Successful Treatment of Peripheral Nerve Sheath Tumor-related Pain with Perineural Steroid Injection: a case report.

Pain associated with Neurofibromatosis Type 1 (NF1) is poorly understood. To date, no treatment options have been approved for NF1-related pain. We present the case of a young female NF1 patient with intermittent buttock pain radiating down the leg who presented with positive dural tension signs. The patient was diagnosed with neurofibroma sciatic nerve compression, which was successfully managed with ultrasound-guided perineural steroid injection. There is sparse literature regarding the efficacy of ultrasound-guided perineural steroid injection in NF1 patients for treatment of benign peripheral nerve sheath tumor compressions. This case describes the utility of perineural steroid injections for symptomatic relief of NF1 neurofibroma-related pain. Perineural steroid injections should be considered when neurofibroma-related pain fails to respond to other conservative treatment. Steroid injections provide an alternative to oral medicinal management and avoid the often morbid risks of surgical intervention.

Healthy first-degree relatives from multiplex families versus simplex families have a higher subclinical intestinal inflammation, a distinct fecal microbial signature, and harbor a higher risk of developing Crohn's disease.

BACKGROUND & AIMS: Unaffected first-degree relatives (FDRs) from families with two or more affected FDRs with Crohn's disease (CD, multiplex families) have a high risk of developing CD, although the underlying mechanisms driving this risk are poorly understood. We aimed to identify differences in biomarkers between FDRs from multiplex versus simplex families and to investigate the risk of future CD onset accounting for potential confounders. METHODS: We assessed the Crohn's and Colitis Canada Genetic Environmental Microbial (CCC-GEM) cohort of healthy FDRs of patients with CD. Genome-wide CD-polygenic risk scores (CD-PRS), urinary fractional excretion of lactulose-to-mannitol ratio (LMR), fecal calprotectin (FCP), and fecal 16S ribosomal RNA microbiome were measured at recruitment. Associations between CD multiplex status and baseline biomarkers were determined using generalized estimating equations models. Cox models were used to assess the risk of future CD onset. RESULTS: There were 4051 participants from simplex families and 334 from CD multiplex families. CD multiplex status was significantly associated with higher baseline FCP (p=0.026) but not with baseline CD-PRS or LMR. Three bacterial genera were found to be differentially abundant between both groups. CD multiplex status at recruitment was independently associated with an increased risk of developing CD (adjusted hazard ratio 3.65, 95% confidence interval 2.18 - 6.11, p < 0.001). CONCLUSION: Within FDRs of patients with CD, participants from multiplex families had a 3-fold increased risk of CD onset, a higher FCP, and an altered bacterial composition, but not genetic burden or altered gut permeability. These results suggest that putative environmental factors might be enriched in FDRs from multiplex families.

Establishing a standard measure of blunt and cigar use for U.S. national surveys.

BACKGROUND: Researchers have drawn attention to the need for modifying survey questions on cigars for distinguishing use intended for tobacco versus cannabis (i.e. blunt) consumption. Yet, most surveys do not distinguish persons who only smoke blunts (POSB) from persons who smoke blunts and unmodified cigars/cigarillos (PSBC). This study was intended to evaluate existing measures in U.S. national surveys for establishing a standard for the field. METHODS: Two of six leading U.S national surveys, the NSDUH and PATH, measured dual use of blunts and cigars. The analytical sample of this study included adult participants of the 2017 NSDUH (n = 2493) and Wave 4 PATH (n = 3175) who smoked a cigar or blunt in the past month and reported cigar brand usually or last smoked; the latter was used as a validation measure. RESULTS: Odds of using Swisher Sweets and other brands (vs. Black & Mild) increased with more frequent blunt use relative to persons who only smoked unmodified cigars/cigarillos (POSC). Further, regression coefficients for the three subgroups of PSBC differed significantly, highlighting the utility of an ordinal versus aggregated measure. Estimates of the former were diminished in magnitude upon expanding the sample to persons who smoked any cigar product. CONCLUSIONS: Validation of the ordinal measure of blunt-cigarillo use in PATH supports the measure's implementation as a standard for U.S. national surveys. Implementation of the measure in other surveys (e.g., NSDUH) would provide a more consistent and accurate assessment of blunt and cigar use for monitoring health risks.

