Evaluating acute nipple inversion, imaging findings and outcomes.

PURPOSE: Acute nipple inversion can be unsettling for patients and is sometimes associated with an underlying breast malignancy. It also poses a diagnostic challenge with lack of consensus management guidelines. This study reviewed institutional experience with new nipple inversion, including malignant association, imaging utilization, and outcomes, in an effort to improve management. METHODS: A multisite institutional retrospective review was conducted of all breast imaging reports from 1/2010 to 6/2022 mentioning nipple inversion as an indication or finding. Patients with new nipple inversion, defined as arising since the time of last breast imaging exam or if reported as new by the patient/provider, were included for analysis. Retroareolar imaging findings, BI-RADS assessments/recommendations, pathology obtained from percutaneous or excisional biopsies, and follow-up imaging and clinical exams were collated. Cases of chronic or stable nipple inversion were excluded. Descriptive statistics were performed. RESULTS: A total of 414 patients had new nipple inversion, 387/414 (93.5 %) with benign or negative results at initial imaging and 27/414 (6.5 %) with malignant lesions. Diagnostic mammography/ultrasound detected 25/27 (92.6 %) cancers (sensitivity 92.6 %, specificity 75.5 %, PPV 20.8 %, NPV 99.3 %). Of 62 breast MRI exams performed in patients with negative mammogram/ultrasound, no cancers were detected in the retroareolar space with 2 incidental malignant lesions discovered distant from the nipple. CONCLUSION: Diagnostic mammography/ultrasound is reliable in workups of acute nipple inversion, with a high sensitivity and NPV for excluding malignancy. Breast MRI and surgical referral should be reserved for patients with suspicious associated symptoms or clinical findings.

The structure of Mn(II)-bound Rubisco from Spinacia oleracea.

The rate of photosynthesis and, thus, CO2 fixation, is limited by the rate of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco). Not only does Rubisco have a relatively low catalytic rate, but it also is promiscuous regarding the metal identity in the active site of the large subunit. In Nature, Rubisco binds either Mg(II) or Mn(II), depending on the chloroplastic ratio of these metal ions; most studies performed with Rubisco have focused on Mg-bound Rubisco. Herein, we report the first crystal structure of a Mn-bound Rubisco, and we compare its structural properties to those of its Mg-bound analogues.

Assessing Leg Blood Flow and Cardiac Output During Running Using Thermodilution.

Cardiac output (Q̇C) and leg blood flow (Q̇LEG) can be measured simultaneously with high accuracy using transpulmonary and femoral vein thermodilution with a single-bolus injection. The invasive measure has offered important insight into leg hemodynamics and blood flow distribution during exercise. Despite being the natural modality of exercise in humans, there has been no direct measure of Q̇LEG while running in humans. We sought to determine the feasibility of the thermodilution technique for measuring Q̇LEG and conductance during high-intensity running, in an exploratory case study. A trained runner (30 years male) completed two maximal incremental tests on a cycle ergometer and motorized treadmill. Q̇LEG and Q̇C were determined using the single-bolus thermodilution technique. Arterial and venous blood were sampled throughout exercise, with continuous monitoring of metabolism, intra-arterial and venous pressure, and temperature. The participant reached a greater peak oxygen uptake (V̇O2peak) during running relative to cycling (74 vs. 68 mL/kg/min) with comparable Q̇LEG (19.0 vs. 19.5 L/min) and Q̇C (27.4 vs. 26.2 L/min). Leg vascular conductance was greater during high-intensity running relative to cycling (82 vs. 70 mL/min/mmHg @ ~80% V̇O2peak). The "beat phenomenon" was apparent in femoral flow while running, producing large gradients in conductance (62-90 mL/min/mmHg @ 70% V̇O2peak). In summary, we present the first direct measure of Q̇LEG and conductance in a running human. Our findings corroborate several assumptions about Q̇LEG during running compared with cycling. Importantly, we demonstrate that using thermodilution in running exercise can be completed effectively and safely.

Cognitive and Salience Network Connectivity Changes following a Single Season of Repetitive Head Impact Exposure in High School Football.

