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1.
Brachytherapy ; 2024 Apr 19.
Article in English | MEDLINE | ID: mdl-38643046

ABSTRACT

PURPOSE: To compare patient and tumor characteristics, dosimetry, and toxicities between interstitial Syed-Neblett and intracavitary Fletcher-Suit-Delclos Tandem and Ovoid (T&O) applicators in high dose rate (HDR) cervical cancer brachytherapy. METHODS: A retrospective analysis was performed for cervical cancer patients treated with 3D-based HDR brachytherapy from 2011 to 2023 at a single institution. Dosimetric parameters for high-risk clinical target volume and organs at risk were obtained. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 5.0. RESULTS: A total of 115 and 58 patients underwent Syed and T&O brachytherapy, respectively. Patients treated with Syed brachytherapy were more likely to have larger tumors and FIGO stage III or IV disease. The median D2cc values to the bladder, small bowel, and sigmoid colon were significantly lower for Syed brachytherapy. Patients treated with Syed brachytherapy were significantly more likely to be free of acute gastrointestinal (44% vs. 21%, p = 0.003), genitourinary (58% vs. 36%, p = 0.01), and vaginal toxicities (60% vs. 33%, p = 0.001) within 6 months following treatment compared to patients treated with T&O applicators. In contrast, Syed brachytherapy patients were more likely to experience late gastrointestinal (68% vs. 49%, p = 0.082), genitourinary (51% vs. 35%, p = 0.196), and vaginal toxicities (70% vs. 57%, p = 0.264). CONCLUSIONS: Syed-Neblett and T&O applicators are suitable for HDR brachytherapy for cervical cancer in distinct patient populations. Acute toxicities are more prevalent with T&O applicators, while patients treated with Syed-Neblett applicators are more likely to develop late toxicities.

2.
J Surg Educ ; 81(4): 564-569, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38388306

ABSTRACT

OBJECTIVE: The significance of thought differences has always held importance in medicine, but it could be considered as increasingly acknowledged and valued to a greater extent in recent times as more emphasis is placed on diversity, equity, and inclusion. These unique perspectives have been examined according to race, gender, and ethnicity, but there is limited published data examining the prevalence of leadership roles within surgical departments in terms of training background. Our main objective is to identify trends in surgical leaders' education, and emphasize training diversity in surgical leadership. DESIGN: A descriptive study of the training background of all surgical academic leaders. SETTING: This internet search was performed at a tertiary care, academic medical center. PARTICIPANTS: Academic chairpersons, division directors, and program directors. RESULTS: 124 programs had pertinent information available. There was a mean of 7.6 leaders per institute examined: total 939 positions (119 chairs, 704 division directors, 116 program directors). 90/119 (76%) of the Chairs led at institutions outside of the places they completed their training. 4/119 (3%) did all their training at the same institution they chaired. 25/119 (21%) completed at least some but not all their training there, and later rose to the role of Chair. Among division directors, 217/704 (31%) did some training at that institution, and program directors were significantly more likely to have completed some training at their current institute (53/116, 46%; p = 0.001). There were no statistically significant differences when examined geographically. Women made up 18% of the leaders and were significantly more likely to lead as program director rather than a chair or division director (p < 0.001). CONCLUSION: A majority of surgery chairs hold positions at institutions where they did not complete their medical training. This suggests that outside perspective could be a contributing factor when searching for this position.


Subject(s)
Leadership , Medicine , Humans , Female , United States , Male , Faculty, Medical , Educational Status , Academic Medical Centers
3.
J Trauma Acute Care Surg ; 96(2): 232-239, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-37872666

ABSTRACT

BACKGROUND: The opioid epidemic in the United States continues to lead to a substantial number of preventable deaths and disability. The development of opioid dependence has been strongly linked to previous opioid exposure. Trauma patients are at particular risk since opioids are frequently required to control pain after injury. The purpose to this study was to examine the prevalence of opioid use before and after injury and to identify risk factors for persistent long-term opioid use after trauma. METHODS: Records for all patients admitted to a Level 1 trauma center over a 1-year period were analyzed. Demographics, injury characteristics, and hospital course were recorded. A multistate Prescription Drug Monitoring Program database was queried to obtain records of all controlled substances prescribed from 6 months before the date of injury to 12 months after hospital discharge. Patients still receiving narcotics at 1 year were defined as persistent long-term users and were compared against those who were not. RESULTS: A total of 2,992 patients were analyzed. Of all patients, 20.4% had filled a narcotic prescription within the 6 months before injury, 53.5% received opioids at hospital discharge, and 12.5% had persistent long-term use after trauma with the majority demonstrating preinjury use. Univariate risk factors for long-term use included female sex, longer length of stay, higher Injury Severity Score, anxiety, depression, orthopedic surgeries, spine injuries, multiple surgical locations, discharge to acute inpatient rehab, and preinjury opioid use. On multivariate analysis, the only significant predictors of persistent long-term prescription opioid use were preinjury use and a much smaller effect associated with use at discharge. CONCLUSION: During a sustained opioid epidemic, concerns and caution are warranted in the use of prescription narcotics for trauma patients. However, persistent long-term opioid use among opioid-naive patients is rare and difficult to predict after trauma. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level III.


