Inpatient outcomes of transcatheter aortic valve replacement based on class of obesity.

Transcatheter aortic valve replacement (TAVR) is a transformative option for severe aortic stenosis, especially in elderly patients. obesity's impact on TAVR outcomes is limited. Using the National Inpatient Sample from 2016 to 2020, We analyzed 217,300 TAVR hospitalizations across BMI groups. No difference in in-hospital mortality was observed, class III obesity experienced longer hospital stays (adjusted ß: 0.43 days, P < 0.05), higher costs (adjusted ß: $3,126, P < 0.05), increased heart failure exacerbation (adjusted odds ratio [aOR]: 2.68, 95% confidence interval [CI]: [1.03-7.01], p < 0.05), vascular access complications (aOR: 1.29, 95% CI: [1.07-1.52], P < 0.05), and post-operative pulmonary complications (Pneumonia (aOR: 1.42, 95% CI: [1.16-1.74], p < 0.05), acute hypoxic respiratory failure (aOR: 1.99, 95% CI: [1.67-2.36], p < 0.05), and non-invasive ventilation (aOR: 1.62, 95% CI: [1.07-2.44], p < 0.05). Complete heart block and permanent pacemaker requirement were higher in both class II and class III ((aOR: 1.30, 95% CI: [1.11-1.51], P < 0.05), (aOR:1.25, 95% CI: [1.06-1.46], P < 0.05) and ((aOR: 1.18, 95% CI: [1.00-1.40], P < 0.05), (aOR:1.22, 95% CI: [1.02-1.45], P < 0.05)) respectively. Understanding these links is crucial for optimizing TAVR care in obesity, ensuring enhanced outcomes, and procedural safety.

Serum Cholesterol and Impact of Age on Coronary Heart Disease Death in More Than 4 Million Veterans.

Background The lipid hypothesis postulates that lower blood cholesterol is associated with reduced coronary heart disease (CHD) risk, which has been challenged by reports of a U-shaped relation between cholesterol and death in recent studies. We sought to examine whether the U-shaped relationship is true and to assess the impact of age on this association. Method and Results We conducted a prospective cohort study of 4 467 942 veterans aged >18 years, with baseline outpatient visits from 2002 to 2007 and follow-up to December 30, 2018, in the Veterans Health Administration electronic health record system. We observed a J-shaped relation between total cholesterol (TC) and CHD mortality after a comprehensive adjustment of confounding factors: flat for TC <180 mg/dL, and greater risk was present at higher cholesterol levels. Compared with veterans with TC between 180 and 199 mg/dL, the multiadjusted hazard ratios (HRs) for CHD death were 1.03 (95% CI, 1.02-1.04), 1.07 (95% CI, 1.06-1.09), 1.15 (95% CI, 1.13-1.18), 1.25 (95% CI, 1.22-1.28), and 1.45 (95% CI, 1.42-1.49) times greater among veterans with TC (mg/dL) of 200 to 219, 220 to 239, 140 to 259, 260 to 279 and ≥280, respectively. Similar J-shaped TC-CHD mortality patterns were observed among veterans with and without statin use at or before baseline. Conclusions The cholesterol paradox, for example, higher CHD death in patients with a low cholesterol level, was a reflection of reverse causality, especially among older participants. Our results support the lipid hypothesis that lower blood cholesterol is associated with reduced CHD. Furthermore, the hypothesis remained true when TC was low due to use of statins or other lipid-lowering medication.

A Treatment Dilemma: Bentall vs Transcatheter Paravalvular Leak Closure with Aortic Aneurysm Repair in a High Surgical Risk Patient.

This case presentation involves an 80-year-old male with a history of surgically repaired patent ductus arteriosus and surgical aortic valve replacement due to infective endocarditis, who presented with progressive heart failure symptoms and was found to have a severe aortic paravalvular leak (PVL) and ascending thoracic aortic aneurysm. Due to complex surgical anatomy and multiple chronic comorbidities, he was considered a poor candidate for traditional valve replacement surgery including the Bentall procedure. Instead, a multidisciplinary team opted for transcatheter paravalvular leak closure (TPLC) with an Amplatzer plug followed by planned endovascular aortic aneurysm repair. The patient showed significant improvement in symptoms and reduction in aneurysm size post-procedure leading to avoidance of the open-heart surgery. This case highlights the effectiveness of the percutaneous approach in high-risk surgical patients with PVL and complex anatomical considerations.

Differential mitochondrial roles for α-synuclein in DRP1-dependent fission and PINK1/Parkin-mediated oxidation.

