A Scoping Review on Complications in Modern Hair Transplantation: More than Just Splitting Hairs.

BACKGROUND: Hair restoration surgery (HRS) is a commonly performed elective procedure but to date lacks a review of the full scope of complications. OBJECTIVES: To provide a comprehensive overview of observed complications associated with follicular unit extraction (FUE) and follicular unit transplantation (FUT). ELIGIBILITY CRITERIA: Randomized control trials, cohort studies, case series, and case reports published in 1985 or later on adults (age>18). Nontraumatic or autoimmune etiologies of alopecia were excluded as procedure indications. SOURCES OF EVIDENCE: PubMed, EMBASE, Cochrane databases (last search December 31, 2022). CHARTING METHODS: Data-charting and extraction were independently performed with two reviewers using Covidence. RESULTS: Forty-three publications were included. Two large series reported the overall complication rate to be 1.2 and 4.7%. Common complications included bleeding requiring intervention (up to 8%), persistent numbness (up to 11%), infection (up to 11% with two reports of Kaposi varicelliform eruptions and one of mucormycosis), effluvium at donor and recipient sites (up to 4.1% and 6.5%, respectively). The most common donor-site complication was hypertrophic scarring/keloid formation after FUT (up to 15.1%). Complications at the recipient site, including crusting (up to 54.8%), frontal edema (up to 50%), and sterile folliculitis (up to 53.3%), tended to be poorly defined with a broad range of incidences. CONCLUSION: Serious complications associated with HRS are rare in the hands of experienced providers. However, comprehensive discussions of risk must be had with prospective patients as any complication in the context of an elective procedure may be significant and psychologically devastating for the individual patient. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Hereditary chronic neutrophilic leukemia in a four-generation family without transformation to acute leukemia.

Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm (MPN) characterized by peripheral blood neutrophilia, marrow granulocyte hyperplasia, hepatosplenomegaly, and driver mutations in the colony-stimulating factor 3 receptor (CSF3R). Designation of activating CSF3R mutations as a defining genomic abnormality for CNL has led to increased recognition of the disease. However, the natural history of CNL remains poorly understood with most patients reported being of older age, lacking germline data, and having poor survival, in part due to transformation to acute leukemia. CSF3R driver mutations in most patients with CNL have been reported to be acquired, although rare cases of germline mutations have been described. Here, we report the largest pedigree to date with familial CNL, spanning four generations with affected family members ranging in age from 4 to 53 years, none of whom have transformed to acute leukemia. A heterozygous T618I CSF3R mutation was identified in peripheral blood and mesenchymal stromal cells from the proband and in all affected living family members, while the unaffected family members tested were homozygous wild type. We show that the T618I mutation also confers a survival advantage to neutrophils in an MCL1-dependent manner. Collectively, these data provide additional insights into the natural history of familial CNL arising from T618I CSF3R mutations and suggest that enhanced neutrophil survival also contributes to the high neutrophil count observed in patients with CNL.

Clinical Variables and Radiomics Features for Predicting Pneumothorax in Patients Undergoing CT-guided Transthoracic Core Needle Biopsy.

