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1.
Gastroenterology ; 164(6): 906-920, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36736437

RESUMEN

BACKGROUND & AIMS: The use of computer-aided detection (CAD) increases the adenoma detection rates (ADRs) during colorectal cancer (CRC) screening/surveillance. This study aimed to evaluate the requirements for CAD to be cost-effective and the impact of CAD on adenoma detection by endoscopists with different ADRs. METHODS: We developed a semi-Markov microsimulation model to compare the effectiveness of traditional colonoscopy (mean ADR, 26%) to colonoscopy with CAD (mean ADR, 37%). CAD was modeled as having a $75 per-procedure cost. Extensive 1-way sensitivity and threshold analysis were performed to vary cost and ADR of CAD. Multiple scenarios evaluated the potential effect of CAD on endoscopists' ADRs. Outcome measures were reported in incremental cost-effectiveness ratios, with a willingness-to-pay threshold of $100,000/quality-adjusted life year. RESULTS: When modeling CAD improved ADR for all endoscopists, the CAD cohort had 79 and 34 fewer lifetime CRC cases and deaths, respectively, per 10,000 persons. This scenario was dominant with a cost savings of $143 and incremental effectiveness of 0.01 quality-adjusted life years. Threshold analysis demonstrated that CAD would be cost-effective up to an additional cost of $579 per colonoscopy, or if it increases ADR from 26% to at least 30%. CAD reduced CRC incidence and mortality when limited to improving ADRs for low-ADR endoscopists (ADR <25%), with 67 fewer CRC cases and 28 CRC deaths per 10,000 persons compared with traditional colonoscopy. CONCLUSIONS: As CAD is implemented clinically, it needs to improve mean ADR from 26% to at least 30% or cost less than $579 per colonoscopy to be cost-effective when compared with traditional colonoscopy. Further studies are needed to understand the impact of CAD when used in community practice.


Asunto(s)
Adenoma , Neoplasias Colorrectales , Humanos , Análisis Costo-Beneficio , Colonoscopía , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/epidemiología , Adenoma/diagnóstico , Detección Precoz del Cáncer , Computadores
2.
Opt Express ; 32(12): 21909-21924, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38859533

RESUMEN

Mueller matrices provide a complete description of a medium's response to excitation by polarized light, and their characterization is important across a broad range of applications from ellipsometry in material science to polarimetry in biochemistry, medicine and astronomy. Here we introduce single-shot Mueller matrix polarimetry based on generalized measurements performed with a Poincaré beam. We determine the Mueller matrix of a homogeneous medium with unknown optical activity by detecting its optical response to a Poincaré beam, which across its profile contains all polarization states, and analyze the resulting polarization pattern in terms of four generalized measurements, which are implemented as a path-displaced Sagnac interferometer. We illustrate the working of our Mueller matrix polarimetry on the example of tilted and rotated wave plates and find excellent agreement with predictions as well as alternative Stokes measurements. After initial calibration, the alignment of the device stays stable for up to 8 hours, promising suitability for the dynamic characterization of Mueller matrices that change in time. Unlike traditional rotating waveplate polarimetry, our method allows the acquisition of a sample's dynamic Mueller matrix. We expect that our feasibility study could be developed into a practical and versatile tool for the real-time analysis of optical activity changes, with applications in biomedical and biochemical research and industrial monitoring.

3.
Phys Rev Lett ; 132(22): 221004, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38877907

RESUMEN

We argue that there is a lower bound of order 10^{-19} eV on dark matter mass if it is produced after inflation via a process with finite correlation length. We rely on nondetection of free-streaming suppression and white-noise enhancement of density perturbations as the observational inputs.

4.
Phys Rev Lett ; 132(19): 193803, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38804954

RESUMEN

We investigate the transmission of vector beams, correlated in their polarization and spatial degrees of freedom, through cold atoms in the presence of a transverse magnetic coupling field. The resulting phase-dependent dynamics allow us to imprint the spatially varying polarization of a vector beam onto atomic spin polarizations, thereby establishing a direct link between optical space-polarization correlations and atomic-state interference. We find that the resulting absorption profiles show interference fringes whose modulation strength is given by the squared concurrence of the vector beam, letting us identify optical concurrence from a single absorption image. We expect impact across a diverse range of applications, including spintronics, quantum memories, metrology, and clocks.

5.
Artículo en Inglés | MEDLINE | ID: mdl-38935270

RESUMEN

PURPOSE OF REVIEW: The burdens of pancreatic ductal adenocarcinoma (PDAC) and acute pancreatitis are increasing globally. We reviewed current literature on whether acute pancreatitis is a causal factor for PDAC and examined clinical manifestations of PDAC-associated acute pancreatitis. RECENT FINDINGS: Recent findings detail the timing of acute pancreatitis before and after PDAC occurrence, further solidifying the evidence for PDAC-associated acute pancreatitis and for acute pancreatitis as a causal risk factor for PDAC. The risk of PDAC remains elevated above the general population in patients with distant history of acute pancreatitis. PDAC risk also increases with recurrent acute pancreatitis episodes, independent of smoking and alcohol. Mechanisms linking acute pancreatitis to PDAC include inflammation and neutrophil infiltration, which can be attenuated by suppressing inflammation and/or epigenetic modulation, thus slowing the progression of acinar-to-ductal metaplasia. Clinical presentation and management of acute pancreatitis in the context of PDAC are discussed, including challenges acute pancreatitis poses in the diagnosis and treatment of PDAC, and novel interventions for PDAC-associated acute pancreatitis. SUMMARY: PDAC risk may be reduced with improved acute pancreatitis prevention and treatment, such as antiinflammatories or epigenetic modulators. Increased acute pancreatitis and PDAC burden warrant more research on better diagnosis and management of PDAC-associated acute pancreatitis.