Subject(s)
Analgesics, Opioid , Opioid-Related Disorders , Humans , Female , United States/epidemiology , Analgesics, Opioid/adverse effects , Incidence , Opioid-Related Disorders/epidemiology , Opioid-Related Disorders/etiology , Risk Factors , Narcotics , Pain, Postoperative/drug therapy , Retrospective Studies , Practice Patterns, Physicians'
4.
Cancer Med ; 12(23): 21172-21187, 2023 12.
Article in English | MEDLINE | ID: mdl-38037545

ABSTRACT

AIMS: Macrophages play an essential role in cancer development. Tumor-associated macrophages (TAMs) have predominantly M2-like attributes that are associated with tumor progression and poor patient survival. Numerous methods have been reported for differentiating and polarizing macrophages in vitro, but there is no standardized and validated model for creating TAMs. Primary cells show varying cytokine responses depending on their origin and functional studies utilizing these cells may lack generalization and validity. A distinct cell line-derived TAM-like M2 subtype is required to investigate the mechanisms mediated by anti-inflammatory TAMs in vitro. Our previous work demonstrated a standardized protocol for creating an M2 subtype derived from a human THP-1 cell line. The cell expression profile, however, has not been validated. The aim of this study was to characterize and validate the TAM-like M2 subtype macrophage created based on our protocol to introduce them as a standardized model for cancer research. METHODS AND RESULTS: Using qRT-PCR and ELISA, we demonstrated that proinflammatory, anti-inflammatory, and tumor-associated marker expression changed during THP-1-derived marcrophage development in vitro, mimicking a TAM-related profile (e.g., TNFα, IL-1ß). The anti-inflammatory marker IL-8/CXCL8, however, is most highly expressed in young M0 macrophages. Flow cytometry showed increased expression of CD206 in the final TAM-like M2 macrophage. Single-cell RNA-sequencing analysis of primary human monocytes and colon cancer tissue macrophages demonstrated that cell line-derived M2 macrophages resembled a TAM-related gene profile. CONCLUSIONS: The THP-1-derived M2 macrophage based on a standardized cell line model represents a distinct anti-inflammatory TAM-like phenotype with an M2a subtype profile. This model may provide a basis for in vitro investigation of functional mechanisms in a variety of anti-inflammatory settings, particularly colon cancer development.


Subject(s)
Colonic Neoplasms , Macrophages , Humans , THP-1 Cells , Cell Line, Tumor , Macrophages/metabolism , Colonic Neoplasms/pathology , Anti-Inflammatory Agents
5.
Int J Obes (Lond) ; 47(10): 911-921, 2023 10.
Article in English | MEDLINE | ID: mdl-37626126

ABSTRACT

BACKGROUND: Obesity is a well-established risk factor in the development of colorectal cancer; however, the mechanism mediating this relationship is not well understood. The adipokine, adiponectin, has an inverse relationship with obesity. Experimental studies have shown adiponectin to have dichotomous inflammatory and tumorigenic roles. Its role in the development of colorectal cancer, including the potential effect of its increase following bariatric surgery, is not yet clear. There are conflicting results from studies evaluating this relationship. This study sought to provide a systematic review and meta-analysis to examine the association between systemic adiponectin levels in patients with colorectal cancer and adenoma. METHODS: An electronic literature search was performed using PubMed, EMBASE, Web of Science as well as gray literature. Articles were screened for inclusion criteria and assessed for quality using the Newcastle-Ottawa Scale. Pooled mean differences were calculated using a random effects model. Subgroup and meta-regression analyses were performed to identify potential sources of heterogeneity. RESULTS: Thirty-two observational studies comparing systemic adiponectin in colorectal cancer vs healthy controls were included. Colorectal cancer cases had lower systemic adiponectin levels (overall pooled mean difference = -1.05 µg/ml [95% CI: -1.99; -0.12] p = 0.03); however, significant heterogeneity was present (I2 = 95% p < 0.01). Subgroup and meta- regression analyses results could not identify a source of the significant heterogeneity across the studies. CONCLUSIONS: Studies suggest a trend towards lower systemic adiponectin levels in colorectal cancer patients, but the heterogeneity observed showed current evidence is not sufficient to definitively draw any conclusions. These data, however, suggest rising adiponectin is unlikely to account for the reported observation of increased CRC following bariatric surgery. Further studies with prospective age, race, and BMI-matched cohorts, and standardized adiponectin measurements may provide a better understanding of this relationship.


