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.

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.

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.

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.

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.

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.

Proximal Hamstring Repair With All-Suture Anchors and an Accelerated Rehabilitation and Bracing Protocol Demonstrates Good Outcomes at 1-Year Follow-Up.

Purpose: To evaluate patient-reported outcomes and risk for rerupture after surgical treatment of proximal hamstring tendon ruptures using all-suture anchors and a unique postoperative bracing strategy. Methods: A retrospective review of a prospectively collected database was conducted of patients undergoing proximal hamstring repair or reconstruction from 2020 to 2022 at a tertiary, academic institution. Patients were included if they reached minimum 1-year follow-up and completed postoperative patient-reported outcomes. The surgical protocol for proximal hamstring repairs included all-suture anchors placed either in an open or endoscopic fashion in the ischial tuberosity. After surgery, all patients underwent an accelerated rehabilitation protocol, including 6 weeks touchdown weight-bearing in a hinged knee brace locked in extension for ambulation, allowing passive knee flexion to 90° while seated. Descriptive statistics were used to analyze the data. Results: Twenty-one patients were included (mean age 50.4 ± 9.5 years, body mass index 24.4 ± 3.5, 66.7% female). Lower Extremity Functional Scale score achieved postoperatively was 74.2 ± 7.5 (out of 80). Patients had minimal pain (mean visual analog scale pain score of 0.9 ± 1.2). 61.9% of patients were able to return to the same level of activity after based on Tegner score by 1 year. Postoperative Single Assessment Numeric Evaluation activity of daily living was 94.3 ± 8.3, and Single Assessment Numeric Evaluation Sports was 82.3 ± 19.0. Mean Short Form Survey (SF-12) postoperative scores were 51.6 ± 6.8 for SF-12 Physical Component Score and 53.9 ± 9.7 for Mental Component Score. 95.2% (20 of 21) patients were satisfied with their outcome. There were no reruptures, infections, or reoperations. One patient of 21 (4.8%) incurred a postoperative deep venous thrombosis, which was treated with therapeutic anticoagulation for 3 months. Conclusions: All-suture anchors for proximal hamstring repair with a unique accelerated postoperative rehabilitation and bracing protocol result in good outcomes and patient satisfaction with minimal risk of complications. Level of Evidence: Level IV, case series, therapeutic.

Outcomes of Serum Food-Specific Immunoglobulin G 4 to Guide Elimination Diet in Patients With Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic esophagitis (EoE) is associated with atopy; however, recent studies have identified an association with food-specific immunoglobulin G 4 (FS-IgG 4 ) rather than immunoglobulin E antibodies. This study aimed to evaluate the role of serum FS-IgG 4 in guiding an elimination diet and its outcomes. METHODS: Patients with and without EoE were enrolled in a prospective, controlled, single tertiary center trial. Serum FS-IgG 4 titers, esophageal eosinophil counts, and dysphagia symptom questionnaire scores were assessed, and participants with elevated FS-IgG 4 (ImmunoCAP, cutoff of 10 mgA/L) commenced 6-week targeted elimination diet. Repeat serum FS-IgG 4 and endoscopic and histologic examination were performed at 6-week follow-up. RESULTS: Twenty-two patients with active EoE and 13 controls were recruited. Serum FS-IgG 4 to milk, wheat, soy, eggs, and nuts was significantly higher in EoE ( P = 0.0002, P = 0.002, P = 0.003, P = 0.012, and P < 0.001, respectively). Elevated serum FS-IgG 4 to 1 or more food groups (median 2) was identified in 21/22 (95.4%) patients with EoE; 20/21 underwent 6-week dietary elimination. Median reductions in dysphagia symptom questionnaire score and EoE endoscopic reference score after elimination were 8 ( P = 0.0007) and 1 ( P = 0.002), respectively. Nine (45%) patients had histological remission (<15 eosinophils per high-power field). Fall in median esophageal eosinophil count was not statistically significant (50 vs 23; P = 0.068). Serum FS-IgG 4 did not decline by 6-week follow-up. DISCUSSION: Serum FS-IgG 4 to milk, wheat, soy, egg, and nuts was present at higher levels in EoE, with targeted elimination resulting in 45% histologic remission rate. Serum FS-IgG 4 has potential as a noninvasive biomarker in EoE. When successful, FS-IgG 4 -led elimination diet can negate need for medications and be viewed more favorably by patients because of its smaller endoscopic burden compared with empirical elimination diets.

Preoperative factors that predict pathologic nodal involvement in early-stage HER2+ breast cancer: selecting cT1cN0 patients for treatment with neoadjuvant chemotherapy versus upfront surgery.

