The Association Between Preoperative Pectoralis Muscle Quantity and Outcomes After Cardiac Transplantation.

BACKGROUND: Sarcopenia is underappreciated in advanced heart failure and is not routinely assessed. In patients receiving a left ventricular assist device, preoperative sarcopenia, defined by using computed-tomography (CT)-derived pectoralis muscle-area index (muscle area indexed to body-surface area), is an independent predictor of postoperative mortality. The association between preoperative sarcopenia and outcomes after heart transplant (HT) is unknown. OBJECTIVES: The primary aim of this study was to determine whether preoperative sarcopenia, diagnosed using the pectoralis muscle-area index, is an independent predictor of days alive and out of the hospital (DAOHs) post-transplant. METHODS: Patients who underwent HT between January, 2018, and June, 2022, with available preoperative chest CT scans were included. Sarcopenia was diagnosed as pectoralis muscle-area index in the lowest sex-specific tertile. The primary endpoint was DAOHs at 1 year post-transplant. RESULTS: The study included 169 patients. Patients with sarcopenia (n = 55) had fewer DAOHs compared to those without sarcopenia, with a median difference of 17 days (320 vs 337 days; P = 0.004). Patients with sarcopenia had longer index hospitalizations and were also more likely to be discharged to a facility other than home. In a Poisson regression model, sarcopenia was a significant univariable and the strongest multivariable predictor of DAOHs at 1 year (parameter estimate = -0.17, 95% CI -0.19 to -14; P = < 0.0001). CONCLUSIONS: Preoperative sarcopenia, diagnosed using the pectoralis muscle-area index, is an independent predictor of poor outcomes after HT. This parameter is easily measurable from commonly obtained preoperative CT scans and may be considered in transplant evaluations.

"Durable left ventricular assist devices as a bridge to transplantation in The Old and The New World".

Heart transplantation remains the gold standard treatment for end-stage heart failure patients without contraindications. However, limited donor availability and long wait times have created a need for left ventricular assist devices (LVAD) to be used as a bridge to transplantation in appropriately selected patients. Improvements in LVAD technology have resulted in improved short- and long-term outcomes, further supporting the use of these devices for a bridge-to-transplant (BTT) indication. LVAD utilization as BTT exhibits notable disparities worldwide, mainly due to variations in organ availability, allocation policies, and financial constraints. Although Europe has experienced a consistent increase in the use of LVAD for this purpose, the United Network for Organ Sharing 2018 policy amendment resulted in a significant reduction in the number of LVADs used for BTT in the US. To overcome this issue, modifications in the US allocation policy to consider factors such as days on device support, age, and type of complications may be necessary to potentially increase implantation rates.The authors provide an overview comparing the current state of heart transplantation in the US and Europe, with a particular focus on how distinct allocation policies and organ availability impact medical practices. Additionally, the review will examine critical aspects ranging from patient selection and pre-implantation optimization to post-transplant outcomes.

Relationships of Hematocrit With Chronic Covert and Acute Symptomatic Lacunar Ischemic Lesions.

BACKGROUND AND OBJECTIVES: Red blood cell (RBC) concentrations are known to associate with ischemic stroke. It is unclear whether RBC concentrations associate specifically with small vessel disease lacunar infarcts. We investigated the hypothesis that RBC concentrations associate with both chronic covert and acute symptomatic brain MRI lacunar infarcts. METHODS: A cross-sectional observational analysis was performed across 2 cohorts with available hematocrit (as the assessment of RBC concentration exposure) and MRI outcome data. The primary setting was a population-based cohort of stroke-free, older adult (>50 years) participants from the Northern Manhattan Study (NOMAS) enrolled between 2003 and 2009. A second replication sample consisted of patients admitted with acute stroke and enrolled into the Columbia Stroke Registry (CSR) between 2005 and 2020. Associations of hematocrit with (1) chronic, covert lacunar infarcts and (2) symptomatic (i.e., acute) lacunar strokes were separately assessed from the NOMAS and CSR cohorts, respectively, using general additive models after adjusting for relevant covariates. RESULTS: Of 1,218 NOMAS participants analyzed, 6% had chronic, covert lacunar infarcts. The association between hematocrit and these covert lacunar infarcts was U-shaped (χ2 = 9.21 for nonlinear associations; p = 0.03), with people with hematocrit extremes being more likely to have covert lacunar infarcts. Of the 1,489 CSR patients analyzed, 23% had acute lacunar strokes. In this sample, only the relationships of increased hematocrit concentrations and lacunar strokes were replicated (adjusted coefficient ß = 0.020; SE = 0.009; p = 0.03). DISCUSSION: We identified relationships of hematocrit with MRI lacunar infarcts in both stroke-free and ischemic stroke cohorts, respectively. The relationship between increased hematocrit concentrations with lacunar infarcts was replicated in both cohorts. Further studies are required to clarify the mechanisms behind the relationships of hematocrit with ischemic cerebral small vessel disease.

The utilization of molecular microscope in management of heart transplant recipients in the era of noninvasive monitoring.

INTRODUCTION: Monitoring for graft rejection is a fundamental tenet of post-transplant follow-up. In heart transplantation (HT) in particular, rejection has been traditionally assessed with endomyocardial biopsy (EMB). EMB has potential complications and noted limitations, including interobserver variability in interpretation. Additional tests, such as basic cardiac biomarkers, cardiac imaging, gene expression profiling (GEP) scores, donor-derived cell-free DNA (dd-cfDNA) and the novel molecular microscope diagnostic system (MMDx) have become critical tools in rejection surveillance beyond standard EMB. METHODS: This paper describes an illustrative case followed by a review of MMDx within the context of other noninvasive screening modalities for rejection. CONCLUSIONS: We suggest MMDx be used to assist with early detection of rejection in cases of discordance between EMB and other noninvasive studies.

