Genome-wide loss of heterozygosity predicts aggressive, treatment-refractory behavior in pituitary neuroendocrine tumors.

Pituitary neuroendocrine tumors (PitNETs) exhibiting aggressive, treatment-refractory behavior are the rare subset that progress after surgery, conventional medical therapies, and an initial course of radiation and are characterized by unrelenting growth and/or metastatic dissemination. Two groups of patients with PitNETs were sequenced: a prospective group of patients (n = 66) who consented to sequencing prior to surgery and a retrospective group (n = 26) comprised of aggressive/higher risk PitNETs. A higher mutational burden and fraction of loss of heterozygosity (LOH) was found in the aggressive, treatment-refractory PitNETs compared to the benign tumors (p = 1.3 × 10-10 and p = 8.5 × 10-9, respectively). Within the corticotroph lineage, a characteristic pattern of recurrent chromosomal LOH in 12 specific chromosomes was associated with treatment-refractoriness (occurring in 11 of 14 treatment-refractory versus 1 of 14 benign corticotroph PitNETs, p = 1.7 × 10-4). Across the cohort, a higher fraction of LOH was identified in tumors with TP53 mutations (p = 3.3 × 10-8). A machine learning approach identified loss of heterozygosity as the most predictive variable for aggressive, treatment-refractory behavior, outperforming the most common gene-level alteration, TP53, with an accuracy of 0.88 (95% CI: 0.70-0.96). Aggressive, treatment-refractory PitNETs are characterized by significant aneuploidy due to widespread chromosomal LOH, most prominently in the corticotroph tumors. This LOH predicts treatment-refractoriness with high accuracy and represents a novel biomarker for this poorly defined PitNET category.

FGFR1/2/3-rearranged carcinoma of the head and neck: expanded histological spectrum crossing path with high-risk HPV in the sinonasal tract.

AIMS: Oncogenic FGFR1/2/3 rearrangements are found in various cancers. Reported cases in head and neck (HN) are mainly squamous cell carcinomas (SCCs) with FGFR3::TACC3 fusions, a subset of which also harbour high-risk human papillomavirus (HPV). However, the knowledge of the clinicopathological spectrum of FGFR-rearranged head and neck carcinomas (FHNC) is limited. METHODS AND RESULTS: A retrospective MSK-fusion clinical sequencing cohort 2016-23 was searched to identify malignant tumours in the HN region harbouring FGFR1/2/3 fusion. FHNC were characterised by histological examination, immunohistochemistry and molecular analysis. Electronic medical records were reviewed. Three FHNC were identified. Two cases (cases 1 and 2) involved sinonasal tract and were high-grade carcinomas with squamous, basaloid, glandular and/or ductal-myoepithelial features. Case 1 arose in a 79-year-old man and harboured FGFR2::KIF1A fusion. Case 2 arose in a 58-year-old man, appeared as HPV-related multiphenotypic sinonasal carcinoma (HMSC), and was positive for FGFR2::TACC2 fusion and concurrent high-risk HPV, non-type 16/18. Case 3 was FGFR3::TACC3 fusion-positive keratinising SCCs arising in the parotid of a 60-year-old man. All three cases presented at stage T4. Clinical follow-up was available in two cases; case 1 remained disease-free for 41 months post-treatment and case 3 died of disease 2 months after the diagnosis. CONCLUSIONS: FHNC include a morphological spectrum of carcinomas with squamous features and may occur in different HN locations, such as parotid gland and the sinonasal tract. Sinonasal cases can harbour FGFR2 rearrangement with or without associated high-risk HPV. Timely recognition of FHNC could help select patients potentially amenable to targeted therapy with FGFR inhibitors. Further studies are needed (1) to determine if FGFR2 rearranged/HPV-positive sinonasal carcinomas are biologically distinct from HMSC, and (2) to elucidate the biological and clinical significance of FGFR2 rearrangement in the context of high-risk HPV.

Differences in Primary Care Follow-up After Acute Care Discharge Within and Across Health Systems: a Retrospective Cohort Study.