Evolutionary dynamics in gut-colonizing Candida glabrata during caspofungin therapy: Emergence of clinically important mutations in sphingolipid biosynthesis.

Invasive fungal infections are associated with high mortality, which is exacerbated by the limited antifungal drug armamentarium and increasing antifungal drug resistance. Echinocandins are a frontline antifungal drug class targeting ß-glucan synthase (GS), a fungal cell wall biosynthetic enzyme. Echinocandin resistance is generally low but increasing in species like Candida glabrata, an opportunistic yeast pathogen colonizing human mucosal surfaces. Mutations in GS-encoding genes (FKS1 and FKS2 in C. glabrata) are strongly associated with clinical echinocandin failure, but epidemiological studies show that other, as yet unidentified factors also influence echinocandin susceptibility. Furthermore, although the gut is known to be an important reservoir for emergence of drug-resistant strains, the evolution of resistance is not well understood. Here, we studied the evolutionary dynamics of C. glabrata colonizing the gut of immunocompetent mice during treatment with caspofungin, a widely-used echinocandin. Whole genome and amplicon sequencing revealed rapid genetic diversification of this C. glabrata population during treatment and the emergence of both drug target (FKS2) and non-drug target mutations, the latter predominantly in the FEN1 gene encoding a fatty acid elongase functioning in sphingolipid biosynthesis. The fen1 mutants displayed high fitness in the gut specifically during caspofungin treatment and contained high levels of phytosphingosine, whereas genetic depletion of phytosphingosine by deletion of YPC1 gene hypersensitized the wild type strain to caspofungin and was epistatic to fen1Δ. Furthermore, high resolution imaging and mass spectrometry showed that reduced caspofungin susceptibility in fen1Δ cells was associated with reduced caspofungin binding to the plasma membrane. Finally, we identified several different fen1 mutations in clinical C. glabrata isolates, which phenocopied the fen1Δ mutant, causing reduced caspofungin susceptibility. These studies reveal new genetic and molecular determinants of clinical caspofungin susceptibility and illuminate the dynamic evolution of drug target and non-drug target mutations reducing echinocandin efficacy in patients colonized with C. glabrata.

Healthcare-related carbon footprinting-lower impact of a coronary stenting compared to a coronary surgery pathway.

Healthcare is a major generator of greenhouse gases, so consideration of this contribution to climate change needs to be quantified in ways that can inform models of care. Given the availability of activity-based financial data, environmentally-extended input-output (EEIO) analysis can be employed to calculate systemic carbon footprints for healthcare activities, allowing comparison of different patient care pathways. We thus quantified and compared the carbon footprint of two common care pathways for patients with stable coronary artery disease, with similar clinical outcomes: coronary stenting and coronary artery bypass surgery (CABG). Healthcare cost data for these two pathways were disaggregated and the carbon footprint associated with this expenditure was calculated by connecting the flow of money within the economy to the greenhouse gases emitted to support the full range of associated activities. The systemic carbon footprint associated with an average stable patient CABG pathway, at a large tertiary referral hospital in Sydney, Australia in 2021-22, was 11.5 tonnes CO2-e, 4.9 times greater than the 2.4 tonnes CO2-e footprint of an average comparable stenting pathway. These data suggest that a stenting pathway for stable coronary disease should be preferred on environmental grounds and introduces EEIO analysis as a practical tool to assist in health-care related carbon footprinting.

Wildlife health capacity enhancement in Thailand through the World Organisation for Animal Health Twinning Program.

