a brief overview of photoprotection updates, from assessing sun-damaged skin to the most effective photoprotective agents.

Up-to-date information will help providers identify and manage this rare group of disorders.
Genetics of neuroendocrine prostate cancer: recent progress in genetic understanding is translating into therapeutic opportunities
Authors: Rinott Mizrahi Gal , Williams Isabella , Azad Arun , Lawrentschuk Nathan
Published: July 2022

Purpose of review

Neuroendocrine prostate cancer (NEPC) is a rare histologic subtype of prostate cancer with extremely aggressive clinical behaviour and very limited data regarding treatment options. This review is intended to relay new research advances in the understanding of the genetic and epigenetic aberrations underlying NEPC development and to review new targeted therapeutic options developed based on NEPC genetics.

Recent findings

Multiple genomic alterations and epigenetic regulators have been identified in NEPC development. Among these are amplifications of oncogenic transcriptional factors, changes in expression of cell surface markers and epigenetic alterations. This in turn has facilitated a number of new targeted therapies for NEPC that act via different mechanisms including catalytic inhibitors, immune-modulators and epigenetic modifiers. These targeted therapies are now being studied in different phases of clinical trials with some preliminary results showing efficacy.

NEPC is a highly aggressive malignancy with currently lack of effective treatments. Considerable challenges still remains to improve clinical outcomes in NEPC; however, ongoing trials exploiting novel genetic and epigenetic alterations hold promise for patients suffering from this aggressive disease.
Brief update of the new WHO classification for urothelial carcinoma
Authors: Compérat Eva , Wasinger Gabriel , Oszwald André , Shariat Shahrokh
Published: July 2022

Purpose of review

Six years after the release of the 4th edition of the WHO classification on male and genitourinary tumors in 2016, the upcoming 5th edition will be released in 2022. This review will discuss significant changes in the new WHO classification for urothelial carcinoma.

Recent findings

Substantial progress has been made during the last 6 years, especially in the molecular definition of bladder cancer, but also in treatment approaches. The authors have incorporated these and other changes relating to surgical pathology and made relevant changes to provide a more logical and consistent structure in separating chapters.

As the WHO bluebook is intended to be used worldwide, the authors believe that the impact of these changes will be considerable.
Conceptualization, use, and outcomes associated with empathy and compassion in physical medicine and rehabilitation: a scoping review
Authors: Posa Stephanie , Wasilewski Marina B. , Mercer Stewart W. , Simpson Sharon , Robinson Lawrence R. , Simpson Robert
Published: July 2022

The purpose of this review is to scope the literature on the conceptualization, use, and outcomes associated with empathy and compassion in physical medicine and rehabilitation. Eligible studies included quantitative, qualitative, or mixed-methods research that presented primary data on the conceptualization, use, and outcomes associated with empathy and compassion in physical medicine and rehabilitation. Relevant studies were identified through CINAHL, Cochrane Library, EMBASE, MEDLINE, and PEDRO. Twenty-four studies were included (participant n = 3715): 13 quantitative, six mixed-methods, and five qualitative. In qualitative analysis, empathy and compassion were conceptualized as both intrinsic and exhibitory. Where self-compassion was examined as an intervention for patients, improvements in anxiety, depression, and quality of life were reported. Survey data suggested that when rehabilitation health care providers were perceived to be more empathic, patients reported greater treatment satisfaction, acceptance, adherence, and goal attainment. Individuals receiving and health care providers who deliver rehabilitative care conceptualize empathy and compassion as valuable in physical medicine and rehabilitation settings, with cognitive and behavioural elements described. Health care provider empathy and compassion-based interventions may influence outcomes positively in this context. More research is needed to understand the mechanisms of action of empathy and compassion and effectiveness in physical medicine and rehabilitation settings.
Low to Intermediate (Borderline) Grade Breast Spindle Cell Lesions on Needle Biopsy: Diagnostic Approach and Clinical Management
Authors: Russell Daniel H. , Montgomery Elizabeth A. , Susnik Barbara
Published: July 2022

