Gut microbiota, vitamin A deficiency and autism spectrum disorder: an interconnected trio - a systematic review.

Accumulating evidence proves that children with autism have gastrointestinal problems. However, a significant difference in gut microbiota (GM) exists between autistic and non-autistic children. These changes in the GM may stem from several factors. Recently, researchers focused on nutritional factors, especially vitamin deficiency. Thus, our systematic review investigates the connections among autism, GM alterations, and vitamin A deficiency (VAD), by analyzing studies sourced from PubMed and Embase databases spanning from 2010 to 2022. Adhering to PRISMA guidelines, we meticulously selected 19 pertinent studies that established links between autism and GM changes or between autism and VAD. Our findings uniformly point to significant alterations in the GM of individuals with autism, indicating these changes as promising biomarkers for the disorder. Despite the consistent association of GM alterations with autism, our analysis revealed no notable differences in GM composition between individuals with autism and those experiencing VAD. This suggests that VAD, especially when encountered early in life, might play a role in the onset of autism. Furthermore, our review underscores a distinct correlation between reduced levels of retinoic acid in children with autism, a disparity that could relate to the severity of autism symptoms. The implications of our findings are twofold: they not only reinforce the significance of GM alterations as potential diagnostic markers but also spotlight the critical need for further research into nutritional interventions. Specifically, vitamin A supplementation emerges as a promising avenue for alleviating autism symptoms, warranting deeper investigation into its therapeutic potential.

Contemporary Pediatric Heart Transplant Waitlist Mortality.

BACKGROUND: In 2016, the United Network for Organ Sharing revised its pediatric heart transplant (HT) allocation policy. OBJECTIVES: This study sought to determine whether the 2016 revisions are associated with reduced waitlist mortality and capture patient-specific risks. METHODS: Children listed for HT from 1999 to 2023 were identified using Organ Procurement and Transplantation Network data and grouped into 3 eras (era 1: 1999-2006; era 2: 2006-2016; era 3: 2016-2023) based on when the United Network for Organ Sharing implemented allocation changes. Fine-Gray competing risks modeling was used to identify factors associated with death or delisting for deterioration. Fixed-effects analysis was used to determine whether allocation changes were associated with mortality. RESULTS: Waitlist mortality declined 8 percentage points (PP) across eras (21%, 17%, and 13%, respectively; P < 0.01). At listing, era 3 children were less sick than era 1 children, with 6 PP less ECMO use (P < 0.01), 11 PP less ventilator use (P < 0.01), and 1 PP less dialysis use (P < 0.01). Ventricular assist device (VAD) use was 13 PP higher, and VAD mortality decreased 9 PP (P < 0.01). Non-White mortality declined 10 PP (P < 0.01). ABO-incompatible listings increased 27 PP, and blood group O infant mortality decreased 13 PP (P < 0.01). In multivariable analyses, the 2016 revisions were not associated with lower waitlist mortality, whereas VAD use (in era 3), ABO-incompatible transplant, improved patient selection, and narrowing racial disparities were. Match-run analyses demonstrated poor correlation between individual waitlist mortality risk and the match-run order. CONCLUSIONS: The 2016 allocation revisions were not independently associated with the decline in pediatric HT waitlist mortality. The 3-tier classification system fails to adequately capture patient-specific risks. A more flexible allocation system that accurately reflects patient-specific risks and considers transplant benefit is urgently needed.

Safety and utility of mechanical circulatory support in patients with acute myocardial infarction complicated by cardiogenic shock: A systematic review and meta-analysis.