There is an increasing need for robust wildlife health programs that provide surveillance and management for diseases in wildlife and wild aquatic populations to manage associated risks. This paper illustrates the value of a systematic method to enhancing wildlife health programs. The U.S. Geological Survey and Mahidol University, Faculty of Veterinary Science, Thailand National Wildlife Health Center formally twinned under the auspices of the World Organisation for Animal Health to enhance wildlife health capacity in Thailand and the Southeast Asia Region. We used a system-wide approach to holistically and interdependently enhance capacity. The project commenced with a wildlife health program needs assessment, and capacity enhancement focused on strengthening the general wildlife health surveillance network and improving wildlife health information management. Activities included partner surveys, interactive and didactic workshops, and individual personnel training. Topics included development of wildlife health information management systems, analysis of the current surveillance network, development of a Theory of Change for a strengthened surveillance network, planning workshops to create a wildlife health network, training on wildlife disease outbreak investigation and field sample collection, leading networks, and individual training on bioinformatics and laboratory techniques. Engagement of stakeholders at all levels, continuous communication throughout the project, use of both strategic planning tools and pedagogical methods, and using iterative and adaptive approaches, were key factors to the success of this project.

Birth in the Operating Room for Immediate Cardiac Surgery: A Rare but Effective Strategy.

Background: With significant advancements in fetal cardiac imaging, patients with complex congenital heart disease (CHD) carrying a high risk for postnatal demise are now being diagnosed earlier. We sought to assess an interdisciplinary strategy for delivering these children in an operating room (OR) adjacent to a cardiac OR for immediate surgery or stabilization. Methods: All children prenatally diagnosed with CHD at risk for immediate postnatal hemodynamic instability and cardiogenic shock who were delivered in the operating room (OR) between 2012 and 2023 in which the senior author was consulted were included. Results: Eight patients were identified. Six (75%) patients were operated on day-of-life zero, all requiring obstructed total anomalous pulmonary venous return (TAPVR) repair. Of these six patients, 2 (33%) required a simultaneous Norwood procedure, 2 (33%) required pulmonary artery unifocalization and modified Blalock-Taussig-Thomas shunt, and 2 (33%) patients had repair of obstructed mixed TAPVR. The remaining 2 patients potentially planned for immediate surgery had nonimmune hydrops fetalis and went into cardiogenic shock at 12 and 72 hours postnatally, requiring a novel Norwood procedure with left-ventricular exclusion for severe aortic/mitral valve insufficiency. The median ventilation and inpatient durations were 19 [IQR: 11-26] days and 41 [IQR: 32-128] days, respectively. Three(38%) patients required one or more in-hospital reoperations. Subsequent staged procedures included Glenn (n = 5), Fontan (n = 3), biventricular repair (n = 2), ventricular assist device placement (n = 1), and heart transplant (n = 1). Median follow-up was 5.7 [IQR:1.3-7.8] years. The five-year postoperative survival was 88% (n = 7/8). Conclusion: While children with these diagnoses have historically had poor survival, the strategy of birth in the OR adjacent to a cardiac OR where emergent surgery is planned is a potentially promising strategy with excellent clinical outcomes. However, this is a high-resource strategy whose feasibility in any program requires thoughtful assessment.

E. coli FtsN coordinates synthesis and degradation of septal peptidoglycan by partitioning between a synthesis track and a denuded glycan track.

The E. coli cell division protein FtsN was proposed to coordinate septal peptidoglycan (sPG) synthesis and degradation to ensure robust cell wall constriction without lethal lesions. Although the precise mechanism remains unclear, previous work highlights the importance of two FtsN domains: the E domain, which interacts with and activates the sPG synthesis complex FtsWIQLB, and the SPOR domain, which binds to denuded glycan (dnG) strands, key intermediates in sPG degradation. Here, we used single-molecule tracking of FtsN and FtsW (a proxy for the sPG synthesis complex FtsWIQLB) to investigate how FtsN coordinates the two opposing processes. We observed dynamic behaviors indicating that FtsN's SPOR domain binds to dnGs cooperatively, which both sequesters the sPG synthesis complex on dnG (termed as the dnG-track) and protects dnGs from degradation by lytic transglycosylases (LTs). The release of the SPOR domain from dnGs leads to activating the sPG synthesis complex on the sPG-track and simultaneously exposing those same dnGs to degradation. Furthermore, FtsN's SPOR domain self-interacts and facilitates the formation of a multimeric sPG synthesis complex on both tracks. The cooperative self-interaction of the SPOR domain creates a sensitive switch to regulate the partitioning of FtsN between the dnG- and sPG-tracks, thereby controlling the balance between sequestered and active populations of the sPG synthesis complex. As such, FtsN coordinates sPG synthesis and degradation in space and time.

