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Co-existing chronic hepatitis B virus (CHB) infection and metabolic dysfunction associated steatotic liver disease (MASLD) can exert complex effects on hepatic metabolism, requiring mechanistic study. CHB participants were assessed for MASLD and the impact of hepatic steatosis/metabolic syndrome (MetS) on novel viral and immunological markers. In this prospective, cohort study, untreated CHB subjects were assessed for liver disease by non-invasive tests (i.e. FibroScan, controlled attenuation parameter, CAP). Subjects were tested for cytokines and IFN-γ ELISPOT assay to HBV Surface (S) and Core (C) proteins. Standard HBV serological, exploratory biomarkers and deep sequencing of HBV S and C genes were performed. In 53 subjects (median age 45 years [SD = 10.6], 35% F, 56% Asian, 20% Black, 3% White), 94% (50) HBeAg negative, 63% genotype B/C, mean HBV DNA 3.2 log10 IU/mL (SD = 1.8), quantitative HBsAg 2.9 log10 IU/mL (SD = 1.2) and HBV pgRNA 2.1 log10 copies/mL (SD = 1.3). In enrolled subjects, the mean ALT was 41.9 U/L (SD = 24.0), FibroScan was 5.7 kPa (SD = 1.9) and CAP was 306.4 dB/m (SD = 49.0). The mean BMI was 28.2 kg/m2 (SD = 4.2), 20% (11/53) had diabetes, 35% (19/53) dyslipidaemia and 24% (13/53) hypertension. Subjects with MetS and steatosis showed lower HBV markers (p < .01), higher HBV S diversity (p = .02) and greater frequency of HBV variants associated with host-anti-viral immune escape. Pro-inflammatory cytokine levels and HBV-specific cellular responses were higher in participants with hepatic steatosis. In CHB, MASLD/hepatic steatosis was associated with HBV variants and systemic immune responses potentially impacting liver disease progression despite low-level viraemia.
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Rare recurrent copy number variants (CNVs) at chromosomal loci 22q11.2 and 16p11.2 are genetic disorders with lifespan risk for neuropsychiatric disorders. Microdeletions and duplications are associated with neurocognitive deficits, yet few studies compared these groups using the same measures to address confounding measurement differences. We report a prospective international collaboration applying the same computerized neurocognitive assessment, the Penn Computerized Neurocognitive Battery (CNB), administered in a multi-site study on rare genomic disorders: 22q11.2 deletions (n = 492); 22q11.2 duplications (n = 106); 16p11.2 deletion (n = 117); and 16p11.2 duplications (n = 46). Domains examined include executive functions, episodic memory, complex cognition, social cognition, and psychomotor speed. Accuracy and speed for each domain were included as dependent measures in a mixed-model repeated measures analysis. Locus (22q11.2, 16p11.2) and Copy number (deletion/duplication) were grouping factors and Measure (accuracy, speed) and neurocognitive domain were repeated measures factors, with Sex and Site as covariates. We also examined correlation with IQ. We found a significant Locus × Copy number × Domain × Measure interaction (p = 0.0004). 22q11.2 deletions were associated with greater performance accuracy deficits than 22q11.2 duplications, while 16p11.2 duplications were associated with greater specific deficits than 16p11.2 deletions. Duplications at both loci were associated with reduced speed compared to deletions. Performance profiles differed among the groups with particularly poor memory performance of the 22q11.2 deletion group while the 16p11.2 duplication group had greatest deficits in complex cognition. Average accuracy on the CNB was moderately correlated with Full Scale IQ. Deletions and duplications of 22q11.2 and 16p11.2 have differential effects on accuracy and speed of neurocognition indicating locus specificity of performance profiles. These profile differences can help inform mechanistic substrates to heterogeneity in presentation and outcome, and can only be established in large-scale international consortia using the same neurocognitive assessment. Future studies could aim to link performance profiles to clinical features and brain function.