BACKGROUND: Timely primary care follow-up after acute care discharge may improve outcomes. OBJECTIVE: To evaluate whether post-discharge follow-up rates differ among patients discharged from hospitals directly affiliated with their primary care clinic (same-site), other hospitals within their health system (same-system), and hospitals outside their health system (outside-system). DESIGN: Retrospective cohort study. PATIENTS: Adult patients of five primary care clinics within a 14-hospital health system who were discharged home after a hospitalization or emergency department (ED) stay. MAIN MEASURES: Primary care visit within 14 days of discharge. A multivariable Poisson regression model was used to estimate adjusted rate ratios (aRRs) and risk differences (aRDs), controlling for sociodemographics, acute visit characteristics, and clinic characteristics. KEY RESULTS: The study included 14,310 discharges (mean age 58.4 [SD 19.0], 59.5% female, 59.5% White, 30.3% Black), of which 57.7% were from the same-site, 14.3% same-system, and 27.9% outside-system. By 14 days, 34.5% of patients discharged from the same-site hospital received primary care follow-up compared to 27.7% of same-system discharges (aRR 0.88, 95% CI 0.79 to 0.98; aRD - 6.5 percentage points (pp), 95% CI - 11.6 to - 1.5) and 20.9% of outside-system discharges (aRR 0.77, 95% CI [0.70 to 0.85]; aRD - 11.9 pp, 95% CI - 16.2 to - 7.7). Differences were greater for hospital discharges than ED discharges (e.g., aRD between same-site and outside-system - 13.5 pp [95% CI, - 20.8 to - 8.3] for hospital discharges and - 10.1 pp [95% CI, - 15.2 to - 5.0] for ED discharges). CONCLUSIONS: Patients discharged from a hospital closely affiliated with their primary care clinic were more likely to receive timely follow-up than those discharged from other hospitals within and outside their health system. Improving care transitions requires coordination across both care settings and health systems.

A preliminary analysis of patient reported outcomes following posterolateral mandible reconstruction: The role of flap type.

BACKGROUND: The choice of tissue type for free flap reconstruction of posterolateral mandible resections is dependent on patient and defect characteristics. We compared clinical and patient-reported outcomes following reconstruction of these defects with a soft tissue or bony free flap. METHODS: A retrospective review was performed on patients who underwent posterolateral segmental mandibulectomy with immediate free flap reconstruction at MSKCC from 2006 to 2021. Outcomes of interest were patient-reported outcome measures (PROMs) assessed by FACE-Q surveys and complications at the flap recipient site. RESULTS: Ninety patients received a bony flap and 24 patients received a soft tissue flap. Patients reconstructed with soft tissue flaps had greater rates of composite soft tissue defects (p < 0.0001), condyle resection (p = 0.001), and peripheral vascular disease (p = 0.035). Complication rates were similar between the cohorts (p > 0.05). Bony flaps scored higher on multiple FACE-Q scales: Facial Appearance (p = 0.023) Eating/Drinking (p = 0.029), Smiling (p = 0.012), Speaking (p < 0.001), Swallowing (p = 0.012), Smiling Distress (p = 0.037), and Speaking Distress (p = 0.001). CONCLUSION: Reconstruction of posterolateral mandibular defects has a similar complication profile when utilizing a bony or soft tissue free flap. Bony flaps may perform better with respect to PROMs. Reconstructive surgeons should consider using bony flap reconstruction to achieve higher patient satisfaction and quality of life.

Different patient versus provider perspectives on living with Cushing's disease.

CONTEXT: Patients with Cushing's disease (CD) face challenges living with and receiving appropriate care for this rare, chronic condition. Even with successful treatment, many patients experience ongoing symptoms and impaired quality of life (QoL). Different perspectives and expectations between patients and healthcare providers (HCPs) may also impair well-being. OBJECTIVE: To examine differences in perspectives on living with CD between patients and HCPs, and to compare care goals and unmet needs. DESIGN: Memorial Sloan Kettering Pituitary Center established an annual pituitary symposium for pituitary patients and HCPs. Through anonymous pre-program surveys distributed at the 2020 and 2022 symposia, patients and HCPs answered questions related to their own sense, or perception of their patients' sense, of hope, choice, and loneliness in the context of living with CD. PARTICIPANTS: From 655 participants over two educational events, 46 patients with CD and 116 HCPs were included. Median age of both groups was 51 years. 78.3% of the patients were female vs. 53.0% of the HCPs. RESULTS: More patients than HCPs reported they had no choices in their treatment (21.7% vs. 0.9%, P < 0.001). More patients reported feeling alone living with CD than HCPs' perception of such (60.9% vs. 45.5%, P = 0.08). The most common personal care goal concern for patients was 'QoL/mental health,' vs. 'medical therapies/tumor control' for HCPs. The most common CD unmet need reported by patients was 'education/awareness' vs. 'medical therapies/tumor control' for HCPs. CONCLUSIONS: CD patients experience long term symptoms and impaired QoL which may in part be due to a perception of lack of effective treatment options and little hope for improvement. Communicating experiences and care goals may improve long term outcomes for CD patients.