Quality-of-Life Outcomes from NRG/NSABP B-39/RTOG 0413: Whole-breast Irradiation vs Accelerated Partial-breast Irradiation after Breast Conserving Surgery.

PURPOSE: NRG Oncology (NRG)/NSABP B-39/RTOG 0413 compared whole-breast irradiation (WBI) to accelerated partial-breast irradiation (APBI). APBI was not equivalent to WBI in local tumor control. Secondary outcome was Quality-of-life (QOL). METHODS: The QOL sub-study used validated self-report questionnaires including the Breast Cancer Treatment Outcome Scale (BCTOS) and SF-36 vitality scale. Assessments occurred: before randomization, at treatment completion (chemotherapy or radiotherapy), 4-weeks later, at 6-, 12-, 24-, and 36-months. Primary aims: cosmesis change equivalency (baseline to 3 years; a priori margin of equivalence 0.4 standard deviations) and fatigue change superiority (baseline to end-of-treatment (EOT)) for APBI vs WBI, by patient groups treated with or without chemotherapy when appropriate. RESULTS: From 3/21/05-5/25/09, 975 patients enrolled in this sub-study; 950 had follow-up data. APBI had 3-year cosmesis equivalent to WBI (95%CI,-0.0001-0.16; equivalence margin -0.22-0.22) in all patients. The APBI group without chemotherapy had less EOT fatigue (p = .011; mean score APBI 63 vs WBI 59); APBI group receiving chemotherapy had worse EOT fatigue (p = .011; APBI 43 vs WBI 49). The APBI group reported less pain (BCTOS) at EOT (WBI 2.29 vs APBI 1.97), but worse pain at 3-years (WBI 1.62 vs APBI 1.71). APBI patients reported greater convenience of care than with WBI and reported less symptom severity at EOT and 4-weeks later. CONCLUSION: Cosmetic outcomes were similar for APBI and WBI groups, with small statistically significant differences in other outcomes that varied over time. Differences in fatigue and other symptoms appeared to resolve by ≥ 6 months. APBI may be preferred by some patients, for whom extended treatment is burdensome.

Contractile regulation of the glucocorticoid-sensitive transcriptome in young and aged skeletal muscle.

Elevated glucocorticoids alter the skeletal muscle transcriptome to induce a myopathy characterized by muscle atrophy, muscle weakness, and decreased metabolic function. These effects are more likely to occur and be more severe in aged muscle. Resistance exercise can blunt development of glucocorticoid myopathy in young muscle, but the potential to oppose the signals initiating myopathy in aged muscle is unknown. To answer this, young (4-month-old) and aged (24-25-month-old) male C57BL/6 mice were randomized to receive either an intraperitoneal (IP) injection of dexamethasone (DEX; 2 mg/kg) or saline as a control. Two hours post-injections, tibialis anterior (TA) muscles of mice were subjected to unilateral high force contractions. Muscles were harvested four hours later. The glucocorticoid- and contraction-sensitive genes were determined by RNA sequencing. The number of glucocorticoid-sensitive genes was similar between young and aged muscle. Contractions opposed changes to more glucocorticoid-sensitive genes in aged muscle, with this outcome primarily occurring when hormone levels were elevated. Glucocorticoid-sensitive gene programs opposed by contractions were primarily related to metabolism in young mice and muscle size regulation and inflammation in aged mice. In silico analysis implied Peroxisome proliferator-activated receptor gamma-1 (PPARG) contributed to the contraction-induced opposition of glucocorticoid-sensitive genes in aged muscle. Increasing PPARG expression in the TA of aged mice using Adeno-associated virus serotype 9 partially counteracted the glucocorticoid-induced reduction in Runt-related transcription factor 1 (Runx1) mRNA content, recapitulating the effects observed by contractions. Overall, these data contribute to our understanding of the contractile regulation of the glucocorticoid transcriptome in aged skeletal muscle.