Purpose To develop a prediction model combining both clinical and CT texture analysis radiomics features for predicting pneumothorax complications in patients undergoing CT-guided core needle biopsy. Materials and Methods A total of 424 patients (mean age, 65.6 years ± 12.7 [SD]; 232 male, 192 female) who underwent CT-guided core needle biopsy between January 2021 and October 2022 were retrospectively included as the training data set. Clinical and procedure-related characteristics were documented. Texture analysis radiomics features were extracted from the subpleural lung parenchyma traversed by needle. Moderate pneumothorax was defined as a postprocedure air rim of 2 cm or greater. The prediction model was developed using logistic regression with backward elimination, presented by linear fusion of the selected features weighted by their coefficients. Model performance was assessed using the area under the receiver operating characteristic curve (AUC). Validation was conducted in an external cohort (n = 45; mean age, 58.2 years ± 12.7; 19 male, 26 female) from a different hospital. Results Moderate pneumothorax occurred in 12.0% (51 of 424) of the training cohort and 8.9% (four of 45) of the external test cohort. Patients with emphysema (P < .001) or a longer needle path length (P = .01) exhibited a higher incidence of moderate pneumothorax in the training cohort. Texture analysis features, including gray-level co-occurrence matrix cluster shade (P < .001), gray-level run-length matrix low gray-level run emphasis (P = .049), gray-level run-length matrix run entropy (P = .003), gray-level size-zone matrix gray-level variance (P < .001), and neighboring gray-tone difference matrix complexity (P < .001), showed higher values in patients with moderate pneumothorax. The combined clinical-radiomics model demonstrated satisfactory performance in both the training (AUC 0.78, accuracy = 71.9%) and external test cohorts (AUC 0.86, accuracy 73.3%). Conclusion The model integrating both clinical and radiomics features offered practical diagnostic performance and accuracy for predicting moderate pneumothorax in patients undergoing CT-guided core needle biopsy. Keywords: Biopsy/Needle Aspiration, Thorax, CT, Pneumothorax, Core Needle Biopsy, Texture Analysis, Radiomics, CT Supplemental material is available for this article. © RSNA, 2024.

Conceptualizing Fit in Surgical Residency Selection: The Experience in Otolaryngology-Head and Neck Surgery.

OBJECTIVE: Fit is a crucial factor in surgical residency selection, but how this abstract concept is applied in practice is poorly understood. Person-environment (PE) fit theory suggests that there are multiple fit domains that can clarify usage: person-job, person-organization, and person-workgroup fit. We used PE fit theory to explore how otolaryngology residency selection committee (RSC) members operationalize the concept of fit. DESIGN: One-hour focus groups were conducted in November 2022. Interview questions explored participants' definitions and uses of fit in the resident selection process. Transcripts were analyzed using directed qualitative content analysis to generate themes and evaluate how these align with PE fit domains. SETTING: Society of University Otolaryngologists Annual Meeting breakout session in November 2022. PARTICIPANTS: 21 RSC members from 20 different otolaryngology-head and neck surgery departments participated in three seven-person focus groups. RESULTS: Participants described aspects of fit that aligned with PE fit domains. Person-job included how applicants fit as both surgeons and residents. Person-organization included how applicants fit with the program's characteristics, program's mission, and the local community. Person-workgroup emphasized how applicants fit with current residents. Various challenges in the selection process limited the extent to which PE fit was operationalized, including 1) ambiguous uses of fit, 2) unique features of the match process, 3) lack of outcomes data for selection decisions, and 4) interactions with diversity, equity, and inclusion goals. CONCLUSIONS: Fit manifests in various ways during the surgical residency selection process that parallel domains of PE fit theory. Recommendations are made to assist programs in using fit in resident selection, including clearly articulating definitions of fit to increase transparency in conversations. Further work on selection challenges is needed to maximize the utility of fit in practice.

Gender Disparities in Mentorship and Career Outcomes in Ophthalmology.

Background: Gender disparities in the field of ophthalmology have been increasingly recognized. Although mentorship has been proposed as a contributing factor, there are limited data on the differences in mentorship experiences by gender among ophthalmologists. Objective: The purpose of this study was to evaluate gender disparities in mentorship experiences among ophthalmologists, and the impact of mentorship disparities on career outcomes. Design: Prospective, cross-sectional study. Setting: Web-based survey distributed through ophthalmology listservs. Participants: Ophthalmologists and ophthalmologists-in-training who completed the survey. Exposure: Training and practicing in the field of ophthalmology. Main Outcome Measures: Mentorship score based on 10 items from a previously published scale of mentorship quality and self-reported career outcomes (income, job satisfaction, achievement of career goals, and support to achieve future career goals). Results: We received survey responses from 202 male and 245 female ophthalmologists. Female ophthalmologists reported significantly lower mentorship satisfaction and worse quality of mentorship (p < 0.03). Female ophthalmologists also reported significantly lower income, worse job satisfaction, and lower rates of goal achievement and support to achieve future goals; all of these career outcomes, except income level, were partly mediated by mentorship score (mediation effect ranged from 29% to 68%, p < 0.014). Conclusions and Relevance: Gender-based inequities in achievement of career goals and job satisfaction are partly mediated by disparities in mentorship. Therefore, focused mentorship of women in ophthalmology at all career stages is imperative to reduce these inequities.

