Fear of Cancer Recurrence in Adult Survivors of Childhood Cancer.

Importance: Fear of cancer recurrence is common among survivors of adult-onset cancer and associated with increased distress, functional impairment, and health care utilization. However, little is known about the prevalence and risk factors of fear of cancer recurrence among adult survivors of childhood cancer who are also at high risk for subsequent malignant neoplasms. Objective: To characterize the prevalence of and risk factors for clinically significant fear of cancer recurrence in adult survivors of childhood cancer. Design, Setting, and Participants: This cross-sectional investigation included participants recruited from the Childhood Cancer Survivor Study, a retrospective cohort study of long-term childhood cancer survivors treated at 31 institutions between 1970 and 1999 across North America. Participants were recruited and completed psychosocial measures via online survey between October 2018 and April 2019. Cancer and treatment-related variables were abstracted from medical records. Data were analyzed from May 2023 to July 2024. Main Outcomes and Measures: Clinically significant fear of cancer recurrence was assessed via the Fear of Cancer Recurrence Inventory-Short Form. Poisson regression models estimated prevalence ratios (PRs) with 95% CIs adjusted for age and sex to examine the associations of demographic, disease, treatment, and psychosocial variables with fear of cancer recurrence. Results: The final sample included 229 adult survivors of childhood cancer (115 female [50.2%]; mean [SD] age, 39.6 [9.9] years; mean [SD] time since diagnosis, 31.7 [8.4] years). Among survivors, 38 (16.6%; 95% CI, 11.6%-21.6%) reported clinically significant fear of cancer recurrence, and an additional 36 (15.7%) reported high fear of cancer recurrence. Clinically significant fear of cancer recurrence was associated with unemployment (PR, 2.5; 95% CI, 1.3-4.8), presence of neurologic chronic health conditions (PR, 3.3; 95% CI, 1.8-6.1), treatment with pelvic radiation (PR, 2.9; 95% CI, 1.5-5.6), and amputation or limb sparing surgery (PR, 2.4; 95% CI, 1.2-4.9). Higher risk of clinically significant fear of cancer recurrence was also associated with having either elevated anxiety or depression (PR, 2.6; 95% CI, 1.2-5.9), having both elevated (PR, 3.2; 95% CI, 1.2-8.4), and perceived poor health status (PR, 3.0; 95% CI, 3.1-9.7). Conclusions and Relevance: Decades following treatment, one-third of childhood cancer survivors in this study reported elevated fear their cancer will recur or a subsequent malignant neoplasm will develop. Findings suggest that fear of cancer recurrence should be routinely screened, and clinically significant symptoms intervened upon as a part of survivorship care.

General Obesity and Prostate Cancer in Relation to Abdominal Obesity and Ethnic Groups: A US Population-Based Cross-Sectional Study.

Background: Research suggests inconsistent evidence regarding the association between general obesity and prostate cancer among men in the United States. This study aimed to examine whether the association between general obesity and prostate cancer is influenced by abdominal obesity and ethnic groups. Methods: The study utilized data from the National Health and Nutrition Examination Survey (NHANES). The analysis was restricted to non-Hispanic men (10,683 White and 6,020 Black). Obesity was defined as body mass index (BMI) ≥30 and abdominal obesity as waist circumference (WC) ≥102 cm. Results: No significant difference was identified in the overall prevalence of prostate cancer between obese and non-obese (2.14% vs 2.25%, P = 0.678). When both obesity measures were combined, the general and abdominal obesity category was associated with a significant increase in the odds of prostate cancer in Black men [odds ratio (OR) = 1.49, 95% confidence interval (CI) (1.09, 2.04)], but not in White men [OR = 1.29, 95% CI (0.91, 1.82)]. In both Black [OR = 2.46, 95% CI (1.48, 4.06)] and White men [OR = 1.60, 95% CI (1.16, 2.21)], abdominal obesity was associated with significant increase in the odds of prostate cancer. Conclusion: The association between general obesity and prevalence of prostate cancer depends on abdominal obesity and ethnic groups. Our study utilized a nationally representative survey and emphasized the potential of combined effect of general and abdominal obesity as a modifiable factor to decrease racial disparity in prostate cancer screening and poor outcomes.

Neighborhood Vulnerability and Associations with Poor Health-Related Quality-of-Life Among Adult Survivors of Childhood Cancer.