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BACKGROUND: A sizeable proportion of pathogenic genetic variants identified in young children tested for congenital differences are associated with neurodevelopmental psychiatric disorders (NPD). In this growing group, a genetic diagnosis often precedes the emergence of diagnosable developmental concerns. Here, we describe DAGSY (Developmental Assessment of Genetically Susceptible Youth), a novel interdisciplinary 'genetic-diagnosis-first' clinic integrating psychiatric, psychological and genetic expertise, and report our first observations and feedback from families and referring clinicians. METHODS: We retrieved data on referral sources and indications, genetic and NPD diagnoses and recommendations for children seen at DAGSY between 2018 and 2022. Through a survey, we obtained feedback from twenty families and eleven referring clinicians. RESULTS: 159 children (mean age 10.2 years, 57.2% males) completed an interdisciplinary (psychiatry, psychology, genetic counselling) DAGSY assessment during this period. Of these, 69.8% had a pathogenic microdeletion or microduplication, 21.5% a sequence-level variant, 4.4% a chromosomal disorder, and 4.4% a variant of unknown significance with emerging evidence of pathogenicity. One in four children did not have a prior NPD diagnosis, and referral to DAGSY was motivated by their genetic vulnerability alone. Following assessment, 76.7% received at least one new NPD diagnosis, most frequently intellectual disability (24.5%), anxiety (20.7%), autism spectrum (18.9%) and specific learning (16.4%) disorder. Both families and clinicians responding to our survey expressed satisfaction, but also highlighted some areas for potential improvement. CONCLUSIONS: DAGSY addresses an unmet clinical need for children identified with genetic variants that confer increased vulnerability for NPD and provides a crucial platform for research in this area. DAGSY can serve as a model for interdisciplinary clinics integrating child psychiatry, psychology and genetics, addressing both clinical and research needs for this emerging population.
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Trastornos Mentales , Trastornos del Neurodesarrollo , Humanos , Niño , Trastornos del Neurodesarrollo/genética , Femenino , Masculino , Trastornos Mentales/genética , Predisposición Genética a la Enfermedad , AdolescenteRESUMEN
Background: Phenytoin (PHT) has been approved for the treatment of epilepsy. It belongs to the category of medications with a limited therapeutic window and requires therapeutic drug monitoring (TDM). PTH has been observed to induce a variety of Adverse drug reactions (ADRs) including ataxia, dystonia, nystagmus, dyskinesia, etc. Phenytoin-induced ataxia is an uncommonly observed ADR of Phenytoin whose reports are extremely limited. Case: Herein, we present a case report of a 16-year-old Asian patient with a past history of epilepsy that was admitted to a tertiary care hospital due to the development of ataxia, giddiness, and vomiting when taking Phenytoin in addition to Oxcarbazepine, Clobazam, and Levetiracetam to treat seizures. On admission, Magnetic resonance imaging (MRI) findings revealed bilateral variable cerebrospinal fluid (CSF) lesions in the parieto-occipital region of the periventricular area (periventricular leukomalacia). Additionally, serum Phenytoin levels were observed to be in the toxic range (40 µg/mL) due to which physicians confirmed the ADR to be due to Phenytoin toxicity. Thus, the Phenytoin drug was discontinued in the patient gradually and he was continued on clobazam, oxcarbazepine, and brivaracetam which led to reversal of the ADR in the patient. Conclusion: In this case, ataxia resulted from Phenytoin overdose, as confirmed by MRI and serum tests suggesting that TDM of Phenytoin is essential to prevent ADRs. Given the scarcity of ataxia cases caused by Phenytoin, awareness is lacking within the scientific community. Our aim is to provide insights to promote better monitoring and patient-centered treatment outcomes for epileptic patients.
