Citations

Abstract Although follicular lymphoma (FL) typically follows an indolent course, patients with FL who experience early events, such as transformation or progression, have increased risk of death related to lymphoma. The FL24Cx is an algorithm based on a 45-target gene expression profiling (GEP) assay, which was developed and trained using 265 formalin-fixed, paraffin-embedded tissue samples on a reliable platform to predict, at the time of diagnosis, whether a patient will experience an event within 24 months. The modeling also confirmed and relied upon previously reported synergy between immune response (IR) gene expression signatures IR1 and IR2. Once locked, the 5-factor logistic regression FL24Cx model was independently validated in a retrospectively assessed cohort of 232 patients from 2 immunochemotherapy-treated arms of SWOG Cancer Research Network S0016 phase 3 clinical trial, in which it assigned 169 patients to the low-risk group with 29 events before 24 months (17.2%) and 63 patients to the high-risk group with 24 events before 24 months (38.1%). The relative risk of an event within 24 months after registration among patients who were classified into the high-risk group relative to patients who were classified into the low-risk group was 2.2 (95% confidence interval, 1.41 to 3.51). An up-front GEP biomarker, such as the FL24Cx, rigorously validated in a clinical laboratory and with a clinically relevant turnaround time, could identify and steer enrollment of patients at high risk for early events in clinical trials, thus enabling timely interpretation of such trials and increasing the pace of innovation.

Abstract Obesity has been associated with non‐Hodgkin lymphoma (NHL), but the evidence is inconclusive. We examined the association between genetically determined adiposity and four common NHL subtypes: diffuse large B‐cell lymphoma (DLBCL), follicular lymphoma, chronic lymphocytic leukemia, and marginal zone lymphoma, using eight genome‐wide association studies of European ancestry ( N = 10,629 cases, 9505 controls) and constructing polygenic scores for body mass index (BMI), waist‐to‐hip ratio (WHR), and waist‐to‐hip ratio adjusted for BMI (WHRadjBMI). Higher genetically determined BMI was associated with an increased risk of DLBCL [odds ratio (OR) per standard deviation (SD) = 1.18, 95% confidence interval (95% CI): 1.05–1.33, p = .005]. This finding was consistent with Mendelian randomization analyses, which demonstrated a similar increased risk of DLBCL with higher genetically determined BMI (OR per SD = 1.12, 95% CI: 1.02–1.23, p = .03). No significant associations were observed with other NHL subtypes. Our study demonstrates a positive link between a genetically determined BMI and an increased risk of DLBCL, providing additional support for increased adiposity as a risk factor for DLBCL.

ABSTRACT Anaplastic lymphoma kinase‐positive large B‐cell lymphoma (ALK+ LBCL) is a rare, aggressive subtype of diffuse large B‐cell lymphoma with poor outcomes using standard chemotherapy. In this multi‐institutional retrospective study, we analyzed 39 cases of ALK+ LBCL identified at six US academic centers from 2002 to 2024, with treatment including conventional cytotoxic regimens in frontline and biologically informed and nonchemotherapy‐based strategies in the relapsed setting. Ninety‐two percent of patients received frontline anthracycline‐based chemotherapy; 43% received intensified regimens, and 15% underwent upfront autologous stem cell transplantation (ASCT). Despite these approaches, outcomes remained poor. At a median follow‐up of 5.4 years, median event‐free survival (EFS) was 0.6 years (95% CI, 0.4–0.9), and median overall survival (OS) was 1.5 years (95% CI, 1.3–NR). One‐ and five‐year EFS rates were 28% and 17%, while corresponding OS rates were 72% and 42%, respectively. Advanced stage and high IPI scores were associated with inferior outcomes. Twelve patients received ALK inhibitors, with alectinib showing more durable responses than crizotinib. Lenalidomide and immune checkpoint inhibitors also demonstrated activity, including durable complete responses. Five patients underwent allogeneic stem cell transplantation, with three achieving sustained remission. In conclusion, our findings highlight the limited benefit of chemotherapy, even when intensified or followed by ASCT, and support the integration of biologically targeted therapies, which may have contributed to improved OS in our cohort compared to historical outcomes. Prospective, collaborative studies are needed to better understand disease biology and define optimal use of modern therapies in this rare lymphoma.