PURPOSE: The goal of this study was to identify the preoperative predictors of pathologic nodal metastases (pN+) in cT1cN0 HER2+ breast cancer undergoing upfront surgery. METHODS: We retrospectively reviewed data from women with cT1-T2N0 HER2+ breast cancer treated with neoadjuvant therapy (NAC) or upfront surgery at our institution between 2012 and 2023. Factors associated with management strategy were evaluated, and in those undergoing upfront surgery, univariate analyses were performed to identify the clinicopathologic factors associated with nodal metastases. RESULTS: Overall, 255 women with cT1-T2N0 HER2+ breast cancer met inclusion criteria, including 170 (68.6%) upfront surgery patients and 85 (31.4%) who underwent NAC. The median age at diagnosis was 59 years (range, 27-90 years). Younger age, larger clinical tumor size, high-grade disease, ER-PR-HER2+ subtype, and year of diagnosis after 2019 were significantly associated with receipt of NAC (p < 0.05). In those undergoing upfront surgery, 25.3% were pN+ , including 32.5% of cT1cN0 tumors. Factors associated with nodal involvement included age under 50, larger clinical tumor size, lymphovascular invasion (LVI), multifocality/multicentricity, and abnormal lymph nodes on axillary ultrasound (p < 0.05). In subset analysis of cT1cN0 HER2+ cases, LVI remained the strongest predictor of pN + disease (73.3% vs. 22.6%, p < 0.001). Patients with cT1cN0 HER2+ breast cancer under 50 years had a 47.1% likelihood of pN+ disease. CONCLUSION: Patients with cT1cN0 breast cancer have a 32.5% likelihood of nodal metastases, with higher incidence with younger age, LVI, multifocality/multicentricity, and abnormal axillary ultrasound. The presence of these factors may identify the patients who would benefit from treatment with neoadjuvant chemotherapy.

Counselling Framework for Germline BRCA1/2 and PALB2 Carriers Considering Risk-Reducing Mastectomy.

Female BRCA1/2 and PALB2 germline pathogenic variant carriers have an increased lifetime risk of breast cancer and may wish to consider risk-reducing mastectomy (RRM) for surgical prevention. Quantifying the residual lifetime risk and absolute benefit from RRM requires careful consideration of a patient's age, pathogenic variant, and their personal history of breast or ovarian cancer. Historically, patients have been counselled that RRM does not necessarily prolong survival relative to high-risk surveillance, although recent studies suggest a possible survival benefit of RRM in BRCA1 carriers. The uptake of RRM has increased dramatically over the last several decades yet varies according to sociodemographic factors and geographic region. The increased adoption of nipple-sparing mastectomy techniques, ability to avoid axillary staging, and availability of reconstructive options for most germline pathogenic variant carriers has helped to minimize the morbidity of RRM. Preoperative discussions should include evidence regarding postmastectomy sensation, the potential for supplemental surgery, pregnancy-related chest wall changes, and the need for continued clinical surveillance. Approaches that include sensation preservation and robotic nipple-sparing mastectomy are an area of evolving research that may be more widely adopted in the future.

Unique Challenges in Biomarkers for Psychotic Disorders.

Biomarkers are observations that provide information about the risk of certain conditions (predictive) or their underlying mechanisms (explanatory) [...].

Evidence for a multidimensional account of cognitive and affective theory of mind: A state-trace analysis.

Theory of mind (ToM) has been argued to be a multidimensional construct, with ToM inferences depending on distinct processes across affective and cognitive ToM tasks and across first-order cognitive and second-order cognitive ToM tasks. Behavioural evidence for a multidimensional account has primarily depended on dissociations identified via analysis of variance, a statistical approach insufficient for assessing dimensionality. Instead, state-trace analysis (STA) is a more appropriate statistical technique to uncover dimensionality. The current study first applied STA to two summary datasets that had previously identified key dissociations between cognitive and affective ToM; these reanalyses did not support a multidimensional account of ToM. Next, STA was applied to a more detailed dataset to reveal whether ToM is based on multiple processes in a sample of 115 older adults aged 60-85 years (M = 68.5, SD = 5.92, 61.7% female) with higher or lower emotion perception ability. Participants made ToM judgements about different social exchanges (e.g., sarcasm or lying). STA results supported a multidimensional account of ToM across first-order cognitive, second-order cognitive, and affective ToM subdomains. These results lay a more rigorous foundation for subsequent studies to further examine the dimensionality of ToM and to apply formal modelling, progressing the field's understanding and measurement of the cognitive processes driving ToM judgements.

Physiochemical effects of acid exposure on bone composition and function.