Subject(s)
Adenoma , Colorectal Neoplasms , Humans , Adiponectin , Prospective Studies , Obesity
6.
Genes (Basel) ; 14(7)2023 06 28.
Article in English | MEDLINE | ID: mdl-37510272

ABSTRACT

Cellular communication through biochemical signaling is fundamental to every biological activity. Investigating cell signaling diffusions across cell types can further help understand biological mechanisms. In recent years, this has become an important research topic as single-cell sequencing technologies have matured. However, cell signaling activities are spatially constrained, and single-cell data cannot provide spatial information for each cell. This issue may cause a high false discovery rate, and using spatially resolved transcriptomics data is necessary. On the other hand, as far as we know, most existing methods focus on providing an ad hoc measurement to estimate intercellular communication instead of relying on a statistical model. It is undeniable that descriptive statistics are straightforward and accessible, but a suitable statistical model can provide more accurate and reliable inference. In this way, we propose a generalized linear regression model to infer cellular communications from spatially resolved transcriptomics data, especially spot-based data. Our BAyesian Tweedie modeling of COMmunications (BATCOM) method estimates the communication scores between cell types with the consideration of their corresponding distances. Due to the properties of the regression model, BATCOM naturally provides the direction of the communication between cell types and the interaction of ligands and receptors that other approaches cannot offer. We conduct simulation studies to assess the performance under different scenarios. We also employ BATCOM in a real-data application and compare it with other existing algorithms. In summary, our innovative model can fill gaps in the inference of cell-cell communication and provide a robust and straightforward result.


Subject(s)
Gene Expression Profiling , Transcriptome , Transcriptome/genetics , Bayes Theorem , Cell Communication/genetics , Signal Transduction
7.
J Gastrointest Surg ; 27(9): 1971-1987, 2023 09.
Article in English | MEDLINE | ID: mdl-37430092

ABSTRACT

BACKGROUND: Several contemporary risk stratification tools are now being used since the development of the Charlson Comorbidity Index (CCI) in 1987. The purpose of this systematic review and meta-analysis was to compare the utility of commonly used co-morbidity indices in predicting surgical outcomes. METHODS: A comprehensive review was performed to identify studies reporting an association between a pre-operative co-morbidity measurement and an outcome (30-day/in-hospital morbidity/mortality, 90-day morbidity/mortality, and severe complications). Meta-analysis was performed on the pooled data. RESULTS: A total of 111 included studies were included with a total cohort size 25,011,834 patients. The studies reporting the 5-item Modified Frailty Index (mFI-5) demonstrated a statistical association with an increase in the odds of in-hospital/30-day mortality (OR:1.97,95%CI: 1.55-2.49, p < 0.01). The pooled CCI results demonstrated an increase in the odds for in-hospital/30-day mortality (OR:1.44,95%CI: 1.27-1.64, p < 0.01). Pooled results for co-morbidity indices utilizing a scale-based continuous predictor were significantly associated with an increase in the odds of in-hospital/30-day morbidity (OR:1.32, 95% CI: 1.20-1.46, p < 0.01). On pooled analysis, the categorical results showed a higher odd for in-hospital/30-day morbidity (OR:1.74,95% CI: 1.50-2.02, p < 0.01). The mFI-5 was significantly associated with severe complications (Clavien-Dindo ≥ III) (OR:3.31,95% CI:1.13-9.67, p < 0.04). Pooled results for CCI showed a positive trend toward severe complications but were not significant. CONCLUSION: The contemporary frailty-based index, mFI-5, outperformed the CCI in predicting short-term mortality and severe complications post-surgically. Risk stratification instruments that include a measure of frailty may be more predictive of surgical outcomes compared to traditional indices like the CCI.


Subject(s)
Frailty , Humans , Frailty/complications , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Morbidity , Comorbidity , Hospital Mortality , Retrospective Studies
8.
Am J Obstet Gynecol ; 229(4): 430.e1-430.e6, 2023 10.
Article in English | MEDLINE | ID: mdl-37419167

ABSTRACT

BACKGROUND: Percutaneous tibial nerve stimulation is a third-line treatment for overactive bladder and urgency urinary incontinence. During the procedure, a needle is inserted cephalad to the medial malleolus and posterior to the tibia. In recent years, permanent implants and leads have been developed for insertion into the medial ankle via a small incision. There are many important structures present in the medial compartment of the ankle, including the great saphenous vein, saphenous nerve, tibial nerve, posterior tibial vessels, and tendons of the posterior compartment leg muscles. OBJECTIVE: The primary objective of this study was to identify the proximity of the percutaneous tibial nerve stimulation needle placed per Food and Drug Administration-approved device instructions to nearby important anatomic structures. The secondary objectives were to identify the proximity of the tibial nerve to the needle site, identify clinically relevant ankle anatomic structures, and confirm the tibial nerve and posterior tibial vasculature by histologic analysis. STUDY DESIGN: Detailed medial ankle dissections were performed bilaterally on 10 female lightly embalmed anatomic donors (cadavers) obtained from the Willed Body Program at the University of Louisville. A pin was inserted at the percutaneous tibial nerve stimulation needle site, and the medial ankle was minimally dissected so the surrounding anatomic structures were visible but not disrupted. The shortest distance from the pin to the selected structures of the medial ankle region was measured. On completion of each dissection and set of measurements, tissue was harvested for histologic examination. The distances between the pin and each structure were assessed using means and standard deviations. A paired t test was used to assess the difference in the locations between the left and right ankles. Statistical analysis was performed on left-sided, right-sided, and combined measurements. An 80% prediction interval was found to represent the expected range of values for the measurement of a new cadaver or patient, and the 95% confidence interval of the mean was computed to characterize the average distance across all cadavers or patients. RESULTS: The medial ankle of 10 adult female lightly embalmed cadavers were examined bilaterally. Dissections were completed from October 2021 to July 2022. Of note, 80% prediction intervals for the tibial nerve, the posterior tibial artery or vein, and the flexor digitorum longus tendon had a lower range of 0.0 mm from the pin and extending to 12.1, 9.5, and 13.9 mm, respectively. Moreover, 2 of the structures were found to be asymmetrical between the right and left ankles. The great saphenous vein was further from the pin on the left (20.5 mm [standard deviation of 6.4 mm] on the left vs 18.1 mm [standard deviation of 5.3 mm] on the right; P=.04). The calcaneal (Achilles) tendon was further from the pin on the right side (13.2 mm [standard deviation of 6.8 mm] vs 7.9 mm [standard deviation of 6.7 mm]; P=.04). Tibial neurovascular structures were confirmed with microscopic analysis. CONCLUSION: The anatomic structures within the medial ankle lie unexpectedly close to the percutaneous tibial nerve stimulation needle site as noted per Food and Drug Administration-approved device instructions. There is a possibility that some medial ankle structures are not symmetrical. It is crucial that practitioners understand medial ankle anatomy when performing percutaneous tibial nerve stimulation or permanent device insertion.