Surgical outcomes and perioperative factors associated with pediatric cranioplasty remain incompletely understood. The authors queried the National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database to evaluate outcomes and intraoperative/postoperative blood transfusions in patients undergoing cranioplasty between 2019 and 2023. A total of 249 patients (mean age 9.1 ± 5.4 y) were included. Most cranioplasties (70.7%) utilized alloplastic materials compared with autologous. Blood transfusion was required in 24.1% of cases, predominantly on the day of surgery (86.7%). Multivariable analysis identified age (OR: 0.86 per year, 95% CI: 0.80–0.93, P < 0.001) and cranioplasty size >5 cm (versus ≤5 cm) (OR: 2.10, 95% CI: 1.01–4.50, P = 0.049) as predictors of transfusion. The 30-day unplanned readmission rate was 5.3% at a mean of 14.6 ± 7.9 days from surgery, most commonly for a surgical site infection (33.0%). The 30-day unplanned reoperation rate was 2.9%, at a mean of 10.2 ± 5.6 days. Autologous cranioplasty was not associated with higher odds of readmission (OR: 0.79, 95% CI: 0.25–2.13, P = 0.66) or reoperation (OR: 5.04, 95% CI: 0.96–36.99, P = 0.07) compared with alloplastic cranioplasty. Rates of readmission and reoperation following pediatric cranioplasty are comparable to other complex craniofacial procedures. Younger age and larger cranioplasty size are associated with higher rates of blood transfusion. Our results show that autologous reconstruction is not associated with higher short-term complication rates compared with alloplastic reconstruction, although future studies are still needed to further the understanding of the optimal cranioplasty material.

Background: Pediatric orthopaedic surgery encompasses many areas of subspecialization. To improve patient care, quality improvement efforts should focus on high-volume procedures with high complication rates. This study aims to identify these procedures to better target research and quality-improvement initiatives. Methods: Patients undergoing one of the 30 most common orthopaedic procedures in NSQIP pediatric data from 2012 to 2022 were analyzed for 30-day complications, infections, unplanned reoperations, and unplanned readmissions. Multivariable models assessed associations between procedure type and adverse events, adjusted for patient characteristics. Tibial osteotomy (TO) was defined as the reference category for procedure in each model as it is a common procedure with a moderate risk profile and a similar complication rate across the cohort. Results: 191,381 patients were included in the analysis (median: 10 y, IQR: 5 to 13; 48.7% male). The 30-day overall complication rate was 2.3% (n=4401), with infections occurring in 1.6% of cases (n=3005). Unplanned reoperations occurred in 1.7% (n=3207), and the unplanned readmission rate was 2.0% per 30 person-days. The most performed procedures were posterior spine fusion (PSF; n=45,542; 23.8%), supracondylar humeral fracture (SCHfx) repair (n=45,479; 23.8%). Complication rates were highest for PSF in non-idiopathic cases (10.3%), followed by pelvic and femoral osteotomy (4.9%). Infectious complications were most frequent in PSF for non-idiopathic cases (6.1%) and tibial osteotomy (3.1%). Unplanned reoperation rates were elevated for non-idiopathic PSF (5.6%) and pelvic/femoral osteotomy (4.9%). On multivariable analysis, PSF for adolescent idiopathic scoliosis (OR=1.39; 95% CI: 1.05-1.86) and non-idiopathic causes (OR=2.16; 95% CI: 1.61-1.89) demonstrated increased odds of complications compared with TO. Factors associated with higher complication rates included BMI >95th percentile (OR=1.52; 95% CI: 1.40-1.65), developmental delay (OR=1.57; 95% CI: 1.43-1.73), seizure disorder (OR=1.41; 95% CI: 1.27-1.56), and ASA ≥2 (OR=2.14;95% CI: 1.90-2.41). Although PSF for non-idiopathic causes had the highest unplanned readmission rates (9.4% per 30 person-days), adjusted analysis showed a strong association with increased readmissions for pelvic/femoral osteotomy (HR=2.52; 95% CI: 1.58-4.03) compared with TO. SCHfx repair and calcaneal osteotomy consistently had lower rates of complications, infections, reoperations, and readmissions. Conclusions: After adjusting for covariates, PSF and tibial and femoral osteotomies, demonstrated significantly higher risks for adverse surgical outcomes compared with TO. Our findings identify SCHfx repair as a high-volume procedure with low complication, infection, reoperation, and readmission rates in contrast to PSF, one of the most common procedures with the highest complication rate.

