Universal Genetic Testing for Newly Diagnosed Invasive Breast Cancer.

Importance: Between 5% and 10% of breast cancer cases are associated with an inherited germline pathogenic or likely pathogenic variant (GPV) in a breast cancer susceptibility gene (BCSG), which could alter local and systemic therapy recommendations. Traditional genetic testing criteria misses a proportion of these cases. Objective: To evaluate the prevalence and clinicopathological associations of GPVs in 2 groups of BCSGs among an ethnically diverse cohort of women with newly diagnosed breast cancer. Design, Setting, and Participants: This cross-sectional study, conducted at 3 Montreal hospitals between September 2019 and April 2022, offered universal genetic counseling and testing to all women with a first diagnosis of invasive breast cancer. Women were offered an obligatory primary panel of BRCA1, BRCA2, and PALB2 (B1B2P2) and an optional secondary panel of 14 additional BCSGs. Eligible participants were women 18 years of age or older who received a diagnosis of a first primary invasive breast cancer not more than 6 months before the time of referral to the study. Data were analyzed from November 2023 to June 2024. Results: Of 1017 referred patients, 805 were eligible and offered genetic counseling and testing, and 729 of those 805 (90.6%) consented to be tested. The median age at breast cancer diagnosis was 53 years (range, 23-91 years), and 65.4% were White and of European ancestry. Fifty-four GPVs were identified in 53 patients (7.3%), including 39 patients (5.3%) with B1B2P2 and 15 patients (2.1%) with 6 of the 14 secondary panel BCSGs (ATM, BARD1, BRIP1, CHEK2, RAD51D, and STK11). On multivariable analysis, clinical factors independently associated with B1B2P2-positive status included being younger than 40 years of age at diagnosis (odds ratio [OR], 6.83; 95% CI, 2.22-20.90), triple-negative breast cancer (OR, 3.19; 95% CI, 1.20-8.43), high grade disease (OR, 1.68; 95% CI, 1.05-2.70), and family history of ovarian cancer (OR, 9.75; 95% CI, 2.65-35.85). Of 39 B1B2P2-positive patients, 13 (33.3%) were eligible for poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors. Conclusions and Relevance: In this cross-sectional universal genetic testing study of women with newly diagnosed invasive breast cancer, the prevalence of GPVs was 7.3%, with 5.3% of patients testing positive for B1B2P2. Among B1B2P2-women women, one-third were eligible for PARP inhibitors.

Psychologists aspiring to leadership positions in public sector health care.

Psychologists are well-positioned to take on leadership roles in health care systems as a result of the broad-based skills included in doctoral level, professional training programs. These include knowledge of evidence-based practice, extensive training in applied research and clinical practice, emphasis on critical thinking in scientific methods and hypothesis testing, teaching, supervision, team consultation, and continuous learning (APA Presidential Task Force on Evidence-Based Practice, 2006; Korman, 1974; McFall, 2007). Formal opportunities to learn how to apply these skills in leadership and organizational management roles are, however, limited during graduate training. There have been recent efforts within the American Psychological Association to foster interest and readiness for leadership roles among psychologists. These efforts have included a leadership development fellowship, on-demand webinars, and online learning for continuing education (American Psychological Association, 2023). The content of these training opportunities is typically general in nature so that it can be applied to all types of organizational settings. Psychologists interested in leadership positions within public sector health care organizations are likely to benefit from information that aligns more specifically with the mission and organizational structures of such systems. This article presents a conceptual framework to prepare psychologists aspiring to leadership positions in public sector health care. Leadership theories and models from organizational management science are outlined which capture the context and organizational goals of such programs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Preoperative Hip Injection Response Does Not Reliably Predict 2-Year Postoperative Outcomes Following Hip Arthroscopy for Femoroacetabular Impingement.