BACKGROUND: Few studies investigate the relationship between neighborhood vulnerability and health-related quality-of-life (HRQOL) in the childhood cancer population. This study evaluated the impact of neighborhood vulnerability on HRQOL among adult survivors of childhood cancer. METHODS: This cross-sectional study included 4,393 adult survivors of childhood cancer from the St Jude Lifetime Cohort Study. At the baseline (2007-2020), HRQOL was assessed using the SF36v2's physical/mental components summaries (PCS/MCS). Neighborhood vulnerability was assessed using the overall, domain, and indicator-specific scores of the Social Vulnerability Index (SVI) and Minority Health SVI (MHSVI). Multivariable logistic regression was used to evaluate associations of neighborhood vulnerability (quartiles: Q1-Q4) with impaired HRQOL (1SD below the norm), adjusting for diagnosis, demographics, personal socioeconomic status (SES), lifestyle, and chronic health condition burden. Interactions of SVI/MHSVI with personal SES on impaired HRQOL were analyzed. RESULTS: Among survivors, 51.9% were male, averaging 30.3 years of age at evaluation and 21.5 years since diagnosis. Comparing neighborhoods with higher vs lower vulnerability (Q4 vs Q1), overall (OR = 1.60, 95%CI = 1.19-2.16) and domain-specific vulnerability (socioeconomic: OR = 1.59, 95%CI = 1.18-2.15; household composition: OR = 1.54, 95%CI = 1.16-2.06; housing/transportation: OR = 1.33, 95%CI = 1.00-1.76; medical vulnerability: OR = 1.60, 95%CI = 1.22-2.09) were significantly associated with impaired PCS, but not MCS. Residing in neighborhoods lacking urgent care clinics was significantly associated with impaired PCS (OR = 1.39, 95%CI = 1.08-1.78). Having lower vs higher personal education and living in higher vulnerability neighborhoods were associated with more impaired PCS (P  interaction=0.021). CONCLUSIONS: Specific aspects of neighborhood vulnerability increase the risk for impaired physical HRQOL. Addressing these neighborhood factors is essential to enhance the HRQOL of survivors.

Frequent CHD1 deletions in prostate cancers of African American men is associated with rapid disease progression.

We analyzed genomic data from the prostate cancer of African- and European American men to identify differences contributing to racial disparity of outcome. We also performed FISH-based studies of Chromodomain helicase DNA-binding protein 1 (CHD1) loss on prostate cancer tissue microarrays. We created CHD1-deficient prostate cancer cell lines for genomic, drug sensitivity and functional homologous recombination (HR) activity analysis. Subclonal deletion of CHD1 was nearly three times as frequent in prostate tumors of African American than in European American men and it associates with rapid disease progression. CHD1 deletion was not associated with HR deficiency associated mutational signatures or HR deficiency as detected by RAD51 foci formation. This was consistent with the moderate increase of olaparib and talazoparib sensitivity with several CHD1 deficient cell lines showing talazoparib sensitivity in the clinically relevant concentration range. CHD1 loss may contribute to worse disease outcome in African American men.

Using mHealth Technology to Evaluate Daily Symptom Burden among Adult Survivors of Childhood Cancer: A Feasibility Study.

BACKGROUND: Cancer therapies predispose survivors to a high symptom burden. This study utilized mobile health (mHealth) technology to assess the feasibility of collecting daily symptoms from adult survivors of childhood cancer to evaluate symptom fluctuation and associations with future health-related quality-of-life (HRQOL). METHODS: This prospective study used an mHealth platform to distribute a 20-item cancer-related symptom survey (5 consecutive days each month) and an HRQOL survey (the day after the symptom survey) over 3 consecutive months to participants from the Childhood Cancer Survivor Study. These surveys comprised a PROMIS-29 Profile and Neuro-QOL assessed HRQOL. Daily symptom burden was calculated by summing the severity (mild, moderate, or severe) of 20 symptoms. Univariate linear mixed-effects models were used to analyze total, person-to-person, day-to-day, and month-to-month variability for the burden of 20 individual symptoms. Multivariable linear regression was used to analyze the association between daily symptom burden in the first month and HRQOL in the third month, adjusted for covariates. RESULTS: Out of the 60 survivors invited, 41 participated in this study (68% enrollment rate); 83% reported their symptoms ≥3 times and 95% reported HRQOL in each study week across 3 months. Variability of daily symptom burden differed from person-to-person (74%), day-to-day (18%), and month-to-month (8%). Higher first-month symptom burden was associated with poorer HRQOL related to anxiety (regression coefficient: 6.56; 95% CI: 4.10-9.02), depression (6.32; 95% CI: 3.18-9.47), fatigue (7.93; 95% CI: 5.11-10.80), sleep (6.07; 95% CI: 3.43-8.70), pain (5.16; 95% CI: 2.11-8.22), and cognitive function (-6.89; 95% CI: -10.00 to -3.79) in the third month. CONCLUSIONS: Daily assessment revealed fluctuations in symptomology, and higher symptom burden was associated with poorer HRQOL in the future. Utilizing mHealth technology for daily symptom assessment improves our understanding of symptom dynamics and sources of variability.

