Trainee-initiated dictations of endocrine surgeries: Implications for education and reimbursement.

INTRODUCTION: Our university-based surgery department recently transitioned to attending-only authorship of operative reports. We performed a mixed-methods investigation to determine if trainee-initiated endocrine surgical reports were associated with under-coding of specific procedures. METHODS: Endocrine operations performed from July 2020 to June 2022 were identified from billing data. Pre- and post-policy RVU distributions and note modification history were reviewed to determine how often trainees captured billable differentiators over attending note modification. RESULTS: 714 operations and 1138 billed procedures were identified. Parathyroidectomy alone showed greater mean RVUs with attending-only reports attributable to attending practice change in coding for intraoperative parathyroid hormone monitoring. Trainees were more likely to miss coding modifier 22 but RVU losses were prevented by attending note modification. CONCLUSION: Trainee-initiated operative reports were not associated with RVU losses for endocrine operations compared to attending-only reports. Trainee dictation can be improved by emphasizing education on procedural billing differences and surgical reasoning.

The association of payer type on genicular radiofrequency neurotomy treatment outcomes: Results of a cross-sectional study.

Background: Genicular radiofrequency neurotomy (GRFN) is an effective treatment for a subset of individuals with chronic knee pain. Previous studies demonstrate that Medicare and Medicaid beneficiaries report worse outcomes following various interventional procedures compared with commercially insured patients. Objective: Evaluate the association of payer type on GRFN treatment outcomes. Methods: Consecutive patients who underwent GRFN at a tertiary academic center were contacted for participation. Demographic, clinical, and procedural characteristics were collected from electronic medical records. Outcome data were collected by standardized telephone survey at 6-12 months, 12-24 months and ≥24 months. Treatment success was defined as ≥50% numerical pain rating scale (NPRS) score reduction from baseline. Data were analyzed using descriptive statistics for demographic, clinical, and procedural characteristics. Logistic and Poisson regression analyses were performed to examine the association of variables of interest and pain reduction. Results: One hundred thirty-four patients treated with GRFN (mean 65.6 ± 12.7 years of age, 59.7% female) with a mean follow-up time of 23.3 ± 11.3 months were included. Payer type composition was 48.5% commercial (n = 65), 45.5% Medicare (n = 61), 3.7% Medicaid (n = 5), 1.5% government (n = 2), and 0.8% self-pay (n = 1). Overall, 47.8% of patients (n = 64) reported ≥50% NPRS score reduction after GRFN. After adjusting for age, follow-up duration, Kellgren-Lawrence osteoarthritis grade, baseline opioid use, antidepressant/antianxiety medication use, history of knee replacement, and number of RFN lesions placed, the logistic regression model showed no statically significant association between payer type and treatment outcome (OR = 2.11; 95% CI = 0.87, 5.11; p = 0.098). Discussion/conclusion: In this study, after adjusting for demographic, clinical, and procedural characteristics, we found no association between payer type and treatment success following GRFN. This observation contrasts findings from other interventional studies reporting an association between payer category and treatment success.

Evidence that extracellular HSPB1 contributes to inflammation in alcohol-associated hepatitis.

Background and aims: Alcohol-associated hepatitis (AH) is the most life-threatening form of alcohol-associated liver disease (ALD). AH is characterized by severe inflammation attributed to increased levels of ethanol, microbes or microbial components, and damage-associated molecular pattern (DAMP) molecules in the liver. HSPB1 (Heat Shock Protein Family B (Small) Member 1; also known as Hsp25/27) is a DAMP that is rapidly increased in and released from cells experiencing stress, including hepatocytes. The goal of this study was to define the role of HSPB1 in AH pathophysiology. Methods: Serum HSPB1 was measured in a retrospective study of 184 heathy controls (HC), heavy alcohol consumers (HA), patients with alcohol-associated cirrhosis (AC), and patients with AH recruited from major hospital centers. HSPB1 was also retrospectively evaluated in liver tissue from 10 HC and AH patients and an existing liver RNA-seq dataset. Finally, HSPB1 was investigated in a murine Lieber-DeCarli diet model of early ALD as well as cellular models of ethanol stress in hepatocytes and hepatocyte-macrophage communication during ethanol stress. Results: Circulating HSPB1 was significantly increased in AH patients and levels positively correlated with disease-severity scores. Likewise, HSPB1 was increased in the liver of patients with severe AH and in the liver of ethanol-fed mice. In vitro , ethanol-stressed hepatocytes released HSPB1, which then triggered TNFα-mediated inflammation in macrophages. Anti-HSPB1 antibody prevented TNFα release from macrophages exposed to media conditioned by ethanol-stressed hepatocytes. Conclusions: Our findings support investigation of HSPB1 as both a biomarker and therapeutic target in ALD. Furthermore, this work demonstrates that anti-HSPB1 antibody is a rational approach to targeting HSPB1 with the potential to block inflammation and protect hepatocytes, without inactivating host defense. HIGHLIGHTS: HSPB1 is significantly increased in serum and liver of patients with alcohol-associated hepatitis.Ethanol consumption leads to early increases in HSPB1 in the mouse liver.Hepatocytes subjected to ethanol stress release HSPB1 into the extracellular environment where it activates TNFα-mediated inflammation in macrophages.Anti-HSPB1 antibody blocks hepatocyte-triggered TNFα in a model of hepatocyte-macrophage communication during ethanol stress.