PURPOSE: To determine whether response to preoperative local anesthetic or corticosteroid intra-articular injections can predict 2-year postoperative outcomes in patients undergoing hip arthroscopy for femoroacetabular impingement syndrome (FAIS). METHODS: This was a retrospective analysis of patients undergoing hip arthroscopy for FAIS at a single institution from 2014-2020. Patients who underwent preoperative intra-articular hip injection were classified based on injection type (local anesthetic, corticosteroid) and whether they experienced pain relief following injection (responders, non-responders). Responders were matched 2:1 by age, BMI, and sex with non-responders. Patient reported outcomes (PROs) including Hip Disability and Osteoarthritis Outcome Score (HOOS), 12-item Short-Form Survey mental (SF-12-MCS) and physical component summary (SF-12-PCS) and visual analogue scale (VAS) pain were collected preoperatively and 2-years postoperatively. Mean score change and Minimal Clinically Important Difference (MCID) achievement were calculated and compared between groups. RESULTS: The matched cohort included 126 total patients (42 non-responders, 84 responders; 74.6% female; mean ± SD age: 30.9 ± 9.9 years; BMI: 24.7 ± 3.7 kg/m2) with no differences in demographic or radiographic hip variables. Both groups demonstrated significant 2-year postoperative score improvements across all PROs, except SF-12-MCS, which remained unchanged. There was no difference in mean score change or MCID achievement across all PROs between corticosteroid injection responder and non-responder groups. In the local anesthetic group, MCID achievement was similar across all PROs, except VAS pain which showed greater percentage of MCID achievement among local anesthetic non-responders relative responders (Responders: 55.0%, Non-responders: 89.5%; p = 0.03). Significant ceiling effects were most readily apparent among the injection responders group with greater percentages of patients achieving maximal 2-year postoperative survey scores (36.9% HOOS-ADL, 19.0% HOOS-Pain, 15.5% HOOS-QoL, 32.1% HOOS-Sport). CONCLUSIONS: Response to preoperative injection with either corticosteroid or local anesthetic did not predict 2-year outcomes after hip arthroscopy in patients with FAIS. LEVEL OF EVIDENCE: Level III, retrospective matched cohort study.

Mechanisms of crosstalk between the oropharyngeal microbiome and human papillomavirus in oropharyngeal carcinogenesis: a mini review.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer globally. Notably, human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is on the rise, accounting for 70% of all OPSCC cases. Persistent high-risk HPV infection is linked to various cancers, but HPV infection alone is not sufficient to cause cancer. Advances in next-generation sequencing have improved our understanding of changes in the human microbiome of cancerous environments. Yet, there remains a dearth of knowledge on the impact of HPV-microbiome crosstalk in HPV-positive OPSCC. In this review, we examine what is known about the oropharyngeal microbiome and the compositional shifts in this microbiome in HPV-positive OPSCC. We also review potential mechanisms of crosstalk between HPV and specific microorganisms. Additional research is needed to understand these interactions and their roles on cancer development and progression.

The Use of Combined Hip Arthroscopy and Periacetabular Osteotomy for Hip Dysplasia Is Increasing and Has Low Complication Rates.

Purpose: To analyze the annual use of hip arthroscopy (HA) and Bernese periacetabular osteotomy (PAO) for the treatment of hip dysplasia (HD), as well as postoperative outcomes, including ipsilateral reoperations. Methods: International Classification of Diseases, Ninth and Tenth Revision, codes were used to query the PearlDiver Mariner database from January 2010 through January 2022 to identify patients aged 10 to 59 years who had a presenting diagnosis of HD and subsequently underwent (1) HA; (2) PAO; or (3) combined HA and PAO (HA-PAO, defined as PAO on the same day or within 28 days after HA). We analyzed annual rates for each treatment, as well as rates of postoperative emergency visits, readmissions, and 5-year ipsilateral secondary operations (determined via Kaplan-Meier analysis). Results: There were 32,068 patients who underwent surgical treatment of HD. For HA, PAO, and HA-PAO, there were 29,700, 2,083, and 285 patients, respectively. All operations had the greatest percent-increase from 2015 to 2016. HA and HA-PAO peaked in 2021, whereas PAO peaked in 2019. For HA, PAO, and HA-PAO, most cases were performed in female patients and patients aged 30 to 49 years, 10 to 19 years, and 10 to 29 years, respectively. The 5-year incidence of ipsilateral secondary operations, which include revision HA, PAO, or conversion to total hip arthroplasty, was 9.2% (95% confidence interval 8.6%-9.8%) in the HA group and 6.5% (95% confidence interval 4.1%-8.8%) in the PAO group. Combining HA with PAO resulted in so few secondary operations that Kaplan-Meier analysis was infeasible. The PAO cohort had the greatest 30-day emergency visit and 90-day readmission rates, with infection as the most common cause for readmission. Conclusions: HA is more frequently performed than PAO for hip dysplasia. HA-PAO is increasing at the greatest rate, demonstrating fewer complications and reoperations. Level of Evidence: Level III, retrospective comparative trial.