Outcomes of synthetic and biologic mesh in abdominal wall reconstruction: A propensity-matched analysis in Centers for Disease Control and Prevention class 1 and 2 wounds.

INTRODUCTION: The choice of biologic compared with synthetic mesh in abdominal wall reconstruction remains controversial, especially in Centers for Disease Control and Prevention class 1 and 2 wounds. This study evaluated wound complications and hernia recurrence with a 2:1 propensity-matched sample and extended follow-up. METHODS AND PROCEDURES: A prospectively maintained abdominal wall reconstruction database was queried for patients undergoing open abdominal wall reconstruction using biologic or synthetic mesh in Centers for Disease Control and Prevention class 1 and 2 wounds. Patients receiving synthetic or biologic mesh were propensity score matched in a 2:1 fashion. Univariate, bivariate, and inferential analyses were conducted. Unless stated, data are reported as biologic compared with synthetic. RESULTS: In total, 519 patients were compared, 173 with biologic and 346 with synthetic mesh. Defect size (215.2 ± 153.6 cm2 vs 251.5 ± 284.3 cm2), body mass index (33.6 ± 9 kg/m2 vs 34 ±17.7 kg/m2), and comorbidities were well matched (all P > .05). Although Centers for Disease Control and Prevention wound class was used in the match, it was significantly different between groups (Centers for Disease Control and Prevention 1:43.4% vs 81.2%, Centers for Disease Control and Prevention 2:56.6% vs 18.8%; P < .001). The rate of component separation (40.1% vs 44.2%; P = .397), fascial closure (97.7% vs 98.3%; P = .738), and panniculectomy (33.5% vs 29.2%; P = .315) were similar. Mesh size was also similar (816.4 ± 555.5 vs 892.2 ± 487.8 cm2; P = .112). Wound complications were equal, including wound breakdown (10.5% vs 7.5%; P = .315), wound cellulitis (5.2% vs 5.8%; P = .843), wound infection (7.5% vs 4.6%; P = .223), seroma requiring intervention (6.4% vs 7.8%; P = .597), and mesh infection (1.2% vs 0.9%; P > .999). The biologic group had an increased length of stay (6.8 ± 5.5 days vs 5.4 ± 2.3 days; P < .001) and greater hospital charges ($82,181 ± 50,356 vs $62,221 ± 26,817 USD; P < .001). Mean follow-up after biologic repair was longer (33.9 ± 36.6 months vs 23.3 ± 32.3 months; P < .001). Hernia recurrence between the biologic and synthetic groups was not significantly different (2.9% vs 1.4%; P = .313). On multivariable regression, wound complications were predictive of recurrence, and panniculectomy was predictive of wound complications. CONCLUSION: In a 2:1 matched analysis of Centers for Disease Control and Prevention 1 and 2 wounds with nearly 3-years of follow-up, biologic and synthetic mesh had similar rates of wound complications and recurrence in abdominal wall reconstruction.

Implementation of a penicillin allergy protocol in open abdominal wall reconstruction: Preoperative optimization program.

INTRODUCTION: Beta-lactam prophylaxis is the first-line preoperative antibiotic in open abdominal wall reconstruction. However, of the 11% patients reporting a penicillin allergy (PA), most receive second-line, non-ß-lactam prophylaxis. Previously, abdominal wall reconstruction research from our institution demonstrated increased wound complications, readmissions, and reoperations with non-ß-lactam prophylaxis. Therefore, a collaborative quality improvement initiative was developed with the infectious disease service, and a penicillin allergy protocol was instituted that stratified patients' risk of allergic reaction with a goal to increase ß-lactam prophylaxis use. The effect of the penicillin allergy protocol on open abdominal wall reconstruction outcomes was prospectively evaluated. METHODS: Patients with penicillin allergy undergoing open abdominal wall reconstruction were identified and grouped according to penicillin allergy protocol implementation. Pre-penicillin allergy protocol underwent open abdominal wall reconstruction before January 1, 2020, predominantly receiving non-ß-lactam prophylaxis; post-penicillin allergy protocol underwent open abdominal wall reconstruction between January 1, 2020-November 1, 2023, predominantly receiving ß-lactam prophylaxis. Incidence of surgical site infection was the primary outcome. Standard and inferential statistical analyses were performed. RESULTS: Of 315 patients with penicillin allergy, 250 underwent open abdominal wall reconstruction pre-penicillin allergy protocol and 65 post-penicillin allergy protocol. Pre- and post-penicillin allergy protocol were similar in allergic reaction severity history, sex, race, age, diabetes, American Society of Anesthesiologists score, hernia defect size, and mesh type (P > .05). Post-penicillin allergy protocol had lower body mass index (33.4 ± 7.9 vs 29.8 ± 5.3 kg/m2; P = .002) and fewer active smokers (12.4% vs 1.5%; P = .019). Expectedly, post-penicillin allergy protocol received more ß-lactam prophylaxis (22.8% vs 83.1%; P < .001) and no antibiotic-induced allergic reactions. Post-penicillin allergy protocol had significantly fewer surgical site infections (24.4% vs 3.1%; P < .001), wound breakdown (16.0% vs 3.1%; P = .004), reoperations (19.2% vs 0.0%; P < .001), and readmissions (25.3% vs 9.2%; P = .006) but no statistically significant reduction in recurrence (8.4% vs 1.5%; P = .057). CONCLUSIONS: The penicillin allergy protocol safely increased the number of patients with penicillin allergy undergoing open abdominal wall reconstruction receiving ß-lactam prophylaxis and decreased the rate of surgical site infections, wound complications, reoperations, and readmissions. These data supported the systemwide implementation of the penicillin allergy protocol for both general and orthopedic surgery, which has been incorporated into the electronic medical record of 13 hospitals within the system.

