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Abstract Objective Sex-specific differences impact vulnerability to alcohol effects, dependence (AD) and related phenotypes. Previous studies demonstrated that sex-related hormone and protein levels may contribute to those differences in sex-specific manner. However, previous studies were limited by sample size, the depths of phenotyping assessments and/or the number of hormones and proteins measured at the same time. Here, we investigated the association of the sex-related hormone (testosterone, estrogens, and progesterone) and protein (FSH, LH, SHBG, and albumin) levels with AD in males and females treated in community-based programs compared to age and sex-matched controls. We also investigated the associations of AD with the combined plasma sex-related hormone/protein “signatures” in the same groups of study subjects. Methods Sex-related hormone and protein levels were measured in plasma samples collected from 401 male and female subjects meeting DSM-IV-TR criteria for AD and 401 age and sex matched controls. Psychiatric Research Interview for Substance and Mental Disorder (PRISM) was used to capture DSM-IV diagnoses of substance use and other psychiatric disorders. All analyses were stratified by sex. Associations between each plasma sex-related hormone/protein level and AD was assessed with multivariable linear regression adjusted for age and BMI for males and age, BMI, and menopause status for females. Progesterone was defined as a continuous variable and a binary variable based on a lower laboratory detection limit of 0.1 ng/mL. We used principal component analysis to define hormone/protein signatures. Hormones and proteins with factor loadings =/> |0.4| were considered important drivers for the corresponding principal components (PCs). Resulting PCs were entered into a sex-stratified logistic regression model with adjustment of age and BMI to determine which PCs were associated with AD. Results Male AD subjects had higher estradiol and albumin levels (p <0.00625) as well as progesterone and LH levels (p <0.05) compared to controls. Progesterone was detected in a larger proportion of AD subjects than in the controls (62.6% vs. 47.7%; p = 0.017). In females, albumin levels were significantly higher (p <0.00385) while estrone and progesterone levels were lower (p <0.05) in AD subjects than the controls. Total testosterone (TT) levels were relatively higher in AD subjects but differences between groups were not significant (p >0.05). In males, the first PC (PC1) that accounted for the majority of data variance was significantly associated with AD (p=0.016) and was mostly driven by TT, estrone, estradiol and SHBG. PC3 (driven by albumin, progesterone and estradiol) and PC4 (driven by albumin and SHBG) were also associated with AD (p=0.007 and p<0.001, respectively). In females, PC1 (driven by estrone, estradiol, SHBG) was not significantly associated with AD. However, PC3 (driven by Albumin and progesterone), PC4 (driven by TT and Albumin) and PC5 (driven by progesterone and TT), were significantly associated with AD (p=0.009, p=0.001, p=0.004, respectively). Conclusion Our findings indicate that individual hormone/protein levels as well as hormone/protein combination signatures associated with AD are different in male and female alcoholics. Future studies should investigate physiological mechanisms reflected in hormone/protein signatures captured by PC analyses.

Background/Objectives: Both poor bone quality and paraspinal sarcopenia have been suggested as risk factors for proximal junctional kyphosis (PJK) at the upper instrumented vertebra (UIV) following long-segment thoracolumbar fusion. Methods: Adults ≥50 with a T1-6 UIV were identified, and data were gathered on pre- and postoperative spinopelvic parameters, bone quality (using Hounsfield units and vertebral bone quality score), and paraspinal cross-sectional area at L3 and the UIV. PJK was defined by a ≥10° increase in the proximal junctional angle. Cox regressions were performed to identify PJK risk factors; PJK was subdivided into types 1–3 based on the Yagi–Boachie classification. Results: In total, 15/76 patients (median age 66; 72.4% female) experienced PJK; 10 experienced type 1, 4 experienced type 2, and one experienced type 3. Univariable Cox regression showed that PJK was negatively correlated with total paraspinal muscle CSA at the UIV (HR 0.74/100 mm2; 95% CI [0.57, 0.6]; p = 0.02). Lower total paraspinal CSA at L3 (HR 0.94/100 mm2; p = 0.07) and higher postoperative global tilt (HR 1.03; p = 0.09) also trended toward significance. Similarly, type 1 PJK was predicted by smaller total paraspinal CSA at the UIV (HR 0.64/100 mm2; [0.45, 0.92]; p = 0.02). Paraspinal CSA was not predictive of type 2 PJK, but lower HU at the UIV and UIV + 1 trended toward significance (HR 0.98/unit; p = 0.16). A comparison of type 1 and 2 PJK showed a higher average of paraspinal CSA and a lower average of HU at the UIV. Conclusions: Global alignment and paraspinal sarcopenia were most predictive of PJK, though paraspinal sarcopenia was only predictive of type 1. Type 2 may be better predicted by bone quality.