Impact of Margin Status on Local Recurrence in Patients with Breast Cancer Undergoing Breast-Conserving Surgery After Neoadjuvant Chemotherapy: A Retrospective Multi-Institutional Cohort Study.

BACKGROUND: Questions have been raised as to an increased risk of local recurrence with breast-conserving surgery (BCS) post NAC highlighting the uncertainty around optimal margin width in this patient population. We examined the association between margin status and local recurrence-free survival (LRFS) in patients who underwent BCS following NAC. METHODS: We performed a retrospective cohort study of adult female patients with stage I-III breast cancer who underwent NAC followed by BCS between 2012 and 2021 at two cancer centers. Margins were categorized as "close" if they were < 1 mm. RESULTS: The full cohort included 544 patients with a median age of 53 years (interquartile range [IQR] 44-64). Pathologic complete response (pCR) was achieved in 41.2% of the overall cohort (n = 224). Of the 320 with residual disease, 29.4% (n = 94) had at least one close margin, and 10.9% (n = 35) had ≥2 close margins. Median follow-up was 55 months (IQR 32-83); 4.8% had an ipsilateral breast recurrence (n = 26). Patients with pCR had a higher 5-year LRFS than those with residual disease (98.0% vs. 91.6%, p = 0.02). There was no difference in 5-year LRFS between the margin categories (clear vs. 1 close margin vs. ≥2 close margins) in those with residual disease (92.2% vs. 88.9% vs. 92.9%) (p = 0.78). CONCLUSIONS: In patients undergoing BCS post-NAC, those who achieved pCR had a significantly higher LRFS compared with those with residual disease at the time of surgery, but LRFS was not associated with margin width nor the number of close margins.

Auditory brainstem response findings in autism spectrum disorder speech delay population.

OBJECTIVES: Evaluate pediatric auditory brainstem response (ABR) findings in children with Autism Spectrum Disorder (ASD) after the 2013 DSM-5 update. STUDY DESIGN: This was an IRB-approved, six-year retrospective chart review evaluating ABR results from pediatric patients with speech delay. Diagnosis of ASD and other neurodevelopmental abnormalities were collected for patient stratification. METHODS: From 2017 to 2023, 148 pediatric patients with speech delay were identified through diagnosis of speech delay and underwent ABR testing. Patients were then separated into two groups: Neurotypical (N = 79) and ASD (N = 69). ABR results were obtained through chart review and waveform and interpeak latency (IPL) results were recorded. Differences in waveform and IPL results were determined via Pearson's chi-square test, with multivariate analysis accounting for race, sex, and age. RESULTS: 28 patients with ASD (40.6 %) had at least one waveform/IPL prolongation. Analysis showed an increased incidence of waveform III (p = 0.028) and IPL III-V (p = 0.03) prolongation in the ASD group compared to their neurotypical counterparts. Waveform III prolongation was noted more in females with ASD (p = 0.001) than in males. No statistically significant difference when comparing race and age was found, except in the 2-3 age range (p = 0.003). CONCLUSIONS: There were higher percentages of prolongation for all waveforms and IPLs in the ASD group versus neurotypical, though not as high as previously reported. Race and age did not appear to be factors in ABR findings though more data is needed to make clinical associations.

Management of Proximal Hamstring Injuries: Non-operative and Operative Treatment.