Spindle cell proliferations of the breast are a heterogeneous group of lesions ranging from benign or reactive lesions to aggressive malignant neoplasms. Diagnosis on core biopsy can be particularly challenging as lesions displaying different lineages associated with variable outcomes share overlapping morphologies (scar vs. fibromatosis-like metaplastic carcinoma) whereas individual entities can exhibit a large variety of appearances (myofibroblastoma). In this review, lesions are grouped into lineage, when possible, including those showing fibroblastic/myofibroblastic differentiation, ranging from entities that require no additional management, such as scar and nodular fasciitis, to those with unpredictable clinical outcomes such as fibromatosis and solitary fibrous tumor or locally aggressive behavior such as dermatofibrosarcoma protuberans. The review of low-grade vascular lesions includes atypical vascular lesion and low-grade angiosarcoma. Also discussed are various adipocytic lesions ranging from lipoma to liposarcoma, and rare smooth muscle and neural entities more commonly encountered in locations outside the breast, such as leiomyoma, neurofibroma, schwannoma, or granular cell tumor. Optimal histological evaluation of these entities merges clinical and radiologic data with morphology and ancillary testing. We present our approach to immunohistochemical and other ancillary testing and highlight issues in pathology correlation with imaging. Recent updates in the management of breast spindle cell lesions are addressed. In a well-sampled lesion with radiographic concordance, the core biopsy diagnosis reliably guides management and we advocate the inclusion of management recommendations in the pathology report. Precise characterization using up to date guidelines is important to identify a subset of patients who may safely avoid unnecessary surgical procedures. A multidisciplinary approach with close collaboration with our clinical colleagues is emphasized.
Early Peritoneal Dialysis and Postoperative Outcomes in Infants After Pediatric Cardiac Surgery: A Systematic Review and Meta-Analysis*
Authors: Namachivayam Siva P. , Law Suvikrom , Millar Johnny , d’Udekem Yves
Published: July 2022

Objective:

Peritoneal dialysis (PD) is used in several cardiac surgical units after cardiac surgery, and early initiation of PD after surgery may have the potential to influence postoperative outcomes. This systematic review and meta-analysis aims to summarize the evidence for the association between early PD after cardiac surgery and postoperative outcomes.

Data Sources:

MEDLINE, Embase, and PubMed from 1981 to November 1, 2021.

Study Selection:

Observational studies and randomized trials reporting on early PD after pediatric cardiac surgery.

Data Extraction:

Random-effects meta-analysis was used to estimate the pooled odds ratios (ORs) and their 95% CIs for postoperative mortality and pooled mean difference (MD) (95% CI) for duration of mechanical ventilation and ICU length of stay.

Data Synthesis:

We identified nine studies from the systematic review, and five were considered suitable for meta-analysis. Early initiation of PD after cardiac surgery was associated with a reduction in postoperative mortality (OR, 0.43 (95% CI, 0.23–0.80); number of estimates = 4). Early commencement of PD shortened duration of mechanical ventilation (MD [95% CI], –1.09 d [–1.86 to −0.33 d]; I
2 = 56.1%; p = 0.06) and intensive care length of stay (MD [95% CI], –2.46 d [–3.57 to –1.35 d]; I
2 = 18.7%; p = 0.30], respectively. All three estimates had broad 95% prediction intervals (crossing null) denoting major heterogeneity between studies and wide range of possible study estimates in similar future studies. Overall, studies reporting on the effects of early PD included only a subset of infants undergoing cardiac surgery (typically high-risk infants), so selection bias may be a major issue in published studies.

