The Concealment of Health Information at the Intersection of Sexual Orientation and Race.

Purpose: Sexually and racially minoritized people often have mistrust toward the healthcare system due to both perceived and actual experiences of discrimination. This may result in increased privacy concerns and a reluctance to share health-related information with health care providers. Drawing upon minority stress and an intersectionality framework, this study examines how rates of concealing health information differ between non-Hispanic White heterosexual people, non-Hispanic White lesbian, gay, and bisexual (LGB) people, racially minoritized heterosexual people, and those who are both sexually and racially minoritized. Methods: Using nationally representative cross-sectional data from the Health Information National Trends Survey from 2017 and 2018 (n = 4575), we fit logistic regression models to examine (1) whether sexually and racially minoritized people conceal health information from their providers more than their counterparts and (2) whether this tendency increases for those with multiple marginalized identities. Furthermore, we fit linear regression models to examine whether and how concealing health information from providers are linked to health outcomes. Results: Sexually and racially minoritized people had higher odds of concealing health information from providers than their counterparts. Those with multiple marginalized identities had even higher odds of withholding health information than other groups. Finally, we found a significant negative association between concealing health information and mental health. Conclusion: Our findings underscore the need to consider how the intersection of multiple marginalized identities shape health experiences and concerns over privacy in health care matters. We call for further research to better understand the complex dynamics of patient-provider relationships for marginalized populations.

Neurocognitive profiles of 22q11.2 and 16p11.2 deletions and duplications.

Rare recurrent copy number variants (CNVs) at chromosomal loci 22q11.2 and 16p11.2 are genetic disorders with lifespan risk for neuropsychiatric disorders. Microdeletions and duplications are associated with neurocognitive deficits, yet few studies compared these groups using the same measures to address confounding measurement differences. We report a prospective international collaboration applying the same computerized neurocognitive assessment, the Penn Computerized Neurocognitive Battery (CNB), administered in a multi-site study on rare genomic disorders: 22q11.2 deletions (n = 492); 22q11.2 duplications (n = 106); 16p11.2 deletion (n = 117); and 16p11.2 duplications (n = 46). Domains examined include executive functions, episodic memory, complex cognition, social cognition, and psychomotor speed. Accuracy and speed for each domain were included as dependent measures in a mixed-model repeated measures analysis. Locus (22q11.2, 16p11.2) and Copy number (deletion/duplication) were grouping factors and Measure (accuracy, speed) and neurocognitive domain were repeated measures factors, with Sex and Site as covariates. We also examined correlation with IQ. We found a significant Locus × Copy number × Domain × Measure interaction (p = 0.0004). 22q11.2 deletions were associated with greater performance accuracy deficits than 22q11.2 duplications, while 16p11.2 duplications were associated with greater specific deficits than 16p11.2 deletions. Duplications at both loci were associated with reduced speed compared to deletions. Performance profiles differed among the groups with particularly poor memory performance of the 22q11.2 deletion group while the 16p11.2 duplication group had greatest deficits in complex cognition. Average accuracy on the CNB was moderately correlated with Full Scale IQ. Deletions and duplications of 22q11.2 and 16p11.2 have differential effects on accuracy and speed of neurocognition indicating locus specificity of performance profiles. These profile differences can help inform mechanistic substrates to heterogeneity in presentation and outcome, and can only be established in large-scale international consortia using the same neurocognitive assessment. Future studies could aim to link performance profiles to clinical features and brain function.

Surgical stabilization of rib fractures in the geriatric trauma population is associated with equivalent outcomes to a younger cohort: A propensity matched analysis.