Matching-Adjusted Indirect Comparison of Brexucabtagene Autoleucel (ZUMA-2) and Pirtobrutinib (BRUIN) in Patients with Relapsed/Refractory Mantle Cell Lymphoma Previously Treated with a Covalent Bruton Tyrosine Kinase Inhibitor.

INTRODUCTION: Patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) often require multiple lines of treatment and have a poor prognosis, particularly after failing covalent Bruton tyrosine kinase inhibitor (cBTKi) therapy. Newer treatments such as brexucabtagene autoleucel (brexu-cel, chimeric antigen receptor T cell therapy) and pirtobrutinib (non-covalent BTKi) show promise in improving outcomes. METHODS: Without direct comparative evidence, an unanchored matching-adjusted indirect comparison was conducted to estimate the relative treatment effects of brexu-cel and pirtobrutinib for post-cBTKi R/R MCL. Using logistic propensity score models, individual patient-level data from ZUMA-2 brexu-cel-infused population (N = 68) were weighted to match pre-specified clinically relevant prognostic factors based on study-level data from the BRUIN cBTKi pre-treated cohort (N = 90). The base-case model incorporated the five most pertinent factors reported in ≥ 50% of both trial populations: morphology, MCL International Prognostic Index, number of prior lines of therapy, disease stage, and prior autologous stem cell transplant. A sensitivity analysis additionally incorporated TP53 mutation and Ki-67 proliferation. Relative treatment effects were expressed as odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS: In the base-case model, brexu-cel was associated with higher rates of objective response (OR 10.39 [95% CI 2.81-38.46]) and complete response (OR 10.11 [95% CI 4.26-24.00]), and improved progression-free survival (HR 0.44 [95% CI 0.25-0.75]), compared to pirtobrutinib. Overall survival and duration of response favored brexu-cel over pirtobrutinib but the differences crossed the bounds for statistical significance. Findings were consistent across the adjusted and unadjusted analyses. CONCLUSIONS: Findings suggest that brexu-cel may offer clinically and statistically significant benefits regarding objective response, complete response, and progression-free survival compared to pirtobrutinib among patients with R/R MCL after prior cBTKi therapy. Given the short follow-up and high degree of censoring in BRUIN, an analysis incorporating updated BRUIN data may provide more definitive overall survival results.

Research Progress on the Antitumor Molecular Mechanism of Ginsenoside Rh2.

Cancer has evolved into a substantial public health concern as the second-leading cause of mortality globally. Radiotherapy and chemotherapy have been the two most widely used cancer therapies in recent years; however, both have drawbacks. Therefore, the focus has shifted to the creation of herbal medicines, the extraction of active ingredients, replacement therapy, and the adverse effects of these medications. Ginsenoside Rh2, which is extracted from ginseng, has been identified in many cancer cells. The immune system of the body is strengthened by ginsenoside Rh2, which can also cause the proliferation, death, and differentiation of tumor cells through various pathways. For instance, it inhibits the expression of the NF-[Formula: see text]B signaling pathway and induces cell apoptosis, affects the expression levels of mitochondrial apoptosis proteins Bcl-2 and Bax, and cooperates with the PD-1 blockade to reactivate T cells to promote an antitumor immune response. Furthermore, ginsenosides Rh2 has the effect of reversing the toxic effect of chemotherapy drugs on normal cells, reducing myocardial damage, and relieving bone marrow function suppression. For clinical applications, it is mainly used as an adjuvant drug for preoperative neoadjuvant chemotherapy, postoperative adjuvant chemotherapy, and rescue treatment of advanced cancer. This paper summarizes the pharmacological action and mechanism of ginsenosides Rh2 in all kinds of cancer and looks forward to its future development and application.

PET/MRI in Endometrial Cancer: Imaging Biomarkers are Associated with Disease Progression and Overall Survival.