Clinical Outcomes, Costs, and Value of Surgery Among Older Patients with Colon Cancer at US News and World Report Ranked Versus Unranked Hospitals.

BACKGROUND: US News and World Report (USNWR) hospital rankings influence patient choice of hospital, but their association with surgical outcomes remains ill-defined. We sought to characterize clinical outcomes and costs of surgery for colon cancer among USNWR top ranked and unranked hospitals. METHODS: Using Medicare Standard Analytic Files, patients aged ≥65 years undergoing surgery for colon cancer were identified. Hospitals were categorized as 'ranked' or 'unranked' based on USNWR cancer hospital rankings. One-to-one matching was performed between patients treated at ranked and unranked hospitals, and clinical outcomes and costs of surgery were compared. RESULTS: Among 50 ranked and 2522 unranked hospitals, 13,650 patient pairs were compared. Overall, 30-day mortality was 2.13% in ranked hospitals versus 3.68% in unranked hospitals (p < 0.0001), and the overall paired cost difference was $8159 (p < 0.0001). As patient risk increased, 30-day mortality differences became larger, with the ranked hospitals having 30-day mortality of 7.59% versus 11.84% for unranked hospitals among the highest-risk patients (p < 0.0001). Overall paired cost differences also increased with increasing patient risk, with cost of care being $72,229 for ranked hospitals versus $56,512 for unranked hospitals among the highest-risk patients (difference = $14,394; p = 0.02). The difference in cost per 1% reduction in 30-day mortality was $9009 (95% confidence interval [CI] $6422-$11,597) for lowest-risk patients, which dropped to $3387 (95% CI $2656-$4119) for highest-risk patients (p < 0.0001). CONCLUSION: Treatment at USNWR-ranked hospitals, particularly for higher-risk patients, was associated with better outcomes but higher-cost care. The benefit of being treated at highly ranked USNWR hospitals was most pronounced among high-risk patients.

Association of chronic kidney disease with postoperative outcomes: a national surgical quality improvement program (NSQIP) multi-specialty surgical cohort analysis.

BACKGROUND: Chronic kidney disease (CKD) is associated with higher incidence of major surgery. No studies have evaluated the association between preoperative kidney function and postoperative outcomes across a wide spectrum of procedures. We aimed to evaluate the association between CKD and 30-day postoperative outcomes across surgical specialties. METHODS: We selected adult patients undergoing surgery across eight specialties. The primary study endpoint was major complications, defined as death, unplanned reoperation, cardiac complication, or stroke within 30 days following surgery. Secondary outcomes included Clavien-Dindo high-grade complications, as well as cardiac, pulmonary, infectious, and thromboembolic complications. Multivariable regression was performed to evaluate the association between CKD and 30-day postoperative complications, adjusted for baseline characteristics, surgical specialty, and operative time. RESULTS: In total, 1,912,682 patients were included. The odds of major complications (adjusted odds ratio [aOR] 2.14 [95% confidence interval (CI): 2.07, 2.21]), death (aOR 3.03 [95% CI: 2.88, 3.19]), unplanned reoperation (aOR 1.57 [95% CI: 1.51, 1.64]), cardiac complication (aOR 3.51 [95% CI: 3.25, 3.80]), and stroke (aOR 1.89 [95% CI: 1.64, 2.17]) were greater for patients with CKD stage 5 vs. stage 1. A similar pattern was observed for the secondary endpoints. CONCLUSION: This population-based study demonstrates the negative impact of CKD on operative outcomes across a diverse range of procedures and patients.

Behind the pattern: General surgery residsent autonomy in robotic surgery.