BACKGROUND: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) is a major cause of morbidity and mortality. Although mechanical circulatory support (MCS) is an increasingly utilized therapeutic option in AMI-CS, studies evaluating the efficacy and safety of different forms of MCS have yielded conflicting results. This systematic review and meta-analysis aims to evaluate the safety and efficacy of different forms of MCS. METHODS: A database search was performed for studies reporting on the association of different forms of MCS with clinical outcomes in patients with AMI-CS. The primary efficacy endpoints were short term (≤30 days) and long term (>30 days) all-cause mortality. Secondary efficacy endpoints included recurrent AMI, cardiovascular (CV) mortality, device-related limb complications, moderate to severe bleeding events, and cerebrovascular accidents (CVA). RESULTS: 2752 patients with AMI-CS met inclusion criteria. Results were available comparing ECMO to other MCS or medical therapy alone, comparing IABP to medical therapy alone, and comparing pLVAD to IABP. Use of ECMO was not associated with lower risk of 30-day or long-term mortality compared to pVAD or standard medical therapy with or without IABP placement but was associated with higher risk of device-related limb complications and moderate to severe bleeding compared to pVAD. IABP use was not associated with a lower risk of 30 day or long-term mortality but was associated with higher risk of recurrent AMI and moderate to severe bleeding compared to medical therapy. Compared to IABP, pVAD use was associated with lower risk of CV mortality but not recurrent AMI. pVAD was associated with a higher risk of device-related limb complications and moderate to severe bleeding compared to IABP use. CONCLUSION: Use of ECMO or IABP in patients with AMI-CS is not associated with significant improvement in mortality. pVAD is associated with a lower risk of CV mortality. All MCS types are associated with increased risk of complications. Additional high-quality studies are needed to determine the optimal MCS therapy for patients with AMI-CS.

Neuroprotective effect of GJ-4 against cognitive impairments in vascular dementia by improving white matter damage.

BACKGROUND: White matter lesions (WMLs) are increasingly linked to the pathological process of chronic vascular dementia (VaD). An effective crocins fraction extracted from Gardenia Fructus, GJ-4, has been shown to improve cognitive function in several Alzheimer's disease models and VaD models. OBJECTIVES: To explore the potential mechanisms of GJ-4 on WMLs in a chronic VaD mouse model. METHODS: The chronic VaD mouse model was established, and WMLs were characterized by cerebral blood flow (CBF), behavioral tests, LFB staining, and immunohistochemistry. The anti-oxidative effect of GJ-4 was validated by examining biochemical parameters (SOD, MDA, and GSH) and the Keap1-Nrf2/HO-1 pathway. The impact of GJ-4 on lipid metabolism in WM was further investigated through lipidomic analysis. RESULTS: GJ-4 significantly attenuated cognitive impairments and improved the CBF of BCAS (bilateral common carotid artery stenosis)-induced mice. Mechanism research showed that GJ-4 could enhance cognition by promoting the repair of WMLs by inhibiting oxidative stress. Furthermore, GJ-4 treatment significantly reduced chronic cerebral hypoperfusion (CCH)-induced WMLs via improving lipid metabolism disorder in the WM. CONCLUSION: This research has provided valuable insights into the significance of WMLs in CCH-induced VaD and underscored the potential of GJ-4 as a therapeutic agent for improving cognitive function by targeting WMLs. These findings suggest that GJ-4 is a promising candidate for the treatment of VaD.

Silencing of tropomodulin 1 inhibits acute myeloid leukemia cell proliferation and tumor growth by elevating karyopherin alpha 2-mediated autophagy.

Evidence shows that tropomodulin 1 (TMOD1) is a powerful diagnostic marker in the progression of several cancer types. However, the regulatory mechanism of TMOD1 in tumor progression is still unclear. Here, we showed that TMOD1 was highly expressed in acute myeloid leukemia (AML) specimens, and TMOD1-silencing inhibited cell proliferation by inducing autophagy in AML THP-1 and MOLM-13 cells. Mechanistically, the C-terminal region of TMOD1 directly bound to KPNA2, and TMOD1-overexpression promoted KPNA2 ubiquitylation and reduced KPNA2 levels. In contrast, TMOD1-silencing increased KPNA2 levels and facilitated the nuclear transfer of KPNA2, then subsequently induced autophagy and inhibited cell proliferation by increasing the nucleocytoplasmic transport of p53 and AMPK activation. KPNA2/p53 inhibitors attenuated autophagy induced by silencing TMOD1 in AML cells. Silencing TMOD1 also inhibited tumor growth by elevating KPNA2-mediated autophagy in nude mice bearing MOLM-13 xenografts. Collectively, our data demonstrated that TMOD1 could be a novel therapeutic target for AML treatment.

Morphological Features of the Vertebrobasilar System Predict Ischemic Stroke Risk in Spontaneous Vertebral Artery Dissection.