PURPOSE OF REVIEW: To evaluate the current evidence and literature on treatment options for proximal hamstring injuries. RECENT FINDINGS: Patients with 3-tendon complete tears with greater than 2 cm of retraction have worse outcomes and higher complication rates compared to those with less severe injuries. Endoscopic and open proximal hamstring repair both have favorable patient reported outcomes at 5-year follow up. Proximal hamstring repair in patients who are male, with isolated semimembranosus injury, and have proximal hamstring free tendon rupture are more likely to have earlier return to sports. The Parisian Hamstring Avulsion Score (PHAS) is a validated patient-reported outcome measure to predict return to sports. Proximal hamstring injuries may occur in both elite and recreational athletes and may present with varying degrees of chronicity and severity. Injuries occur most commonly during forceful eccentric contraction of the hamstrings and often present with ischial tuberosity tenderness, ecchymosis, and hamstring weakness. Treatment decision-making is dictated by the tendons involved and chronicity. Many proximal hamstring injuries can be successfully treated with non-surgical measures. However, operative treatment of appropriately indicated proximal hamstring tendon injuries can result in significantly better functional outcomes and faster and more reliable return to sports compared to nonoperative treatment. Both endoscopic and open surgical repair techniques show high satisfaction levels and excellent patient-reported outcomes at short- and mid-term follow-up. Postoperative rehabilitation protocols vary across the literature and ongoing study is needed to clarify the optimal program, though emphasis on eccentric hamstring strengthening may be beneficial.

Comparison of networks of loneliness, depressive symptoms, and anxiety symptoms in at-risk community-dwelling older adults before and during COVID-19.

Network analysis provides an innovative approach to examining symptom-to-symptom interactions in mental health, and adverse external conditions may change the network structures. This study compared the networks of common risk factors and mental health problems (loneliness, depressive symptoms, and anxiety symptoms) in community-dwelling older people before and during COVID-19. Older adults (aged ≥ 60) at risk for depression were recruited through non-governmental organizations. Loneliness, depressive symptoms and anxiety symptoms were measured using the three-item Loneliness Scale (UCLA-3), nine-item Patient Health Questionnaire (PHQ-9), and seven-item Generalized Anxiety Disorder Scale (GAD-7), respectively. Data from 2549 (before) and 3506 (during COVID-19) respondents were included using propensity score matching. Being restless (GAD-7-item5) was most central, indicated by Expected Influence, in both pre and during COVID-19 networks despite low severity (mean score). The network during COVID-19 had higher global strength and edge variability than the pre-pandemic network, suggesting easier symptom spread and potentially more complex symptom presentation. In addition, feeling isolated from others (UCLA-3-item3) had stronger connections with feeling worthless/guilty (PHQ-9-item6) and anticipatory anxiety (GAD-7-item7) during COVID-19 than before. These findings may enhance our knowledge of the symptom structure of common mental health problems and the impacts of the pandemic. Targeting central symptoms may offer novel preventive strategies for older people.

Socioeconomic Factors Including Patient Income, Education Level, and Health Insurance Influence Postoperative Secondary Surgery and Hospitalization Rates Following Hip Arthroscopy.

PURPOSE: To evaluate a large cross-sectional sample of patients utilizing administrative database records and analyze the effects of income, insurance type, and education level on outcomes after hip arthroscopy, including 2-year revision surgery, conversion to total hip arthroplasty (THA), and 90-day hospitalizations. METHODS: Current Procedural Terminology codes were used to query the PearlDiver Mariner database from October 2015 to January 2020 for patients undergoing hip arthroscopy with a minimum 2-year follow-up. Patients were categorized by mean family income in their zip code of residence (MFIR), health insurance type, and educational attainment in their zip code of residence (EAR). Two-year revision arthroscopy, conversion to THA, and 90-day hospital readmissions or emergency department (ED) visits were analyzed along socioeconomic strata. RESULTS: Multivariate analysis of 33,326 patients revealed that patients with MFIR between $30,000 and $70,000 had lower odds of 2-year revision arthroscopy (odds ratio [OR], 0.63; P < .001), THA conversion (OR, 0.76; P = .050), and 90-day readmission (OR, 0.53; P = .007) compared to MFIR >$100,000. Compared to patients with commercial insurance, patients with Medicare had lower odds of revision arthroscopy (OR, 0.60; P = .035) and THA conversion (OR, 0.46, P < .001) but greater odds of 90-day readmission (OR, 1.74; P = .007). Patients with Medicaid had higher odds of 90-day ED visits (OR, 1.84; P < .001). Patients with low EAR had higher odds of revision arthroscopy (OR, 1.42; P = .005) and THA conversion (OR, 1.58; P = .002) compared to those with high EAR. CONCLUSIONS: Following hip arthroscopy, patients residing in areas with lower mean family income were less likely to undergo reoperations and readmissions. Medicare patients showed lower reoperation but higher readmission odds, while Medicaid patients showed higher odds of ED visits. Additionally, higher educational attainment in the zip code of residence is protective against future reoperation. LEVEL OF EVIDENCE: Level III, retrospective case series.