Objective: Robotic surgery is increasingly utilized and common in general surgery training programs. This study sought to better understand the factors that influence resident operative autonomy in robotic surgery. We hypothesized that resident seniority, surgeon work experience, surgeon robotic-assisted surgery (RAS) case volume, and procedure type influence general surgery residents' opportunities for autonomy in RAS as measured by percentage of resident individual console time (ICT). Methods: General surgery resident ICT data for robotic cholecystectomy (RC), inguinal hernia (RIH), and ventral hernia (RVH) operations performed on the dual-console Da Vinci surgical robotic system between July 2019 and June 2021 were extracted. Cases with postgraduate year (PGY) 2-5 residents participating as a console surgeon were included. A sequential explanatory mixed-methods approach was undertaken to explore the ICT results and we conducted secondary qualitative interviews with surgeons. Descriptive statistics and thematic analysis were applied. Results: Resident ICT data from 420 robotic cases (IH 200, RC 121, and VH 99) performed by 20 junior residents (PGY2-3), 18 senior residents (PGY4-5), and 9 attending surgeons were extracted. The average ICT per case was 26.8 % for junior residents and 42.4 % for senior residents. Compared to early-career surgeons, surgeons with over 10 years' work experience gave less ICT to junior (18.2 % vs. 32.0 %) and senior residents (33.9 % vs. 56.6 %) respectively. Surgeons' RAS case volume had no correlation with resident ICT (r = 0.003, p = 0.0003). On average, residents had the most ICT in RC (45.8 %), followed by RIH (36.7 %) and RVH (28.6 %). Interviews with surgeons revealed two potential reasons for these resident ICT patterns: 1) Surgeon assessment of resident training year/experience influenced decisions to grant ICT; 2) Surgeons' perceived operative time pressure inversely affected resident ICT. Conclusions: This study suggests resident ICT/autonomy in RC, RIH, and RVH are influenced by resident seniority level, surgeon work experience, and procedure type, but not related to surgeon RAS case volume. Design and implementation of an effective robotic training program must consider the external pressures at conflict with increased resident operative autonomy and seek to mitigate them.

Comparing Satisfaction Among Providers Treating Both Pediatric and Adult Otolaryngology Patients.

Objective: Although pediatric otolaryngology providers are reported to garner lower patient satisfaction than adults, this difference is not well characterized. This study investigates whether patient satisfaction differences exist in providers who treat both pediatric and adult patients. Study Design: Retrospective review. Setting: Tertiary medical center. Methods: In this cross-sectional study, Press Ganey surveys (PGS) completed by patients or parents on their first-time visit with 5 general otolaryngology providers from July 2014 to March 2022 were analyzed. Surveys were categorized by child (<18 years old) or adult and consisted of 14 items including 6 service domains of access, visit, nursing, provider, personal issues, and assessment. Analysis was performed with Walsh's t test and analysis of variance. Multivariable logistic regression, controlling for wait times and provider, evaluated the likelihood of highest satisfaction scores (HI-SCORES) based on age. Results: A total of 2549 patients (135 pediatric, 2414 adults) completed the PGS on their initial visit. There was no significant difference in the mean overall satisfaction scores between pediatric and adult patients. Further analysis of service domains among pediatric patients found the mean score in the access domain to be higher for the 6- to 11-year-old age group (0-5 years old: 85.5 ± 20.5 [mean ± SD], 6-11 years old: 94.7 ± 11.5, 12-17 years old: 87.3 ± 15.4, P = .03). Pediatric patients did not have a significantly higher likelihood (odds ratio = 1.1, 95% confidence interval: 0.8-1.6, P > .05) of reporting HI-SCORES compared to adults after covariate adjustment. Conclusion: There was no significant difference in patient satisfaction scores for providers who treat pediatric and adult patients utilizing the same facility and scheduling team.

Genomic context sensitizes regulatory elements to genetic disruption.

Genomic context critically modulates regulatory function but is difficult to manipulate systematically. The murine insulin-like growth factor 2 (Igf2)/H19 locus is a paradigmatic model of enhancer selectivity, whereby CTCF occupancy at an imprinting control region directs downstream enhancers to activate either H19 or Igf2. We used synthetic regulatory genomics to repeatedly replace the native locus with 157-kb payloads, and we systematically dissected its architecture. Enhancer deletion and ectopic delivery revealed previously uncharacterized long-range regulatory dependencies at the native locus. Exchanging the H19 enhancer cluster with the Sox2 locus control region (LCR) showed that the H19 enhancers relied on their native surroundings while the Sox2 LCR functioned autonomously. Analysis of regulatory DNA actuation across cell types revealed that these enhancer clusters typify broader classes of context sensitivity genome wide. These results show that unexpected dependencies influence even well-studied loci, and our approach permits large-scale manipulation of complete loci to investigate the relationship between regulatory architecture and function.