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Full-spectrum flow cytometry has increased antibody-based multiplexing, yet further increases remain potentially impactful. We recently proposed how fluorescence multiplexing using spectral imaging and combinatorics (MuSIC) could do so using tandem dyes and an oligo-based antibody labeling method. In this work, we found that such labeled antibodies had significantly lower signal intensities than conventionally labeled antibodies in human cell experiments. To improve signal intensity, we tested moving the fluorophores from the original external (ext.) 5' or 3' end-labeled orientation to internal (int.) fluorophore modifications. Cell-free spectrophotometer measurements showed a â¼6-fold signal intensity increase of the new int. configuration compared to the previous ext. configuration. Time-resolved fluorescence and fluorescence correlation spectroscopy showed that the â¼3-fold brightness difference is due to static quenching most likely by the oligo or solution in the ext. configuration. Spectral flow cytometry experiments using peripheral blood mononuclear cells show int. MuSIC probe-labeled antibodies (i) retained increased signal intensity while having no significant difference in the estimated % of CD8+ lymphocytes and (ii) labeled with Atto488, Atto647, and Atto488/647 combinations can be demultiplexed in triple-stained samples. The antibody labeling approach is general and can be broadly applied to many biological and diagnostic applications where spectral detection is available.
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Anticuerpos , Citometría de Flujo , Colorantes Fluorescentes , Humanos , Colorantes Fluorescentes/química , Citometría de Flujo/métodos , Anticuerpos/inmunología , Anticuerpos/química , Leucocitos Mononucleares/inmunología , Espectrometría de FluorescenciaRESUMEN
Background: Hepatitis B virus (HBV)/Hepatitis D Virus (HDV) co-infection increases the risk of severe liver disease compared to HBV mono-infection. Adaptive immune responses to HDV are weakly detectable, and the involvement of innate immunity in the progression of HDV-related liver fibrosis is suggested. We hypothesize that an overall innate immune activation in HBV/HDV co-infection plays a role in liver disease progression and also impacts virus specific T cell response. Methods: Sixteen HBV/HDV-co-infected-patients (median age 42y/7F/6 Asian/4 White/6 Black/15 HBeAg-) and 8 HBV monoinfected-patients (median age 39y/4F/4 Asian/3 Black/1 White/HBeAg-) with median follow-up of 5 years were enrolled. Liver fibrosis was assessed by liver stiffness measurement (LSM, FibroScan®). Proliferation of CD3 + CD4+ T cells in response to viral antigens using CFSE assays and cytokine secreting monocytes was analyzed by flow cytometry. Results: Of 16 HBV/HDV, 11 were HDV-RNA+ (HBV-DNA 0-1,040 IU/mL), 5/11 Interferon (IFN) + Nucleos/tide Analog (NA), 3/11 NA monotherapy, median ALT 77 U/L at the time of sample collection, median LSM of 9.8. In 5 HDV RNA-, median HBV DNA 65 IU/mL, 4/5 prior IFN and/or NA, ALT 31 U/L, and median LSM 8.5 kPa. In 8 HBV controls, median HBV-DNA, ALT, LSM was 69 IU/mL, 33 U/L,5 kPa, respectively. PBMC stimulation with HBV core antigen (HBcAg) and HDV antigen (HDAg) showed weaker CD3 + CD4 + T-cell proliferation in HDV-RNA+ vs. HDV RNA- and HBV-mono-infected patients (p < 0.05). In HDV-RNA+ patients, a correlation between ALT and TNF-α (r = 0.76, p = 0.008), higher IL-10 levels and increased proportion of CD14 + TNF-α+ cells were found. Conclusion: In summary, during HBV/HDV coinfection, HDV RNA+ patients had weaker HBV and HDV specific responses, associated with increased TNF-α + monocytes irrespective of IFN treatment.