The vertebral artery's morphological characteristics are crucial in spontaneous vertebral artery dissection (sVAD). We aimed to investigate morphologic features related to ischemic stroke (IS) and develop a novel prediction model. Out of 126 patients, 93 were finally analyzed. We constructed 3D models and morphological analyses. Patients were randomly classified into training and validation cohorts (3:1 ratio). Variables selected by LASSO - including five morphological features and five clinical characteristics - were used to develop prediction model in the training cohort. The model exhibited a high area under the curve (AUC) of 0.944 (95%CI, 0.862-0.984), with internal validation confirming its consistency (AUC = 0.818, 95%CI, 0.597-0.948). Decision curve analysis (DCA) indicated clinical usefulness. Morphological features significantly contribute to risk stratification in sVAD patients. Our novel developed model, combining interdisciplinary parameters, is clinically useful for predicting IS risk. Further validation and in-depth research into the hemodynamics related to sVAD are necessary.

The Predictive Role of Metabolic Volume Segmentation Compared to Semiquantitative PET Parameters in Diagnosis of LVAD Infection using [18F]FDG Imaging.

PURPOSE: Left ventricular assisting device (LVAD) is a vital mechanical circulatory assist device for patients with end-stage heart disease, serving as either a bridge to transplantation or palliative destination therapy. Yet device infection represents a major lethal complication, warranting a multi-step, complex therapy approach including an urgent device exchange or heart transplantation. Still, timely diagnosis of site and extent of VAD-specific infection for a proper therapy planning poses challenges in regular clinical care. This single-center, retrospective study aimed to evaluate the impact of volumetric PET parameters with different thresholding compared to semiquantitative PET parameters for accurate diagnosis of VAD-specific infection. PROCEDURES: Seventeen patients (1 female, 16 males; mean age 57 ± 11 years) underwent [18F]FDG imaging for suspected VAD-specific infection between April 2013 and October 2023. Various metabolic and volumetric PET parameters with different thresholding were collected for specific LVAD components including driveline entry point, subcutaneous driveline, pump pocket, inner cannula and outflow tract. Microbiology and clinical follow-up were used as the final diagnosis standard. RESULTS: Nine of eleven patients with VAD-specific infection underwent urgent heart transplantation, and one had a surgical revision of LVAD. Two patients had non-VAD specific infections, and two had non-VAD related infections. Metabolic burden determination using a fixed absolute threshold provided the best outcome compared to relative thresholding or other metabolic SUV parameters. The total metabolic tumor volume (MTV) cutoff value was 9.3 cm3, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.43%, 82.5%, and 0.814 (95% CI 0.555-0.958), respectively. The total lesion glycolysis (TLG) was 30.6, and the corresponding sensitivity, specificity, accuracy, and AUC were 90.0%, 71.4%, 82.5%, and 0.829 (95% CI 0.571-0.964), respectively. CONCLUSIONS: Volumetric PET parameters with fixed absolute thresholding appear to be a valuable auxiliary tool in the evaluation of [18F]FDG imaging to enhance the diagnostic accuracy of VAD-specific infection.

Mental Health and Substance Use Disorders in Transplant Waitlist, VAD, and Heart Transplant Patients: A TriNetX Database Analysis.

Background/Objectives: Mental health and substance use disorders (MHDs and SUDs) affect cardiac allograft and VAD recipients and impact their quality of life and compliance. Limited research currently exists on MHDs and SUDs in this population. Methods: This study compares the incidence of MHDs and SUDs in the transplant list, VAD, and post-transplant patients with that in heart failure patients. Study cohorts were derived from the TriNetX database using ICD-10 codes. Differences in incidence were examined using the log-rank test. Adults with MHDs and SUDs before the window of time were excluded. All comparisons were made between propensity-matched cohorts. Statistical significance was set at p < 0.05. Results: Transplant waitlist patients showed a significant increase in the incidence of anxiety, depression, panic, adjustment, mood, alcohol use, and eating disorders. Post-transplant patients showed a significant increase in depression and opioid use. VAD patients showed a significant increase in depression and a decrease in panic disorder and anxiety. These results allow for further investigations on prevention and coping strategies. Conclusions: The deterioration of mental health can significantly impact medication compliance, survival, and quality of life. Opioid use for pain management in the early postoperative period should be further investigated to assess its impact on long-term substance use and addiction.