BACKGROUND AND PURPOSE: During a season of high school football, adolescents with actively developing brains experience a considerable number of head impacts. Our aim was to determine whether repetitive head impacts in the absence of a clinically diagnosed concussion during a season of high school football produce changes in cognitive performance or functional connectivity of the salience network and its central hub, the dorsal anterior cingulate cortex. MATERIALS AND METHODS: Football players were instrumented with the Head Impact Telemetry System during all practices and games, and the helmet sensor data were used to compute a risk-weighted exposure metric (RWEcp), accounting for the cumulative risk during the season. Participants underwent MRI and a cognitive battery (ImPACT) before and shortly after the football season. A control group of noncontact/limited-contact-sport athletes was formed from 2 cohorts: one from the same school and protocol and another from a separate, nearly identical study. RESULTS: Sixty-three football players and 34 control athletes were included in the cognitive performance analysis. Preseason, the control group scored significantly higher on the ImPACT Visual Motor (P = .04) and Reaction Time composites (P = .006). These differences increased postseason (P = .003, P < .001, respectively). Additionally, the control group had significantly higher postseason scores on the Visual Memory composite (P = .001). Compared with controls, football players showed significantly less improvement in the Verbal (P = .04) and Visual Memory composites (P = .01). A significantly greater percentage of contact athletes had lower-than-expected scores on the Verbal Memory (27% versus 6%), Visual Motor (21% versus 3%), and Reaction Time composites (24% versus 6%). Among football players, a higher RWEcp was significantly associated with greater increments in ImPACT Reaction Time (P = .03) and Total Symptom Scores postseason (P = .006). Fifty-seven football players and 13 control athletes were included in the imaging analyses. Postseason, football players showed significant decreases in interhemispheric connectivity of the dorsal anterior cingulate cortex (P = .026) and within-network connectivity of the salience network (P = .018). These decreases in dorsal anterior cingulate cortex interhemispheric connectivity and within-network connectivity of the salience network were significantly correlated with deteriorating ImPACT Total Symptom (P = .03) and Verbal Memory scores (P = .04). CONCLUSIONS: Head impact exposure during a single season of high school football is negatively associated with cognitive performance and brain network connectivity. Future studies should further characterize these short-term effects and examine their relationship with long-term sequelae.

Regiochemical Analysis of the ProTide Activation Mechanism.

ProTides are nucleotide analogues used for the treatment of specific viral infections. These compounds consist of a masked nucleotide that undergoes in vivo enzymatic and spontaneous chemical transformations to generate a free mononucleotide that is ultimately transformed to the pharmaceutically active triphosphorylated drug. The three FDA approved ProTides are composed of a phosphoramidate (P-N) core coupled with a nucleoside analogue, phenol, and an l-alanyl carboxylate ester. The previously proposed mechanism of activation postulates the existence of an unstable 5-membered mixed anhydride cyclic intermediate formed from the direct attack of the carboxylate group of the l-alanyl moiety with expulsion of phenol. The mixed anhydride cyclic intermediate is further postulated to undergo spontaneous hydrolysis to form a linear l-alanyl phosphoramidate product. In the proposed mechanism of activation, the 5-membered mixed anhydride intermediate has been detected previously using mass spectrometry, but the specific site of nucleophilic attack by water (P-O versus C-O) has not been determined. To further interrogate the mechanism for hydrolysis of the putative 5-membered cyclic intermediate formed during ProTide activation, the reaction was conducted in 18O-labeled water using a ProTide analogue that could be activated by carboxypeptidase Y. Mass spectrometry and 31P NMR spectroscopy were used to demonstrate that the hydrolysis of the mixed anhydride 5-membered intermediate occurs with exclusive attack at the phosphorus center.

Psychosocial burden after the death of a child from cancer: Results of a bereaved parent survey.

Parents experience lasting psychological distress after a child's death from cancer. Limited evidence exists regarding difficult life events, duration of psychosocial impacts, and associated risk factors among bereaved parents. Alex's Lemonade Stand Foundation surveyed self-selected, bereaved parents regarding difficult life events and psychosocial wellbeing (life satisfaction, unanswered questions, and missing the care team) through a public, cross-sectional survey. 176 bereaved parents (89% mothers) participated a median of 7 y after their child's death. The most difficult events were family vacations (80%), their child's birthday (80%), and anniversary of their child's death (76%). Only the latter did not improve with time. Greater life satisfaction was associated with male sex (ARR = 1.2, 95% CI:1.1-1.4) and being married/partnered (ARR = 1.2, 95% CI = 1.0-1.3). Having unanswered questions and missing the child's team were associated with annual income <$50,000 (ARR = 1.2, 95% CI:1.1-1.2; ARR = 1.2, 95% CI:1.0-1.3, respectively). Pediatric oncology programs need robust bereavement programs that include prolonged contact with families.