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Introduction: Serum hepatitis B virus (HBV) RNA is a promising new biomarker to manage and predict clinical outcomes of chronic hepatitis B (CHB) infection. However, the HBV serum transcriptome within encapsidated particles, which is the biomarker analyte measured in serum, remains poorly characterized. This study aimed to evaluate serum HBV RNA transcript composition and proportionality by PCR-cDNA nanopore sequencing of samples from CHB patients having varied HBV genotype (gt, A to F) and HBeAg status. Methods: Longitudinal specimens from 3 individuals during and following pregnancy (approximately 7 months between time points) were also investigated. HBV RNA extracted from 16 serum samples obtained from 13 patients (73.3% female, 84.6% Asian) was sequenced and serum HBV RNA isoform detection and quantification were performed using three bioinformatic workflows; FLAIR, RATTLE, and a GraphMap-based workflow within the Galaxy application. A spike-in RNA variant (SIRV) control mix was used to assess run quality and coverage. The proportionality of transcript isoforms was based on total HBV reads determined by each workflow. Results: All chosen isoform detection workflows showed high agreement in transcript proportionality and composition for most samples. HBV pregenomic RNA (pgRNA) was the most frequently observed transcript isoform (93.8% of patient samples), while other detected transcripts included pgRNA spliced variants, 3' truncated variants and HBx mRNA, depending on the isoform detection method. Spliced variants of pgRNA were primarily observed in HBV gtB, C, E, or F-infected patients, with the Sp1 spliced variant detected most frequently. Twelve other pgRNA spliced variant transcripts were identified, including 3 previously unidentified transcripts, although spliced isoform identification was very dependent on the workflow used to analyze sequence data. Longitudinal sampling among pregnant and post-partum antiviral-treated individuals showed increasing proportions of 3' truncated pgRNA variants over time. Conclusions: This study demonstrated long-read sequencing as a promising tool for the characterization of the serum HBV transcriptome. However, further studies are needed to better understand how serum HBV RNA isoform type and proportion are linked to CHB disease progression and antiviral treatment response.
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BACKGROUND: Dyskinesia is a movement disorder categorized by involuntary movement of muscle. Although dyskinesia can be brought on by taking medications, it can also be a symptom of a variety of diseases. Antiepileptic drug-induced involuntary movements have been well researched. Rare reports have been made for dyskinesia, a type of dystonia caused by phenytoin. The mechanism of its occurrence must be succinctly studied. CASE PRESENTATION: A 53-year-old Asian patient taking phenytoin (100 mg twice daily) experienced symptoms of perioral muscle involuntary movement, impaired speech, and generalized tremors and was admitted to the hospital. Brain magnetic resonance imaging showed significant development of encephalomalacia and porencephaly. The serum phenytoin levels were in the toxic range (33 g/ml). These were suggestive of phenytoin-induced dyskinesia. Levetiracetam and clonazepam were initiated, and the patient showed significant improvement in the symptoms. CONCLUSION: This case presented a substantial reference value for the differential diagnosis and treatment prognosis of phenytoin-induced dyskinesia. The phenytoin-induced dyskinesia in this patient was successfully reversed with prompt identification and treatment. According to the case study's findings, such people may benefit from periodic therapeutic drug monitoring.
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Discinesia Inducida por Medicamentos , Distonía , Humanos , Persona de Mediana Edad , Fenitoína/efectos adversos , Discinesia Inducida por Medicamentos/etiología , Discinesia Inducida por Medicamentos/tratamiento farmacológico , Anticonvulsivantes/efectos adversos , Levetiracetam/uso terapéuticoRESUMEN
Systematic, genome-scale genetic screens have been instrumental for elucidating genotype-phenotype relationships, but approaches for probing genetic interactions have been limited to at most â¼100 pre-selected gene combinations in mammalian cells. Here, we introduce a theory for high-throughput genetic interaction screens. The theory extends our recently developed Multiplexing using Spectral Imaging and Combinatorics (MuSIC) approach to propose â¼105 spectrally unique, genetically encoded MuSIC barcodes from 18 currently available fluorescent proteins. Simulation studies based on constraints imposed by spectral flow cytometry equipment suggest that genetic interaction screens at the human genome-scale may be possible if MuSIC barcodes can be paired to guide RNAs. While experimental testing of this theory awaits, it offers transformative potential for genetic perturbation technology and knowledge of genetic function. More broadly, the availability of a genome-scale spectral barcode library for non-destructive identification of single cells could find more widespread applications such as traditional genetic screening and high-dimensional lineage tracing.