RATIONALE AND OBJECTIVES: To evaluate the association between positron emission tomography (PET)/magnetic resonance imaging (MRI) biomarkers and survival outcomes in patients with endometrial cancer. MATERIALS AND METHODS: Between April 2014 and April 2016, 88 patients with newly diagnosed endometrial cancer participated this prospective study and underwent [18F] fluorodeoxyglucose PET/MRI. Sixty-nine patients with measurable tumors on PET/MRI were included in the image analysis. Imaging biomarkers included the minimum and mean apparent diffusion coefficients (ADCmin and ADCmean), maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors. The log-rank test and Cox proportional hazards model were used to assess the relationship between imaging biomarkers and survival. RESULTS: After a median follow-up of 80 months, 15 (22%) patients had tumor progression and six (9%) patients died. The results of ADCmin, ADCmean, and SUVmax did not show a significant association with progression-free survival (PFS) and overall survival (OS). Significantly shorter PFS was noted in patients with primary tumors with higher MTV (P < 0.001) and TLG (P < 0.001). Significantly shorter OS was also noted in patients with primary tumors with higher MTV (P = 0.048) and TLG (P = 0.034). In the multivariate analysis, MTV was an independent predictor of PFS (hazard ratio = 10.84, P = 0.033). CONCLUSION: PET/MRI biomarkers, particularly MTV and TLG, are associated with PFS and OS in patients with endometrial cancer. MTV was an independent predictor of PFS.

Indirect treatment comparison of brexucabtagene autoleucel (ZUMA-2) versus standard of care (SCHOLAR-2) in relapsed/refractory mantle cell lymphoma.

The SCHOLAR-2 retrospective study highlighted poor overall survival (OS) with standard of care (SOC) regimens among patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) who failed a covalent Bruton tyrosine kinase inhibitor (BTKi). In the ZUMA-2 single-arm trial, brexucabtagene autoleucel (brexu-cel; autologous anti-CD19 CAR T-cell therapy) demonstrated high rates of durable responses in patients with R/R MCL who had previous BTKi exposure. Here, we compared OS in ZUMA-2 and SCHOLAR-2 using three different methods which adjusted for imbalances in prognostic factors between populations: inverse probability weighting (IPW), regression adjustment (RA), and doubly robust (DR). Brexu-cel was associated with improved OS compared to SOC across all unadjusted and adjusted comparisons. Hazard ratios (95% confidence intervals) were 0.38 (0.23, 0.61) for IPW, 0.45 (0.28, 0.74) for RA, and 0.37 (0.23, 0.59) for DR. These results suggest a substantial survival benefit with brexu-cel versus SOC in patients with R/R MCL after BTKi exposure.

Association Between Hearing Difficulty and Mobility in Adults of All Ages: National Health Interview Survey.

OBJECTIVE: To investigate the relationship between hearing difficulty and measures of mobility for US adults. STUDY DESIGN: Cross-sectional study. SETTING: 2021 National Health Interview Survey. METHODS: The survey asked US adults about hearing difficulty and mobility measures, including difficulty walking 100 yards, difficulty climbing 12 steps, and injury from falling within the past 3 months. Multivariable logistic regressions examined the associations between hearing and mobility outcomes, controlling for visual difficulty, medical comorbidities, and various demographic characteristics (age [18-39, 40-64, 65+], race/ethnicity, sex, socioeconomic status). RESULTS: The 2021 NHIS surveyed 29,467 adults, representing 253 million people in weighted responses (52% female; mean age 48.3, standard deviation = 18.6). Controlling for covariates, hearing difficulty was associated with increased odds of difficulty walking 100 yards (odds ratio, OR = 1.47, P < .001), difficulty climbing stairs (OR = 1.62, P < .001), and injury from falling in the past 3 months (OR = 1.51, P < .001). There was a significant interaction between age and hearing difficulty for injurious falls; stratifying by age revealed that younger adults (ages 18-39) with hearing difficulty were more likely to report recent harmful falls than their normal hearing peers; this increased risk was greater in magnitude than that observed comparing older adults with and without hearing difficulty. CONCLUSION: The hearing difficulty is associated with worsened mobility for US adults and may be a stronger independent predictor of injury from falls for younger adults as compared to older adults. These findings can inform interventions to reduce the burden of declining mobility in adults with hearing difficulty.