Characterization of HER2-low breast cancer in young women with germline BRCA1/2 pathogenetic variants: Results of a large international retrospective cohort study.

BACKGROUND: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset. METHODS: Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤ .05. RESULTS: Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor-positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p < .001), hormone receptor-positive (p < .001), and node-positive (p = .003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p < .001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76-0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64-0.95) and overall survival (HR, 0.65; 95% CI, 0.46-0.93) in the TN subgroup. Luminal A-like tumors in HER2-low (p = .014) and TN and luminal A-like in HER2-0 (p = .019) showed the worst DFS. CONCLUSIONS: In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis.

Omission of Axillary Dissection Following Nodal Downstaging With Neoadjuvant Chemotherapy.

Importance: Data on oncological outcomes after omission of axillary lymph node dissection (ALND) in patients with breast cancer that downstages from node positive to negative with neoadjuvant chemotherapy are sparse. Additionally, the best axillary surgical staging technique in this scenario is unknown. Objective: To investigate oncological outcomes after sentinel lymph node biopsy (SLNB) with dual-tracer mapping or targeted axillary dissection (TAD), which combines SLNB with localization and retrieval of the clipped lymph node. Design, Setting, and Participants: In this multicenter retrospective cohort study that was conducted at 25 centers in 11 countries, 1144 patients with consecutive stage II to III biopsy-proven node-positive breast cancer were included between April 2013 and December 2020. The cumulative incidence rates of axillary, locoregional, and any invasive (locoregional or distant) recurrence were determined by competing risk analysis. Exposure: Omission of ALND after SLNB or TAD. Main Outcomes and Measures: The primary end points were the 3-year and 5-year rates of any axillary recurrence. Secondary end points included locoregional recurrence, any invasive (locoregional and distant) recurrence, and the number of lymph nodes removed. Results: A total of 1144 patients (median [IQR] age, 50 [41-59] years; 78 [6.8%] Asian, 105 [9.2%] Black, 102 [8.9%] Hispanic, and 816 [71.0%] White individuals; 666 SLNB [58.2%] and 478 TAD [41.8%]) were included. A total of 1060 patients (93%) had N1 disease, 619 (54%) had ERBB2 (formerly HER2)-positive illness, and 758 (66%) had a breast pathologic complete response. TAD patients were more likely to receive nodal radiation therapy (85% vs 78%; P = .01). The clipped node was successfully retrieved in 97% of TAD cases and 86% of SLNB cases (without localization). The mean (SD) number of sentinel lymph nodes retrieved was 3 (2) vs 4 (2) (P < .001), and the mean (SD) number of total lymph nodes removed was 3.95 (1.97) vs 4.44 (2.04) (P < .001) in the TAD and SLNB groups, respectively. The 5-year rates of any axillary, locoregional, and any invasive recurrence in the entire cohort were 1.0% (95% CI, 0.49%-2.0%), 2.7% (95% CI, 1.6%-4.1%), and 10% (95% CI, 8.3%-13%), respectively. The 3-year cumulative incidence of axillary recurrence did not differ between TAD and SLNB (0.5% vs 0.8%; P = .55). Conclusions and Relevance: The results of this cohort study showed that axillary recurrence was rare in this setting and was not significantly lower after TAD vs SLNB. These results support omission of ALND in this population.