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Ensayos Analíticos de Alto Rendimiento , Mamíferos , Animales , Humanos , Clonación MolecularRESUMEN
While full-spectrum flow cytometry has increased antibody-based multiplexing, yet further increases remain potentially impactful. We recently proposed how fluorescence Multiplexing using Spectral Imaging and Combinatorics (MuSIC) could do so using tandem dyes and an oligo-based antibody labeling method. In this work, we found that such labeled antibodies had significantly lower signal intensity than conventionally-labeled antibodies in human cell experiments. To improve signal intensity, we tested moving the fluorophores from the original external (ext.) 5' or 3' end-labeled orientation to internal (int.) fluorophore modifications. Cell-free spectrophotometer measurements showed a ~6-fold signal intensity increase of the new int. configuration compared to the previous ext. configuration. Time-resolved fluorescence spectroscopy and fluorescence correlation spectroscopy showed that ~3-fold brightness difference is due to static quenching. Spectral flow cytometry experiments using peripheral blood mononuclear cells stained with anti-CD8 antibodies showed that int. MuSIC probe-labeled antibodies have signal intensity equal to or greater than conventionally-labeled antibodies with similar estimated proportion of CD8+ lymphocytes. The antibody labeling approach is general and can be broadly applied to many biological and diagnostic applications.
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Left ventricular assist devices (LVAD) can be utilized for heart failure patients as a bridge to transplant, bridge to destination, or bridge to recovery. Given the lack of a universally accepted consensus for assessing myocardial recovery, techniques and strategies in LVAD explantation also vary. In addition, the incidence of LVAD explantation remains relatively low, and surgical techniques of explantation continue to be areas of interest. Our approach using a felt-plug Dacron technique is an effective way to preserve left ventricular geometry and cardiac function.
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Insuficiencia Cardíaca , Corazón Auxiliar , Humanos , Estudios Retrospectivos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/cirugía , Miocardio , Remoción de Dispositivos/métodosRESUMEN
INTRODUCTION: Frequent right ventricular (RV) pacing is associated with cardiomyopathy. The impact of RV pacing on left ventricular (LV) global longitudinal strain (GLS) and clinical outcomes is unclear. METHODS: We analyzed GLS via two-dimensional speckle tracking and LV ejection fraction (EF) on pre- and post-implantation transthoracic echocardiograms of patients undergoing dual chamber pacemaker implantation. We collected long-term data on strain, LVEF, and clinical outcomes. RESULTS: One hundred and ten patients (mean age 76 ± 12 years; 59 [54%] female) were followed for mean 23 ± 17 months. Mean baseline LVEF was 58 ± 11% and mean GLS was -17 ± 4%. Twenty-four (22%) patients had an absolute decrease in LVEF > 10% and 43 (39%) patients had a relative reduction of GLS > 15%. Among patients with a reduction of GLS, a larger proportion of patients had RV pacing burden ≥20% (67% vs. 46%; p = .048). Compared to patients without GLS reduction, more patients with a reduction in GLS reached a composite endpoint of HF hospitalization, CRT upgrade or death (47% vs. 16%; p = .001). CONCLUSION: Reduction in LV GLS was seen in nearly four in 10 patients undergoing pacemaker implantation and was significantly associated with increased RV pacing burden. LV GLS reduction was associated with increased risk of adverse outcomes. LV GLS may have utility in predicting outcomes among patients with RV pacing.