Diabetes, Hypertension, and Smoking Do Not Affect Outcomes of Iliofemoral Vein Stenting for Chronic Proximal Venous Outflow Obstruction.

BACKGROUND: Diabetes, hypertension, and smoking are well-recognized risk factors for peripheral artery disease (PAD), but little is known of their impact on chronic venous insufficiency (CVI). This study evaluates these factors in patients undergoing iliac vein stenting (IVS) for CVI. METHODS: A registry of 708 patients who underwent IVS from August 2011 to June 2021 was retrospectively analyzed. Symptoms were quantified using venous clinical severity score (VCSS) and CEAP classification. Both major and minor reinterventions were recorded. Logistic regression models were used to determine the unadjusted and adjusted odds ratio of any reintervention. Log-rank test was used to assess differences in reintervention-free survival. RESULTS: The prevalence of hypertension was 51.1% (N = 362), diabetes was 23.0% (N = 163), and smoking was 22.2% (N = 157). Patients with diabetes (3.6 vs. 3.4; P = 0.062), hypertension (3.6 vs. 3.3; P < 0.001), and smoking (3.7 vs. 3.4; P = 0.003) had higher CEAP scores than those without these comorbidities. Improvement in VCSS composite scores showed no differences postoperatively (diabetes: P = 0.513; hypertension: P = 0.053; smoking: P = 0.608), at 1-year follow-up (diabetes: P = 0.666; hypertension: P = 0.681; smoking: P = 0.745), or at 5-year follow-up (diabetes: P = 0.525; hypertension: P = 0.953; smoking: P = 0.146). Diabetes (P = 0.454), smoking (P = 0.355), and hypertension (P = 0.727) were not associated with increased odds of major reintervention. Log-rank test similarly showed no differences in reintervention-free survival for major or minor reoperations between those with and without diabetes (P = 0.79), hypertension (P = 0.14), and smoking (P = 0.80). CONCLUSIONS: Diabetes, hypertension, and smoking were prevalent among CVI patients, but unlike in PAD patients, they had little to no impact on long-term outcomes or reinterventions after IVS.

Prognostic nutritional index and neutrophil-lymphocyte ratio predict toxicities and prognosis in patients with cervical cancer treated with curative radiochemotherapy.

BACKGROUND: This study aimed to investigate the influence of immunonutritional factors on treatment-related toxicities and survival outcomes in patients with cervical cancer undergoing definitive radiochemotherapy. METHODS: Patients with cervical cancer who received curative radiochemotherapy between 2016 and 2021 were retrospectively investigated. Pretreatment prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) were measured. Survival outcomes, acute and late toxicities were evaluated. RESULTS: Among the 138 patients, those with larger tumor diameters had significantly lower pre-treatment PNI (p = 0.005). Pre-treatment immunonutritional factors were predictive of clinical survival, whereas post-treatment factors did not correlate with prognosis. Patients with low pre-treatment PNI (<49.5) or high NLR (>2.4) had shorter progression-free survival (PFS, HR: 1.86, p = 0.045 for PNI; HR: 3.15, p = 0.002 for NLR) and overall survival (OS, HR: 1.80, p = 0.048 for PNI; HR: 3.83, p = 0.015 for NLR). High pre-treatment NLR was associated with an increased risk of acute diarrhea (p = 0.049) and late severe toxicities (p = 0.046). Combined analysis revealed that pre-treatment good nutritional status and low systemic inflammation were linked to longer PFS (p = 0.007) and OS (p = 0.002), and poor nutritional status and substantial systemic inflammation were associated with higher rates of late severe toxicities (p = 0.036), with higher prognostic value in advanced stage patients. CONCLUSIONS: Pretreatment immunonutritional measures serve as quantitative biomarkers for predicting survivals and treatment toxicities in patients with cervical cancer treated with definitive radiochemotherapy.