Sex-based Differences in Patient Perspectives and Experiences With Shoulder, Hip, and Knee Arthroplasty.

INTRODUCTION: Sex disparities in presentation of osteoarthritis and utilization of joint replacement surgery (JRS) have been demonstrated. The role of patients' unique perspectives on JRS on their treatment decisions is poorly understood. METHODS: JRS candidates who were offered JRS but declined surgical treatment completed this survey. Survey questions included demographic information, patient experiences and current opinions around JRS, patient experiences with providers, goals and concerns, and barriers to JRS. RESULTS: More women experience barriers to undergoing JRS compared with men (53% versus 16%; P = 0.014). While both men and women indicated pain relief as their primary goal for treatment, women were significantly more likely to prioritize regaining the ability to complete daily tasks and responsibilities when compared with men (P = 0.007). Both men and women indicated that low symptom severity and nonsurgical treatment options were the reasons for not undergoing JRS (P = 0.455). Compared with men, women trended toward feeling that they were not sufficiently educated about JRS (P = 0.051). CONCLUSION: Women have unique perspectives and goals for JRS that may pose sex-specific barriers to care. A better understanding of how patients' gendered experiences affect their decision making is necessary to improve treatment of osteoarthritis and decrease disparities in care.

Tendon cross-sectional area on magnetic resonance imaging and anthropometric characteristics can be used to predict insufficient four-strand hamstring autograft diameter in anterior cruciate ligament reconstruction: A systematic review.

PURPOSE: To evaluate the utility of semitendinosus tendon (ST) and gracilis tendon (GT) cross-sectional area (CSA) on magnetic resonance imaging (MRI) and anthropometric characteristics in preoperative estimation of graft diameter in patients undergoing anterior cruciate ligament reconstruction (ACLR) with four-strand hamstring autografts. METHODS: Three databases were searched on 29 August 2023. The authors adhered to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and R-AMSTAR (Revised Assessment of Multiple Systematic Review) guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. Data on demographics, anthropometric characteristics, imaging techniques, tendon CSA, correlation coefficients, sensitivities, specificities, regression models and cutoffs for predicting intraoperative graft diameters above 8 mm were recorded. RESULTS: Forty-six studies comprising 4140 patients were included. Twelve of 19 (63.2%) studies reporting on ST + GT CSA found a moderate to very high correlation with intraoperative graft diameter. Five of 10 (50%) and one of seven (14.3%) studies reporting on ST CSA and GT CSA, respectively, found a moderate to high correlation with intraoperative graft diameter. Cutoffs of ST + GT CSA for predicting graft diameters above 8 mm ranged from 15.8 to 31.2 mm2. Nine of 35 (25.7%) studies that reported on height found a moderate to very high correlation with graft diameter. Seven of 33 (21.2%) studies reporting on weight found a moderate correlation with graft diameter. CONCLUSION: Of the MRI parameters assessed, ST + GT CSA was the most reliable predictor of graft diameter. However, cutoffs, sensitivities, and specificities for predicting diameters above 8 mm were highly variable. Anthropometric characteristics in general were less predictive of graft diameter than MRI parameters. This information can be used by clinicians to predict patients at risk for ACLR failure due to insufficient graft size. LEVEL OF EVIDENCE: Level IV.

Timing of genetic testing in BRCA1/2 and PALB2-Associated breast cancer: Preoperative result disclosure increases uptake of risk-reducing mastectomy and reduces unnecessary exposure to radiotherapy.