Sleep disruption in patients with active and treated endogenous Cushing's syndrome.

CONTEXT: The hypothalamic-pituitary-adrenal axis is a critical regulator of circadian rhythm in humans. Impaired sleep adversely affects metabolic, emotional, and cognitive health. OBJECTIVE: To characterize sleep disturbances in patients with active and treated Cushing's syndrome (CS), and identify factors associated with impaired sleep in treated patients. DESIGN: Single-center cross-sectional study. METHODS: Patients with pituitary or adrenal CS enrolled in an observational study completed Nottingham Health Profile (NHP), CushingQoL, and Hospital Anxiety and Depression assessments. Cross-sectional analysis was conducted including patients with active and treated disease. RESULTS: 113 (94 female) patients with CS were included, 104 pituitary and 9 adrenal, with mean age at diagnosis of 43.9 ± 13.4 years. Mean and maximum duration of follow up was 5.1 and 23 years. Mean NHP sleep score was lower (i.e., improved) in patients with treated vs. active disease (29.6 ± 30.2 vs. 51.9 ± 30.9, p = 0.0005), as was CushingQoL sleep score (p = 0.015), but 41.5% of patients with treated disease stated they often or always had trouble sleeping. The proportion of treated vs. active patients taking medication for sleep, mood, or pain was not different. Neither NHP nor CushingQoL pain scores were lower in treated vs. active patients (p = 0.39 and 0.53). In patients with treated CS, anxiety and depression correlated with worse sleep scores. CONCLUSIONS: Patients with treated CS report improved sleep quality compared to those with active disease, but almost half of treated patients still report sleep challenges. The need for sleep medications, reported by one third of patients, was not different after CS treatment. Ongoing mood disturbances may play a role in persistent sleep disruption. Further work should focus on determinants of sleep impairments in treated CS patients.

Development and Deployment of a Pre-Planned Hospital Emergency Response Team (HERT) for EMS Augmentation: Case Report and Program Review.

With the establishment and growth of the Emergency Medical Services (EMS) subspecialty, significant attention has been focused on clinical activities performed by EMS physicians in the out-of-hospital environment. An EMS fellowship includes special operations education to develop preparedness for responding to field situations requiring physician expertise. With only a thousand Board Certified EMS physicians in North America, EMS physicians may not be available 24 h per day to respond to field emergencies. Non-EMS physicians with minimal experience in prehospital or austere care may be called upon to respond to complex prehospital emergencies requiring advanced skills. The Los Angeles County EMS Agency implemented a policy in 1992 to establish Hospital Emergency Response Teams (HERT) as a regional resource to provide time-critical, specialized prehospital services within an EMS system. Activation of the HERT is rare, most frequently prompted by need for field amputation to enable extrication. We describe one such incident of a field intervention by HERT and detail the staffing, training, and equipment considerations within our large regional EMS system.

Investigating the Relationship Between Acne and Vasodilatory Medications in a Hospital-Wide Adult Population.

Acne vulgaris is a common chronic dermatological condition characterized by obstruction and inflammation of pilosebaceous units. Recent research on a different dermatologic condition has demonstrated that the use of vasodilatory medications is associated with a decreased relative risk of rosacea. This finding is significant due to the overlapping inflammatory pathways involved in rosacea and acne. Herein, a retrospective cohort study was designed to determine the correlation between vasodilator usage and the risk of developing acne within 5 years, contrasting it with thiazide diuretics, chosen as a control due to its non-vasodilatory antihypertensive mechanism and availability of data. Angiotensin-converting enzyme (ACE) inhibitors (RR, 0.775; 95% CI, 0.727-0.826; P<0.05), angiotensin receptor blockers (ARBs) (RR, 0.739; 95% CI, 0.685-0.797; P<0.05), beta-blockers (BB) (RR, 0.829; 95% CI, 0.777-0.885; P<0.05), and calcium channel blockers (CCB) usage (RR, 0.821, 95% CI, 0.773-0.873; P<0.05) were associated with a significantly lower risk of developing acne within 5 years of initiating therapy compared to thiazide diuretics. It is unclear if thiazide diuretics are more likely to cause acne within the adult population or if vasodilators are protective against the development of acne. Finding mechanisms and therapeutics that lower the risk of developing acne is of significant public health interest, and this study provides a step toward this endeavor. Further research is required to uncover the underlying mechanisms for this reduction in the development of acne.  J Drugs Dermatol. 2024;23(6):446-449.     doi:10.36849/JDD.8362.