BACKGROUND: Surgical stabilization of rib fractures (SSRF) improves outcomes in chest wall trauma. Geriatric patients are particularly vulnerable to poor outcomes; yet, this population is often excluded from SSRF studies. Further delineating patient outcomes by age is necessary to optimize care for the aging trauma population. METHODS: A retrospective cohort study was conducted examining outcomes among patients aged 40+ for whom an SSRF consult was placed between 2017 and 2022 at a level 1 trauma center. Patients were categorized into geriatric (65+) and adult (40-64), as well as 80 years and older (80+) and 79 and younger (40-79). Patient outcomes were assessed comparing non-operative and operative management of chest wall trauma. Propensity matched analysis was performed to evaluate mortality differences between adult and geriatric patients who did and did not undergo SSRF. RESULTS: A total of 543 patients had an SSRF consult. Of these, 227 were 65+, and 73 were 80+. A total of 129 patients underwent SSRF (24 %). The percentage of patients undergoing SSRF did not vary between 40 and 64 and 65+ (23.7 % and 23.6 %, respectively, p = 0.97) or 40-79 and 80+ (24.0 vs 21.9, p = 0.69). Patients undergoing SSRF had higher chest injury burden and were more likely to require mechanical ventilation and ICU level care on admission. Overall, in-hospital mortality rate was 4.6 %. Among patients who underwent SSRF, mortality rate did not significantly differ between 65+ and 40-64 (7.8% vs 2.7 %, p = 0.18) or 80+ and 40-79 (6.3% vs 4.6 %, p = 0.77). This remained true in propensity matched analysis. CONCLUSION: Geriatric and octogenarian patients with rib fractures underwent SSRF at similar rates and achieved equivalent outcomes to their younger counterparts. SSRF did not differentially affect mortality outcomes based on age group in propensity matched analysis. SSRF is safe for geriatric patients including octogenarians.

Causes and Timing of Unplanned ICU Admissions Among Trauma Patients at a Level 1 Trauma Center.

BACKGROUND: Unexpected ICU admissions are a key quality metric in trauma care. The purpose of this study is to identify the most common causes of unplanned ICU admissions among trauma patients at an ACS-verified level 1 trauma center. METHODS: A retrospective review was conducted of all trauma patients with unplanned admission to the ICU at a level 1 trauma center between 2019 and 2021. Unplanned ICU admissions were categorized into (1) "bounce-backs," patients previously admitted to the ICU and (2) "upgrades," patients who had not previously been cared for in the ICU. RESULTS: Of 300 unexpected ICU transfers, bounce-backs accounted for 69% and upgrades 31%. The most common injuries were traumatic brain injuries (40%) and rib fractures (41.3%). In-hospital mortality rate was 10% and did not significantly differ between bounce-backs and upgrades (12 vs 5%, P = .92). Respiratory distress was the most common cause of transfer (41.1%), followed by neurologic (29.6%) and cardiovascular decline (21.2%). Patients were on average 928 mL fluid positive 72 hours prior to transfer (t > 0, P < .0001), and 295 mL fluid positive in the 24 hours prior to transfer (t > 0, P .0003). Patients transferred for respiratory distress were no more fluid over-balanced than those transferred for other reasons. CONCLUSION: We found a large percent of unplanned transfers occurring within 48 hours of admission or transfer out of the ICU suggesting under-triage as a leading cause of bounce-backs and upgrades. Respiratory distress was the leading cause of transfer. These findings highlight opportunities for targeted interventions.

Valvular Heart Disease.

Valvular heart disease is a common abnormality seen in the primary care setting. There are many causes of valvular heart disease including congenital, degenerative, infectious, traumatic, and many more. There is a wide variety of types of valvular heart disease with each valve having the ability to develop both regurgitation and stenosis by multiple mechanisms. All these complexities make diagnosis and management of valvular heart disease complicated, especially in the context of comorbidities. For this reason, it is important for primary care physicians to have a thorough understanding of how these diseases present and when interventions are indicated.

Atherosclerosis Vindicated: A Case of Chest Pain Due to Capecitabine-Induced Coronary Artery Spasm.