INTRODUCTION: The impact of timing of genetic testing on uptake of risk reducing mastectomy (RRM) in affected female BRCA1/2 or PALB2 carriers remains an area of evolving interest, particularly with the introduction of mainstream genetic testing initiatives. METHODS: Women with stage I-III breast cancer and a confirmed germline pathogenic variant in BRCA1/2 or PALB2 between 2000 and 2023 were identified from an institutional genetics database. Uptake of RRM was evaluated according to disclosure of genetic testing results before or after index surgery for a first diagnosis of breast cancer. RESULTS: The cohort included 287 female BRCA1/2 or PALB2 carriers with a median age of 44 years (IQR, 36-52). Overall, 155 (54 %) carriers received genetic testing results before and 132 (46 %) after index breast surgery. Receipt of genetic testing results before surgery was associated with a higher rate of index bilateral mastectomy (58.7 % vs. 7.6 %, p < 0.001) and a commensurate decrease in adjuvant radiation (41.9 % vs. 74.2 %, p < 0.001). At a median follow up of 4.4 years after genetic testing, 219 (76.3 %) affected carriers had undergone bilateral RRM, including 83.9 % with preoperative knowledge and 67.4 % of patients with postoperative knowledge of their germline pathogenic variant (log rank, p < 0.001). On multivariate regression, disclosure of genetic testing results before index breast surgery was independently associated with long-term uptake of bilateral mastectomy (HR 1.69, 95 % CI 1.21-2.38). CONCLUSION: Genetic testing results delivered prior to index breast surgery increase uptake of bilateral RRM in affected BRCA1/2 and PALB2 carriers. Efforts to mainstream genetic testing would help optimize surgical decision-making.

Generation of an Inhibitory NK Cell Subset by TGF-ß1/IL-15 Polarization.

NK cells have been shown to exhibit inflammatory and immunoregulatory functions in a variety of healthy and diseased settings. In the context of chronic viral infection and cancer, distinct NK cell populations that inhibit adaptive immune responses have been observed. To understand how these cells arise and further characterize their immunosuppressive role, we examined in vitro conditions that could polarize human NK cells into an inhibitory subset. TGF-ß1 has been shown to induce regulatory T cells in vitro and in vivo; we therefore investigated if TGF-ß1 could also induce immunosuppressive NK-like cells. First, we found that TGF-ß1/IL-15, but not IL-15 alone, induced CD103+CD49a+ NK-like cells from peripheral blood NK cells, which expressed markers previously associated with inhibitory CD56+ innate lymphoid cells, including high expression of GITR and CD101. Moreover, supernatant from ascites collected from patients with ovarian carcinoma also induced CD103+CD49a+ NK-like cells in vitro in a TGF-ß-dependent manner. Interestingly, TGF-ß1/IL-15-induced CD103+CD56+ NK-like cells suppressed autologous CD4+ T cells in vitro by reducing absolute number, proliferation, and expression of activation marker CD25. Collectively, these findings provide new insight into how NK cells may acquire an inhibitory phenotype in TGF-ß1-rich environments.

Oncologic safety of breast conserving surgery after neoadjuvant chemotherapy in patients with multiple ipsilateral breast cancer: A retrospective multi-institutional cohort study.

INTRODUCTION: The recent ACOSOG Z11102 trial demonstrated low recurrence rates with breast conserving surgery (BCS) in women with multiple ipsilateral breast cancers (MIBC). Questions remain regarding the oncologic safety of BCS in women with MIBC receiving neoadjuvant chemotherapy (NAC). METHODS: We conducted a retrospective cohort study of adult patients who underwent BCS following NAC for stage I-III breast cancer from 2012 to 2021 at two academic centers. Descriptive statistics were used to summarize the data and the Kaplan-Meier method was used to provide estimates for recurrence and survival outcomes. MIBC was defined as ≥2 foci of malignancy. RESULTS: A total of 544 patients were included; 29.4% (n = 160) ER+/HER2-, 17.7% (n = 96) ER+/HER2+, 18.2% (n = 99) ER-/HER2+, and 34.7% (n = 189) with ER-/HER2-disease. Overall, 80.5% (n = 438) had unifocal breast cancer while 19.5% (n = 106) had MIBC. Of patients with MIBC, 90.6% (n = 96) had multifocal and 9.4% (n = 10) had multicentric disease. Pathologic complete response was achieved in 41.1% of patients with MIBC versus 41.5% of patients with unifocal disease (p = 0.94). At a median follow-up of 55 months (IQR 32-83); 4.8% of patients in the unifocal group and 4.7% of patients in the MIBC group had had a local recurrence (p = 0.97). There was no difference in 5-year local recurrence-free survival (p = 0.92), recurrence-free survival (p = 0.06), or overall survival (p = 0.07) between the groups. CONCLUSION: In this large cohort of women undergoing BCS post-NAC, there was no significant difference in in breast tumor recurrence or survival outcomes between patients with unifocal disease and those with MIBC.