Total brain volume is associated with severity of transverse sinus stenosis in idiopathic intracranial hypertension.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a complex neurological condition characterized by symptoms of increased intracranial pressure of unclear etiology. While transverse sinus stenosis (TSS) is often present in patients with IIH, how and why it occurs remains unclear. METHODS: IIH patients and a set of age-matched normal controls were identified from our single-center tertiary care institution from 2016 to 2024. Brain MRIs before treatment were computationally segmented and parcellated using FreeSurfer software. Extent of TSS on MR venograms was graded using the Farb scoring system. Relationship between normalized brain volume, normalized brain-to-CSF volume, and TSS was investigated. Multiple linear regression was conducted to investigate the association between continuous variables, accounting for the covariates body mass index, sex, and age. RESULTS: In total, 84 IIH patients (mean age, 29.8 years; 87% female) and 15 normal controls (mean age, 28.1 years) were included. Overall, increasing/worsening TSS was found to be significantly associated with normalized total brain volume (p=0.018, R=0.179) and brain-to-CSF ratio volume (p=0.026, R=0.184). Additionally, there was a significant difference between controls and IIH patients with mild and severe stenosis regarding normalized total brain volume (ANCOVA, p=0.023) and brain-to-CSF ratio volume (ANCOVA, p=0.034). Likewise, IIH patients with severe TSS had a significantly higher brain-to-CSF volume compared with controls (p=0.038) and compared with IIH patients with mild TSS (p=0.038). CONCLUSIONS: These findings suggest that total brain volume is associated with extent of TSS, which may reflect extramural venous compression due to enlarged brain and/or venous hypertension with associated cerebral congestion/swelling.

Embryoid Bodies and Related Proliferations in Ovarian Germ Cell Tumors.

We investigated the frequency and associated pathology of embryoid bodies in ovarian tumors by evaluating neoplasms in which they are known to occur: 100 immature teratomas, 125 malignant mixed germ cell tumors, and 6 polyembryomas. Three immature teratomas contained a single relatively well-formed embryoid body, whereas these and 11 others showed foci we categorized as embryoid body remnants consisting of microscopic aggregates of embryonal or yolk sac-type epithelium associated with spaces consistent with yolk sac or amniotic cavity but lacking a classic embryoid body structure. Teratomas with these foci were all high grade. A well-formed embryoid body was found in only 1 malignant mixed tumor, but embryoid body remnants were present in 25%, invariably associated with foci of immature teratoma (100%) and often with yolk sac tumor (97%), embryonal carcinoma (35%), or both (32%). These foci usually took the form of round to oval aggregates, often well-circumscribed, for which the term "polyembryoma background" has been proposed. The polyembryomas were typically grossly hemorrhagic and occurred in patients from 9 to 43 years of age. The embryoid bodies in them generally grew in lobules within an edematous to occasionally myxoid stroma. Four tumors contained liver-like cells, 4 numerous glands likely recapitulating the allantois, 3 syncytiotrophoblast cells, 2 prominent cysts, and 2 striking vascular proliferations. This study indicates that (1) typical embryoid bodies are rare in immature teratomas but about 14% of them have embryoid body remnants. (2) Embryoid body remnants are seen in 25% of malignant mixed germ cell tumors with a teratomatous component and often proliferate to form yolk sac tumor and embryonal carcinoma. (3) Well-formed embryoid bodies growing in a confluent manner (polyembryoma) are rare, and minor foci of teratoma, yolk sac tumor, or embryonal carcinoma are almost always present, indicating that these are fundamentally malignant mixed germ cell tumors but the polyembryoma component is dominant and distinctive which, in our opinion, justifies its own nomenclature. (4) Embryoid bodies are not a feature of other germ cell tumors.

Elevated meningioma risk among individuals who are Non-Hispanic Black is strongest for grade 2-3 tumors and synergistically modified by male sex.