Conclusions:

This review suggests that early initiation of PD may be associated with beneficial postoperative outcomes in infants after cardiac surgery. However, these results were based on studies of varying qualities and risk of bias. Early identification of high-risk infants after cardiac surgery is important so that prevention or early mitigation strategies can be applied to this cohort. Future prospective studies in high-risk populations are needed to study the role of early PD in influencing postoperative outcomes.
The Utility of Ultrasound in Evaluation of Traumatic Hallux Valgus: a Case Report
Authors: Fultz Connor , Luetmer Marianne T. , Onishi Kentaro
Published: July 2022

Isolated disruption of the medial collateral ligament (MCL) of the great toe is rare and often misdiagnosed as turf toe. It may progress to acquired traumatic hallux valgus (THV), often requiring operative intervention, and a longer return to play. This case of a grade II MCL injury highlights the importance of a thorough physical examination and consideration of the mechanism of injury. It demonstrates the utility of diagnostic musculoskeletal ultrasound in establishing a specific diagnosis upon initial patient presentation with great toe pain. It is an example of the use of ultrasound in guiding treatment and monitoring interval healing. In this case, differentiation of the injury from the classic ‘turf toe’ led to proper stabilization with a toe spacer and activity modification, thus preventing progression of THV and leading to successful nonoperative treatment with full return to sport.

LEVEL OF EVIDENCE

Level V
Lung and Plasma Metabolome in HIV-Associated Obstructive Lung Disease
Authors: Wendt Chris H. , Samorodnitsky Sarah , Lock Eric F. , Kruk Monica , Morris Alison , Leung Janice M. , Kunisaki Ken M. , Griffin Timothy J.
Published: July 2022

Background:

HIV is a risk factor for obstructive lung disease (OLD), independent of smoking. We used mass spectrometry (MS) approaches to identify metabolomic biomarkers that inform mechanistic pathogenesis of OLD in persons with HIV (PWH).

Methods:

We obtained bronchoalveolar lavage fluid (BALF) samples from 52 PWH, in case:control (+OLD/−OLD) pairs matched on age, smoking status, and antiretroviral treatment. Four hundred nine metabolites from 8 families were measured on BALF and plasma samples using a MS-based Biocrates platform. After filtering metabolites with a high proportion of missing values and values below the level of detection, we performed univariate testing using pairedttests followed by false discovery rate corrections. We used distance-weighted discrimination (DWD) to test for an overall difference in the metabolite profile between cases and controls.

Results:

After filtering, there were 252 BALF metabolites for analysis from 8 metabolite families. DWD testing found that collectively, BALF metabolites differentiated cases from controls, whereas plasma metabolites did not. In BALF samples, we identified 3 metabolites that correlated with OLD at the false discovery rate of 10%; all were in the phosphatidylcholine family. We identified additional BALF metabolites when analyzing lung function as a continuous variable, and these included acylcarnitines, triglycerides, and a cholesterol ester.

Conclusions:

Collectively, BALF metabolites differentiate PWH with and without OLD. These included several BALF lipid metabolites. These findings were limited to BALF and were not found in plasma from the same individuals. Phosphatidylcholine, the most common lipid component of surfactant, was the predominant lipid metabolite differentially expressed.
Left Forearm Langerhans Cell Sarcoma Demonstrated by 18F-FDG PET/CT
Authors: He Limeng , Deng Yujiao , Huang Jing , Xie Hongjun , Zhang Wei
Published: July 2022

Langerhans cell sarcoma is a rare neoplastic proliferation of Langerhans cells with a poor prognosis. We report FDG PET/CT findings of Langerhans cell sarcoma in the left forearm of a 77-year-old woman who presented with progressive enlargement of the left forearm mass for over 2 months. 18F-FDG PET/CT demonstrated a high FDG uptake by the mass along with several FDG-avid enlarged lymph nodes in the left arm and axilla. Pathology examination of the biopsied specimen from the left forearm mass led to a diagnosis of Langerhans cell sarcoma.
Fistula Risk Score for Auditing Pancreatoduodenectomy
Authors: van Dongen Jelle C. , van Dam Jacob L. , Besselink Marc G. , Bonsing Bert A. , Bosscha Koop , Busch Olivier R. , van Dam Ronald M. , Festen Sebastiaan , van der Harst Erwin , de Hingh Ignace H. , Kazemier Geert , Liem Mike S.L. , de Meijer Vincent E. , Mieog Jan S.D. , Molenaar Izaak.Q. , Patijn Gijs A. , van Santvoort Hjalmar C. , Wijsman Jan H. , Stommel Martijn W.J. , Wit Fennie , De Wilde Roeland F. , van Eijck Casper H.J. , Groot Koerkamp Bas ,   on behalf of the Dutch Pancreatic Cancer Group
Published: July 2022