Chemotherapy, immunotherapy, or combination first-line treatment for metastatic urothelial carcinoma of the bladder: A large real-world experience.

INTRODUCTION: First-line systemic therapy for metastatic urothelial carcinoma of the bladder (mUC) consists of platinum-based chemotherapy in most patients and PD1/L1 inhibitors in selected patients. Multiple combination chemoimmunotherapy trials failed to show a clear benefit over chemotherapy alone. We used real-world data to evaluate clinical and sociodemographic factors associated with receipt of first-line chemotherapy, immunotherapy, or combination chemoimmunotherapy treatment for metastatic bladder cancer and examined differences in overall survival (OS). MATERIALS AND METHODS: We used the National Cancer Database to identify patients with stage IV mUC diagnosed between 2014 and 2018, who were treated with first-line immunotherapy, chemotherapy, or combination treatment. We performed multivariable logistic regression modeling to determine factors associated with treatment receipt Adjusted Kaplan-Meier survival analysis and multivariable Cox proportional hazards regression were used to evaluate the association between treatment and OS. RESULTS: In our cohort of 4,169 patients, multivariable analysis identified increasing age (RRR: 1.07, 95%CI, 1.06-1.08) and comorbidity burden (, as independent predictors of receiving immunotherapy. Treatment at an academic facility was associated with increased likelihood of combination treatment (RRR: 1.29, 95%CI, 1.01-1.65). After IPTW, we found that combination therapy (hazard ratio [HR]: 0.72; 95%CI, 0.62-0.83) was associated with improved survival compared to chemotherapy. CONCLUSIONS: Patients with older age and more comorbidities were more likely to receive immunotherapy than chemotherapy for first-line treatment of metastatic urothelial carcinoma of the bladder. Utilization of chemoimmunotherapy was observed to be higher in academic centers and was associated with improved survival compared to chemotherapy.

Tracking amyotrophic lateral sclerosis disease progression using passively collected smartphone sensor data.

BACKGROUND: Passively collected smartphone sensor data provide an opportunity to study physical activity and mobility unobtrusively over long periods of time and may enable disease monitoring in people with amyotrophic lateral sclerosis (PALS). METHODS: We enrolled 63 PALS who used Beiwe mobile application that collected their smartphone accelerometer and GPS data and administered the self-entry ALS Functional Rating Scale-Revised (ALSFRS-RSE) survey. We identified individual steps from accelerometer data and used the Activity Index to summarize activity at the minute level. Walking, Activity Index, and GPS outcomes were then aggregated into day-level measures. We used linear mixed effect models (LMMs) to estimate baseline and monthly change for ALSFRS-RSE scores (total score, subscores Q1-3, Q4-6, Q7-9, Q10-12) and smartphone sensor data measures, as well as the associations between them. FINDINGS: The analytic sample (N = 45) was 64.4% male with a mean age of 60.1 years. The mean observation period was 292.3 days. The ALSFRS-RSE total score baseline mean was 35.8 and had a monthly rate of decline of -0.48 (p-value <0.001). We observed statistically significant change over time and association with ALSFRS-RSE total score for four smartphone sensor data-derived measures: walking cadence from top 1 min and log-transformed step count, step count from top 1 min, and Activity Index from top 1 min. INTERPRETATION: Smartphone sensors can unobtrusively track physical changes in PALS, potentially aiding disease monitoring and future research.

Contemporary morbidity and mortality of open versus robotic cystectomy for bladder cancer: An analysis of the National Surgical Quality Improvement Program (NSQIP) procedure targeted cystectomy database.

OBJECTIVES: To evaluate the association between surgical modality (RARC vs. ORC) and the risk of 30-day complications. MATERIALS AND METHODS: We utilized the American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) Cystectomy-Targeted database from 2019 to 2021. The primary outcome was a composite of major complications including 30-day mortality, reoperation, cardiac events, and stroke. Secondary outcomes included individual major and cystectomy-specific complications. Propensity score matching (PSM) was employed to minimize inherent differences within our cohort. We performed logistic regression to assess the association between outcomes of interest and operative modality. RESULTS: We found no difference between operative modality and the primary outcome, however, RARC was associated with a 70% lower risk of 30-day mortality (OR 0.30, 95% CI 0.13-0.70) and had favorable outcomes with respect to respiratory, deep venous thrombosis, wound complications, and length of stay. Limitations are related to residual confounding given the observational methodology. CONCLUSIONS: RARC was associated with reduced risk of multiple 30-day complications, including mortality, as well as organ system and cystectomy-specific outcomes. These data support the clinical benefit of increased adoption of RARC.