Dual immunoadsorption for ABO-incompatible heart transplantation in a 35 kg child.

Intraoperative anti-A/B immunoadsorption (ABO-IA) was recently introduced for ABO-incompatible (ABOi) heart transplantation. Here we report the first case of a patient transplanted with ABO-IA, that was of an age and weight that required two ABO-IA columns run in parallel, to enable the reduction in antibody titres to a sufficiently low level in the time available during implantation of the donor organ.

Miniplate Versus Reconstruction Bar Fixation for Oncologic Mandibular Reconstruction with Free Fibula Flaps.

BACKGROUND: Fibula free flaps (FFF) are the gold standard tissue for the reconstruction of segmental mandibular defects. A comparison of miniplate (MP) and reconstruction bar (RB)-based fixation of FFFs has been previously described in a systematic review; however, long-term, single-center studies comparing the two plating methods are lacking. The authors aim to examine the complication profile between MPs and RBs at a single tertiary cancer center. We hypothesized that increased components and a lack of rigid fixation inherent to MPs would lead to higher rates of hardware exposure/failure. METHODS: A retrospective review was performed from a prospectively maintained database at Memorial Sloan Kettering Cancer Center. All patients who underwent FFF-based reconstruction of mandibular defects between 2015 and 2021 were included. Data on patient demographics, medical risk factors, operative indications, and chemoradiation were collected. The primary outcomes of interest were perioperative flap-related complications, long-term union rates, osteoradionecrosis (ORN), return to the operating room (OR), and hardware exposure/failure. Recipient site complications were further stratified into two groups: early (<90 days) and late (>90 days). RESULTS: In total, 96 patients met the inclusion criteria (RB = 63, MP = 33). Patients in both groups were similar with respect to age, presence of comorbidities, smoking history, and operative characteristics. The mean follow-up period was 17.24 months. In total, 60.6 and 54.0% of patients in the MP and RB cohorts received adjuvant radiation, respectively. There were no differences in rates of hardware failure overall; however, in patients with an initial complication after 90 days, MPs had significantly higher rates of hardware exposure (3 vs. 0, p = 0.046). CONCLUSION: MPs were found to have a higher risk of exposed hardware in patients with a late initial recipient site complication. It is possible that improved fixation with highly adaptive RBs designed by computer-aided design/manufacturing technology explains these results. Future studies are needed to assess the effects of rigid mandibular fixation on patient-reported outcome measures in this unique population.

How Medicaid Financial Eligibility Rules Exclude Financially and Medically Vulnerable Older Adults.

Millions of older Americans rely on Medicaid because it is the largest payer of long-term services and supports. To qualify for the program, low-income individuals age 65 and over must meet income standards based on the dated Federal Poverty Level as well as asset tests that are often viewed as quite stringent. There has long been concern that current eligibility standards exclude many adults with significant health and financial vulnerabilities. We use updated household socio-demographic and financial information to simulate the impacts of five alternative financial eligibility standards on the number and profile of older adults that would gain Medicaid coverage. The study clearly demonstrates that a large number of financially- and health-vulnerable older adults are excluded from the Medicaid program under current policy. The study highlights the implications for policymakers of updating Medicaid financial eligibility standards to assure that Medicaid benefits are targeted to vulnerable older adults who need them.

Understanding frozen section histopathology in Sinonasal and anterior skull base malignancy and proposed reporting guidelines.