Subject(s)
Ankle Joint , Ankle , United States , Adult , Humans , Female , Ankle/innervation , Ankle/surgery , Ankle Joint/pathology , Ankle Joint/surgery , Foot/anatomy & histology , Foot/surgery , Tibial Nerve/anatomy & histology , Tibial Nerve/surgery , Cadaver
9.
Stat Med ; 42(19): 3353-3370, 2023 08 30.
Article in English | MEDLINE | ID: mdl-37276864

ABSTRACT

Covariance estimation for multiple groups is a key feature for drawing inference from a heterogeneous population. One should seek to share information about common features in the dependence structures across the various groups. In this paper, we introduce a novel approach for estimating the covariance matrices for multiple groups using a hierarchical latent factor model that shrinks the factor loadings across groups toward a global value. Using a sparse spike and slab model on these loading coefficients allows for a sparse formulation of our model. Parameter estimation is accomplished through a Markov chain Monte Carlo scheme, and a model selection approach is used to select the number of factors to use. We validate our model through extensive simulation studies. Finally, we apply our methodology to the NICHD Consecutive Pregnancies Study to estimate the correlations between birth weights and gestational ages of three consecutive birth within four different subgroups (underweight, normal, overweight, and obese) of women.


Subject(s)
Bayes Theorem , Humans , Female , Pregnancy , Computer Simulation , Markov Chains , Monte Carlo Method
10.
Parkinsonism Relat Disord ; 109: 105354, 2023 04.
Article in English | MEDLINE | ID: mdl-36863114

ABSTRACT

OBJECTIVE: To assess the effect of Parkinson's disease (PD) on perioperative outcomes following gynecologic surgery. BACKGROUND: Gynecological complaints are common among women with PD but under-reported, under-diagnosed and under-treated, in part due to surgical hesitancy. Non-surgical management options are not always acceptable to patients. Advanced gynecologic surgeries are effective for symptom management. Hesitancy toward elective surgery in PD stems from concern regarding perioperative risks. METHODS: This retrospective cohort study derived data by querying the Nationwide Inpatient Sample (NIS) database between 2012 and 2016 to identify women who underwent advanced gynecologic surgery. Non-parametric Mann-Whitney U and Fisher exact tests were used to compare quantitative and categorical variables respectively. Age and Charlson Comorbidity Index values were used to create matched cohorts. RESULTS: 526 (0.1%) women with and 404,758 without a diagnosis of PD underwent gynecological surgery. Median age of patients with PD (70 years vs 44 years, p < 0.001) and median comorbid conditions (4 vs 0, p < 0.001) were higher compared to counterparts. Median length of stay (LOS) was longer in PD group (3 days vs 2 days, p < 0.001) with lower rates of routine discharge (58% vs 92%, p = 0.001). Groups were comparable in post-operative mortality (0.8% vs 0.3%, p = 0.076). After matching, there was no difference in LOS (p = 0.346) or mortality (0.8% vs 1.5%, p = 0.385) and PD group was more likely to be discharged to skilled nursing facilities. CONCLUSION: PD does not worsen perioperative outcomes following gynecologic surgery. Neurologists may use this information to provide reassurance to women with PD undergoing such procedures.


Subject(s)
Parkinson Disease , Humans , Female , Aged , Male , Retrospective Studies , Parkinson Disease/complications , Parkinson Disease/surgery , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Length of Stay , Gynecologic Surgical Procedures/methods
11.
Cancer Med ; 12(10): 11462-11474, 2023 05.
Article in English | MEDLINE | ID: mdl-36991580