Noninvasive cardiac radioablation for ventricular tachycardia: dosimetric comparison between linear accelerator- and robotic CyberKnife-based radiosurgery systems.

BACKGROUND: Few dosimetric comparisons have been published between linear accelerator (LA)-based systems and CyberKnife (CK)-based robotic radiosurgery systems for cardiac radio-ablation in ventricular tachycardia. This study aimed to compare the dosimetry of noninvasive cardiac radio-ablation deliverable on LA with that on CK. METHODS: Thirteen patients who underwent noninvasive cardiac radio-ablation by LA were included. The prescribed dose was 25 Gy in 1 fraction, and the average planning target volume was 49.8 ± 31.0 cm3 (range, 14.4-93.7 cm3). CK plans were generated for comparison. RESULTS: Both the CK and LA plans accomplished appropriate dose coverage and normal tissue sparing. Compared with the LA plans, the CK plans achieved significantly lower gradient indices (3.12 ± 0.71 vs. 3.48 ± 0.55, p = 0.031) and gradient measures (1.00 ± 0.29 cm vs. 1.17 ± 0.29 cm, p < 0.001). They had similar equivalent conformity indices (CK vs. LA: 0.84 ± 0.08 vs. 0.87 ± 0.07, p = 0.093) and maximum doses 2 cm from the planning target volume (PTV) in any direction (CK vs. LA: 50.8 ± 9.9% vs. 53.1 ± 5.3%, p = 0.423). The dosimetric advantages of CK were more prominent in patients with a PTV of ≤ 50 cm3 or a spherical PTV. In patients with a PTV of > 50 cm3 or a non-spherical PTV, the LA and CK plans were similar regarding dosimetric parameters. CK plans involved more beams (232.2 ± 110.8 beams vs. 10.0 ± 1.7 arcs) and longer treatment times (119.2 ± 43.3 min vs. 22.4 ± 1.6 min, p = 0.007). CONCLUSIONS: Both CK and LA are ideal modalities for noninvasive cardiac radio-ablation. Upfront treatment should be considered based on clinical intent.

Matching-Adjusted Indirect Comparisons of Brexucabtagene Autoleucel with Alternative Standard Therapies for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia in Adult Patients.

INTRODUCTION: Brexucabtagene autoleucel (brexu-cel), a CD19-directed chimeric antigen receptor T-cell therapy, is approved for relapsed/refractory B-cell precursor acute lymphoblastic leukemia in adults aged 18+/26+ years in the US/European Union (EU), based on efficacy results from the single-arm ZUMA-3 trial. This study aimed to estimate the relative treatment effects of brexu-cel versus inotuzumab ozogamicin (InO), blinatumomab (blina), and chemotherapies using unanchored matching-adjusted indirect comparison (MAIC) methods. METHODS: Individual patient data from ZUMA-3 and published aggregate level data from two randomized controlled trials, INO-VATE (InO versus chemotherapy) and TOWER (blina versus chemotherapy), were used. Patient-level data from ZUMA-3 were weighted to match the mean of the following prognostic variables at baseline, which were pre-specified based on clinical input, for each comparator population: primary refractory disease, duration of first remission < 12 months, prior stem-cell transplantation, age, performance status, salvage status, bone marrow blast, complex karyotype, and Philadelphia chromosome status. The base case analysis was conducted using the modified intention-to-treat population (i.e., received brexu-cel) from ZUMA-3. Relative treatment effects for overall survival (OS) and event-free survival (EFS) were expressed as hazard ratios (HR) and differences in restricted mean survival time (RMST) with 95% confidence intervals (CI). RESULTS: The base case MAIC results suggested brexu-cel improved OS and EFS compared to blina (OS HR 0.46 [95% CI 0.28, 0.75]; EFS HR 0.37 [95% CI 0.25, 0.56]) and pooled INO-VATE/TOWER chemotherapy (OS HR 0.32 [95% CI 0.18, 0.56]; EFS HR 0.27 [0.18, 0.40]). Brexu-cel also improved OS compared to InO (HR 0.45 [95% CI 0.24, 0.85]). The point estimate for EFS favored brexu-cel over Ino but the difference was not statistically significant (HR 0.67 [95% CI 0.41, 1.10]). Findings were consistent between the HR and RMST analyses. CONCLUSION: Despite limitations, these MAIC results suggest that brexu-cel may improve OS and EFS versus currently used therapies in this population.