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Insuficiencia Cardíaca , Marcapaso Artificial , Disfunción Ventricular Izquierda , Humanos , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Tensión Longitudinal Global , Marcapaso Artificial/efectos adversos , Función Ventricular Izquierda , Ecocardiografía/métodos , Insuficiencia Cardíaca/terapia , Insuficiencia Cardíaca/complicaciones , Volumen SistólicoRESUMEN
The oxidation of various aryl and aliphatic thiols with the commercially available and environmentally benign reagent Bobbitt's salt (1) has been investigated. The reaction affords the corresponding disulfide products in good to excellent yields (71-99%) and can be accomplished in water, methanol, or acetonitrile solvent. Moreover, the process is highly chemoselective, tolerating traditionally oxidation-labile groups such as free amines and alcohols. Combined experimental and computational studies reveal that the oxidation takes place via a polar two-electron process with concomitant and unexpected deoxygenation of the oxoammonium cation through homolysis of the weak N-O bond, differing from prototypical radical-based thiol couplings. This unusual consumption of the oxidant has significant implications for the development of new nitroxide-based radical traps for probing S-centered radicals, the advancement of new electrochemical or catalytic processes involving nitroxide/oxoammonium salt redox couples, and applications to biological systems.
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Rare recurrent copy number variants (CNVs) at chromosomal loci 22q11.2 and 16p11.2 are among the most common rare genetic disorders associated with significant risk for neuropsychiatric disorders across the lifespan. Microdeletions and duplications in these loci are associated with neurocognitive deficits, yet there are few studies comparing these groups using the same measures. We address this gap in a prospective international collaboration applying the same computerized neurocognitive assessment. The Penn Computerized Neurocognitive Battery (CNB) was administered in a multi-site study on rare genomic disorders: 22q11.2 deletion (n = 397); 22q11.2 duplication (n = 77); 16p11.2 deletion (n = 94); and 16p11.2 duplication (n = 26). Domains examined include executive functions, episodic memory, complex cognition, social cognition, and sensori-motor speed. Accuracy and speed for each neurocognitive domain were included as dependent measures in a mixed-model repeated measures analysis, with locus (22q11.2, 16p11.2) and copy number (deletion/duplication) as grouping factors and neurocognitive domain as a repeated measures factor, with age and sex as covariates. We also examined correlation with IQ and site effects. We found that 22q11.2 deletions were associated with greater deficits in overall performance accuracy than 22q11.2 duplications, while 16p11.2 duplications were associated with greater deficits than 16p11.2 deletions. Duplications at both loci were associated with reduced speed. Performance profiles differed among the groups with particularly poor performance of 16p11.2 duplication on non-verbal reasoning and social cognition. Average accuracy on the CNB was moderately correlated with Full Scale IQ. No site effects were observed. Deletions and duplications of 22q11.2 and 16p11.2 have varied effects on neurocognition indicating locus specificity, with performance profiles differing among the groups. These profile differences can help inform mechanistic substrates to heterogeneity in presentation and outcome. Future studies could aim to link performance profiles to clinical features and brain function.
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PURPOSE: There is a need for effective and affordable treatments that achieve hepatitis B virus (HBV) functional cure and prevent long-term complications. The use of immune-modulators combined with HBV antivirals is a promising therapeutic strategy to achieve these goals. Based on ribavirin (RBV) monotherapy data, we hypothesized that RBV could improve virological responses when used in combination with tenofovir. Methods: In this randomized, open label, controlled pilot trial, we evaluated RBV (n=4) dosed for the initial 24 weeks of treatment versus no RBV (n=4) in tenofovir recipients dosed over 48 weeks. Results: Although well tolerated and safe in combination with tenofovir, RBV demonstrated no beneficial effects on virologic, biochemical or immunological markers of chronic HBV infection over 48 weeks of serial evaluation. Conclusions: Our data does not suggest a HBV-specific immunomodulatory effect or an impact of RBV on HBV virological and antigen suppression.