BACKGROUND: Intraoperative frozen section histopathology (IFSH) in sinonasal and skull base surgery although widely used is not well studied. METHODS: We reviewed a database of sinonasal and anterior skull base tumors, between 1973 and 2019, and identified 312 suitable operative cases. Clinicopathologic data was collected and analyzed, in addition to descriptive data for histopathological reports classified as "ambiguous," or "limited/insufficient-quality/quantity." RESULTS: Overall, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for IFSH were 90.2%, 97.5%, 94.2%, 95.6%, and 95.2%, respectively. IFSH for adenocarcinoma, salivary carcinoma, and SCC all demonstrated a better clinical utility with a sensitivity of 90% or greater, while it was less than 90% for esthesioneuroblastoma, melanoma, and sarcoma. Other factors such as unclear reporting, poor quality specimens, or limited quality specimens were shown to lower diagnostic performance. Based on limitations identified, we proposed a novel IFSH reporting algorithm to improve IFSH in sinonasal and skull base surgery. CONCLUSIONS: IFSH is an accurate and clinically useful technique in sinonasal and skull base surgery patients; however, limitations exist.

Advances in surgical approaches for refractory pituitary adenomas.

Refractory pituitary adenomas are difficult to control tumors that progress through optimal surgical, medical, and radiation management. Repeat surgery is a valuable tool to reduce tumor volume for more effective radiation and/or medical therapy, and to decompress critical neurovascular structures. Advances in surgical techniques and technologies, including minimally invasive cranial approaches, intraoperative MRI suites, and cranial nerve monitoring, have improved surgical outcomes and expanded indications. Today, repeat transsphenoidal surgery has similar complications rates to upfront surgery in historical cohorts. The decision to operate on refractory adenomas should be made with multidisciplinary teams, balancing the benefit of tumor reduction with the potential for complications, including cranial nerve injury, carotid injury, and cerebrospinal fluid leak.

The Association Between Herpes Simplex Virus and Alzheimer's Disease: A Systematic Review.

Alzheimer's disease (AD) is a significant public health concern, affecting more than 6 million Americans; and currently, there are no cure or effective treatment options. The underlying etiology and pathogenesis are not fully understood, presenting a barrier to therapy. A substantial amount of data exists associating infection with Herpes simplex virus 1 (HSV-1) and AD. This review of published studies highlights the epidemiological associations between HSV-1 and AD. A systematic search of PubMed, Embase, and Web of Science was conducted on January 6, 2022, using PRISMA guidelines. Articles that presented epidemiological data correlating HSV-1 with AD were included. Bibliographies were screened for additional relevant articles as well. After review, 21 studies were included: 2 review articles and 19 population-based studies including case control, cohort, and cross-sectional studies.  The quantitative data derived from the studies in this report substantiate a relationship between infection with HSV-1 and AD. Based on these results, it may be of reasonable benefit to more consistently treat latent or active HSV-1 infection with anti-viral medications to potentially reduce the risk of AD. Furthermore, a prospective randomized controlled clinical trial could elucidate the benefit of anti-viral therapy to prevent or limit AD.J Drugs Dermatol. 2023;22(10):1046-1052     doi:10.36849/JDD.6785.

Patient selection for long-term secondary prevention with ticagrelor: insights from PEGASUS-TIMI 54.

AIM: In patients with prior myocardial infarction (MI) on aspirin, the addition of ticagrelor reduces ischaemic risk but increases bleeding risk. The simultaneous assessment of baseline ischaemic and bleeding risk may assist clinicians in selecting patients who are most likely to have a favourable risk/benefit profile with long-term ticagrelor. METHODS AND RESULTS: PEGASUS-TIMI 54 randomized 21 162 prior MI patients, 13 956 of which to the approved 60 mg dose or placebo and who had all necessary data. The primary efficacy endpoint was cardiovascular death, MI, or stroke, and the primary safety outcome was TIMI major bleeding; differences in Kaplan-Meier event rates at 3 years are presented. Post-hoc subgroups based on predictors of bleeding and ischaemic risk were merged into a selection algorithm. Patients were divided into four groups: those with a bleeding predictor (n = 2721, 19%) and then those without a bleeding predictor and either 0-1 ischaemic risk factor (IRF; n = 3004, 22%), 2 IRF (n = 4903, 35%), or ≥3 IRF (n = 3328, 24%). In patients at high bleeding risk, ticagrelor increased bleeding [absolute risk difference (ARD) +2.3%, 95% confidence interval (CI) 0.6, 3.9] and did not reduce the primary efficacy endpoint (ARD +0.08%, 95% CI -2.4 to 2.5). In patients at low bleeding risk, the ARDs in the primary efficacy endpoint with ticagrelor were -0.5% (-2.2, 1.3), -1.5% (-3.1, 0.02), and -2.6% (-5.0, -0.24, P = 0.03) in those with ≤1, 2, and 3 risk factors, respectively (P = 0.076 for trend across groups). There were significant trends for greater absolute risk reductions for cardiovascular death (P-trend 0.018), all-cause mortality (P-trend 0.027), and net outcomes (P-trend 0.037) with ticagrelor across these risk groups. CONCLUSION: In a post-hoc exploratory analysis of patients with prior MI, long-term ticagrelor therapy appears to be best suited for those with prior MI with multiple IRFs at low bleeding risk. CLINICAL TRIAL REGISTRATION: NCT01225562 ClinicalTrials.gov.