Surgery Improves Patient-Reported Outcomes in Patients with Intestinal and Pancreatic NETs: A Prospective Analysis.

BACKGROUND: Incorporation of patient-reported outcomes such as health-related quality of life has become increasingly important in the management of chronic diseases such as cancer. In this prospective study, we examined the effect of surgical resection on quality of life in patients with intestinal and pancreatic neuroendocrine tumors (NETs). METHODS: Thirty-two patients underwent NET resection at our institution from January 2020 to January 2022. All patients completed the 12-item short-form quality-of-life survey prior to surgery, as well as at the 3-, 6-, and 12-month postoperative time points. The presence and severity of specific carcinoid syndrome symptoms (diarrhea, flushing, and abdominal pain) were also recorded during pre- and postoperative appointments. RESULTS: Patients experienced significant increases in both mental and physical health after surgery. Mental health scores significantly increased at all three time points (baseline: 51.33; 3-month: 53.17, p = 0.02; 6-month: 57.20, p < 0.001; 12-month: 57.34, p = 0.002), and physical health scores increased at 6 and 12 months (baseline: 50.39; 6-month: 53.16, p = 0.04; 12-month: 55.02, p = 0.003). Younger patients benefited more in terms of physical health, while older patients had more significant increases in mental health. Patients with metastatic disease, larger primary tumors, and those receiving medical therapy had lower baseline quality-of-life scores and greater improvements after surgery. The vast majority of patients in this study also experienced alleviation of carcinoid syndrome symptoms. CONCLUSIONS: In addition to prolonging survival, resection of intestinal and pancreatic NETs leads to significantly improved patient-reported quality of life.

Cytotoxicity of the CD3×CD20 bispecific antibody epcoritamab in CLL is increased by concurrent BTK or BCL-2 targeting.

Chronic lymphocytic leukemia (CLL) is an immunosuppressive disease characterized by increased infectious morbidity and inferior antitumor activity of immunotherapies. Targeted therapy with Bruton's tyrosine kinase inhibitors (BTKis) or the Bcl-2 inhibitor venetoclax has profoundly improved treatment outcomes in CLL. To overcome or prevent drug resistance and extend the duration of response after a time-limited therapy, combination regimens are tested. Anti-CD20 antibodies that recruit cell- and complement-mediated effector functions are commonly used. Epcoritamab (GEN3013), an anti-CD3×CD20 bispecific antibody that recruits T-cell effector functions, has demonstrated potent clinical activity in patients with relapsed CD20+ B-cell non-Hodgkin lymphoma. Development of CLL therapy is ongoing. To characterize epcoritamab-mediated cytotoxicity against primary CLL cells, peripheral blood mononuclear cells from treatment-naive and BTKi-treated patients, including patients progressing on therapy, were cultured with epcoritamab alone or in combination with venetoclax. Ongoing treatment with BTKi and high effector-to-target ratios were associated with superior in vitro cytotoxicity. Cytotoxic activity was independent of CD20 expression on CLL cells and observed in samples from patients whose condition progressed while receiving BTKi. Epcoritamab induced significant T-cell expansion, activation, and differentiation into Th1 and effector memory cells in all patient samples. In patient-derived xenografts, epcoritamab reduced the blood and spleen disease burden compared with that in mice receiving a nontargeting control. In vitro, the combination of venetoclax with epcoritamab induced superior killing of CLL cells than either agent alone. These data support the investigation of epcoritamab in combination with BTKis or venetoclax to consolidate responses and target emergent drug-resistant subclones.

A Practical Introduction to Growth Mindsets in Surgical Training.

This Viewpoint summarizes the research behind psychological mindsets and their possible applications to surgical training and introduces some practical recommendations to harness growth mindsets for optimizing the learning of otolaryngology residents.