ABSTRACT

BACKGROUND: Anal squamous cell cancer (ASCC) incidence in Kentucky is increasing at an alarming rate. In 2009, the incidence surpassed the US national average (2.66 vs. 1.77/100,000 people), and currently, Kentucky ranks second by state per capita. The reasons for this rise are unclear. We hypothesize individuals with ASCC in Kentucky have some unique risk factors associated with worse outcomes. METHODS: Individuals with ASCC in a population-level state database (1995-2016), as well as those treated at two urban university-affiliated tertiary care centers (2011-2018), were included and analyzed separately. We evaluated patient-level factors including demographics, tobacco use, stage of disease, HIV-status, and HPV-type. We evaluated factors associated with treatment and survival using univariable and multivariable survival analyses. RESULTS: There were 1698 individuals in state data and 101 in urban center data. In the urban cohort, 77% of patients were ever-smokers. Eighty-four percent of patients had positive HPV testing, and 58% were positive for HPV 16. Seventy-two percent of patients were positive for p16. Neither smoking, HPV, nor p16 status were associated with disease persistence, recurrence-free survival, or overall survival (all p > 0.05). Poorly controlled HIV (CD4 count <500) at time of ASCC diagnosis was associated disease persistence (p = 0.032). Stage III disease (adjusted HR = 5.25, p = 0.025) and local excision (relative to chemoradiation; aHR = 0.19, p = 0.017) were significantly associated with reduced recurrence-free survival. CONCLUSIONS: The rate of ASCC in Kentucky has doubled over the last 10 years, which is outpacing anal SCC rates in the US with the most dramatic rates seen in Kentucky women. The underlying reasons for this are unclear and require further study. There may be other risk factors unique to Kentucky.


Subject(s)
Anus Neoplasms , Carcinoma, Squamous Cell , HIV Infections , Papillomavirus Infections , Humans , Female , Incidence , Papillomavirus Infections/complications , Papillomavirus Infections/epidemiology , Papillomavirus Infections/pathology , Kentucky/epidemiology , Anus Neoplasms/epidemiology , Anus Neoplasms/therapy , Anus Neoplasms/pathology , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/etiology , HIV Infections/complications , HIV Infections/epidemiology
12.
Int J Clin Oncol ; 28(4): 565-575, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36745265

ABSTRACT

BACKGROUND: The optimal access for thermal ablation of the liver has not been evaluated in the literature for the laparoscopic versus percutaneous techniques. The aim of this manuscript was to determine the optimal ablation technique and patient selection for hepatic malignancies by comparing the efficacy and recurrence-free survival of laparoscopic and percutaneous thermal ablation. METHODS: A detailed literature search was made in PubMed, Web of Science, Google scholar, and EMBASE for related research publications. The data were extracted and assessed by two reviewers independently. Analysis of pooled data was performed, and Odds Ratio (OR) or Hazard Ratio (HR) with corresponding confidence intervals (CIs) was calculated and summarized respectively. RESULTS: A total of 10 articles were included with 1916 ablation patients. Laparoscopic ablation success (Median 100%) was found to be higher than percutaneous ablation success (median 89.4%) (p = ns). There was a higher percentage of both local and non-local hepatic recurrence in the patients treated with percutaneous ablation versus laparoscopic ablation. Meta-analysis indicated no difference in the adjusted hazard rate of recurrence by procedure type (p = 0.94). Laparoscopic ablation had a higher percentage of complications compared to percutaneous ablation (median lap 14.5% vs. perc 3.3%). CONCLUSIONS: While laparoscopic and percutaneous ablation are both effective interventions for hepatic malignancies, laparoscopic ablation was found to have improved ablation success and less local and non-local hepatic recurrence compared to percutaneous ablation.


Subject(s)
Carcinoma, Hepatocellular , Catheter Ablation , Laparoscopy , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/pathology , Catheter Ablation/methods , Liver Neoplasms/pathology
13.
Heliyon ; 9(2): e13132, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36825172

ABSTRACT

Background: Chronic inflammation is a key feature of obesity and a hallmark of colon cancer (CC). The obesity-related hormones leptin and adiponectin alter inflammatory gene profiles in cancer, but their specific role in CC is unclear. We have previously studied the effects of leptin and the macrophage-specific mediator itaconate on M2-like macrophages. This current study evaluates their effects on CC cells. Methods: HT-29 CC cells (derived from a young patient, stage III CC) were treated with either leptin, adiponectin, 4-octyl itaconate (OI) or dimethyl itaconate (DI). Gene expression after treatment was analyzed at four time points (3, 6, 18, and 24 h). Results: CCL22 was upregulated after treatment with adiponectin (at 18 h [FC 16.3, p < 0.001]). IL-8 expression increased following both adiponectin (at 3 h [FC 68.1, p < 0.001]) and leptin treatments (at 6 h [FC 7.3, p < 0.001]), while OI induced downregulation of IL-8 (at 24 h [FC -5.0, p < 0.001]). CXCL10 was upregulated after adiponectin treatment (at 6 h [FC 3.0, p = 0.025]) and downregulated by both OI and DI at 24 h, respectively (OI [FC -10.0, p < 0.001]; DI [FC -10.0, p < 0.001]). IL-1ß was upregulated after adiponectin treatment (at 3 h [FC 10.6, p < 0.001]) and downregulated by DI (at 24 h [FC -5.0, p < 0.001]). TNF-α expression was induced following adiponectin (at 6 h [FC 110.7, p < 0.001]), leptin (at 18 h [FC 5.8, p = 0.027]) and OI (at 3 h [FC 91.1, p = 0.001]). PPARγ was affected by both OI (at 3 h [FC 10.1, p = 0.031], at 24 h [FC -10.0, p = 0.031]) and DI (at 18 h [FC -1.7, p = 0.033]). Conclusions: Obesity hormones directly affect inflammatory gene expression in HT29 CC cells, potentially enhancing cancer progression. Itaconate affects the prognostic marker PPARγ in HT29 CC cells. Leptin, adiponectin and itaconate may represent a link between obesity and CC.