Piracetam reduces oxidative stress and mitochondrial function impairment in an in vitro model of vascular dementia.

Vascular dementia (VaD) is the most common cause of dementia in older adults. Due to the lack of effective treatment options, there is an urgent need to find an effective pharmaceutical compound to combat VaD. Piracetam has been reported to improve impaired cognitive function in a variety of conditions in both human and animal models. However, the role and mechanism of Piracetam in VaD remain unclear. Therefore this study aimed to elucidate the effect of Piracetam on a cellular model of VaD in vitro. We found that Piracetam enhanced the growth of OGD-stimulated SH-SY5Y cells. In addition, Piracetam inhibited the oxidative stress of OGD-stimulated SH-SY5Y cells. Further, Piracetam improved mitochondrial function of OGD-stimulated SH-SY5Y cells. Mechanistically, Piracetam inhibited the PI3K/Akt/mTOR pathway in OGD-stimulated SH-SY5Y cells. Collectively, Piracetam improved oxidative stress and mitochondrial dysfunction of OGD-stimulated SH-SY5Y cells through PI3K/Akt/mTOR axis. Hence, Piracetam has the potential to serve as a promising drug of VaD.

Implantation of short-term biventricular assist device (BiVAD) using the CentriMag™ system: the Manchester technique.

Biventricular assist devices (BiVADs) using the CentriMag™ system are being used increasingly as a form of short-term mechanical circulatory support for the treatment of acute cardiogenic shock from any aetiology. They can be used as a bridge to decision, recovery or transplantation. BiVADs are associated with better clinical outcomes when compared to veno-arterial (VA) extracorporeal membrane oxygenator (ECMO) systems. In this paper, we describe a safe and reproducible method of BiVAD implantation using the CentriMag™ system at our institution.

Three-dimensional analysis of partial restoration of spermatogenesis in vitamin A-deficient mice.

BACKGROUND: An animal model of the partial restoration of spermatogenesis may be useful in the field of reproductive biology and medicine. Vitamin A deficiency (VAD) induces the restorable arrest of spermatogenesis at the level of spermatogonia and is used as a mouse model of spermatogenesis disorder. OBJECTIVE: We aimed to establish an animal model in which spermatogenesis is partially restored by switching a vitamin A deficiency diet to a normal vitamin A-containing diet and conduct a comprehensive analysis to identify vulnerable sites in the seminiferous tubules that affect the efficient restoration of spermatogenesis in this model. MATERIALS AND METHODS: Mice fed a vitamin A deficiency diet until 12 weeks old and then reared with a normal diet for 15 weeks served as the restoration model. We performed three-dimensional reconstructions of the seminiferous tubules and analyzed the three-dimensional distribution of restored spermatogenesis throughout the testis. RESULTS: Fifteen weeks after the switch to the normal diet, spermatogenesis was restored in 78% of the length of seminiferous tubules. The percentage of restored spermatogenesis was lower in longer seminiferous tubules. An analysis of the distribution of spermatogenesis throughout the testis in this model revealed that it was restored less in portions of seminiferous tubules near the rete testis and hairpin curves and also in those located in the caudal region of the testis. These sites tended to correspond to sites with fewer spermatogonia in the vitamin A deficiency testis. DISCUSSION AND CONCLUSIONS: We established an animal model of the partial restoration of spermatogenesis and examined the three-dimensional distribution of restored spermatogenesis in seminiferous tubules. The results obtained provide insights into the mechanisms underlying spermatogenesis disorders and may contribute to better clinical practices, such as the screening of drugs or therapeutic interventions for human male infertility and improvements in fertility preservation techniques for individuals undergoing chemotherapy.

Biventricular assist device implant using biatrial cannulation for restrictive cardiomyopathy.