Proteomics identifies complement protein signatures in patients with alcohol-associated hepatitis.

Diagnostic challenges continue to impede development of effective therapies for successful management of alcohol-associated hepatitis (AH), creating an unmet need to identify noninvasive biomarkers for AH. In murine models, complement contributes to ethanol-induced liver injury. Therefore, we hypothesized that complement proteins could be rational diagnostic/prognostic biomarkers in AH. Here, we performed a comparative analysis of data derived from human hepatic and serum proteome to identify and characterize complement protein signatures in severe AH (sAH). The quantity of multiple complement proteins was perturbed in liver and serum proteome of patients with sAH. Multiple complement proteins differentiated patients with sAH from those with alcohol cirrhosis (AC) or alcohol use disorder (AUD) and healthy controls (HCs). Serum collectin 11 and C1q binding protein were strongly associated with sAH and exhibited good discriminatory performance among patients with sAH, AC, or AUD and HCs. Furthermore, complement component receptor 1-like protein was negatively associated with pro-inflammatory cytokines. Additionally, lower serum MBL associated serine protease 1 and coagulation factor II independently predicted 90-day mortality. In summary, meta-analysis of proteomic profiles from liver and circulation revealed complement protein signatures of sAH, highlighting a complex perturbation of complement and identifying potential diagnostic and prognostic biomarkers for patients with sAH.

Membrane-bound O-acyltransferase 7 (MBOAT7) shapes lysosomal lipid homeostasis and function to control alcohol-associated liver injury.

Recent genome-wide association studies (GWAS) have identified a link between single-nucleotide polymorphisms (SNPs) near the MBOAT7 gene and advanced liver diseases. Specifically, the common MBOAT7 variant (rs641738) associated with reduced MBOAT7 expression is implicated in non-alcoholic fatty liver disease (NAFLD), alcohol-associated liver disease (ALD), and liver fibrosis. However, the precise mechanism underlying MBOAT7-driven liver disease progression remains elusive. Previously, we identified MBOAT7-driven acylation of lysophosphatidylinositol lipids as key mechanism suppressing the progression of NAFLD (Gwag et al., 2019). Here, we show that MBOAT7 loss of function promotes ALD via reorganization of lysosomal lipid homeostasis. Circulating levels of MBOAT7 metabolic products are significantly reduced in heavy drinkers compared to healthy controls. Hepatocyte- (Mboat7-HSKO), but not myeloid-specific (Mboat7-MSKO), deletion of Mboat7 exacerbates ethanol-induced liver injury. Lipidomic profiling reveals a reorganization of the hepatic lipidome in Mboat7-HSKO mice, characterized by increased endosomal/lysosomal lipids. Ethanol-exposed Mboat7-HSKO mice exhibit dysregulated autophagic flux and lysosomal biogenesis, associated with impaired transcription factor EB-mediated lysosomal biogenesis and autophagosome accumulation. This study provides mechanistic insights into how MBOAT7 influences ALD progression through dysregulation of lysosomal biogenesis and autophagic flux, highlighting hepatocyte-specific MBOAT7 loss as a key driver of ethanol-induced liver injury.

Association of county-level food deserts and food swamps on postoperative outcomes among patients undergoing colorectal surgery.

BACKGROUND: Although malnutrition has been linked to worse healthcare outcomes, the broader context of food environments has not been examined relative to surgical outcomes. We sought to define the impact of food environment on postoperative outcomes of patients undergoing resection for colorectal cancer (CRC). METHODS: Patients who underwent surgery for CRC between 2014 and 2020 were identified from the Medicare database. Patient-level data were linked to the United States Department of Agriculture data on food environment. Multivariable regression was used to examine the association between food environment and the likelihood of achieving a textbook outcome (TO). TO was defined as the absence of an extended length of stay (≥75th percentile), postoperative complications, readmission, and mortality within 90 days. RESULTS: A total of 260,813 patients from 3017 counties were included in the study. Patients from unhealthy food environments were more likely to be Black, have a higher Charlson Comorbidity Index, and reside in areas with higher social vulnerability (all P < .01). Patients residing in unhealthy food environments were less likely to achieve a TO than that of patients residing in the healthiest food environments (food swamp: 48.8% vs 52.4%; food desert: 47.9% vs 53.7%; P < .05). On multivariable analysis, individuals residing in the unhealthy food environments had lower odds of achieving a TO than those of patients living in the healthiest food environments (food swamp: OR, 0.86; 95% CI, 0.83-0.90; food desert: OR, 0.79; 95% CI, 0.76-0.82); P < .05). CONCLUSION: The surrounding food environment of patients may serve as a modifiable sociodemographic risk factor that contributes to disparities in postoperative CRC outcomes.