Objective:

To develop a fistula risk score for auditing, to be able to compare postoperative pancreatic fistula (POPF) after pancreatoduodenectomy among hospitals.

Background:

For proper comparisons of outcomes in surgical audits, case-mix variation should be accounted for.

Methods:

This study included consecutive patients after pancreatoduodenectomy from the mandatory nationwide Dutch Pancreatic Cancer Audit. Derivation of the score was performed with the data from 2014 to 2018 and validation with 2019 to 2020 data. The primary endpoint of the study was POPF (grade B or C). Multivariable logistic regression analysis was performed for case-mix adjustment of known risk factors.

Results:

In the derivation cohort, 3271 patients were included, of whom 479 (14.6%) developed POPF. Male sex [odds ratio (OR)=1.34; 95% confidence interval (CI): 1.09–1.66], higher body mass index (OR=1.07; 95% CI: 1.05–1.10), a final diagnosis other than pancreatic ductal adenocarcinoma/pancreatitis (OR=2.41; 95% CI: 1.90–3.06), and a smaller duct diameter (OR=1.43/mm decrease; 95% CI: 1.32–1.55) were independently associated with POPF. Diabetes mellitus (OR=0.73; 95% CI: 0.55–0.98) was independently associated with a decreased risk of POPF. Model discrimination was good with aC-statistic of 0.73 in the derivation cohort and 0.75 in the validation cohort (n=913). Hospitals differed in particular in the proportion of pancreatic ductal adenocarcinoma/pancreatitis patients, ranging from 36.0% to 58.1%. The observed POPF risk per center ranged from 2.9% to 25.4%. The expected POPF rate based on the 5 risk factors ranged from 11.6% to 18.0% among hospitals.

Conclusions:

The auditing fistula risk score was successful in case-mix adjustment and enables fair comparisons of POPF rates among hospitals.
Intraoperative Blood Loss Estimation in Hepato-pancreato-biliary Surgery—Relevant, Not Reported, Not Standardized
Authors: Perri Giampaolo , Marchegiani Giovanni , Reich Federico , Casetti Luca , Fontana Martina , Esposito Alessandro , Ruzzenente Andrea , Salvia Roberto , Bassi Claudio
Published: July 2022

Objective:

To provide an overview of the current practice of intraoperative blood loss (BL) estimation in hepato-pancreato-biliary (HPB) surgery.

Background:

Intraoperative BL is a major quality marker in HPB surgery and a predictor of perioperative outcomes. However, the method for BL estimation is not standardized.

Methods:

A systematic review was performed of original studies published between 2006 and 2021 reporting the intraoperative BL of patients undergoing pancreatic or hepatic resections. A web-based snapshot survey was distributed globally to all members of the International Hepato-Pancreato-Biliary Association (IHPBA).

Results:

A total of 806 studies were included; 480 (60%) had BL as their primary outcome, and 105 (13%) had BL as their secondary outcome. However, 669 (83%) did not specify how BL estimation was performed, and 9 different methods were found among the remaining 136 (17%) studies.

The survey was completed by 252 surgeons. Most of the responders (94%) declared that they systematically performed BL estimation and considered BL predictive of postoperative complications after pancreatic (73%) and liver (74%) resection. All methods previously identified in the literature were used by responders with different frequencies. A calculation based on suction fluid amounts, operative gauze weight, and irrigation was the most used method in the literature (7%) and among responders (51%). Most responders (83%) felt that BL estimation in HPB surgery needs improved standardization.