14.
Int Urogynecol J ; 34(9): 2033-2039, 2023 09.
Article in English | MEDLINE | ID: mdl-36811633

ABSTRACT

INTRODUCTION AND HYPOTHESIS: The objective was to compare outcomes in patients receiving general versus regional anesthesia when undergoing obliterative vaginal surgery for pelvic organ prolapse. METHODS: Obliterative vaginal procedures performed from 2010 to 2020 were identified in the American College of Surgeons National Surgical Quality Improvement Program database using Current Procedural Terminology codes. Surgeries were categorized into general anesthesia (GA) or regional anesthesia (RA). Rates of reoperation, readmission, operative time, and length of stay were determined. A composite adverse outcome was calculated including any of the following: nonserious or serious adverse events, 30-day readmission, or reoperation. Propensity score-weighted analysis of perioperative outcomes was performed. RESULTS: The cohort included 6,951 patients, of whom 6,537 (94%) underwent obliterative vaginal surgery under GA and 414 (6%) received RA. When comparing outcomes under the propensity score-weighted analysis, operative times were shorter (median 96 vs 104 min, p<0.01) in the RA group versus GA. There were no significant differences between composite adverse outcomes (10% vs 12%, p=0.06), or readmission (5% vs 5%, p=0.83) and reoperation rates (1% vs 2%, p=0.12) between the RA and GA groups. Length of stay was shorter in patients receiving GA than in those receiving RA, especially when undergoing concomitant hysterectomy (67% discharged within 1 day in GA vs 45% in RA, p<0.01). CONCLUSIONS: Composite adverse outcomes, reoperation rates, and readmission rates were similar in patients who received RA for obliterative vaginal procedures compared with GA. Operative times were shorter in patients receiving RA than in those receiving GA, and length of stay was shorter in patients receiving GA than in those receiving RA.


Subject(s)
Anesthesia, Conduction , Pelvic Organ Prolapse , Female , Humans , Gynecologic Surgical Procedures/adverse effects , Gynecologic Surgical Procedures/methods , Postoperative Complications/etiology , Retrospective Studies , Anesthesia, Conduction/adverse effects , Pelvic Organ Prolapse/surgery , Pelvic Organ Prolapse/etiology , Anesthesia, General/adverse effects , Treatment Outcome
15.
Surgery ; 173(5): 1231-1239, 2023 05.
Article in English | MEDLINE | ID: mdl-36707272

ABSTRACT

BACKGROUND: The aim of this meta-analysis and systematic review was to evaluate the association between intraoperative bile cultures and postoperative complications of patients undergoing pancreaticoduodenectomy. METHODS: A detailed literature search was performed from January 2015 to July 2022 in PubMed, Web of Science, Google Scholar, and EMBASE for related research publications. The data were extracted, screened, and graded independently. An analysis of pooled data was performed, and a risk ratio with corresponding confidence intervals was calculated and summarized. RESULTS: A total of 8 articles were included with 1,778 pancreaticoduodenectomy patients who had an intraoperative bile culture performed. A systematic review demonstrated that some of the most common organisms isolated in a positive intraoperative bile culture were Enterococcus species, Klebsiella species, and E. coli. Four studies also showed that specific microorganisms were associated with specific postoperative complications (surgical site infection and intra-abdominal abscess). The postoperative complications that were evaluated for an association with a positive intraoperative bile culture were surgical site infections (risk ratio = 2.33, 95% confidence interval [1.47-3.69], P < .01), delayed gastric emptying (risk ratio = 1.23, 95% confidence interval [0.63-2.38], P = n.s.), 90-day mortality (risk ratio = 0.68, 95% confidence interval [0.01-52.76], P = n.s.), postoperative pancreatic hemorrhage (risk ratio = 1.70, 95% confidence interval [0.33-8.74], P = n.s.), intra-abdominal abscess (risk ratio = 1.70, 95% confidence interval [0.38-7.56], P = n.s.), and postoperative pancreatic fistula (risk ratio = 0.97, 95% confidence interval [0.72-1.32], P = n.s.). CONCLUSION: The cumulative data suggest that a positive intraoperative bile culture has no association with predicting the postoperative complications of delayed gastric emptying, 90-day mortality, postoperative pancreatic hemorrhage, intra-abdominal abscess, or postoperative pancreatic fistula. However, the data also suggest that a positive intraoperative bile culture was associated with a patient developing a surgical site infection.