Protocol for Designing a Model to Predict the Likelihood of Psychosis From Electronic Health Records Using Natural Language Processing and Machine Learning.

INTRODUCTION: Rapid identification of individuals developing a psychotic spectrum disorder (PSD) is crucial because untreated psychosis is associated with poor outcomes and decreased treatment response. Lack of recognition of early psychotic symptoms often delays diagnosis, further worsening these outcomes. METHODS: The proposed study is a cross-sectional, retrospective analysis of electronic health record data including clinician documentation and patient-clinician secure messages for patients aged 15-29 years with ≥ 1 primary care encounter between 2017 and 2019 within 2 Kaiser Permanente regions. Patients with new-onset PSD will be distinguished from those without a diagnosis if they have ≥ 1 PSD diagnosis within 12 months following the primary care encounter. The prediction model will be trained using a trisourced natural language processing feature extraction design and validated both within each region separately and in a modified combined sample. DISCUSSION: This proposed model leverages the strengths of the large volume of patient-specific data from an integrated electronic health record with natural language processing to identify patients at elevated chance of developing a PSD. This project carries the potential to reduce the duration of untreated psychosis and thereby improve long-term patient outcomes.

Emergency and non-emergency routes to cancer diagnoses in 2020 and 2021: A Population-based study of 154,863 patients.

INTRODUCTION: The COVID-19 pandemic disrupted normal pathways to cancer diagnosis, particularly for screening and non-acute symptomatic patients. While reductions in overall cancer diagnoses have been reported elsewhere, any differential effects on emergency presentations, which are associated with poorer outcomes, have not been described. MATERIAL AND METHODS: Cross-sectional descriptive study from 2015 to 2021, based on International Cancer Benchmarking Partnership methods, where emergency route to diagnosis is defined as presenting as an emergency admission in the 30 days prior to cancer incidence date. Acute hospital records and cancer registrations were individually linked. Includes all individuals with a new diagnosis of specific cancers on the national cancer registry. RESULTS: All cancers included showed reductions in non-emergency diagnoses in 2020, with varying recovery in 2021. The largest reductions in non-emergency diagnoses of about a third were for colorectal and cervical cancers in 2020. Non-emergency diagnoses of prostate cancer remained lower but upper GI higher in 2021. Emergency routes to diagnosis were significantly higher in 2020 for breast, cervical, colorectal and upper GI cancers and were higher in 2021 for breast and cervical cancers. The absolute magnitude of reductions in non-emergency diagnoses was greater than any increases in emergency diagnoses. CONCLUSIONS: In 2020, there were large reductions in numbers of cancers diagnosed through non-emergency pathways in Scotland, while those diagnosed via emergency routes fell only for prostate cancer. Some effects persisted or emerged through 2021. It is likely that opportunities to diagnose cancers in a favourable, elective manner have been lost. Further work is needed to describe outcomes among these patients.

Balloon Angioplasty vs Medical Management for Intracranial Artery Stenosis: The BASIS Randomized Clinical Trial.