Preoperative calculations showed that the 9-mm inlet, 6-mm outlet, 25-cc pump chambers and 65-73 bpm would be optimal for a 5-year-old patient suffering from restrictive cardiomyopathy, with a body surface area of 0.59 m2 (1.5 L/min flow for a cardiac index of 2.5). After re-sternotomy and standard bicaval cannulation for cardiopulmonary bypass, the procedure was performed under normothermic conditions and on the beating heart. Biventricular support was established with the Berlin Heart Excor using biatrial cannulation. For left atrial cannulation, induced ventricular fibrillation was used. The 9-mm inlet cannulas were inserted into the left and right atria, respectively. The 6-mm outlet cannulas were implanted using 8-mm interposition vascular grafts for the aorta and the main pulmonary artery, respectively. Cannulas were tunnelled through the epigastric space, with systems crossing outside of the body. The 25-cc chambers were used for both right ventricular assist device and left ventricular assist device support, which subsequently showed full emptying and filling.

Deactivation of LVAD support for myocardial recovery-surgical perspectives.

Left ventricular assist devices (LVADs) are excellent therapies for advanced heart failure patients either bridged to transplant or for lifetime use. LVADs also allow for reverse remodeling of the failing heart that is often associated with functional improvement. Indeed, growing enthusiasm exists to better understand this population of patients, whereby the LVAD is used as an adjunct to mediate myocardial recovery. When patients achieve benchmarks suggesting that they no longer need LVAD support, questions related to the discontinuation of LVAD therapy become front and center. The purpose of this review is to provide a surgical perspective on the practical and technical issues surrounding LVAD deactivation.

Vertebral Artery Dissection in a Young Adult: A Case Report.

Vertebral artery dissections (VAD) pose a significant risk for strokes, particularly in young adults. This case report details the presentation and management of a 48-year-old patient who was diagnosed with an extracranial VAD following cervical spine manipulation (CSM). The patient's symptoms included acute right-sided ataxia, giddiness, vertigo, nausea, vomiting, and persistent pain behind the right ear, prompting immediate evaluation. After ruling out acute intracerebral hemorrhages, a computed tomography angiogram (CTA) of the head and neck identified a severe narrowing of the right distal vertebral artery with a string sign at the level of the right C1 loop (V3 segment), indicating an extracranial VAD. This finding was further supported when ultrasound (US) imaging revealed a high resistance flow pattern in the right distal vertebral artery. Furthermore, T2 and diffusion-weighted magnetic resonance imaging (MRI) confirmed a 1.8 cm VAD/hematoma and a 1.4 cm acute/subacute infarct in the right posterior inferior cerebellar artery (PICA) territory. This research accentuates the importance of recognizing and addressing that neck pain can be a symptom of musculoskeletal dysfunction or could have neurovascular origins. In this case, the patient's neck pain may have been musculoskeletal or could have been due to a previous dissection. Thus, differentiation should be considered before cervical spine manipulation.

Long-term outcomes of a novel fully magnetically levitated ventricular assist device for the treatment of advanced heart failure in China.

PURPOSE: Left ventricular assist devices (LVADs) are well-established for treating end-stage heart failure, but this therapy is only available to Chinese patients in recent years. The CH-VAD is the first used fully magnetically levitated pump and the most widely used device in China. This study reports the long-term outcomes of a cohort supported by the CH-VAD for the first time. METHODS: From June 2017 to August 2023, 50 consecutive patients received CH-VAD implantation in Fuwai Hospital. Clinical data were collected during follow-up and retrospectively analyzed. RESULTS: Baseline characteristics included a mean age of 47.9±13.9 years, 90% male, and 26% ischemic etiology. The INTERMACS profile revealed 12% Profile 1, 56% Profile 2, 26% Profile 3 and 6% Profile 4. Mean support duration was 868 ± 630 days (range 33 days-6.4 years). Kaplan-Meier survival rate was 96% (95% confidence interval [CI], 85 to 99) at 6 months, 93% (95% CI, 79-98) at 1 year, 93% (95% CI, 79-98) at 2 years and 89% (95% CI, 71-96) at 3 years. 40 patients (80%) currently remain on support, 3 were bridged to recovery, 2 received transplant, and 5 expired during support. Major adverse events included right heart failure (10%), surgical related bleeding (8%), arrhythmia (8%) and driveline infection (16%). Major hemocompatibility-related adverse events were limited to 3 non-disabling strokes and 1 gastrointestinal bleeding. There was no major device malfunction during the follow-up period. CONCLUSIONS: The largest single-center experience with the leading LVAD in China shows high survival with low complication rates, demonstrating the CH-VAD is safe and efficient in providing long-term support for end-stage heart failure patients.