Subject(s)
Abdominal Abscess , Gastroparesis , Pancreatic Diseases , Humans , Pancreaticoduodenectomy/adverse effects , Surgical Wound Infection/etiology , Pancreatic Fistula/etiology , Bile , Gastroparesis/etiology , Escherichia coli , Pancreatic Diseases/complications , Postoperative Hemorrhage/etiology , Abdominal Abscess/epidemiology , Abdominal Abscess/etiology , Postoperative Complications/epidemiology , Postoperative Complications/etiology
16.
Surg Endosc ; 37(3): 2247-2252, 2023 03.
Article in English | MEDLINE | ID: mdl-35902402

ABSTRACT

BACKGROUND: Gastroparesis is characterized by delayed gastric emptying without a significant obstructive pathology and is estimated to effect more than 5 million adults in the United States. Therapies for this condition are divided into two categories: gastric electrical stimulation or pyloric therapies to facilitate gastric emptying. Pyloric procedures include pyloroplasty, a well-documented procedure, and per-oral endoscopic myotomy (POP), a relatively novel endoscopic procedure that disrupts the pyloric muscles endoscopically. There is a paucity of literature comparing the two procedures. The aim of this study is to compare the outcomes of these two techniques. METHODS: Under an IRB protocol, data were collected prospectively from September 2018 through April 2021 at our institution for patients undergoing POP (n = 63 patients) or robotic pyloroplasty (RP) (n = 48). Preoperative and postoperative data including sex, race, age, BMI, and Gastroparesis Cardinal Symptom Index (GCSI) score were analyzed using univariate and multivariate analysis. RESULTS: There was no significant difference in sex, age, and BMI for both cohorts, but patients with RP were more likely to have private insurance, pre-op reflux, and PPI (p < .05 for all). Patients who underwent POP had significantly shorter operative time compared to RP (median 27 min vs 90, p < 0.001). The average change between preoperative and postoperative GCSI scores was significantly decreased for both interventions (POP mean = 8.2, RP 16.8, p < 0.001 both). However, comparing both data, RP has significantly better improvement in postoperative GCSI score than POP in both univariate (p < 0.001) and multivariate analysis (p = 0.030). This was reflected in the individual symptoms with nausea (p < 0.001), ability to finish meal (p = 0.037), abdomen visibly larger (p = 0.037) and bloating (p = 0.022) all showing improvement in both groups, but with RP having a more significant decrease in the scoring of these symptoms than POP. There was no significant difference in the number of postoperative complications (POP 19% vs RP 13%, p = 0.440). CONCLUSION: Even though both interventions are significantly associated with improvement of symptoms in patients with gastroparesis, our data demonstrates that robotic pyloroplasty has a superior response in comparison to per-oral endoscopic myotomy for the management of these symptoms. Per-oral pyloromyotomy has a similar complication rate to robotic pyloroplasty with a shorter operative time.


Subject(s)
Gastroparesis , Pyloromyotomy , Robotic Surgical Procedures , Adult , Humans , Pyloromyotomy/methods , Gastroparesis/etiology , Gastroparesis/surgery , Robotic Surgical Procedures/adverse effects , Treatment Outcome , Pylorus/surgery , Gastric Emptying
17.
Cancer Rep (Hoboken) ; 5(10): e21591, 2022 10.
Article in English | MEDLINE | ID: mdl-35075817

ABSTRACT

BACKGROUND: Verrucous vulvar carcinoma (VC) is an uncommon and distinct histologic subtype of squamous cell carcinoma (SCC). The available literature on VC is currently limited to case reports and small single institution studies. AIMS: The goals of this study were to analyze data from the National Cancer Database (NCDB) to quantitate the incidence of VC and to investigate the effects of patient demographics, tumor characteristics, and treatment regimens on overall survival (OS) in women with verrucous vulvar carcinoma. METHODS AND RESULTS: Patients diagnosed with vulvar SCC or VC between the years of 2004 and 2016 were identified in the NCDB. OS was assessed with Kaplan-Meier curves and the log-rank test. Construction of a Cox model compared survival after controlling for confounding variables. The reported incidence of SCC of the vulva has significantly increased since 2004 (p < .0001). In contrast, the incidence of VC has remained stable (p = .344) since 2004. Compared to SCC, VC was significantly more likely to be diagnosed in older women (p < .0001) and treated with surgery alone (p < .0001). However, on propensity score weighted analysis there was a trend toward improved 5-year OS in women with VC compared to those with SCC (63.4% vs. 57.7%, p = .0794). Multivariable Cox survival analysis showed an improvement in OS in VC patients treated with both primary site and regional lymph node surgery compared to primary site surgery alone (adjusted hazard ratio [aHR] 0.67, 95% confidence interval [CI] 0.46-0.97, p = .0357). CONCLUSION: Verrucous carcinoma is more likely to present in older women. Regional lymph node surgery in addition to primary site surgery significantly improves OS in VC patients.