Abstract Monomorphic posttransplant lymphoproliferative disorders (PTLDs) beyond diffuse large B-cell lymphoma (DLBCL) are rare, biologically heterogeneous entities with limited prospective data to guide treatment. DLBCL-PTLD, which comprises most cases, is managed using approaches informed by prospective phase 2 studies, including reduction in immunosuppression and a risk-adapted sequential immunochemotherapy approach. In contrast, non-DLBCL subtypes such as Burkitt lymphoma, PTLDs of T/NK-cell origin, and plasmacytic variants are less common and are typically treated using strategies extrapolated from established treatment algorithms used in immunocompetent patients and sporadic case reports. Classic Hodgkin lymphoma PTLD, although not classified as monomorphic, represents another distinct and clinically relevant subtype. This review summarizes the epidemiology, clinical features, treatment strategies, and outcomes associated with these less common PTLDs, aiming to provide a practical framework for their management.

ImportanceIdentification of factors associated with variation in outpatient surgery may further quality improvement efforts to safely reduce postoperative hospital length of stay nationally.ObjectivesTo explore variation in the use of outpatient surgery, incorporating patient, geographic, and hospital factors.Design, Setting, and ParticipantsThis retrospective cross-sectional study used deidentified administrative claims data from OptumLabs Data Warehouse. Participants included adults who underwent 1 of 10 general, urological, or gynecological operations between January 1, 2015, and June 30, 2021, in the US. Patients who underwent combined procedures or reoperations or had at least 15 Elixhauser comorbidities were excluded. Data were analyzed from July 26 to December 16, 2023.ExposureInpatient or outpatient surgical procedures.Main Outcomes and MeasuresMultilevel logistic regression assessed variation in the use of outpatient surgery rates by hospital characteristics (bed size, presence of trainees, and rural referral center status) and hospital census division, adjusting for patient factors (age, sex, number of Elixhauser comorbidities, year, and rural-urban commuting area). This multilevel model allowed for the sources of variability to be quantitatively attributed to patient characteristics, geography, and hospital characteristics.ResultsA total of 330 424 (72.3%) of 456 954 included patients underwent outpatient surgery. The median age was 54 (IQR, 41-67) years, and of those with data available, most patients were female (268 692 of 414 193 [64.9%]). The likelihood of outpatient surgery varied significantly by hospital census division for all 10 operations (eg, MIS salpingo-oophorectomy range, 29.6%-58.8%; P &amp;lt; .001). Variation in hospital census division contributed most to outpatient surgery for 8 of 10 operations compared with other patient and hospital characteristics. Hospital census division contributed the greatest degree to the variation in outpatient simple mastectomy (20.6%) and the least to outpatient open ventral hernia repair (0.7%). Multivariable analysis showed that the odds of outpatient surgery for patients from metropolitan areas were higher for minimally invasive salpingo-oophorectomy (odds ratio [OR], 1.62; 95% CI, 1.34-1.95) and open ventral hernia repair (OR, 1.16; 95% CI, 1.09-1.24). Hospitals with 400 or more beds were independently associated with decreased odds of outpatient surgery compared with hospitals with 50 to 199 beds for 4 of 7 operations (MIS paraesophageal hernia repair [OR, 0.58; 95% CI, 0.47-0.71; P &amp;lt; .001]; MIS cholecystectomy [OR, 0.73; 95% CI, 0.68-0.78; P &amp;lt; .001]; open ventral hernia [OR, 0.51; 95% CI, 0.46-0.57; P &amp;lt; .001]; MIS ventral hernia repair [OR, 0.66; 95% CI, 0.56-0.77; P &amp;lt; .001]). The presence of a residency training program was independently associated with increased odds of outpatient surgery for simple mastectomy (OR, 1.35; 95% CI, 1.16-1.58; P &amp;lt; .001) and mastectomy with reconstruction (OR, 1.50; 95% CI, 1.27-1.77; P &amp;lt; .001) and decreased odds of outpatient surgery for minimally invasive cholecystectomy (OR, 0.96; 95% CI, 0.92-1.00; P = .04), open ventral hernia repair (OR, 0.93; 95% CI, 0.86-1.00; P = .04), and total thyroidectomy (OR, 0.84; 95% CI, 0.71-1.00; P = .04).Conclusions and RelevanceIn this cross-sectional study, significant variation existed in the use of outpatient surgery in the US and appeared to be driven primarily by hospital geography. Addressing these variations may improve the use of resources.