Conclusions:

Standardization of intraoperative BL estimation is urgently needed in HPB surgery to ensure the consistency of reporting and reproducibility.
Early Outcomes Following Implementation of a Multispecialty Geriatric Surgery Pathway
Authors: Ehrlich April L. , Owodunni Oluwafemi P. , Mostales Joshua C. , Qin Caroline Xu , Hadvani Priyanka J. , Sirisegaram Luxey , Bettick Dianne , Gearhart Susan L.
Published: July 2022

Objective:

To examine geriatric-specific outcomes following implementation of a multispecialty geriatric surgical pathway (GSP).

Background:

In 2018, we implemented a GSP in accordance with the proposed 32 standards of American College of Surgeons’ Geriatric Surgery Verification Program.

Methods:

This observational study combined data from the electronic health record system (EHR) and ACS-National Surgery Quality Improvement Program (NSQIP) to identify patients ≥65 years undergoing inpatient procedures from 2016 to 2020. GSP patients (2018–2020) were identified by preoperative high-risk screening. Frailty was measured with the modified frailty index. Surgical procedures were ranked according to the operative stress score (1–5). Loss of independence (LOI), length of stay, major complications (CD II–IV), and 30-day all-cause unplanned readmissions were measured in the pre/postpatient populations and by propensity score matching of patients by operative procedure and frailty.

Results:

A total of 533 (300 pre-GSP, 233 GSP) patients similar by demographics (age and race) and clinical profile (frailty) were included. On multivariable analysis, GSP patients showed decreased risk for LOI [odds ratio (OR) 0.26 (0.23, 0.29) P<0.001] and major complications [OR: 0.63 (0.50, 0.78) P<0.001]. Propensity matching demonstrated similar findings. Examining frail patients alone, GSP showed decreased risk for LOI [OR: 0.30 (0.25, 0.37) P<0.001], major complications [OR: 0.31 (0.24, 0.40) P<0.001], and was independently associated with a reduction in length of stay [incidence rate ratios: 0.97 (0.96, 0.98), P<0.001].

Conclusions:

In our diverse patient population, implementation of a GSP led to improved geriatric-specific surgical outcomes. Future studies to examine pathway compliance would promote the identification of further interventions.
Diabetes Mellitus is an Independent Predictor of Spinal Cord Injury After Descending Thoracic and Thoracoabdominal Aneurysm Repair
Authors: Gambardella Ivancarmine , Worku Berhane , Lau Christopher , Tranbaugh Robert F. , Tabaie Sheida , Ivascu Natalia , Girardi Leonard N.
Published: July 2022

Objective:

To discern the impact of diabetes mellitus (DM) on spinal cord injury (SCI) after open descending thoracic and thoracoabdominal aneurysm repair (DTAAAR).

Background:

Compared with euglycemia, hyperglycemia, and ketosis make neurons respectively more vulnerable and more resilient to ischemia.

Methods:

During the study period (1997–2021), patient who underwent DTAAAR were dichotomized according to the presence/absence of DM. The latter was investigated as predictor of our primary (SCI) and secondary [operative mortality (OM), myocardial infarction, stroke, need for tracheostomy, de novo dialysis, and survival] endpoints. Two-level risk-adjustment employed maximum likelihood conditional regression after 1:2 propensity-score matching.

Results:

DTAAAR was performed in 934 patients. Ninety-two diabetics were matched to 184 nondiabetics. All preoperative variables had a standardized mean difference <0.1 between the matched groups. Patients with DM had higher SCI (6.5% vs. 1.6%,P0.03) and OM (14.1% vs. 6.0%,P=0.01), while the other secondary endpoints were similar between groups in the matched sample. DM was an independent predictor for SCI in the matched sample (odds ratio: 5.05, 95% confidence interval: 1.17–21.71). Matched patients with DM presented decreased survival at 1 (70.2% vs. 86.2%), 5 (50.4% vas 67.5%), 10 years (31.7% vs. 36.7%) (P=0.03). The results are summarized in the graphical abstract.