Subject(s)
Carcinoma, Squamous Cell , Carcinoma, Verrucous , Vulvar Neoplasms , Aged , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/surgery , Carcinoma, Verrucous/diagnosis , Carcinoma, Verrucous/epidemiology , Carcinoma, Verrucous/surgery , Female , Humans , Treatment Outcome , Vulva/pathology , Vulva/surgery , Vulvar Neoplasms/diagnosis , Vulvar Neoplasms/epidemiology , Vulvar Neoplasms/surgery
18.
Biostatistics ; 24(1): 209-225, 2022 12 12.
Article in English | MEDLINE | ID: mdl-34296256

ABSTRACT

Across several medical fields, developing an approach for disease classification is an important challenge. The usual procedure is to fit a model for the longitudinal response in the healthy population, a different model for the longitudinal response in the diseased population, and then apply Bayes' theorem to obtain disease probabilities given the responses. Unfortunately, when substantial heterogeneity exists within each population, this type of Bayes classification may perform poorly. In this article, we develop a new approach by fitting a Bayesian nonparametric model for the joint outcome of disease status and longitudinal response, and then we perform classification through the clustering induced by the Dirichlet process. This approach is highly flexible and allows for multiple subpopulations of healthy, diseased, and possibly mixed membership. In addition, we introduce an Markov chain Monte Carlo sampling scheme that facilitates the assessment of the inference and prediction capabilities of our model. Finally, we demonstrate the method by predicting pregnancy outcomes using longitudinal profiles on the human chorionic gonadotropin beta subunit hormone levels in a sample of Chilean women being treated with assisted reproductive therapy.


Subject(s)
Bayes Theorem , Female , Humans , Markov Chains , Monte Carlo Method , Cluster Analysis , Probability
19.
South Med J ; 114(10): 630-635, 2021 10.
Article in English | MEDLINE | ID: mdl-34599340

ABSTRACT

OBJECTIVES: The objective of this analysis was to gauge how the incidence and mortality of uterine cancer in Kentucky have changed from 1995 through 2017. An assessment of the trends in incidence and mortality across different geographic areas and between different races was also performed. METHODS: Age-adjusted annual incidence and mortality rates for uterine cancer were obtained from the Kentucky Cancer Registry. A meta-regression framework was used to assess changes in incidence and mortality rates during the time frame and to determine differences in these rates between rural versus urban counties, Appalachian versus non-Appalachian counties, and Black versus White women. RESULTS: The incidence of uterine cancer has significantly increased throughout the state of Kentucky since 1995. Uterine cancer incidence was 10% and 22% higher in rural and Appalachian counties, respectively, compared with urban and non-Appalachian counties (P < 0.0001) from 1995 through 2017. In contrast, urban and non-Appalachian women had higher or equivalent age-adjusted mortality from uterine cancer, compared with rural and Appalachian women, respectively. The incidence of uterine cancer was significantly higher in White women compared with Black women from 1995 through 2006, but since 2007, there has been no significant difference in uterine cancer incidence based on race. Black women had higher age-adjusted mortality than White women throughout the entire time period examined. CONCLUSIONS: The incidence of uterine cancer is higher in rural and Appalachian Kentucky, without a corresponding geographic trend in mortality. Uterine cancer mortality is significantly higher in Black women.


Subject(s)
Mortality/trends , Uterine Neoplasms/diagnosis , Uterine Neoplasms/mortality , Adult , Female , Humans , Incidence , Kentucky/epidemiology , Middle Aged , Registries/statistics & numerical data , Uterine Neoplasms/epidemiology
20.
Gynecol Oncol ; 163(3): 517-523, 2021 12.
Article in English | MEDLINE | ID: mdl-34563365

ABSTRACT

OBJECTIVE: The optimal treatment for medically inoperable endometrioid endometrial adenocarcinoma is unknown. The goal of this study was to evaluate the patterns of care and efficacy of radiotherapy (RT) or hormone therapy (HT) in the treatment of these patients. METHODS: We performed a query of the National Cancer Database (NCDB) of patients with medically inoperable endometrioid adenocarcinoma of the endometrium diagnosed between 2004 and 2016 and treated with either RT or HT. A multivariate Cox regression model and propensity weighted analyses were used to evaluate overall survival after controlling for confounding variables. A multinomial logistic regression model was used to assess predictors of RT or HT use. RESULTS: A total of 1036 patients were included in this cohort, and 73% (n = 759) were treated with RT alone. Patients who received definitive HT compared to RT were more likely to be older, diagnosed in the earlier years of this analysis, treated at lower-case volume centers, diagnosed with high-grade disease, or located outside of metropolitan areas. On multivariate analysis, treatment with HT alone versus RT alone was associated with significantly worse overall survival in the multivariate Cox model but not on propensity score weighted analysis. Interaction effect testing revealed that older patients and those treated at lower-volume centers had improved survival with RT compared to HT. CONCLUSIONS: We identified factors associated with the receipt of RT or HT in medically inoperable endometrial cancer patients. Treatment with RT correlated with improved survival compared to HT in older patients and those treated at lower-volume centers.


Subject(s)
Carcinoma, Endometrioid/drug therapy , Carcinoma, Endometrioid/radiotherapy , Endometrial Neoplasms/drug therapy , Endometrial Neoplasms/radiotherapy , Adult , Age Factors , Aged , Antineoplastic Agents, Hormonal/therapeutic use , Carcinoma, Endometrioid/pathology , Cohort Studies , Endometrial Neoplasms/pathology , Female , Humans , Middle Aged , Proportional Hazards Models , Retrospective Studies , Survival Rate , Treatment Outcome
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