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Antivirales , Virus de la Hepatitis B , Antivirales/farmacología , Antivirales/uso terapéutico , Ribavirina/uso terapéutico , Ribavirina/farmacología , Proyectos Piloto , Nucleótidos/farmacología , Resultado del Tratamiento , Quimioterapia Combinada , Tenofovir/uso terapéutico , Tenofovir/efectos adversosRESUMEN
Pancreatitis usually presents with characteristic abdominal pain, radiological findings, and elevated lipase. The presence of jaundice may hint at a biliary etiology; however, it is not always present. We hypothesized that the presence of jaundice is associated with worse outcomes in patients admitted with pancreatitis. We conducted a retrospective analysis using the National Inpatient Sample, inquiring about patients admitted with pancreatitis with and without jaundice between October 2015 and December 2017. The primary outcome was in-hospital mortality in patients admitted for pancreatitis with and without jaundice. Secondary outcomes were the median length of stay, hospitalization cost, the incidence of ventilator-dependent respiratory failure (VDRF), acute respiratory distress syndrome (ARDS), sepsis, septic shock, dehydration and electrolyte disturbances, and ascites. A total of 1,267,744 patients were admitted with pancreatitis from October 2015 to December 2017. Among them, 8855 (0.7%) had concomitant jaundice on presentation. In-hospital mortality in this group was 4.3%. The patients with pancreatitis and jaundice had higher odds of in-hospital mortality (adjusted odds ratio [aOR]: 1.51, 99% CI 1.35-1.68, p < 0.0001) as compared to those without jaundice. Patients with jaundice showed a significantly higher incidence of sepsis (15.2% vs. 9.6%, p < 0.0001), septic shock (4.1% vs. 2.9%, p < 0.0001), ascites (6.5% vs. 3.1%, p < 0.0001), and dehydration and electrolyte disorders (47.6% vs. 43.8%, p < 0.0001). Patients with jaundice also had higher total hospital costs ($11,412 vs. $7893, p < 0.0001). There was no statistical difference in ARDS, VDRF, and median length of stay. In conclusion, patients admitted for pancreatitis with jaundice had worse outcomes, including in-hospital mortality and complications, compared to those without jaundice.
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Ambulatory hemodynamic monitoring has demonstrated the ability to reduce heart failure-related hospitalization, regardless of left ventricular ejection fraction; however, real-world data in a Veterans Affairs patient population are limited. The present study retrospectively reviewed 53 patients with New York Heart Association class III heart failure, regardless of left ventricular ejection fraction, implanted with a pulmonary artery pressure sensor (CardioMEMS) at our single Veterans Affairs institution. Heart failure-related hospitalizations were assessed in patients for 6 and 12 months after the implantation of the device and compared with the 6- and 12- month periods before implantation in the same patient cohort. Pulmonary arterial pressures and medication doses were also recorded at baseline, 6- months, and 12- months and procedural safety data were also assessed. Implantation of a remote pulmonary artery pressure sensor was associated with a 52% (95% confidence interval 30% to 68%, p <0.001) and a 44% (95% confidence interval 24% to 59%, p <0.001) reduction in heart failure-related hospitalization at 6 and 12 months after implant, respectively, compared with the 6- and 12-month preimplant periods. Mean pulmonary arterial pressures also demonstrated significant reductions from baseline to 6 and 12 months after implant. A total of 3 procedure-related adverse events were noted. In conclusion, pulmonary artery pressure sensor implantation is relatively safe and associated with significant reductions in heart failure-related hospitalization and decreased mean pulmonary artery pressures in patients within the Veterans Affairs system with New York Heart Association class III symptoms, regardless of ejection fraction.