Objective We sought to characterize the frequency of postoperative opioid prescriptions in patients undergoing cleft lip repair (CLR). Design The NSQIP-P 2023 database was queried to identify patients undergoing CLR using CPT codes. Univariable analysis was conducted to identify factors associated with postoperative opioid prescription. Setting A multicenter sample from 157 participating sites. Patients/participants A total of 1497 cases (1215 unilateral CLR and 282 bilateral CLR) were identified. Main outcomes/measures The postoperative outcomes of interest were whether an opioid was prescribed to a patient at discharge and what factors were independently associated with opioid prescribing at discharge. Results A total of 44.6% of patients with a mean age of 5.1 ± 1.9 months were prescribed opioids at discharge, most commonly oxycodone (76.3%). Univariable analysis identified an increase in weight (kg) (OR: 1.09, 95% CI: 1.02-1.17, P = .03), American Society of Anesthesiologists (ASA) classification (ordinal) (OR: 1.25, 95% CI: 1.06-1.47, P = .01), anesthesia time (10 min) (OR: 1.02, 95% CI: 1.01-1.04, P = .03), and age (months) (OR: 1.06, 95% CI: 1.00-1.12, P = .04) as being associated with opioid prescription at discharge. Bilateral versus unilateral CLR ( P = .49) and outpatient versus inpatient operation ( P = .38) were not associated with opioid prescribing. Conclusion Opioid stewardship is important in pediatric care, with our results showing age, weight, anesthesia time, and ASA classifications are predictors of opioid prescription. Further research examining contributors to patient pain following CLR is necessary to optimize opioid prescribing without negatively impacting the patient.

Objective: To develop an artificial intelligence–based pipeline to assess and triage patient-submitted postoperative wound images. Background: The rise of outpatient surgeries, remote monitoring, and patient-submitted wound images via online portals has contributed to a growing administrative workload on clinicians. Early identification of surgical site infection (SSI) is essential for reducing postoperative morbidity. Methods: Patients ≥18 years old who underwent surgery at 9 affiliated Mayo Clinic hospitals (2019-2022) and were captured by the National Surgical Quality Improvement Program (NSQIP) were included. Eligibility required submission of one image via the patient portal within 30 days after surgery. Images were independently screened in duplicate to determine the presence of an incision. SSI outcomes were obtained from NSQIP. The developed model consisted of 2 stages: incision detection and SSI detection in images with incisions. Four pretrained architectures were evaluated using 10-fold cross-validation, with upsampling and data augmentation to mitigate class imbalance. An end-to-end pipeline, image quality assessment and sensitivity analysis stratified by race were also performed. Results: Among 6060 patients, the median age was 54 years (interquartile range: 40–65), 61.4% (n=3805) were female, and 92.5% (n=5731) identified as White. SSIs were confirmed in 6.2% (n=386) images. Vision Transformer outperformed all others, achieving an incision detection accuracy of 0.94 (area under the curve=0.98) and an SSI detection accuracy of 0.73 (area under the curve=0.81). In addition, it demonstrated strong performance in assessing image quality. Sensitivity analysis revealed comparable performance across racial subgroups. Conclusion: This artificial intelligence pipeline demonstrates promising performance in automating wound image assessment and SSI detection, reducing clinical workload and improving postoperative care.