Mitochondria are highly dynamic organelles with strict quality control processes that maintain cellular homeostasis. Within axons, coordinated cycles of fission-fusion mediated by dynamin related GTPase protein (DRP1) and mitofusins (MFN), together with regulated motility of healthy mitochondria anterogradely and damaged/oxidized mitochondria retrogradely, control mitochondrial shape, distribution and size. Disruption of this tight regulation has been linked to aberrant oxidative stress and mitochondrial dysfunction causing mitochondrial disease and neurodegeneration. Although pharmacological induction of Parkinson's disease (PD) in humans/animals with toxins or in mice overexpressing α-synuclein (α-syn) exhibited mitochondrial dysfunction and oxidative stress, mice lacking α-syn showed resistance to mitochondrial toxins; yet, how α-syn influences mitochondrial dynamics and turnover is unclear. Here, we isolate the mechanistic role of α-syn in mitochondrial homeostasis in vivo in a humanized Drosophila model of Parkinson's disease (PD). We show that excess α-syn causes fragmented mitochondria, which persists with either truncation of the C-terminus (α-syn1-120) or deletion of the NAC region (α-synΔNAC). Using in vivo oxidation reporters Mito-roGFP2-ORP1/GRX1 and MitoTimer, we found that α-syn-mediated fragments were oxidized/damaged, but α-syn1-120-induced fragments were healthy, suggesting that the C-terminus is required for oxidation. α-syn-mediated oxidized fragments showed biased retrograde motility, but α-syn1-120-mediated healthy fragments did not, demonstrating that the C-terminus likely mediates the retrograde motility of oxidized mitochondria. Depletion/inhibition or excess DRP1-rescued α-syn-mediated fragmentation, oxidation, and the biased retrograde motility, indicating that DRP1-mediated fragmentation is likely upstream of oxidation and motility changes. Further, excess PINK/Parkin, two PD-associated proteins that function to coordinate mitochondrial turnover via induction of selective mitophagy, rescued α-syn-mediated membrane depolarization, oxidation and cell death in a C-terminus-dependent manner, suggesting a functional interaction between α-syn and PINK/Parkin. Taken together, our findings identify distinct roles for α-syn in mitochondrial homeostasis, highlighting a previously unknown pathogenic pathway for the initiation of PD.

Paraneoplastic syndromes in cholangiocarcinoma.

Paraneoplastic syndromes are the symptoms or signs which result from damage to tissues that are distant from the site of malignancy, due to complex interactions between the body's immune system and malignant neoplasm. Cholangiocarcinoma (CCA) is an aggressive epithelial malignancy of hepatobiliary tree and it is found to be associated with various paraneoplastic syndromes. These syndromes can present as dermatological, neurological, renal, hematological, or multi-systemic manifestations. Clinical suspicion and timely recognition of these syndromes can lead to early diagnosis of covert malignancies like CCA. The management plan remains the removal of the underlying cause which in this case is CCA.

Life Perspective and Social Health after Acid Burn: An Observational Study of Three Victims.

After an acid attack, also known as vitriolage, many patients suffer from changes in life perspective, behavior, feelings, social withdrawal, social isolation, and depression. Formal and informal social support is vital for the proper and complete rehabilitation of acid burn victims. The government should form separate public help centers for such patients. The need of the hour, however, is the invention of proper legislation for the prevention of this heinous crime.

Excess Rab4 rescues synaptic and behavioral dysfunction caused by defective HTT-Rab4 axonal transport in Huntington's disease.

Huntington's disease (HD) is characterized by protein inclusions and loss of striatal neurons which result from expanded CAG repeats in the poly-glutamine (polyQ) region of the huntingtin (HTT) gene. Both polyQ expansion and loss of HTT have been shown to cause axonal transport defects. While studies show that HTT is important for vesicular transport within axons, the cargo that HTT transports to/from synapses remain elusive. Here, we show that HTT is present with a class of Rab4-containing vesicles within axons in vivo. Reduction of HTT perturbs the bi-directional motility of Rab4, causing axonal and synaptic accumulations. In-vivo dual-color imaging reveal that HTT and Rab4 move together on a unique putative vesicle that may also contain synaptotagmin, synaptobrevin, and Rab11. The moving HTT-Rab4 vesicle uses kinesin-1 and dynein motors for its bi-directional movement within axons, as well as the accessory protein HIP1 (HTT-interacting protein 1). Pathogenic HTT disrupts the motility of HTT-Rab4 and results in larval locomotion defects, aberrant synaptic morphology, and decreased lifespan, which are rescued by excess Rab4. Consistent with these observations, Rab4 motility is perturbed in iNeurons derived from human Huntington's Disease (HD) patients, likely due to disrupted associations between the polyQ-HTT-Rab4 vesicle complex, accessory proteins, and molecular motors. Together, our observations suggest the existence of a putative moving HTT-Rab4 vesicle, and that the axonal motility of this vesicle is disrupted in HD causing synaptic and behavioral dysfunction. These data highlight Rab4 as a potential novel therapeutic target that could be explored for early intervention prior to neuronal loss and behavioral defects observed in HD.

Direct wavefront sensing in adaptive optical microscopy using backscattered light.

Adaptive optics has been used to compensate the detrimental effects of aberrations in a range of high-resolution microscopes. We investigate how backscattered laser illumination can be used as the source for direct wavefront sensing using a pinhole-filtered Shack-Hartmann wavefront sensor. It is found that the sensor produces linear response to input aberrations for a given specimen. The gradient of this response is dependent upon experimental configuration and specimen structure. Cross sensitivity between modes is also observed. The double pass nature of the microscope system leads in general to lower sensitivity to odd-symmetry aberration modes. The results show that there is potential for use of this type of wavefront sensing in microscopes.

Lack of reaction to ferric gluconate in hemodialysis patients with a history of severe reaction to iron dextran.

Iron deficiency is the most common cause of a poor response to recombinant human erythropoietin (rHuEPO) in patients receiving long-term dialysis, who are known to absorb oral iron preparations poorly. This retrospective case series reports our preliminary observation of five patients receiving long-term dialysis in a tertiary care university hospital who had responded poorly to rHuEPO because of iron deficiency. These patients also had a history of severe, potentially life-threatening reaction to intravenous iron dextran preparation, but they tolerated the newly available ferric gluconate complex in sucrose with no untoward effects. These results suggest that the parenteral administration of ferric gluconate can be safe for those who require iron therapy and who have had a severe reaction to iron dextran.