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Insuficiencia Cardíaca , Monitorización Hemodinámica , Veteranos , Humanos , Volumen Sistólico , Arteria Pulmonar , Monitoreo Ambulatorio de la Presión Arterial , Insuficiencia Cardíaca/diagnóstico , Estudios Retrospectivos , Función Ventricular Izquierda , Atención a la SaludRESUMEN
BACKGROUND: Hepatitis B virus (HBV) nucleos(t)ide analog (NA) therapy reduces liver disease but requires prolonged therapy to achieve hepatitis B surface antigen (HBsAg) loss. There is limited North American real-world data using non-invasive tools for fibrosis assessment and few have compared 1st generation NA or lamivudine (LAM) to tenofovir disoproxil fumarate (TDF). AIM: To assess impact of NA on virological response and fibrosis regression using liver stiffness measurement (LSM) (i.e., FibroScan®). METHODS: Retrospective, observational cohort study from the Canadian HBV Network. Data collected included demographics, NA, HBV DNA, alanine aminotransferase (ALT), and LSM. Patients were HBV monoinfected patients, treatment naïve, and received 1 NA with minimum 1 year follow-up. RESULTS: In 465 (median 49 years, 37% female, 35% hepatitis B e antigen+ at baseline, 84% Asian, 6% White, and 9% Black). Percentage of 64 (n = 299) received TDF and 166 were LAM-treated with similar median duration of 3.9 and 3.7 years, respectively. The mean baseline LSM was 11.2 kPa (TDF) vs 8.3 kPa (LAM) (P = 0.003). At 5-year follow-up, the mean LSM was 7.0 kPa in TDF vs 6.7 kPa in LAM (P = 0.83). There was a significant difference in fibrosis regression between groups (i.e., mean -4.2 kPa change in TDF and -1.6 kPa in LAM, P < 0.05). The last available data on treatment showed that all had normal ALT, but more TDF patients were virologically suppressed (< 10 IU/mL) (n = 170/190, 89%) vs LAM-treated (n = 35/58, 60%) (P < 0.05). None cleared HBsAg. CONCLUSION: In this real-world North American study, approximately 5 years of NA achieves liver fibrosis regression rarely leads to HBsAg loss.
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Hepatitis B Crónica , Hepatitis B , Alanina Transaminasa , Antivirales/uso terapéutico , Canadá , ADN Viral/uso terapéutico , Femenino , Hepatitis B/diagnóstico , Hepatitis B/tratamiento farmacológico , Antígenos de Superficie de la Hepatitis B , Antígenos e de la Hepatitis B , Virus de la Hepatitis B/genética , Hepatitis B Crónica/diagnóstico , Hepatitis B Crónica/tratamiento farmacológico , Humanos , Lamivudine/uso terapéutico , Cirrosis Hepática/diagnóstico por imagen , Cirrosis Hepática/tratamiento farmacológico , Masculino , Estudios Retrospectivos , Tenofovir/uso terapéuticoRESUMEN
Precision medicine has greatly aided in improving health outcomes using earlier diagnosis and better prognosis for chronic diseases. It makes use of clinical data associated with the patient as well as their multi-omics/genomic data to reach a conclusion regarding how a physician should proceed with a specific treatment. Compared to the symptom-driven approach in medicine, precision medicine considers the critical fact that all patients do not react to the same treatment or medication in the same way. When considering the intersection of traditionally distinct arenas of medicine, that is, artificial intelligence, healthcare, clinical genomics, and pharmacogenomics-what ties them together is their impact on the development of precision medicine as a field and how they each contribute to patient-specific, rather than symptom-specific patient outcomes. This study discusses the impact and integration of these different fields in the scope of precision medicine and how they can be used in preventing and predicting acute or chronic diseases. Additionally, this study also discusses the advantages as well as the current challenges associated with artificial intelligence, healthcare, clinical genomics, and pharmacogenomics.
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Patients with both a prosthetic aortic valve and prolonged left ventricular assist device support can develop rapid deterioration of their valve prosthesis. In patients with myocardial recovery who are undergoing explantation of their ventricular assist device, preoperative and intraoperative evaluation of the valve prosthesis should be performed to ensure adequate function. (Level of Difficulty: Advanced.).