Medicaid Utilization among Middle-age and Older Adults: A Health and Retirement Study Longitudinal Analysis (1998 to 2014).

With over fifteen million older adults in the United States relying on the means-tested Medicaid program for healthcare coverage, there has been concern over rising Medicaid costs among this rapidly growing age group. Few studies have longitudinally examined trends among older beneficiaries over time to identify factors related to Medicaid utilization and to better understand how potential coverage changes might impact this group. This study used the 1998 to 2014 waves of the Health and Retirement Study (N = 8,162) to analyze a representative sample of those aged 50 and older to ascertain demographic, health, and economic factors associated with Medicaid utilization over a sixteen-year period. The analyses showed stable probabilities of accessing the program over time and observed that the most vulnerable older adults make up the pool of Medicaid beneficiaries. There is no evidence of significant asset divestment in order to qualify for benefits. Multivariate analyses further revealed those who were older, female, minority race/ethnicity, less educated, in poorer health, below the federal poverty line, and with lower net wealth had a higher risk of utilizing Medicaid during the observed time period than their counterparts. Findings highlight the importance of monitoring changes in the documented risk factors over time in terms of their impact on Medicaid utilization and underscore the need to consider how these factors may be interrelated.

Clinical Application of a Novel Genetic Risk Score for Ischemic Stroke in Patients With Cardiometabolic Disease.

BACKGROUND: Genome-wide association studies have identified single-nucleotide polymorphisms that are associated with an increased risk of stroke. We sought to determine whether a genetic risk score (GRS) could identify subjects at higher risk for ischemic stroke after accounting for traditional clinical risk factors in 5 trials across the spectrum of cardiometabolic disease. METHODS: Subjects who had consented for genetic testing and who were of European ancestry from the ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation), SOLID-TIMI 52 (Stabilization of Plaques Using Darapladib), SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus), PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin), and FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) trials were included in this analysis. A set of 32 single-nucleotide polymorphisms associated with ischemic stroke was used to calculate a GRS in each patient and identify tertiles of genetic risk. A Cox model was used to calculate hazard ratios for ischemic stroke across genetic risk groups, adjusted for clinical risk factors. RESULTS: In 51 288 subjects across the 5 trials, a total of 960 subjects had an ischemic stroke over a median follow-up period of 2.5 years. After adjusting for clinical risk factors, a higher GRS was strongly and independently associated with increased risk for ischemic stroke (P trend=0.009). In comparison with individuals in the lowest third of the GRS, individuals in the middle and top tertiles of the GRS had adjusted hazard ratios of 1.15 (95% CI, 0.98-1.36) and 1.24 (95% CI 1.05-1.45) for ischemic stroke, respectively. Stratification into subgroups revealed that the performance of the GRS appeared stronger in the primary prevention cohort with an adjusted hazard ratio for the top versus lowest tertile of 1.27 (95% CI, 1.04-1.53), in comparison with an adjusted hazard ratio of 1.06 (95% CI, 0.81-1.41) in subjects with previous stroke. In an exploratory analysis of patients with atrial fibrillation and CHA2DS2-VASc score of 2, high genetic risk conferred a 4-fold higher risk of stroke and an absolute risk equivalent to those with CHA2DS2-VASc score of 3. CONCLUSIONS: Across a broad spectrum of subjects with cardiometabolic disease, a 32-single-nucleotide polymorphism GRS was a strong, independent predictor of ischemic stroke. In patients with atrial fibrillation but lower CHA2DS2-VASc scores, the GRS identified patients with risk comparable to those with higher CHA2DS2-VASc scores.