Real-time near infrared artificial intelligence using scalable non-expert crowdsourcing in colorectal surgery.

Surgical artificial intelligence (AI) has the potential to improve patient safety and clinical outcomes. To date, training such AI models to identify tissue anatomy requires annotations by expensive and rate-limiting surgical domain experts. Herein, we demonstrate and validate a methodology to obtain high quality surgical tissue annotations through crowdsourcing of non-experts, and real-time deployment of multimodal surgical anatomy AI model in colorectal surgery.

Inflammatory bowel disease-associated colorectal cancer negatively affects surgery outcomes and health care costs.

BACKGROUND: Inflammatory bowel disease may affect the pathogenesis and clinicopathologic course of colorectal cancer. We sought to characterize the impact of inflammatory bowel disease on outcomes after colectomy and/or proctectomy for a malignant indication. METHODS: Patients diagnosed with colorectal cancer as well as a pre-existing comorbid diagnosis of Crohn's disease or ulcerative colitis between 2018 and 2021 were identified from Medicare claims data. The postoperative textbook outcome was defined as the absence of complications, as well as no extended hospital stay, 90-day readmission, or mortality. Postdischarge disposition and expenditures were also examined. RESULTS: Among 191,684 patients with colorectal cancer, 4,770 (2.5%) had a pre-existing diagnosis of inflammatory bowel disease. Patients with inflammatory bowel disease-associated colorectal cancer were less likely to undergo surgical resection (no inflammatory bowel disease: 47.6% vs inflammatory bowel disease: 42.1%; P < .001). Among patients who did undergo colorectal surgery, individuals with inflammatory bowel disease were less likely to achieve a textbook outcome (odds ratio 0.64 [95% confidence interval 0.58-0.70]). In particular, patients with inflammatory bowel disease had higher odds of postoperative complications (odds ratio 1.24 [1.12-1.38]), extended hospital stay (odds ratio 1.41 [1.27-1.58]), and readmission within 90 days (odds ratio 1.56 [1.42-1.72]) (all P < .05). Patients with inflammatory bowel disease-associated colorectal cancer were less likely to be discharged to their home under independent care (odds ratio 0.77 [0.68-0.87]) and had 12.2% higher expenditures, which correlated with whether the patient had a postoperative textbook outcome. CONCLUSION: One in 40 patients with colorectal cancer had concomitant inflammatory bowel disease. Inflammatory bowel disease was associated with a lower probability of achieving ideal postoperative outcomes, higher postdischarge expenditure, as well as worse long-term survival after colorectal cancer resection.

Systemic Bevacizumab for Recurrent Respiratory Papillomatosis: A Single Institution's Experience.

OBJECTIVES: Medical therapies to limit disease recurrence are critically needed for recurrent respiratory papillomatosis (RRP). Systemic bevacizumab is emerging as an exciting adjuvant therapy toward this end, but uptake has been poor due to the lack of experience and awareness of best prescribing practices. The objective of this study was to describe a single tertiary care academic medical center's experience using systemic bevacizumab for the treatment of RRP. METHODS: A retrospective review was performed to identify patients with RRP on systemic bevacizumab. Demographic and clinical characteristics, findings on imaging reports, and disease response at all anatomic subsites involved in papilloma were documented. RESULTS: Of the 17 RRP patients on systemic bevacizumab, 9 (52.9%) were male, and 12 (70.6%) were diagnosed with juvenile-onset RRP. The total lifetime number of surgeries was high, with more than half (n = 9; 52.9%) undergoing more than 50 surgeries. Following induction of systemic bevacizumab, a significant reduction in patients with laryngeal (n = 15; 94.1% vs. n = 7; 41.2%, p < 0.001) and tracheal (n = 11; 64.7% vs. n = 5; 29.4%, p = 0.04) RRP was noted. Surgical frequency was significantly lower following systemic bevacizumab (2.5 vs. 0.5 surgeries per year; p < 0.001). The most common complications were new-onset hypertension (n = 4; 23.5%) and proteinuria (n = 5; 29.4%). CONCLUSION: Systemic bevacizumab is effective in reducing the number of surgeries needed for RRP while exhibiting a relatively safe complication profile. Papillomas in the larynx and trachea are most responsive to systemic bevacizumab, while pulmonary RRP is most likely to exhibit a partial-to-stable response. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3253-3259, 2024.