Background: Meningioma risk factors include older age, female sex, and African-American race. There are limited data exploring how meningioma risk in African-Americans varies across the lifespan, interacts with sex, and differs by tumor grade. Methods: The Central Brain Tumor Registry of the United States (CBTRUS) is a population-based registry covering the entire U.S. population. Meningioma diagnoses from 2004-2019 were used to calculate incidence rate ratios (IRRs) for non-Hispanic Black individuals (NHB) compared to non-Hispanic white individuals (NHW) across 10-year age intervals, and stratified by sex and by WHO tumor grade. Results: 53,890 NHB individuals and 322,373 NHW individuals with an intracranial meningioma diagnosis were included in analyses. Beginning in young adulthood, the NHB-to-NHW IRR was elevated for both grade 1 and grade 2/3 tumors. The IRR peaked in the seventh decade of life regardless of grade, and was higher for grade 2/3 tumors (IRR=1.57; 95% CI: 1.46-1.69) than grade 1 tumors (IRR=1.27; 95% CI: 1.25-1.30) in this age group. The NHB-to-NHW IRR was elevated in females (IRR=1.17; 95% CI: 1.16-1.18) and further elevated in males (IRR=1.28; 95% CI: 1.26-1.30), revealing synergistic interaction between NHB race/ethnicity and male sex (P Interaction =0.001). Conclusions: Relative to NHW individuals, NHB individuals are at elevated risk of meningioma from young adulthood through old age. NHB race/ethnicity conferred higher risk of meningioma among men than women, and higher risk of developing WHO grade 2/3 tumors. Results identify meningioma as a significant source of racial disparities in neuro-oncology and may help to improve preoperative predictions of meningioma grade.

Social media and body image: Relationships between social media appearance preoccupation, self-objectification, and body image.

Nearly 85 % of emerging adults report using at least one social media site. Research suggests that viewing and internalizing unrealistic body ideals often displayed online may pose harmful effects on young people's body image. However, studies on the relationships between social media usage and body image have predominantly focused on women's drive for thinness. We sought to explore the relationships between social media appearance-related preoccupation (SMARP), body shame and surveillance, and drives for leanness, muscularity, and thinness, specifically examining the moderating role of gender within these relationships. Data from 939 undergraduate students (n = 240 men) were analyzed using multigroup structural equation modeling. Surveillance significantly mediated the positive associations between SMARP and drive for leanness for women and men. For SMARP and drive for muscularity, surveillance was a mediator for men only. Shame emerged as a significant mediator of the positive association between SMARP and drive for thinness for women and men. Moderated mediation was supported, such that the indirect effect of SMARP on drive for thinness was significantly stronger for women. These results suggest that for men in particular, SMARP is not necessarily associated with increased drives for leanness and muscularity unless men are also engaging in body surveillance.

Clinical and Radiographic Outcomes of Nitinol Compression Staples for Midfoot and Chopart Arthrodesis.

Nitinol staple use in orthopedic surgery has increased in recent years. Biomechanical studies provide useful data for use in foot/ankle; however, clinical data is limited. This study's purpose is to determine the efficacy of nitinol staples to achieve stable, bony arthrodesis in midfoot and Chopart joints, and examine their clinical outcomes and pain scores. A retrospective chart review was performed on 127 midfoot/Chopart joint arthrodeses (71 patients) using nitinol staples in isolation. The primary outcome variable was radiographic evidence of healing. Radiographs were blinded, randomized, and independently reviewed by three board certified foot and ankle surgeons. Complete/partial union was seen in 89% of all joints (113/127), increasing to 93% when including only midfoot joints (98/106). Chopart joints had significantly lower healing rates (15/21; 71%) compared to all midfoot joints (p = 0.01) and isolated tarsometatarsal joints (86/91; 95%) (p = 0.006). Neuropathy and smoking did not affect arthrodesis, but diabetes did (p = 0.004). Joints requiring bone grafting had worse rates of arthrodesis (38/49; 76%) (p = 0.002). For all joints, post-operative visual analog scale scores were significantly lower than pre-operative (p < 0.001). Pre-operative midfoot and Chopart pain scores were similar (p= 0.30). Midfoot joints had significantly lower pain scores post-operatively than pre-operatively (p < 0.001). No such significance existed in Chopart joints (p = 0.07). Isolated nitinol staples are a viable option for midfoot arthrodesis, especially tarsometatarsal joints, and offer significant pain improvement. Chopart joints may require more rigid fixation than nitinol staples, given the lower healing rate. LEVEL OF CLINICAL EVIDENCE: IV.

Efficacy and safety of upadacitinib in patients with rheumatoid arthritis and inadequate response or intolerance to biological treatments: results through 5 years from the SELECT-BEYOND study.