Importance: Previous randomized clinical trials did not demonstrate the superiority of endovascular stenting over aggressive medical management for patients with symptomatic intracranial atherosclerotic stenosis (sICAS). However, balloon angioplasty has not been investigated in a randomized clinical trial. Objective: To determine whether balloon angioplasty plus aggressive medical management is superior to aggressive medical management alone for patients with sICAS. Design, Setting, and Participants: A randomized, open-label, blinded end point clinical trial at 31 centers across China. Eligible patients aged 35 to 80 years with sICAS defined as recent transient ischemic attack (<90 days) or ischemic stroke (14-90 days) before enrollment attributed to a 70% to 99% atherosclerotic stenosis of a major intracranial artery receiving treatment with at least 1 antithrombotic drug and/or standard risk factor management were recruited between November 8, 2018, and April 2, 2022 (final follow-up: April 3, 2023). Interventions: Submaximal balloon angioplasty plus aggressive medical management (n = 249) or aggressive medical management alone (n = 252). Aggressive medical management included dual antiplatelet therapy for the first 90 days and risk factor control. Main Outcomes and Measures: The primary outcome was a composite of any stroke or death within 30 days after enrollment or after balloon angioplasty of the qualifying lesion or any ischemic stroke in the qualifying artery territory or revascularization of the qualifying artery after 30 days through 12 months after enrollment. Results: Among 512 randomized patients, 501 were confirmed eligible (mean age, 58.0 years; 158 [31.5%] women) and completed the trial. The incidence of the primary outcome was lower in the balloon angioplasty group than the medical management group (4.4% vs 13.5%; hazard ratio, 0.32 [95% CI, 0.16-0.63]; P < .001). The respective rates of any stroke or all-cause death within 30 days were 3.2% and 1.6%. Beyond 30 days through 1 year after enrollment, the rates of any ischemic stroke in the qualifying artery territory were 0.4% and 7.5%, respectively, and revascularization of the qualifying artery occurred in 1.2% and 8.3%, respectively. The rate of symptomatic intracranial hemorrhage in the balloon angioplasty and medical management groups was 1.2% and 0.4%, respectively. In the balloon angioplasty group, procedural complications occurred in 17.4% of patients and arterial dissection occurred in 14.5% of patients. Conclusions and Relevance: In patients with sICAS, balloon angioplasty plus aggressive medical management, compared with aggressive medical management alone, statistically significantly lowered the risk of a composite outcome of any stroke or death within 30 days or an ischemic stroke or revascularization of the qualifying artery after 30 days through 12 months. The findings suggest that balloon angioplasty plus aggressive medical management may be an effective treatment for sICAS, although the risk of stroke or death within 30 days of balloon angioplasty should be considered in clinical practice. Trial Registration: ClinicalTrials.gov Identifier: NCT03703635.

Derivation, external and clinical validation of a deep learning approach for detecting intracranial hypertension.

Increased intracranial pressure (ICP) ≥15 mmHg is associated with adverse neurological outcomes, but needs invasive intracranial monitoring. Using the publicly available MIMIC-III Waveform Database (2000-2013) from Boston, we developed an artificial intelligence-derived biomarker for elevated ICP (aICP) for adult patients. aICP uses routinely collected extracranial waveform data as input, reducing the need for invasive monitoring. We externally validated aICP with an independent dataset from the Mount Sinai Hospital (2020-2022) in New York City. The AUROC, accuracy, sensitivity, and specificity on the external validation dataset were 0.80 (95% CI, 0.80-0.80), 73.8% (95% CI, 72.0-75.6%), 73.5% (95% CI 72.5-74.5%), and 73.0% (95% CI, 72.0-74.0%), respectively. We also present an exploratory analysis showing aICP predictions are associated with clinical phenotypes. A ten-percentile increment was associated with brain malignancy (OR = 1.68; 95% CI, 1.09-2.60), intracerebral hemorrhage (OR = 1.18; 95% CI, 1.07-1.32), and craniotomy (OR = 1.43; 95% CI, 1.12-1.84; P < 0.05 for all).

Expanding the repertoire of GalNAc analogues for cell-specific bioorthogonal tagging of glycoproteins.