Spontaneous type-1 Brugada patterns are associated with an elevated risk of major arrhythmic events, yet the relationship between varying degrees of pattern burden and the occurrence of a first major arrhythmic event remains unclear. This retrospective cohort study included 64 adult patients with a spontaneous type-1 Brugada pattern, who were identified at Mayo Clinic sites and followed for ≥12 months after the initial diagnosis. All patients underwent at least three 12-lead electrocardiograms (ECGs) within the first year. Individuals with prior major arrhythmic events were excluded. The percentage of ECGs showing a type-1 pattern was calculated and categorized as paroxysmal (<50%), persistent (50–99%), or permanent (100%). During a median follow-up of 92 months, seven patients (11%) experienced their first major arrhythmic event. Of these, one had paroxysmal, four had persistent, and two had permanent spontaneous type-1 Brugada patterns. Although statistical significance was not reached, the hazard ratios suggested a trend toward increased risk with persistent and permanent patterns compared to paroxysmal patterns. No sudden cardiac deaths occurred during follow-up. These findings suggest that a higher burden of spontaneous type-1 Brugada patterns may be associated with increased arrhythmic risk.

Cardiovascular diseases and cancer are the leading causes of morbidity and mortality in modern society. Expanding cancer therapies that have improved prognosis may also be associated with cardiotoxicity, and extended life span after survivorship is associated with the increasing prevalence of cardiovascular disease. As such, the field of cardio-oncology has been rapidly expanding, with an aim to identify cardiotoxicity and cardiac disease early in a patient who is receiving treatment for cancer or is in survivorship. Artificial intelligence is revolutionizing modern medicine with its ability to identify cardiac disease early. This article comprehensively reviews applications of artificial intelligence specifically applied to electrocardiograms, echocardiography, cardiac magnetic resonance imaging, and nuclear imaging to predict cardiac toxicity in the setting of cancer therapies, with a view to reduce early complications and cardiac side effects from cancer therapies such as chemotherapy, radiation therapy, or immunotherapy.

Background: Patients with no-option chronic limb-threatening ischemia (NoCLTI), lacking suitable distal arteries for conventional revascularization, face major limb amputation. The 1-year mortality rate after major amputation is 48.3%, increasing to 70.9% in 3 years. Open deep venous arterialization (DVA) offers a promising alternative for limb salvage, achievable through open, endovascular, or hybrid approaches. We aim to provide a comprehensive, step-by-step guide to performing open DVA in NoCLTI patients, addressing preoperative and postoperative considerations as well as the technical details of the procedure. Methods: Patient selection for open DVA focuses on individuals with NoCLTI at high risk for amputation. Preoperative assessments include evaluating risk factors, determining limb threat severity using the Wound, Ischemia, and foot Infection (WIfI) score, and mapping anatomical patterns via the Global Limb Anatomic Staging System (GLASS). The procedure involves identifying the target artery using Doppler ultrasound, performing microdissection to expose the artery and vein, ligating proximal vein branches, and creating a side-to-side anastomosis. Venous valves are disrupted with a valvulotome to allow antegrade flow. A proximal bypass graft may be applied if necessary. Results: Postoperatively, patients are monitored for 2–4 days with frequent Doppler assessments. Anticoagulation therapy begins with a heparin drip, transitioning to oral agents and/or dual antiplatelet therapy. Wound care includes deferred debridement for 2–4 weeks and may involve negative-pressure therapy. Follow-up involves weekly visits for the first month, and then at 3 months, and every 6 months thereafter, with surveillance using transcutaneous oxygen measurement, the toe–brachial index, and arterial duplex ultrasound. Conclusions: Open DVA represents a viable limb salvage option for patients with NoCLTI, potentially avoiding major amputations and improving quality of life. Success depends on careful patient selection, a meticulous surgical technique, and comprehensive postoperative care.