The Utilization of Fine-Needle Vasography to Localize Obstruction of the Male Reproductive Tract.

OBJECTIVE: To report our experience using fine-needle vasography (FNV) to identify a site of obstruction and determine candidacy for reconstructive procedures in patients presenting with suspected obstructive azoospermia (OA) or cryptozoospermia. METHODS: We report a multi-institutional case series of patients with suspected complete or partial OA. Patients that were included had azoospermia or cryptozoospermia, presence of palpable vasa, testicles ≥12 mL, and FSH <7.6 IU/L. All patients underwent testicular biopsy prior to or at the time of FNV to confirm spermatogenesis. FNV was performed using a 25-gauge angiocatheter, with radio-opaque dye visualized under fluoroscopy. Descriptive statistics are reported as median and interquartile range (IQR). RESULTS: A total of 16 patients underwent vasography from 2014 to 2022 with 3 surgeons. Twelve patients presented with azoospermia, and 4 with cryptozoospermia. A total of 7 (44%) men were found to have distal obstruction on FNV. Of the 8 men with prior inguinal hernia repairs, 2 were confirmed to have an obstruction at the level of the inguinal canal. Of the 6 patients with a history of genitourinary infection, 4 had an obstruction at the level of the epididymis (with normal FNV), while 2 had atresia of the vas deferens in the pelvis. CONCLUSION: FNV is an effective, minimally invasive way to identify the site of complete or partial obstruction in patients presenting with suspected OA/cryptozoospermia. It additionally permits identification of men who are candidates for epididymovasostomy reconstruction and helps to differentiate between ejaculatory duct obstruction (EDO) and other causes of blockage.

Clinical Utility of Laser Speckle Contrast Imaging and Real-Time Quantification of Bowel Perfusion in Minimally Invasive Left-Sided Colorectal Resections.