Conclusion:

DM is associated to increased OM and decreased survival, and it is an independent predictor of SCI after open DTAAAR. Strict perioperative glycemic control should be implemented, and exogenous ketones should be investigated as neuroprotective agents to reduce such adverse events.
The Effect of Hyperosmolar Water-Soluble Contrast for the Management of Adhesive Small Bowel Obstruction
Authors: Klingbeil Kyle D. , Wu James X. , Osuna-Garcia Antonia , Livingston Edward H.
Published: July 2022

Objective:

To better understand the efficacy of water-soluble contrast (WSC) in the treatment of adhesive small bowel obstruction (SBO).

Background:

Guidelines recommend using WSC to treat adhesive SBO nonoperatively by acting as a cathartic agent. The evidence supporting this practice is mixed.

Methods:

A systematic review and meta-analysis of published articles describing the effect of WSC compared with control treatments was performed for the period of January 1, 1990 to November 1, 2021. Study quality was assessed using the Cochrane risk-of-bias and the Newcastle-Ottawa tools. The therapeutic effect of WSC was assessed by operative rates and hospital length of stay (HLOS) in nonsurgical patients.

Results:

The initial search yielded 4879 articles, of which, 28 were selected for full text review. We identified 11 eligible randomized controlled trials (RCTs) which included 817 patients and 9 observational studies of 3944 patients. HLOS in nonsurgical patients decreased by 1.95 days (95% confidence interval: 0.56–3.3) in the RCTs and could not be assessed in the observational studies. WSC did not significantly affect operative rates in the RCTs (19.8% vs. 21.4%) but did reduce rates in the observational studies (11% vs. 16%, risk ratio: 0.56, 95% confidence interval: 0.39–0.82).

Conclusion:

WSC studies may reduce HLOS for patients who have SBO and do not require surgery. However, the current literature is heterogenous with considerable design limitations. High-quality RCTs are needed using standardized protocols to determine the full benefit of WSC for the management of SBO.
Endoscopic Retrograde Appendicitis Therapy
Authors: Khan Suliman , Ali Faisal S. , Ullah Saif
Published: July 2022

Endoscopic retrograde appendicitis therapy (ERAT) has emerged as a promising, non-invasive treatment for acute uncomplicated appendicitis (AUA). ERAT involves cannulation, appendicography, appendiceal stone extraction, appendiceal lumen irrigation, and stent deployment. Recent randomized trials comparing ERAT to laparoscopic appendectomy (LA) have provided promising results in terms of safety and efficacy of ERAT. If the current trajectory of research and development is maintained, ERAT will likely become a strong contender for the standard of care for AUA. Standardized training and credentialing for ERAT, akin to procedures established for endoscopic retrograde cholangiopancreatography, will be pivotal to global adoption of this modality.
Geographic Proximity of Family Members and Healthcare Utilization After Complex Surgical Procedures
Authors: Bucher Brian T. , Yang Meng , Richards Steed Rebecca , Fraser Alison , Finlayson Samuel R.G. , Hanson Heidi A.
Published: July 2022

Objective:

We sought to determine the relationship between a patient’s proximal familial social support, defined as the geographic proximity of family members, and healthcare utilization after complex cardiovascular and oncologic procedures.

Background:

Social support mechanisms are increasingly identified as modifiable risk factors for healthcare utilization.

Methods:

We performed a retrospective cohort study of 60,895 patients undergoing complex cardiovascular procedures or oncologic procedures. We defined healthcare utilization outcomes as 30-day all-cause readmission unplanned readmission, nonindex hospital readmission, index hospital length of stay, and home discharge disposition. For each patient, we aggregated the number of first-degree relatives (FDR) living within 30 miles of the patient’s home address at the time of the surgical procedure into the following categories: 0 to 1, 2 to 3, 4 to 5, 6+ FDRs. We developed hierarchical multivariable regression models to determine the relationship between the number of FDR living within 30 miles of the patient and the healthcare utilization outcomes.