6-Thioguanine nucleotide levels are associated with infliximab but not adalimumab levels in inflammatory bowel disease patients on combination therapy.

BACKGROUND: Thiopurine co-therapy with anti-tumour necrosis factor-alpha (anti-TNFα) agents is associated with higher anti-TNFα drug levels and reduced immunogenicity in inflammatory bowel disease (IBD). AIMS: We aimed to evaluate the association between 6-thioguanine nucleotide (6-TGN) and anti-TNFα levels and the optimal 6-TGN threshold level associated with higher anti-TNFα levels in combination therapy. METHODS: We performed a retrospective cross-sectional multicentre study of patients with IBD on combination anti-TNFα and thiopurine maintenance therapy between January 2015 and August 2021. Primary outcomes were infliximab and adalimumab levels. Secondary outcomes were antibodies to infliximab (ATI) or adalimumab (ATA). Univariable and multivariable linear regression were performed to identify variables associated with anti-TNFα levels. Receiver operator characteristic curves were used to define the optimal 6-TGN cut-off levels associated with therapeutic anti-TNFα levels. RESULTS: The study included 743 paired 6-TGN and anti-TNFα levels (640 infliximab and 103 adalimumab). 6-TGN levels were associated with infliximab levels, but not adalimumab levels, on univariable and multivariable regression. The optimal 6-TGN cut-off associated with therapeutic infliximab levels (≥5 mcg/mL) was 261 pmol/8 × 108 red blood cell (RBC) (area under the curve (AUC) = 0.57) for standard infliximab dosing and 227.5 pmol/8 × 108 RBC (AUC = 0.58) for escalated dosing. For therapeutic adalimumab levels (≥7.5 mcg/mL), the 6-TGN cut-off was 218.5 pmol/8 × 108 RBC (AUC = 0.59) for standard adalimumab dosing and 237.5 pmol/8 × 108 RBC (AUC = 0.63) for escalated dosing. CONCLUSION: 6-TGN levels were weakly associated with infliximab but not adalimumab levels in combination therapy. 6-TGN levels in the lower end of the therapeutic range (230-260 pmol/8 × 108 RBC) may be adequate to maintain higher infliximab levels, particularly with escalated infliximab dosing.

Keratinocyte carcinomas in survivors of childhood cancer: A report from the childhood cancer survivor study.

BACKGROUND: Childhood cancer survivors (CCS) are at increased risk for keratinocyte carcinomas (KC) however, the long-term incidence of single and multiple KC is not well established. OBJECTIVE: Identify risk factors and quantify KC cumulative incidence and multiple-incidence burden in CCS. METHODS: KC were identified among Childhood Cancer Survivor Study participants, a cohort of 5-year cancer survivors diagnosed <21 years of age between 1970 and 1999 in North America. Cumulative incidence was estimated and multivariable models assessed relative rates of KC associated with survivor and treatment characteristics. RESULTS: Among 25,658 participants, 1446 developed 5363 KC (93.5% basal cell carcinoma, 6.7% squamous cell carcinoma; mean age 37.0 years (range 7.3-67.4), mean latency 25.7 years; 95.3% White and 88.4% with radiotherapy). Mean lesion count was 3.7 with 26.1% experiencing ≥4. Radiotherapy imparted a 4.5-fold increase in the rate of any KC and 9.4-fold increase in the rate of ≥4 KC. Allogeneic and autologous hematopoietic cell transplant were associated with a 3.4- and 2.3-fold increased rate of KC, respectively. LIMITATIONS: Participant self-reporting of some data including race without skin phototype and past medical history may have impacted analysis. CONCLUSIONS: The burden of KC in CCS remains high, but predictable risk factors should guide screening.