Bone is primarily composed of collagen and apatite, two materials which exhibit a high sensitivity to pH dysregulation. As a result, acid exposure of bone, both clinically and in the laboratory is expected to cause compositional and mechanical changes to the tissue. Clinically, Metabolic acidosis (MA), a condition characterized by a reduced physiological pH, has been shown to have negative implications on bone health, including a decrease in bone mineral density and volume as well as increased fracture risk. The addition of bone-like apatite to ionic solutions such as phosphate buffered saline (PBS) and media has been shown to acidify the solution leading to bone acid exposure. Therefore, is it essential to understand how reduced pH physiochemically affects bone composition and in turn its mechanical properties. This study investigates the specific changes in bone due to physiochemical dissolution in acid. Excised murine bones were placed in PBS solutions at different pHs: a homeostatic pH level (pH 7.4), an acidosis equivalent (pH 7.0), and an extreme acidic solution (pH 5.5). After 5 days, the bones were removed from the solutions and characterized to determine compositional and material changes. We found that bones, without cells, were able to regulate pH via buffering, leading to a decrease in bone mineral content and an increase in collagen denaturation. Both of these compositional changes contributed to an increase in bone toughness by creating a more ductile bone surface and preventing crack propagation. Therefore, we conclude that the skeletal systems' physiochemical response to acid exposure includes multifaceted and spatially variable compositional changes that affect bone mechanics.

Pregnancy After Breast Cancer in Young BRCA Carriers: An International Hospital-Based Cohort Study.

Importance: Young women with breast cancer who have germline pathogenic variants in BRCA1 or BRCA2 face unique challenges regarding fertility. Previous studies demonstrating the feasibility and safety of pregnancy in breast cancer survivors included limited data regarding BRCA carriers. Objective: To investigate cumulative incidence of pregnancy and disease-free survival in young women who are BRCA carriers. Design, Setting, and Participants: International, multicenter, hospital-based, retrospective cohort study conducted at 78 participating centers worldwide. The study included female participants diagnosed with invasive breast cancer at age 40 years or younger between January 2000 and December 2020 carrying germline pathogenic variants in BRCA1 and/or BRCA2. Last delivery was October 7, 2022; last follow-up was February 20, 2023. Exposure: Pregnancy after breast cancer. Main Outcomes and Measures: Primary end points were cumulative incidence of pregnancy after breast cancer and disease-free survival. Secondary end points were breast cancer-specific survival, overall survival, pregnancy, and fetal and obstetric outcomes. Results: Of 4732 BRCA carriers included, 659 had at least 1 pregnancy after breast cancer and 4073 did not. Median age at diagnosis in the overall cohort was 35 years (IQR, 31-38 years). Cumulative incidence of pregnancy at 10 years was 22% (95% CI, 21%-24%), with a median time from breast cancer diagnosis to conception of 3.5 years (IQR, 2.2-5.3 years). Among the 659 patients who had a pregnancy, 45 (6.9%) and 63 (9.7%) had an induced abortion or a miscarriage, respectively. Of the 517 patients (79.7%) with a completed pregnancy, 406 (91.0%) delivered at term (≥37 weeks) and 54 (10.4%) had twins. Among the 470 infants born with known information on pregnancy complications, 4 (0.9%) had documented congenital anomalies. Median follow-up was 7.8 years (IQR, 4.5-12.6 years). No significant difference in disease-free survival was observed between patients with or without a pregnancy after breast cancer (adjusted hazard ratio, 0.99; 95% CI, 0.81-1.20). Patients who had a pregnancy had significantly better breast cancer-specific survival and overall survival. Conclusions and Relevance: In this global study, 1 in 5 young BRCA carriers conceived within 10 years after breast cancer diagnosis. Pregnancy following breast cancer in BRCA carriers was not associated with decreased disease-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03673306.

Comorbidity of autism spectrum and attention deficit/hyperactivity disorder symptoms and their associations with 1-year mental health outcomes in adolescents and young adults.

Autism spectrum (ASD) and attention deficit/hyperactivity disorders (ADHD) share genetic, neurological, and behavioural features. However, related research in Asia is limited. We collected self-reported ASD and ADHD symptoms from 2186 Hong Kong adolescents and young adults aged 15-24 years, among whom, 1200 provided 1-year data on mental health-related outcomes. Comparative and network analyses were performed. Rating scale cutoff scores were used to divide participants into ASD, ADHD, comorbid, and control groups. The prevalence rates of ASD, ADHD, and comorbidities in Hong Kong were 13.3 %, 10.6 %, and 2.7 %, respectively. Compared with the control group, the comorbid group experienced more psychotic-like experiences (PLEs), the ASD group had poorer functioning, and the ADHD group had higher depression and anxiety symptoms and a lower quality of life after 1 year. The ability to switch attention, preference for routines and difficulty with change, and problems with organisation and planning were positively associated with depressive symptoms, forgetfulness and working memory issues with anxiety symptoms, and heightened sensory input and difficulties in sustaining attention and task completion with PLEs after 1 year. Our findings provide insight into support strategies to address the needs of young Asians to improving their well-being and long-term outcomes.