Glycosylation is a ubiquitous modification of proteins, necessitating approaches for its visualization and characterization. Bioorthogonally tagged monosaccharides have been instrumental to this end, offering a chemical view into the cell biology of glycans. Understanding the use of such monosaccharides by cellular biosynthetic pathways has expanded their applicability in cell biology, for instance through the strategy named Bio-Orthogonal Cell-specific TAgging of Glycoproteins (BOCTAG). Here, we show that the cellular use of two azide-tagged analogues of the monosaccharide N-acetylgalactosamine (GalNAzMe and GalNPrAz) can be promoted through expression of two biosynthetic enzymes. More precisely, cellular expression of the bacterial kinase NahK and the engineered human pyrophosphorylase AGX1F383A led to biosynthesis of the corresponding activated nucleotide-sugars and subsequent bioorthogonal tagging of the cellular glycoproteome. We explore the use of both sugars for BOCTAG, demonstrating the visualization of cell surface glycosylation tagged with GalNPrAz in a specific cell line in a co-culture system. Our work adds to the toolbox of glycoprotein analysis in biomedicine.

Better cardiovascular health is associated with slowed clinical progression in autosomal dominant frontotemporal lobar degeneration variant carriers.

INTRODUCTION: Cardiovascular health is important for brain aging, yet its role in the clinical manifestation of autosomal dominant or atypical forms of dementia has not been fully elucidated. We examined relationships between Life's Simple 7 (LS7) and clinical trajectories in individuals with autosomal dominant frontotemporal lobar degeneration (FTLD). METHODS: Two hundred forty-seven adults carrying FTLD pathogenic genetic variants (53% asymptomatic) and 189 non-carrier controls completed baseline LS7, and longitudinal neuroimaging and neuropsychological testing. RESULTS: Among variant carriers, higher baseline LS7 is associated with slower accumulation of frontal white matter hyperintensities (WMHs), as well as slower memory and language declines. Higher baseline LS7 associated with larger baseline frontotemporal volume, but not frontotemporal volume trajectories. DISCUSSION: Better baseline cardiovascular health related to slower cognitive decline and accumulation of frontal WMHs in autosomal dominant FTLD. Optimizing cardiovascular health may be an important modifiable approach to bolster cognitive health and brain integrity in FTLD. HIGHLIGHTS: Better cardiovascular health associates with slower cognitive decline in frontotemporal lobar degeneration (FTLD). Lifestyle relates to the accumulation of frontal white matter hyperintensities in FTLD. More optimal cardiovascular health associates with greater baseline frontotemporal lobe volume. Optimized cardiovascular health relates to more favorable outcomes in genetic dementia.

Transjugular antegrade transvenous obliteration, with and without portal decompression, for management of rectal variceal hemorrhage.

PURPOSE: To report antegrade transvenous obliteration, with or without concurrent portosystemic shunt creation, for the treatment of hemorrhagic rectal varices. MATERIALS AND METHODS: Eight patients, including five (62.5%) females and three (37.5%) males, with mean age of 55.8 ± 13.8 years (range: 30-70 years), underwent transjugular-approach antegrade transvenous obliteration of rectal varices, with or without portosystemic shunt creation. Demographic data, procedural details, technical success of variceal obliteration, clinical success, adverse events, and follow-up outcomes were retrospectively recorded. Clinical success was defined as resolution of rectal hemorrhage. RESULTS: Portal venous access was achieved via a transjugular intrahepatic approach in all patients. The inferior mesenteric vein was selected, and foamy sclerosant (1:2:3 mixture by volume of ethiodized oil: sodium tetradecyl sulfate: air) was injected into the rectal varices with antegrade balloon occlusion in seven (87.5%) and without balloon occlusion in one (12.5%). Five of eight (62.5%) patients underwent concomitant transjugular intrahepatic portosystemic shunt (TIPS) creation (mean diameter 8.4 ± 0.9-mm) immediately following transvenous obliteration. Technical success of variceal obliteration was achieved in all patients. There were no immediate post-procedural adverse events. There were no reported occurrences of rectal ischemia, perforation, or stricture following obliteration. Two (40%) of the patients who underwent concomitant TIPS creation developed hepatic encephalopathy within 30 days of the procedure, which was medically managed. Clinical resolution of hemorrhage was achieved in all patients with no recurrent rectal variceal hemorrhage during mean follow-up of 666 ± 396 days (range: 14 - 1,224 days). CONCLUSION: Transvenous obliteration, with or without concurrent TIPS creation, is feasible with promising results for the management of rectal variceal hemorrhage.