Sugar and sugar-sweetened beverages in relation to premature aging in adult survivors of childhood cancer.

BACKGROUND: Premature aging is a significant concern in adult survivors of childhood cancer as they develop aging-related conditions at a younger age than their peers with no history of childhood cancer. Although modifiable lifestyle factors, such as diet, are postulated to affect aging process, supporting evidence is sparse. METHODS: We examined if the consumption of sugar and sugar-sweetened beverages was related to premature aging in 3322 adult survivors of childhood cancer in the St. Jude Lifetime Cohort. Premature aging was assessed using the Deficit Accumulation Index (DAI) that was a ratio of the number of age-related chronic health conditions each survivor had out of 44 conditions total. Multinomial logistic regressions adjusting for confounders were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: There were 46% of childhood cancer survivors consumed SSBs once or more times per day. High intake of sugar, especially sugars added to foods during preparation or processing, and habitual consumption of sugar-sweetened beverage were associated with an increased risk of premature aging. DISCUSSION: Our findings support a need to include strategies to reduce sugar and sugar-sweetened beverages consumption in lifestyle interventions to promote healthy aging in adult survivors of childhood cancer.

Associations between perceived cancer impact and measures of health behavior in survivors of childhood cancer.

PURPOSE: Perceived cancer impact (PCI) is the degree to which one feels cancer has impacted one's life. It is unknown if PCI is associated with health behaviors. The aim of this study is to determine associations between PCI and health behaviors in childhood cancer survivors. METHODS: Participants were ≥ 5-year survivors enrolled in the St. Jude Lifetime (SJLIFE) cohort. The Brief Cancer Impact (BCIA) assessed PCI across four domains (caregiving/finances, diet/exercise, social/emotional functioning, religiosity). Responses were categorized as negative, neutral, or positive impact. Smoking, risky drinking, illicit drug use, and diet quality data were obtained via self-report. Physical activity (PA) was assessed via self-report and actigraphy. Cross-sectional and longitudinal associations between PCI and health behaviors were evaluated via multivariable logistic regression. RESULTS: A total of 3623 participants (mean age 30.4 ± 8.3 years, 49.6% female, 81.5% NH White) were included in baseline cross-sectional analysis; 1709 had a second visit 5.0 ± 1.4 years later and were included in longitudinal analysis. At baseline, the percentage of participants who endorsed cancer as having a negative impact on caregiving/finances was 37.5%, diet/exercise 30.5%, social/emotional functioning 40.6%, and religiosity 8.7%. Negative and neutral PCI across all four domains were cross-sectionally associated with all behaviors except illicit drug use. Negative and neutral PCI at the first time point across all four domains were associated with smoking, diet quality, and PA (ORs ranging from 1.35 to 2.41) in longitudinal analyses. CONCLUSIONS: Endorsing negative or neutral PCI is associated with adverse health behaviors. IMPLICATIONS FOR CANCER SURVIVORS: Promoting optimal health behavior should include addressing PCI.

Continuity and coordination of care for childhood cancer survivors with multiple chronic conditions: Results from the Childhood Cancer Survivor Study.

INTRODUCTION: Continuity and coordination-of-care for childhood cancer survivors with multiple chronic conditions are understudied but critical for appropriate follow-up care. METHODS: From April through June 2022, 800 Childhood Cancer Survivor Study participants with two or more chronic conditions (one or more severe/life-threatening/disabling) were emailed the "Patient Perceived Continuity-of-Care from Multiple Clinicians" survey. The survey asked about survivors' main (takes care of most health care) and coordinating (ensures follow-up) provider, produced three care-coordination summary scores (main provider, across multiple providers, patient-provider partnership), and included six discontinuity indicators (e.g., having to organize own care). Discontinuity (yes/no) was defined as poor care on one or more discontinuity item. Chi-square tests assessed associations between discontinuity and sociodemographics. Modified Poisson regression models estimated prevalence ratios (PRs) for discontinuity risk associated with the specialty and number of years seeing the main and coordinating provider, and PRs associated with better scores on the three care-coordination summary measures. Inverse probability weights adjusted for survey non-participation. RESULTS: A total of 377 (47%) survivors responded (mean age 48 years, 68% female, 89% non-Hispanic White, 78% privately insured, 74% ≥college graduate); 147/373 (39%) reported discontinuity. Younger survivors were more likely to report discontinuity (chi-square p = .02). Seeing the main provider ≤3 years was associated with more prevalent discontinuity (PR; 95%CI) (1.17; 1.02-1.34 vs ≥ 10 years). Cancer specialist main providers were associated with less prevalent discontinuity (0.81; 0.66-0.99 vs. primary care). Better scores on all three care-coordination summary measures were associated with less prevalent discontinuity: main provider (0.73; 0.64-0.83), across multiple providers (0.81; 0.78-0.83), patient-provider partnership (0.85; 0.80-0.89). CONCLUSIONS: Care discontinuity among childhood cancer survivors is prevalent and requires intervention.