BACKGROUND Capecitabine and other 5-fluorouracil prodrugs are medications widely employed in treating solid tumors, including breast and colorectal cancer. However, they carry a notable risk for cardiotoxicity, including coronary vasospasm, possibly related to their impact on vascular endothelium and smooth muscle. CASE REPORT We present a case of a 45-year-old male with a pancreatic neuroendocrine tumor who developed exertional chest pain after starting capecitabine. Initial evaluations in the emergency department, including a 12-lead electrocardiogram and cardiac enzymes, were normal, but suspicion for coronary vasospasm persisted due to the temporal relationship with drug initiation and symptom characteristics. A graded exercise test reproduced his symptoms, accompanied by hyperacute peaked T waves and subsequent ST segment elevations in the inferior leads. Coronary angiography revealed patent coronary arteries, rendering provocative testing unnecessary due to a high clinical suspicion of capecitabine-induced vasospasm. Discontinuing the patient's medication was a more efficient approach than continuing additional cardiac workup while the drug was still administered. After multidisciplinary discussion, capecitabine was discontinued, leading to symptom resolution and a negative repeat graded exercise test. CONCLUSIONS This case underscores the potential for capecitabine to induce coronary artery vasospasm, emphasizing the importance of prompt medication cessation. Patients receiving capecitabine therapy and experiencing chest pain should undergo an evaluation with consideration of capecitabine-induced vasospasm in the differential diagnosis. Prompt recognition and medication cessation are critical to prevent serious cardiovascular complications including death. In our patient, discontinuing capecitabine resolved his symptoms, emphasizing the significance of discontinuing the causative drug and seeking alternative chemotherapy regimens.

Postoperative Day 1 Discharge in Deep Inferior Epigastric Artery Perforator Flap Breast Reconstruction.

With high success rates of autologous breast reconstruction, the focus has shifted from flap survival to improved patient outcomes. Historically, a criticism of autologous breast reconstruction has been the length of hospital stay. Our institution has progressively shortened the length of stay after deep inferior epigastric artery perforator (DIEP) flap reconstruction and began discharging select patients on postoperative day 1 (POD1). The purpose of this study was to document our experience with POD1 discharges and to identify preoperative and intraoperative factors that may identify patients as candidates for earlier discharge. Methods: An institutional review board-approved, retrospective chart review of patients undergoing DIEP flap breast reconstruction from January 2019 to March 2022 at Atrium Health was completed, consisting of 510 patients and 846 DIEP flaps. Patient demographics, medical history, operative course, and postoperative complications were collected. Results: Twenty-three patients totaling 33 DIEP flaps were discharged on POD1. The POD1 group and the group of all other patients (POD2+) had no difference in age, ASA score, or comorbidities. BMI was significantly lower in the POD1 group (P = 0.039). Overall operative time was significantly lower in the POD1 group, and this remained true when differentiating into unilateral operations (P = 0.023) and bilateral operations (P = 0.01). No major complications occurred in those discharged on POD1. Conclusions: POD1 discharge after DIEP flap breast reconstruction is safe for select patients. Lower BMI and shorter operative times may be predictive in identifying patients as candidates for earlier discharge.

A soldier's return to duty after minimally invasive correction of complex congenital cardiovascular disease.

We report a case of incidental detection of severe aortic coarctation, severe secundum atrial septal defect, and bicuspid aortic valve in an active-duty military service member. A single complex minimally invasive procedure successfully corrected his coarctation and atrial septal defect allowing this patient to continue military service.

Neurocognitive Profiles of 22q11.2 and 16p11.2 Deletions and Duplications.

Rare recurrent copy number variants (CNVs) at chromosomal loci 22q11.2 and 16p11.2 are among the most common rare genetic disorders associated with significant risk for neuropsychiatric disorders across the lifespan. Microdeletions and duplications in these loci are associated with neurocognitive deficits, yet there are few studies comparing these groups using the same measures. We address this gap in a prospective international collaboration applying the same computerized neurocognitive assessment. The Penn Computerized Neurocognitive Battery (CNB) was administered in a multi-site study on rare genomic disorders: 22q11.2 deletion (n = 397); 22q11.2 duplication (n = 77); 16p11.2 deletion (n = 94); and 16p11.2 duplication (n = 26). Domains examined include executive functions, episodic memory, complex cognition, social cognition, and sensori-motor speed. Accuracy and speed for each neurocognitive domain were included as dependent measures in a mixed-model repeated measures analysis, with locus (22q11.2, 16p11.2) and copy number (deletion/duplication) as grouping factors and neurocognitive domain as a repeated measures factor, with age and sex as covariates. We also examined correlation with IQ and site effects. We found that 22q11.2 deletions were associated with greater deficits in overall performance accuracy than 22q11.2 duplications, while 16p11.2 duplications were associated with greater deficits than 16p11.2 deletions. Duplications at both loci were associated with reduced speed. Performance profiles differed among the groups with particularly poor performance of 16p11.2 duplication on non-verbal reasoning and social cognition. Average accuracy on the CNB was moderately correlated with Full Scale IQ. No site effects were observed. Deletions and duplications of 22q11.2 and 16p11.2 have varied effects on neurocognition indicating locus specificity, with performance profiles differing among the groups. These profile differences can help inform mechanistic substrates to heterogeneity in presentation and outcome. Future studies could aim to link performance profiles to clinical features and brain function.