Central venous accesses in prone position during the pandemic period: A narrative review.

The unprecedented challenges posed by the global COVID-19 pandemic have magnified the significance of managing intensive care patients in prone positions, particularly those requiring mechanical ventilation. Central venous access is crucial for delivering essential therapies to patients, particularly in intensive care settings. However, the shift in patient management during the pandemic, necessitating prone positioning for improved oxygenation, presented unique hurdles in maintaining and establishing central venous access. Before the pandemic, scant literature detailed the insertion of vascular access devices in prone or unconventional positions. Limited case reports and letters highlighted the feasibility of procedures like ultrasound-guided central catheter placement in patients undergoing surgery or with specific clinical needs. During the pandemic, a surge in case reports and series illuminated the complexities faced by clinicians in maintaining vascular access during pronation procedures. These reports delineated critical scenarios, ranging from rapid clinical deterioration necessitating immediate interventions to challenges with vascular access device (VAD) malfunctions or misplacements during prone maneuvers. Patient selection and device types emerged as critical considerations. Various scenarios, including patients transitioning to prone position from non-invasive ventilation and those requiring additional access for therapies like dialysis, posed challenges in device selection and placement. Successful VAD insertion techniques in prone patients encompassed multiple anatomical sites, including the internal jugular, brachial, femoral, and popliteal veins. However, challenges persisted, particularly with respect to anatomical variations and technical complexities in cannulation. Further research, standardized protocols, and randomized studies are needed to refine and validate the proposed strategies in both pandemic and non-pandemic settings.

A review of SaiLuoTong (MLC-SLT) development in vascular cognitive impairment and dementia.

The dementia epidemic, attributed to aging populations, represents a growing socio-economic burden. It is estimated that in 2019 about 55 million people worldwide were living with dementia. With many possible causes of dementia and the possibility of mixed dementia combining Alzheimer's disease (AD) and vascular dementia the question is whether diagnostic uncertainty exists or whether diagnostic constructs based on single etiologies are incorrect. Vascular Cognitive Impairment and Dementia (VCID) designates the extent of cognitive dysfunctions from the most benign state to that of dementia, of vascular origin. We reviewed epidemiological, pathophysiological and clinical data on VCID with a focus on VaD, as well as key data on the development of a new therapeutic solution, SaiLuoTong (MLC-SLT). From documentary research executed on different web sources (PubMed, Clintrials.gov, Z-library and Google), our initial selection for the short review of VCID and VaD was based on keywords contained in each paragraph subtitles of this article with exclusion of publications in a language other than English or published before 2010. For the review of SaiLuoTong development, there was just the language exclusion criterion. Sorted by relevance and publication date, 47 references were selected from 140 shortlisted for review. With new evidence-based classification systems, vascular cognitive impairment was proposed as umbrella term covering all forms of cognitive deficits related to vascular causes. The scope of application expanded with the VCID which includes VaD and mixed pathologies. No drugs are approved for the treatment of VaD by major Western regulatory agencies, while some traditional Chinese medicines are registered in China. VCID treatment should have a dual focus: managing the underlying cerebrovascular disease and dementia symptoms. This is the objective set for the development of the MLC-SLT, the essential data of which are reviewed in detail. To strengthen VCID and VaD research, consensus groups should attempt to consolidate scattered local research initiatives into coordinated international programs. In two VaD clinical trials, MLC-SLT improved cognitive symptoms and activities of daily living, with good safety and potential disease-modifying effect. In a placebo-controlled study in 325 patients with mild to moderate VaD and randomized according to a delayed-start design, MLC-SLT demonstrated significant improvement in memory tests and performance in executive function tasks, expanding its place in the management of VCID. At week 26, changes in VADAS-cog scores (SD) from baseline were 23.25 (0.45) for MLC-SLT 180 mg bid), 23.05 (0.45) for MLC-SLT 120 mg bid (both p < 0.0001), and 20.57 (0.45) for placebo (p = 0.15). At week 52, differences between both groups MLC-SLT and placebo were 2.67 and 2.48, respectively (p < 0.0001), without significant difference between MLC-SLT groups.