Frequency of pathogenic germline variants in pediatric medulloblastoma survivors.

Background: Medulloblastoma is the most common malignant brain tumor in children. Most cases are sporadic, but well characterized germline alterations in APC, ELP1, GPR161, PTCH1, SUFU, and TP53 predispose to medulloblastoma. However, knowledge about pathogenic/likely pathogenic (P/LP) variants that predispose to medulloblastoma vary based on genes evaluated, patient demographics, and pathogenicity definitions. Methods: Germline exome sequencing was conducted on 160 childhood survivors of medulloblastoma. Analyses focused on rare variants in 239 known cancer susceptibility genes (CSGs). P/LP variants were identified using ClinVar and InterVar. Variants of unknown significance in known medulloblastoma predisposing genes (APC, ELP1, GPR161, PTCH1, SUFU, TP53) were further classified for loss of function variants. We compared the frequency of P/LP variants in cases to that in 1,259 cancer-free adult controls. Results: Twenty cases (12.5%) had a P/LP variant in an autosomal dominant CSG versus 5% in controls (p=1.0 x10-3), and 10 (6.3%) of these were P/LP variants in a known medulloblastoma gene, significantly greater than 0.2% observed in controls (p=1.4x10-8). The CSGs with the most P/LP variants in cases, and significantly higher than controls, were ELP1 (p=3.0x10-4) and SUFU (p=1.4x10-3). Conclusion: Approximately one in eight pediatric medulloblastoma survivors had an autosomal dominant P/LP CSG variant. We confirm several known associated genes and identify novel genes that may be important in medulloblastoma.

Repair of bucket handle meniscus tears improves patient outcomes versus partial meniscectomy at the time of ACL reconstruction.

Purpose: The aim of this study was to examine demographic and surgical factors that influence patient-reported knee function in patients who undergo anterior crucial ligament reconstruction (ACLR) with concurrent bucket-handle meniscal tear (BHMT) procedures. We hypothesized that repair of BHMT in the setting of concomitant ACLR and shorter time from injury to surgery would lead to improved patient-reported outcomes. Methods: Forty-one patients (mean age: 28.0 ± 9.8 years, 72% male) with BHMT at the time of ACLR completed the International Knee Documentation Committee Subjective Knee Form (IKDC-SKF) via online survey at an average of 15.2 months postop. Patient demographics and surgical characteristics, including time from injury to surgery, were compared between repair (n = 22) and meniscectomy (n = 19) groups using one-way analysis of variances; distributions of sex, graft source, BHMT compartment and zone were compared between groups using χ 2 tests. The association between IKDC-SKF score, demographics and surgical characteristics was evaluated using multivariable linear regression. A priori alpha level was p < 0.05. Results: Meniscal repair and meniscectomy groups differed based on graft source and BHMT zone but not IKDC-SKF score (p = 0.085). Patients undergoing ACLR with autograft (p = 0.003) and with red-red zone BHMT (p < 0.001) more often underwent meniscal repair. The regression model demonstrated longer time from injury to surgery (p = 0.049), red-red tear zone (p = 0.04) and meniscectomy (p = 0.008); these were predictive of poorer IKDC-SKF scores. Conclusion: BHMT repair was more likely performed in ACL autograft and on red-red zone tears. Longer time from injury to surgery is an indicator of poorer IKDC-SKF score, as this may increase the risk of concomitant pathologies. White-white zone BHMTs are associated with better IKDC-SKF scores than red-red zone BHMTs, which may be due to the smaller volume of tissue removed during meniscectomy of white-white zone tears and the avoidance of iatrogenic complications of meniscal repair. Level of Evidence: Level III, therapeutic study.

Comparison of Medical Research Abstracts Written by Surgical Trainees and Senior Surgeons or Generated by Large Language Models.