Utility of mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index in clinical pH-impedance reflux study.

BACKGROUND AND AIMS: Analysis of mean nocturnal baseline impedance (MNBI) and post-reflux swallow-induced peristaltic wave index (PSPWi) have been proposed to increase the diagnostic yield of pH-impedance studies in reflux disease. However, routine use of these indices in clinical studies is yet to be established, particularly with PSPWi, which requires laborious manual analysis. Our study aimed to assess the utility of MNBI and PSPWi and their potential for future incorporation into clinical practice. METHODS: pH-impedance recordings from consecutive patients referred to the Motility Laboratory at Royal Adelaide Hospital for evaluation of gastro-oesophageal reflux disease (GORD) were prospectively collected and manually analysed. Baseline demographic characteristics, symptoms, acid exposure time (AET), number of reflux episodes, and MNBI and PSPWi were collected. RESULTS: Eighty-nine patients were included in the study (age 50 ± 17 years, 35 males). MNBI and PSPWi inversely correlated with AET (R = -0.678, P < 0.0001 and R = -0.460, P < 0.0001 respectively) and with reflux episodes (R = -0.391, P = 0.0002 and R = -0.305, P = 0.0037 respectively). In patients with a negative pH study, but with typical reflux symptoms, 4/30 (13%) had pathologic MNBI and PSPWi. There was a positive correlation between MNBI and PSPWi values (R = 0.525, P < 0.0001). Performing analysis of PSPWi was substantially more laborious than MNBI. CONCLUSION: MNBI and PSPWi are both useful adjuncts in the diagnosis of reflux disease, although in our cohort MNBI showed stronger correlation with AET with less time to analyse. The role of these indices remains to be further explored, particularly in patients with inconclusive AET and in those with positive compared to negative symptom association.

Delayed hip arthroscopy for femoroacetabular impingement syndrome does not increase revision but does increase rates of chronic opiate use.

Introduction: In recent years, the utilization of hip arthroscopy to treat femoroacetabular impingement syndrome (FAIS) has increased due to its low complication rates, positive impact on patient-reported outcomes (PROs), and association with faster rehabilitation. Despite this, there are high rates of revision and conversion to total hip arthroplasty (THA) in some of these patients. It is unclear whether time from initial FAIS diagnosis to surgery is a risk factor for poor outcomes. In this study, we examined the relationship between timing of hip arthroscopy for FAIS and rates of 2-year revision hip procedures, 2-year conversion to total hip arthroplasty (THA), post-operative medical complications, and opioid prescriptions. Methods: This is a retrospective cohort study utilizing the PearlDiver database. Current Procedural Terminology (CPT) and International Classification of Diseases (ICD) codes were used to identify patients who had surgery for FAIS with minimum 2 years follow-up available. Patients were stratified by 3-month intervals into 5 groups based on time from diagnosis of FAIS to hip arthroscopy. Multivariate logistic regression was performed to determine factors independently associated with continued opiate use and subsequent surgeries. Results: A total of 14,677 patients were included in the study. The 2-year rate of revision hip arthroscopy was 4.2%. As time from diagnosis to surgery increased, even in multivariate regression analysis, there was a higher risk of filling an opioid prescription 90 days after surgery (P < 0.001). Regression analysis demonstrated that timing of surgery was not associated with 2-year revision hip arthroscopy or conversion to THA. Age, sex, obesity, and tobacco use were significant predictors of revision hip arthroscopy and conversion to THA (p < 0.001). Conclusion: There is no significant difference between timing of surgery for FAIS and odds of revision or conversion to THA. Prolonged opiate use after hip arthroscopy was significantly higher as duration from initial FAIS diagnosis to surgery increased. Age, sex, obesity, and tobacco use are significant predictors for revision, conversion to THA, and continued opiate prescriptions.