OBJECTIVE: To evaluate the efficacy and safety of upadacitinib over 5 years among patients with rheumatoid arthritis (RA) in a long-term extension (LTE) of the SELECT-BEYOND phase 3 trial. METHODS: Patients refractory to ≥1 biological disease-modifying antirheumatic drug (DMARD) received upadacitinib 15 mg or 30 mg once daily or placebo, in combination with background conventional synthetic DMARD(s). At week 12, patients randomised to placebo were switched to upadacitinib 15 mg or 30 mg. All patients who completed the week 24 visit could enter the LTE for up to 5 years. Efficacy was analysed as observed and by non-responder imputation through week 260. Treatment-emergent adverse events per 100 patient-years were summarised over 5 years. RESULTS: Of the 498 patients randomised, 418 (84%) completed week 24 and entered the LTE. Of those who remained in the trial (n=80, upadacitinib 15 mg; n=81, upadacitinib 30 mg), 36%/36% and 81%/77% randomised to upadacitinib 15/30 mg were in Clinical Disease Activity Index (CDAI) remission or low disease activity at week 260, respectively (as observed). Approximately 47% of all patients who began in high disease activity demonstrated a CDAI improvement >12 at week 260 with upadacitinib 15/30 mg. Functional and pain-related outcomes also showed comparable improvements with both doses. Numerically higher rates of anaemia, herpes zoster and creatine phosphokinase elevation were observed with upadacitinib 30 mg vs 15 mg. No new safety issues were identified. CONCLUSIONS: Upadacitinib 15/30 mg continued to be effective in treating clinical and functional outcomes in patients with RA. The safety profile observed over 5 years was consistent with earlier study-specific and integrated assessments of upadacitinib treatment.

Safety of intracranial venous stenting in patients with nickel allergy.

BACKGROUND: Nickel hypersensitivity is the most common metal related allergy. Nickel containing alloys are frequently used in endovascular devices. The use of intracranial stents in patients with nickel hypersensitivity appears to be safe, but these small series only evaluated arterial stent placement. This case series aimed to assess the safety of intracranial venous stent placement in patients with documented nickel allergy. METHODS: In this retrospective multicenter case series, patients with idiopathic intracranial hypertension and documented nickel allergy underwent treatment with a permanently implanted nickel containing stent in the dural venous sinuses. RESULTS: Nine patients with nickel allergy were included. All patients reported clinical improvement in their idiopathic intracranial hypertension symptoms. Of the five patients who had follow-up intracranial venous imaging, all stents remained patent. No patients experienced intraoperative, postoperative, or long term procedure related complications, with follow-up ranging from 1.8 weeks to 49.1 months. CONCLUSION: In this limited case series, the use of nickel containing stents in intracranial venous sinuses in patients with nickel allergy did not result in any allergic reaction or adverse outcome.

Protective Effects of Authenticity Against Depression, Suicide, and Burnout among Surgeons.

BACKGROUND: Physician burnout and poor mental health are highly prevalent issues within the surgical community. Authenticity, defined as the degree to which individuals align their actions with their true selves, has been identified as a potential factor facilitating positive mental health. This study explores the impact of authenticity on burnout, depression, and suicide among surgeons. STUDY DESIGN: Members of the department of surgery at a large academic medical center were sent an anonymous survey between April to May 2023. The survey evaluated authenticity using Authenticity Scale, depression using Patient Health Questionnaire (PHQ9), burnout using Copenhagen Burnout Inventory, and suicidality using Ask-Suicide Screening Questions (ASQ) tool. RESULTS: Of the 170 surgeons, 94 (55.3%) completed the survey. Higher Authentic Living scores (ALS) correlated with reduced burnout (r=-0.21, p=0.047) and depression (r=-0.37, p=0.0002). Conversely, higher Accepting External Influence (AEI) were associated with increased depression (r=0.23, p=0.023) and higher Self-Alienation (ASA) were associated with increased burnout (r=0.43, p<0.0001) and depression (r=0.48, p<0.0001). While authenticity domain scores were not significantly associated with ASQ, specific AEI and ASA questions indicated an elevated odds ratio (p=0.029 and p=0.010 respectively) of a positive ASQ. ALS increased with advancement in professional rank (p=0.007), while AEI (p=0.0001), ASA (p=0.003), depression (p=0.014), and ASQ (p=0.02) decreased. CONCLUSIONS: In this study, higher authenticity was associated with a lower likelihood of burnout and depression among surgeons. This study contributes valuable insights into the development of targeted intervention and support mechanisms aimed at promoting authenticity and mental health within the surgical profession.