Patient outcomes following implementation of an enhanced recovery after surgery pathway for patients with metastatic spine tumors.

BACKGROUND: Metastatic spine tumor surgery consists of palliative operations performed on frail patients with multiple medical comorbidities. Enhanced recovery after surgery (ERAS) programs involve an evidence-based, multidisciplinary approach to improve perioperative outcomes. This study presents clinical outcomes of a metastatic spine tumor ERAS pathway implemented at a tertiary cancer center. METHODS: The metastatic spine tumor ERAS program launched in April 2019, and data from January 2018 to May 2020 were reviewed. Measured outcomes included the following: hospital length of stay (LOS), time to ambulation, urinary catheter duration, time to resumption of diet, intraoperative fluid intake, estimated blood loss (EBL), and intraoperative and postoperative day 0-5 cumulative opioid use (morphine milligram equivalent [MME]). RESULTS: A total of 390 patients were included in the final analysis: 177 consecutive patients undergoing metastatic spine tumor surgery enrolled in the ERAS program and 213 consecutive pre-ERAS patients. Although the mean case durations were similar in the ERAS and pre-ERAS cohorts (265 vs. 274 min; p = .22), the ERAS cohort had decreased EBL (157 vs. 215 ml; p = .003), decreased postoperative day 0-5 cumulative mean opioid use (178 vs. 396 MME; p < .0001), earlier ambulation (mean, 34 vs. 57 h; p = .0001), earlier discontinuation of urinary catheters (mean, 36 vs. 56 h; p < .001), and shorter LOS (5.4 vs. 7.5 days; p < .0001). CONCLUSIONS: The implementation of a multidisciplinary ERAS program designed for metastatic spine tumor surgery led to improved clinical quality metrics, including shorter hospitalizations and significant reductions in opioid consumption.

Declining Trend of Transapical Access for Transcatheter Aortic Valve Replacement in Patients with Aortic Stenosis.

Introduction: The last decade has witnessed major evolution and shifts in the use of transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS). Included among the shifts has been the advent of alternative access sites for TAVR. Consequently, transapical access (TA) has become significantly less common. This study analyzes in detail the trend of TA access for TAVR over the course of 7 years. Methods: The national inpatient sample database was reviewed from 2011-2017 and patients with AS were identified by using validated ICD 9-CM and ICD 10-CM codes. Patients who underwent TAVR through TA access were classified as TA-TAVR, and any procedure other than TA access was classified as non-TA-TAVR. We compared the yearly trends of TA-TAVR to those of non-TA-TAVR as the primary outcome. Results: A total of 3,693,231 patients were identified with a diagnosis of AS. 129,821 patients underwent TAVR, of which 10,158 (7.8%) underwent TA-TAVR and 119,663 (92.2%) underwent non-TA-TAVR. After peaking in 2013 at 27.7%, the volume of TA-TAVR declined to 1.92% in 2017 (p < 0.0001). Non-TA-TAVR started in 2013 at 72.2% and consistently increased to 98.1% in 2017. In-patient mortality decreased from a peak of 5.53% in 2014 to 3.18 in 2017 (p=0.6) in the TA-TAVR group and from a peak of 4.51% in 2013 to 1.24% in 2017 (p=0.0001) in the non-TA-TAVR group. Conclusion: This study highlights a steady decline in TA access for TAVR, higher inpatient mortality, increased length of stay, and higher costs compared to non-TA-TAVR.

Cutaneous collagenous vasculopathy: A report of three cases.

Cutaneous collagenous vasculopathy is a rare pauci-inflammatory, superficial, cutaneous vasculopathy characterized by progressive fine-branching telangiectasias clinically, while light microscopically one observes dilated venules and capillaries within the superficial dermis exhibiting excessive Type IV collagen within the vessel wall. We present three cases of collagenous vasculopathy. Two cases were associated with certain autoimmune stigmata, including a positive serologic anti-endothelial cell antibody assay and positive lupus anticoagulant in one, while the third case had positive anti-ribonucleoprotein (RNP) antibodies. The latter case was associated with chronic hydroxyurea therapy for an underlying myeloproliferative disorder. We explore the role of immune- and non-immune-based endothelial cell injury in the pathogenesis of collagenous vasculopathy.