Comparative Study on the Phytochemical Characterization and Biological Activities of Azolla caroliniana and Azolla filiculoides: In Vitro Study.

Azolla is a floating fern known for its various biological activities. Azolla caroliniana and Azolla filiculoides are multifunctional plants that exhibit biological activity in multiple ways, making them beneficial for various applications. This study aimed to compare the phytochemical composition and antimicrobial, antioxidant, anti-inflammatory, and cytotoxicity activities of two Azolla species, namely Azolla caroliniana and Azolla filiculoides. GC-MS analysis revealed distinct patterns of phytochemical composition in the two species. The methanol extracts of A. caroliniana and A. filiculoides exhibited moderate antimicrobial activity against Geotrichum candidum, Enterococcus faecalis, and Klebsiella pneumonia. Furthermore, both extracts demonstrated potential antioxidant activity, as evidenced by a dose-dependent increase in a ferric-reducing activity power (FRAP) assay. Additionally, the extracts showed promising anti-inflammatory activities, including inhibition of protein denaturation, heat-induced red blood cell (RBC) hemolysis, and nitric oxide (NO) production by macrophages. Moreover, the methanolic extracts of A. caroliniana displayed higher cytotoxicity against HepG2 cells than those of A. filiculoides in a dose-dependent manner. These findings suggest that the methanolic extracts of A. caroliniana and A. filiculoides contain distinct compounds and exhibit potential antioxidant, anti-inflammatory, and cytotoxic activities against HepG2 cells. In conclusion, our data indicate that the methanolic extracts of A. caroliniana and A. filiculoides have differential phytochemical compositions and possess potential antioxidant, anti-inflammatory, and HepG2 cytotoxic activities.

The role of intracranial artery calcification (IAC) in stroke subtype and risk of vascular events.

OBJECTIVE: To test the hypothesis that intracranial arterial calcification (IAC) is associated with intracranial large artery stenosis (ILAS) and a higher risk of vascular events and mortality. METHOD: We leveraged data from two cohorts, the New York-Presbyterian Hospital/Columbia University Irving Medical Center Stroke Registry Study (NYP/CUIMC-SRS) and the Northern Manhattan Study (NOMAS) to test our hypotheses. We measured IAC using CT scans of participants in both cohorts and expressed IAC as present (vs not) and in tertiles. For the CUIMC-SRS, demographic, clinical and ILAS status was collected retrospectively. In NOMAS, we used research brain MRI and MRA to define asymptomatic ILAS and covert brain infarcts(CBI). We built models adjusted for demographics and vascular risk factors for cross-sectional and longitudinal analyses. RESULTS: Cross-sectionally, IAC was associated with ILAS in both cohorts (OR 1.78, 95% CI: 1.16-2.73 for ILAS-related stroke in the NYP/CUIMC-SRS and OR 3.07, 95%CI 1.13-8.35 for ILAS-related covert brain infarcts in NOMAS). In a meta-analysis of both cohorts, IAC in the upper (HR 1.25, 95%CI 1.01-1.55) and middle tertile (HR 1.27, 95%CI 1.01-1.59) was associated with higher mortality compared with participants with no IAC. There were no longitudinal associations between IAC and risk of stroke or other vascular events. CONCLUSION: In these multiethnic populations, IAC is associated with symptomatic and asymptomatic ILAS as well as higher mortality. IAC may be a useful marker of higher mortality, the role of IAC as an imaging marker of risk of stroke is less certain.

Tretinoin-loaded liposomal formulations: from lab to comparative clinical study in acne patients.

Topical tretinoin is the most commonly used retinoid for acne. However, its irritative potential on the applied area and the barrier properties of the stratum corneum limit its use. The objective of the present study was to formulate tretinoin liposomal gel to obtain a formula with lower skin irritation potential and greater clinical effect. A statistical 2(4) factorial design was adopted. Sixteen formulae prepared and were properly evaluated. A candidate formula (F13G) prepared with 0.025% tretinoin, phospholipid- cholesterol-dicetylphosphate (9:1:0.01) and incorporated in 1% carbopol gel was selected for skin irritation test. Clinical study was conducted on acne patients and compared to marketed product. All liposomes formulations were spherical in shape. The addition of cholesterol in the film hydration method significantly decreased the vesicle size, and increased the percentage of incorporation efficiency at (p < 0.05). The presence of dicetylphosphate significantly increased drug release but did not affect the percentage of incorporation efficiency and vesicle size. The results of the clinical study in acne patients revealed that F13G showed significantly higher efficacy when compared to marketed product (p < 0.05).

Formulation of tretinoin-loaded topical proniosomes for treatment of acne: in-vitro characterization, skin irritation test and comparative clinical study.

Tretinoin (TRT) is a widely used retinoid for the topical treatment of acne, photo-aged skin, psoriasis and skin cancer which makes it a good candidate for topical formulation. Yet side effects, like redness, swelling, peeling, blistering and, erythema, in addition to its high lipophilicity make this challenging. Therefore, the aim of this study was the development of TRT-loaded proniosomes to improve the drug efficacy and to increase user acceptability and compliance by reducing its side effects. Nine formulae were prepared according to 3(2) factorial design and were evaluated for their morphology, vesicle size, entrapment efficiency (EE %), and% of drug released after 5 h. Hydrogel of the candidate formula, N8G (proniosomes prepared with 0.025% TRT, and Span60: cholesterol molar ratio of 3:1 and incorporated in 1% carbopol gel) was developed and evaluated for skin irritation test and clinical study in acne patients compared to marketed product. Candidate formula showed higher efficacy and very low irritation potential when compared to marketed product in human volunteers.