Importance: Artificial intelligence (AI) has permeated academia, especially OpenAI Chat Generative Pretrained Transformer (ChatGPT), a large language model. However, little has been reported on its use in medical research. Objective: To assess a chatbot's capability to generate and grade medical research abstracts. Design, Setting, and Participants: In this cross-sectional study, ChatGPT versions 3.5 and 4.0 (referred to as chatbot 1 and chatbot 2) were coached to generate 10 abstracts by providing background literature, prompts, analyzed data for each topic, and 10 previously presented, unassociated abstracts to serve as models. The study was conducted between August 2023 and February 2024 (including data analysis). Exposure: Abstract versions utilizing the same topic and data were written by a surgical trainee or a senior physician or generated by chatbot 1 and chatbot 2 for comparison. The 10 training abstracts were written by 8 surgical residents or fellows, edited by the same senior surgeon, at a high-volume hospital in the Southeastern US with an emphasis on outcomes-based research. Abstract comparison was then based on 10 abstracts written by 5 surgical trainees within the first 6 months of their research year, edited by the same senior author. Main Outcomes and Measures: The primary outcome measurements were the abstract grades using 10- and 20-point scales and ranks (first to fourth). Abstract versions by chatbot 1, chatbot 2, junior residents, and the senior author were compared and judged by blinded surgeon-reviewers as well as both chatbot models. Five academic attending surgeons from Denmark, the UK, and the US, with extensive experience in surgical organizations, research, and abstract evaluation served as reviewers. Results: Surgeon-reviewers were unable to differentiate between abstract versions. Each reviewer ranked an AI-generated version first at least once. Abstracts demonstrated no difference in their median (IQR) 10-point scores (resident, 7.0 [6.0-8.0]; senior author, 7.0 [6.0-8.0]; chatbot 1, 7.0 [6.0-8.0]; chatbot 2, 7.0 [6.0-8.0]; P = .61), 20-point scores (resident, 14.0 [12.0-7.0]; senior author, 15.0 [13.0-17.0]; chatbot 1, 14.0 [12.0-16.0]; chatbot 2, 14.0 [13.0-16.0]; P = .50), or rank (resident, 3.0 [1.0-4.0]; senior author, 2.0 [1.0-4.0]; chatbot 1, 3.0 [2.0-4.0]; chatbot 2, 2.0 [1.0-3.0]; P = .14). The abstract grades given by chatbot 1 were comparable to the surgeon-reviewers' grades. However, chatbot 2 graded more favorably than the surgeon-reviewers and chatbot 1. Median (IQR) chatbot 2-reviewer grades were higher than surgeon-reviewer grades of all 4 abstract versions (resident, 14.0 [12.0-17.0] vs 16.9 [16.0-17.5]; P = .02; senior author, 15.0 [13.0-17.0] vs 17.0 [16.5-18.0]; P = .03; chatbot 1, 14.0 [12.0-16.0] vs 17.8 [17.5-18.5]; P = .002; chatbot 2, 14.0 [13.0-16.0] vs 16.8 [14.5-18.0]; P = .04). When comparing the grades of the 2 chatbots, chatbot 2 gave higher median (IQR) grades for abstracts than chatbot 1 (resident, 14.0 [13.0-15.0] vs 16.9 [16.0-17.5]; P = .003; senior author, 13.5 [13.0-15.5] vs 17.0 [16.5-18.0]; P = .004; chatbot 1, 14.5 [13.0-15.0] vs 17.8 [17.5-18.5]; P = .003; chatbot 2, 14.0 [13.0-15.0] vs 16.8 [14.5-18.0]; P = .01). Conclusions and Relevance: In this cross-sectional study, trained chatbots generated convincing medical abstracts, undifferentiable from resident or senior author drafts. Chatbot 1 graded abstracts similarly to surgeon-reviewers, while chatbot 2 was less stringent. These findings may assist surgeon-scientists in successfully implementing AI in medical research.

Using Next-Generation Sequencing to Understand Infection Prevention in Surgical Treatment of Upper Extremity Fractures-A Prospective Cohort Study.

INTRODUCTION: Postoperative fracture site infection can lead to notable patient morbidity, increase cost of care, and further contribute to healthcare disparities globally. Dogma suggests surgical blades as a vehicle for introducing bacteria into the surgical site; however, there is a paucity of literature to support this claim. This study uses advanced DNA sequencing to detect bacterial DNA on surgical blades used in upper extremity fracture surgeries. METHODS: This was a prospective study, conducted at a high-volume level 1 trauma center. All acute, closed upper extremity fractures requiring surgical stabilization were consecutively enrolled in a prospective fashion. The primary end point was the presence of bacterial DNA on the surgical blade using next-generation sequencing (NGS). At the time of surgery, two blades were sterilely opened. One blade served as the control while the other was used for the initial skin incision. Two negative control blades were opened directly into a sterile container. Two positive control blades were used for skin incision through known infections. All samples were sent for NGS analysis. RESULTS: Forty patients were enrolled in this study. The median age was 33.5 years, and 30% were female; the median body mass index was 26.52. Humerus fractures were the most common injury (N = 17, 42.5%), followed by clavicle fractures (13, 32.5%) and radius/ulna fractures (10, 25.0%). NGS analysis revealed no contamination of test blades used for skin incision. Three control blades tested positive for bacterial DNA. Negative control blades tested negative for bacterial DNA (0/2); the positive control blades resulted positive for bacterial DNA contamination (2/2). CONCLUSION: Surgical blades used for skin incision in the upper extremity are not contaminated with bacterial DNA as analyzed by NGS. This finding challenges previous surgical dogma regarding surgical blade contamination and supports that the same surgical blade can safely be used for deeper dissection. LEVEL OF EVIDENCE: Level II study: IRB approval-IRB#848938.