We present an 81-year-old male with an extensive past medical history and an enlarging abdominal aortic aneurysm (AAA). Axial imaging showed dense aortoiliac calcification with a complete occlusion of the right common iliac and high-grade stenosis of the left common iliac artery (CIA). Shockwave Intravascular Lithotripsy and the pave-and-crack technique utilizing an endoconduit were used to dilate the left external iliac artery and the CIA to facilitate placement of an aortic stent graft and exclude the patient’s AAA. This method gives surgeons the ability to treat patients with AAAs endovascularly, despite a heavily diseased and/or diminutive iliac anatomy. We also present a contemporary literature review of the utilization of the pave-and-crack technique as well as tips and tricks of how we do it.

Abstract INTRODUCTION We investigated the association between alpha‐synuclein (α‐syn) pathology and brain glucose metabolism across the cognitive spectrum of Alzheimer's disease (AD) co‐pathologies. METHODS Fluorodeoxyglucose positron emission tomography (FDG‐PET) data from 829 Alzheimer's Disease Neuroimaging Initiative participants (648 cognitively impaired [CI], 181 unimpaired [CU]) were compared between α‐syn seed amplification assay (SAA) positive and negative groups. Interactions with cerebrospinal fluid (CSF) AD biomarkers were examined. RESULTS SAA+ was associated with widespread hypometabolism among CI individuals, particularly in posterior cortical regions, independent of CSF amyloid and tau levels in the occipital lobes. Regional hypometabolism mediated the effect of α‐syn SAA on disease severity in CI individuals, independent of CSF amyloid and tau levels. There were no influences of SAA on FDG‐PET in CU individuals. DISCUSSION This study supports a model in which α‐syn aggregation influences metabolic dysfunction, which then influences clinical disease severity, independent of AD. SAA+ could help optimize participant selection and outcome measures for clinical trials in AD. Highlights α‐synuclein seed amplification positivity (SAA+) was associated with hypometabolism in cognitively impaired individuals. Hypometabolism mediated the influence of α‐synuclein on disease severity. Occipital hypometabolism in SAA+ was independent of cerebrospinal fluid levels of Alzheimer's disease pathology. These findings can optimize future clinical trials targeting α‐synuclein pathology.

The peritoneum is the second most common site of metastasis in patients with pancreatic ductal adenocarcinoma (PDAC). Up to half of all patients that undergo curative-intent resection eventually develop peritoneal metastasis (PM), which accounts for significant morbidity and drives mortality. Despite recent advances in management, PM is associated with very poor prognosis, which is often measured in weeks to months. Clinical manifestations including bowel obstruction, ascites, and urinary obstruction have profound impact on quality of life. Even with relatively advanced disease, PM often remains occult on imaging and thus tend to be underdiagnosed and understudied. Many patients with peritoneal-only PM are excluded from clinical trials because response cannot be measured by standard radiographic criteria. Furthermore, as patients with PM are not eligible for surgical resection and low-volume peritoneal disease is often not amenable to percutaneous biopsy, tissue samples for peritoneal-specific translational studies are limited. Intraperitoneal therapeutics have been proposed as an attractive option for PM, as better penetration of tumor tissue can be achieved with less systemic toxicity compared with intravenous chemotherapy. Heated intraperitoneal chemotherapy (HIPEC), typically combined with cytoreductive surgery (CRS), is an option for select patients with PM from gynecologic or gastrointestinal primary, and for patients with primary peritoneal mesothelioma. However, the incorporation of locoregional therapy for PM in patients with PDAC has been poorly studied given the aggressive nature of pancreatic cancer and overall poor prognosis. With recent advances in existing treatment options, there may be a subset of patients who may derive benefits from locoregional control with cytoreduction and/or intraperitoneal chemotherapy. Critically, additional work is needed to determine PM-favorable clinical and tumoral predictive biomarkers to identify patients who may benefit from a more aggressive approach. We describe the current state of management of patients with peritoneal metastasis from PDAC and review the available data exploring peritoneal-directed therapy with cytoreductive surgery and/or intraperitoneal chemotherapy.