Relationship between intelligence quotient measures and computerized neurocognitive performance in 22q11.2 deletion syndrome.

Intelligence quotient (IQ) testing is standard for evaluating cognitive abilities in genomic studies but requires professional expertise in administration and interpretation, and IQ scores do not translate into insights on implicated brain systems that can link genes to behavior. Individuals with 22q11.2 deletion syndrome (22q11.2DS) often undergo IQ testing to address special needs, but access to testing in resource-limited settings is challenging. The brief Penn Computerized Neurocognitive Battery (CNB) provides measures of cognitive abilities related to brain systems and can screen for cognitive dysfunction. To examine the relation between CNB measures and IQ, we evaluated participants with the 22q11.2DS from Philadelphia and Tel Aviv (N = 117; 52 females; mean age 18.8) who performed both an IQ test and the CNB with a maximum of 5 years between administrations and a subsample (n = 24) who had both IQ and CNB assessments at two time points. We estimated domain-level CNB scores using exploratory factor analysis (including bifactor for overall scores) and related those scores (intraclass correlations (ICCs)) to the IQ scores. We found that the overall CNB accuracy score showed similar correlations between time 1 and time 2 as IQ (0.775 for IQ and 0.721 for CNB accuracy), correlated well with the IQ scores (ICC = 0.565 and 0.593 for time 1 and time 2, respectively), and correlated similarly with adaptive functioning (0.165 and 0.172 for IQ and CNB, respectively). We provide a crosswalk (from linear equating) between standardized CNB and IQ scores. Results suggest that one can substitute the CNB for IQ testing in future genetic studies that aim to probe specific domains of brain-behavior relations beyond IQ.

Inter-rater reliability of subthreshold psychotic symptoms in individuals with 22q11.2 deletion syndrome.

BACKGROUND: Pathways leading to psychosis in 22q11.2 deletion syndrome (22q11.2DS) have been the focus of intensive research during the last two decades. One of the common clinical risk factors for the evolution of psychosis in 22q11.2DS is the presence of positive and negative subthreshold psychotic symptoms. The gold standard for measuring subthreshold symptoms is the Structured Interview for Prodromal Syndromes (SIPS) and its accompanying Scale of Prodromal Symptoms (SOPS) ratings. Although the scale has been used by many centers studying 22q11.2DS, the inter-site reliability of the scale in this population has never been established. METHODS: In the present study, experienced clinical assessors from three large international centers studying 22q11.2DS independently rated video recordings of 18 adolescents and young adults with 22q11.2DS. RESULTS: The intraclass correlations coefficients (ICCs) among three raters for the SOPS total scores, as well as for the positive, negative, and disorganization subscale scores, were good-to-excellent (ICCs range 0.73-0.93). The raters were also able to reliably determine the subjects' subthreshold syndrome status (ICC = 0.71). The reliability of individual items was good-to-excellent for all items, ranging from 0.61 for motor disturbances [G3] to 0.95 for bizarre thinking. CONCLUSIONS: Our results show that trained clinicians can reliably screen for subthreshold psychotic symptoms in individuals with 22q11.2DS. To increase assessment reliability, we suggest specific clarifications and simplifications to the standard SIPS interview for future studies.

Coronary Bypass Graft Pseudoaneurysm Successfully Treated by PTFE-Covered Jostent GraftMaster.

A 60-year-old male presented 12 months after CABG surgery with a large pulsatile sternal mass. CT scan of the chest demonstrated a pseudoaneurysm originating from the mid saphenous vein graft to the PDA measuring 7.7 x 7.2 x 6.0 cm. After a multidisciplinary consultation, a decision was made to place a Jostent GraftMaster to completely seal the communication of the extravasation.