A selective CutMix approach improves generalizability of deep learning-based grading and risk assessment of prostate cancer.

The Gleason score is an important predictor of prognosis in prostate cancer. However, its subjective nature can result in over- or under-grading. Our objective was to train an artificial intelligence (AI)-based algorithm to grade prostate cancer in specimens from patients who underwent radical prostatectomy (RP) and to assess the correlation of AI-estimated proportions of different Gleason patterns with biochemical recurrence-free survival (RFS), metastasis-free survival (MFS), and overall survival (OS). Training and validation of algorithms for cancer detection and grading were completed with three large datasets containing a total of 580 whole-mount prostate slides from 191 RP patients at two centers and 6218 annotated needle biopsy slides from the publicly available Prostate Cancer Grading Assessment dataset. A cancer detection model was trained using MobileNetV3 on 0.5 mm × 0.5 mm cancer areas (tiles) captured at 10× magnification. For cancer grading, a Gleason pattern detector was trained on tiles using a ResNet50 convolutional neural network and a selective CutMix training strategy involving a mixture of real and artificial examples. This strategy resulted in improved model generalizability in the test set compared with three different control experiments when evaluated on both needle biopsy slides and whole-mount prostate slides from different centers. In an additional test cohort of RP patients who were clinically followed over 30 years, quantitative Gleason pattern AI estimates achieved concordance indexes of 0.69, 0.72, and 0.64 for predicting RFS, MFS, and OS times, outperforming the control experiments and International Society of Urological Pathology system (ISUP) grading by pathologists. Finally, unsupervised clustering of test RP patient specimens into low-, medium-, and high-risk groups based on AI-estimated proportions of each Gleason pattern resulted in significantly improved RFS and MFS stratification compared with ISUP grading. In summary, deep learning-based quantitative Gleason scoring using a selective CutMix training strategy may improve prognostication after prostate cancer surgery.

Characterization of chronic pain, pain interference, and daily pain experiences in adult survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

ABSTRACT: Although survivors of childhood cancer are at an increased risk, little is known about the prevalence of chronic pain, associated interference, and daily pain experiences. Survivors (N = 233; mean age = 40.8 years, range 22-64 years; mean time since diagnosis = 32.7 years) from the Childhood Cancer Survivor Study completed pain and psychosocial measures. Survivors with chronic pain completed 2-week, daily measures assessing pain and psychological symptoms using mHealth-based ecological momentary assessment. Multivariable-modified Poisson and linear regression models estimated prevalence ratio estimates (PR) and mean effects with 95% confidence intervals (CI) for associations of key risk factors with chronic pain and pain interference, respectively. Multilevel mixed models examined outcomes of daily pain and pain interference with prior day symptoms. Ninety-six survivors (41%) reported chronic pain, of whom 23 (24%) had severe interference. Chronic pain was associated with previous intravenous methotrexate treatment (PR = 1.6, 95% CI 1.1-2.3), respiratory (PR = 1.8, 95% CI 1.2-2.5), gastrointestinal (PR = 1.6, 95% CI 11.0-2.3), and neurological (PR = 1.5, 95% CI 1.0-2.1) chronic health conditions, unemployment (PR = 1.4, 95% CI 1.0-1.9) and clinically significant depression and anxiety (PR = 2.9, 95% CI 2.0-4.2), as well as a diagnosis of childhood Ewing sarcoma or osteosarcoma (PR = 1.9, 95% CI 1.0-3.5). Higher pain interference was associated with cardiovascular and neurological conditions, unemployment and clinical levels of depression and/or anxiety, and fear of cancer recurrence. For male, but not female survivors, low sleep quality, elevated anxiety, and elevated depression predicted high pain intensity and interference the next day. A substantial proportion of childhood cancer survivors experience chronic pain and significant associated interference. Chronic pain should be routinely evaluated, and interventions are needed.