BACKGROUND: Left-sided colorectal surgery demonstrates high anastomotic leak rates, with tissue ischemia thought to influence outcomes. Indocyanine green is commonly used for perfusion assessment, but evidence remains mixed for whether it reduces colorectal anastomotic leaks. Laser speckle contrast imaging provides dye-free perfusion assessment in real-time through perfusion heat maps and quantification. OBJECTIVE: This study investigates the efficacy of advanced visualization (indocyanine green versus laser speckle contrast imaging), perfusion assessment, and utility of laser speckle perfusion quantification in determining ischemic margins. DESIGN: Prospective intervention group using advanced visualization with case-matched, retrospective control group. SETTINGS: Single academic medical center. PATIENTS: Forty adult patients undergoing elective, minimally invasive, left-sided colorectal surgery. INTERVENTIONS: Intraoperative perfusion assessment using white light imaging and advanced visualization at 3 time points: T1-proximal colon after devascularization, before transection, T2-proximal/distal colon before anastomosis, and T3-completed anastomosis. MAIN OUTCOME MEASURES: Intraoperative indication of ischemic line of demarcation before resection under each visualization method, surgical decision change using advanced visualization, post hoc laser speckle perfusion quantification of colorectal tissue, and 30-day postoperative outcomes. RESULTS: Advanced visualization changed surgical decision-making in 17.5% of cases. For cases in which surgeons changed a decision, the average discordance between the line of demarcation in white light imaging and advanced visualization was 3.7 cm, compared to 0.41 cm ( p = 0.01) for cases without decision changes. There was no statistical difference between the line of ischemic demarcation using laser speckle versus indocyanine green ( p = 0.16). Laser speckle quantified lower perfusion values for tissues beyond the line of ischemic demarcation while suggesting an additional 1 cm of perfused tissue beyond this line. One (2.5%) anastomotic leak occurred in the intervention group. LIMITATIONS: This study was not powered to detect differences in anastomotic leak rates. CONCLUSIONS: Advanced visualization using laser speckle and indocyanine green provides valuable perfusion information that impacts surgical decision-making in minimally invasive left-sided colorectal surgeries. See Video Abstract . UTILIDAD CLNICA DE LAS IMGENES DE CONTRASTE MOTEADO CON LSER Y LA CUANTIFICACIN EN TIEMPO REAL DE LA PERFUSIN INTESTINAL EN RESECCIONES COLORRECTALES DEL LADO IZQUIERDO MNIMAMENTE INVASIVAS: ANTECEDENTES:La cirugía colorrectal del lado izquierdo demuestra altas tasas de fuga anastomótica, y se cree que la isquemia tisular influye en los resultados. El verde de indocianina se utiliza habitualmente para evaluar la perfusión, pero la evidencia sobre si reduce las fugas anastomóticas colorrectales sigue siendo contradictoria. Las imágenes de contraste moteado con láser proporcionan una evaluación de la perfusión sin colorantes en tiempo real a través de mapas de calor de perfusión y cuantificación.OBJETIVO:Este estudio investiga la eficacia de la evaluación de la perfusión mediante visualización avanzada (verde de indocianina versus imágenes de contraste moteado con láser) y la utilidad de la cuantificación de la perfusión con moteado láser para determinar los márgenes isquémicos.DISEÑO:Grupo de intervención prospectivo que utiliza visualización avanzada con un grupo de control retrospectivo de casos emparejados.LUGARES:Centro médico académico único.PACIENTES:Cuarenta pacientes adultos sometidos a cirugía colorrectal electiva, mínimamente invasiva, del lado izquierdo.INTERVENCIONES:Evaluación de la perfusión intraoperatoria mediante imágenes con luz blanca y visualización avanzada en tres puntos temporales: T1-colon proximal después de la devascularización, antes de la transección; T2-colon proximal/distal antes de la anastomosis; y T3-anastomosis completa.PRINCIPALES MEDIDAS DE VALORACIÓN:Indicación intraoperatoria de la línea de demarcación isquémica antes de la resección bajo cada método de visualización, cambio de decisión quirúrgica mediante visualización avanzada, cuantificación post-hoc de la perfusión con láser moteado del tejido colorrectal y resultados posoperatorios a los 30 días.RESULTADOS:La visualización avanzada cambió la toma de decisiones quirúrgicas en el 17,5% de los casos. Para los casos en los que los cirujanos cambiaron una decisión, la discordancia promedio entre la línea de demarcación en las imágenes con luz blanca y la visualización avanzada fue de 3,7 cm, en comparación con 0,41 cm (p = 0,01) para los casos sin cambios de decisión. No hubo diferencias estadísticas entre la línea de demarcación isquémica utilizando láser moteado versus verde de indocianina (p = 0,16). El moteado con láser cuantificó valores de perfusión más bajos para los tejidos más allá de la línea de demarcación isquémica y al mismo tiempo sugirió 1 cm adicional de tejido perfundido más allá de esta línea. Se produjo una fuga anastomótica (2,5%) en el grupo de intervención.LIMITACIONES:Este estudio no tuvo el poder estadístico suficiente para detectar diferencias en las tasas de fuga anastomótica.CONCLUSIONES:La visualización avanzada utilizando moteado láser y verde de indocianina proporciona información valiosa sobre la perfusión que impacta la toma de decisiones quirúrgicas en cirugías colorrectales mínimamente invasivas del lado izquierdo. (Traducción-Dr. Ingrid Melo).

On the genetic basis of tail-loss evolution in humans and apes.

The loss of the tail is among the most notable anatomical changes to have occurred along the evolutionary lineage leading to humans and to the 'anthropomorphous apes'1-3, with a proposed role in contributing to human bipedalism4-6. Yet, the genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown. Here we present evidence that an individual insertion of an Alu element in the genome of the hominoid ancestor may have contributed to tail-loss evolution. We demonstrate that this Alu element-inserted into an intron of the TBXT gene7-9-pairs with a neighbouring ancestral Alu element encoded in the reverse genomic orientation and leads to a hominoid-specific alternative splicing event. To study the effect of this splicing event, we generated multiple mouse models that express both full-length and exon-skipped isoforms of Tbxt, mimicking the expression pattern of its hominoid orthologue TBXT. Mice expressing both Tbxt isoforms exhibit a complete absence of the tail or a shortened tail depending on the relative abundance of Tbxt isoforms expressed at the embryonic tail bud. These results support the notion that the exon-skipped transcript is sufficient to induce a tail-loss phenotype. Moreover, mice expressing the exon-skipped Tbxt isoform develop neural tube defects, a condition that affects approximately 1 in 1,000 neonates in humans10. Thus, tail-loss evolution may have been associated with an adaptive cost of the potential for neural tube defects, which continue to affect human health today.