Telomere Length Recovery: A Strong Predictor of Overall Survival in Acute Promyelocytic Leukemia.

Telomeres are the capping ends of chromosomes that protect the loss of genetic material and prevent chromosomal instability. In human tissue-specific stem/progenitor cells, telomere length (TL) is maintained by the telomerase complex, which consists of a reverse transcriptase catalytic subunit (TERT) and an RNA template (TERC). Very short telomeres and loss-of-function mutations in the TERT and TERC genes have been reported in acute myeloid leukemia, but the role of telomeres in acute promyelocytic leukemia (APL) has not been well established. We report the results for a large cohort of 187 PML/RARα-positive APL patients. No germline mutations in the TERT or TERC genes were identified. Codon 279 and 1062 TERT polymorphisms were present at a frequency similar to that in the general population. TL measured in blood or marrow mononuclear cells at diagnosis was significantly shorter in the APL patients than in healthy volunteers, and shorter telomeres at diagnosis were significantly associated with high-risk disease. For patients who achieved complete remission, the median increase in TL from diagnosis to remission (delta TL) was 2.0 kilobase (kb), and we found delta TL to be the most powerful predictor of overall survival when compared with well-established risk factors for poor outcomes in APL.

Novel HSP90 inhibitors effectively target functions of thyroid cancer stem cell preventing migration and invasion.

BACKGROUND: Thyroid cancer stem cells (CSCs) with ALDH and CD44 markers contribute to tumor growth and aggressiveness. We hypothesized that novel HSP90 inhibitors (KU711, WGA-TA) and 17-AAG can effectively target the function of thyroid CSCs in vitro and prevent migration and invasion. METHODS: Validated papillary (TPC1), follicular (FTC238,WRO), and anaplastic (ACT1) human thyroid cancer cell lines were treated with 3 HSP90 inhibitors. CSCs were quantified for aldehyde dehydrogenase by flow cytometry, CD44 expression by Western blot, and thyrosphere formation assay. Cellular pathway proteins were analyzed by Western blot and migration/invasion by Boyden-chambers. RESULTS: WGA-TA and 17-AAG induced HSP70 compensation (not observed with KU711) on Western blot in all cell lines (>1,000 fold vs controls). Only WGA-TA degraded HSP90-Cdc37 complexing by 60-70% versus controls. Expression of HSP90 clients ß-catenin, BRAF, Akt, and phospho-Akt were significantly inhibited by WGA-TA treatment (50-80%, 50-90%, >80%, and >90%) compared with controls, KU711, and 17-AAG treatment. KU711 and WGA-TA decreased CD44 expression in all cell lines (25-60% vs controls/17-AAG), decreased ALDEFLOR activity by 69-98% (P < .005), and decreased sphere formation by 64-99% (P < .05 each). Finally, cell migration was decreased by 31-98%, 100%, and 30-38%, and invasion by 75-100%, 100%, and 47% by KU711,WGA-TA, and 17-AAG treatment (P < .05) each, respectively. CONCLUSION: KU711 and WGA-TA are novel HSP90 inhibitors targeting CSC function and inhibiting cell migration/invasion in differentiated and anaplastic thyroid cancers, warranting further translational evaluation in vivo.

Analysis of Major Withanolides in Physalis longifolia Nutt. by HPLC-PDA.

An analytical method based on high-performance liquid chromatography-photodiode array detection was developed for the simultaneous determination of three anti-proliferative withanolides [withalongolide A ( 1: ), withaferin A ( 2: ) and withalongolide B ( 3: )] present in the aboveground biomass of the long-leaf groundcherry, Physalis longifolia. This method was achieved by biomass extraction followed by chromatographic separation on C18 column eluted with a gradient acetonitrile-water mobile phase. Calibration curves produced satisfactory linear regression (r(2) > 0.9995) for each examined sample. The method was also validated for accuracy, precision and limits of detection and quantification. Such an approach is applicable for the rapid detection and quantitative assessment of withanolides in various P. longifolia accessions.