Results:

Compared with patients with 0 to 1 FDRs, patients with 6+ FDRs living in close proximity had significantly lower rates of all-cause readmission (12.1% vs 13.5%, P<0.001), unplanned readmission (10.9% vs 12.0%, P=0.001), nonindex readmission (2.6% vs 3.2%, P=0.003); higher rates of home discharge (88.0% vs 85.3%, P<0.001); and shorter length of stay (7.3 vs 7.5 days, P=0.02). After multivariable adjustment, a larger number of FDRs living within 30 miles of the patient was significantly associated with a lower likelihood of all-cause readmission (P<0.001 for trend), 30-day unplanned readmission (P<0.001), nonindex readmission (P<0.001); higher likelihood of home discharge (P<0.001); and shorter index length of stay (P<0.001).

Conclusions:

The geographic proximity of family members is significantly associated with decreased healthcare utilization after complex cardiovascular and oncologic surgical procedures.
Characterization of Humanitarian Trauma Care by US Military Facilities During Combat Operations in Afghanistan and Iraq
Authors: Gurney Jennifer M. , Graf Victoria , Staudt Amanda M. , Trevino Jennifer D. , VanFosson Christopher A. , Wild Hannah , Wren Sherry M.
Published: July 2022

Objective:

To characterize humanitarian trauma care delivered by US military treatment facilities (MTFs) in Afghanistan and Iraq during combat operations.

Background:

International Humanitarian Law, which includes the Geneva Conventions, defines protections and standards of treatment to victims of armed conflicts. In 1949, these standards expanded to include injured civilians. In 2001, the Global War on Terror began in Afghanistan and expanded to Iraq in 2003. US MTFs provided care to all military forces, civilians, and enemy prisoners. A thorough understanding of the scope, epidemiology, resource requirements, and outcomes of civilian trauma in combat zones has not been previously characterized.

Methods:

Retrospective cohort analysis of the Department of Defense Trauma Registry from 2005 to 2019. Inclusion criteria were civilians and Non–North Atlantic Treaty Organization (NATO) Coalition Personnel (NNCP) with traumatic injuries treated at MTFs in Afghanistan and Iraq. Patient demographics, mechanism of injury, resource requirements, procedures, and outcomes were categorized.

Results:

A total of 29,963 casualties were eligible from the Registry. There were 16,749 (55.9%) civilians and 13,214 (44.1%) NNCP. The majority of patients were age above 13 years [26,853 (89.6%)] and male [28,000 (93.4%)]. Most injuries were battle-related: 12,740 (76.1%) civilians and 11,099 (84.0%) NNCP. Penetrating trauma was the most common cause of both battle and nonbattle injuries: 12,293 (73.4%) civilian and 10,029 (75.9%) NNCP. Median Injury Severity Score (ISS) was 9 in each cohort with ISS≥25 in 2236 (13.4%) civilians and 1398 (10.6%) NNCP. Blood products were transfused to 35% of each cohort: 5850 civilians received a transfusion with 2118 (12.6%) of them receiving ≥10 units; 4590 NNCPs received a transfusion with 1669 (12.6%) receiving ≥10 units. MTF mortality rates were civilians 1263 (7.5%) and NNCP 776 (5.9%). Interventions, both operative and nonoperative, were similar between both groups.

Conclusions:

In accordance with International Humanitarian Law, as well as the US military’s medical rules of eligibility, civilians injured in combat zones were provided the same level of care as NNCP. Injured civilians and NNCP had similar mechanisms of injury, injury patterns, transfusion needs, and ISS. This analysis demonstrates resource equipoise in trauma care delivered to civilians and NNCP. Hospitals in combat zones must be prepared to manage large numbers of civilian casualties with significant human and material resources allocated to optimize survival. The provision of humanitarian trauma care is resource-intensive, and these data can be used to inform planning factors for current or future humanitarian care in combat zones.