6.
Gastrointest Endosc ; 99(1): 83-90.e1, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37481003

RESUMEN

BACKGROUND AND AIMS: Complete closure after endoscopic resection of large nonpedunculated colorectal lesions (LNPCLs) can reduce delayed bleeding but is challenging with conventional through-the-scope (TTS) clips alone. The novel dual-action tissue (DAT) clip has clip arms that open and close independently of each other, facilitating tissue approximation. We aimed to evaluate the rate of complete closure and delayed bleeding with the DAT clip after endoscopic resection of LNPCLs. METHODS: This was a multicenter prospective cohort study of all patients who underwent defect closure with the DAT clip after EMR or endoscopic submucosal dissection (ESD) of LNPCLs ≥20 mm from July 2022 to May 2023. Delayed bleeding was defined as a bleeding event requiring hospitalization, blood transfusion, or any intervention within 30 days after the procedure. Complete closure was defined as apposition of mucosal defect margins without visible submucosal areas <3 mm along the closure line. RESULTS: One hundred seven patients (median age, 64 years; 42.5% women) underwent EMR (n = 63) or ESD (n = 44) of LNPCLs (median size, 40 mm; 74.8% right-sided colon) followed by defect closure. Complete closure was achieved in 96.3% (n = 103) with a mean of 1.4 ± .6 DAT clips and 2.9 ± 1.8 TTS clips. Delayed bleeding occurred in 1 patient (.9%) without requiring additional interventions. CONCLUSIONS: The use of the DAT clip in conjunction with TTS clips achieved high complete defect closure after endoscopic resection of large LNPCLs and was associated with a .9% delayed bleeding rate. Future comparative trials and formal cost-analyses are needed to validate these findings. (Clinical trial registration number: NCT05852457.).


Asunto(s)
Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Prospectivos , Hemorragia , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Instrumentos Quirúrgicos , Mucosa Intestinal/cirugía , Mucosa Intestinal/patología , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Resultado del Tratamiento , Estudios Retrospectivos
7.
Surg Endosc ; 38(5): 2649-2656, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38503905

RESUMEN

BACKGROUND: Adult patients with biliary acute pancreatitis (BAP) or choledocholithiasis who do not undergo cholecystectomy on index admission have worse outcomes. Given the paucity of data on the impact of cholecystectomy during index hospitalization in children, we examined readmission rates among pediatric patients with BAP or choledocholithiasis who underwent index cholecystectomy versus those who did not. METHODS: Retrospective study of children (< 18 years old) admitted with BAP, without infection or necrosis (ICD-10 K85.10), or choledocholithiasis (K80.3x-K80.7x) using the 2018 National Readmission Database (NRD). Exclusion criteria were necrotizing pancreatitis with or without infected necrosis and death during index admission. Multivariable logistic regression was performed to identify factors associated with 30-day readmission. RESULTS: In 2018, 1122 children were admitted for index BAP (n = 377, 33.6%) or choledocholithiasis (n = 745, 66.4%). Mean age at admission was 13 (SD 4.2) years; most patients were female (n = 792, 70.6%). Index cholecystectomy was performed in 663 (59.1%) of cases. Thirty-day readmission rate was 10.9% in patients who underwent cholecystectomy during that index admission and 48.8% in those who did not (p < 0.001). In multivariable analysis, patients who underwent index cholecystectomy had lower odds of 30-day readmission than those who did not (OR 0.16, 95% CI 0.11-0.24, p < 0.001). CONCLUSIONS: Index cholecystectomy was performed in only 59% of pediatric patients admitted with BAP or choledocholithiasis but was associated with 84% decreased odds of readmission within 30 days. Current guidelines should be updated to reflect these findings, and future studies should evaluate barriers to index cholecystectomy.


Asunto(s)
Colecistectomía , Coledocolitiasis , Pancreatitis , Readmisión del Paciente , Humanos , Readmisión del Paciente/estadística & datos numéricos , Femenino , Masculino , Estudios Retrospectivos , Coledocolitiasis/cirugía , Coledocolitiasis/complicaciones , Adolescente , Niño , Colecistectomía/estadística & datos numéricos , Pancreatitis/cirugía , Enfermedad Aguda , Preescolar
8.
Surg Endosc ; 38(3): 1351-1357, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38114877

RESUMEN

BACKGROUND: Adult patients with cholecystitis who do not undergo cholecystectomy on index admission have worse outcomes, however, there is a paucity of data of the role of cholecystectomy during index hospitalization in the pediatric population. Our aim was to determine outcomes and readmission rates among pediatric patients with cholecystitis who underwent index cholecystectomy versus those who did not. METHODS: We performed a retrospective study of pediatric (< 18 years old) admitted with acute cholecystitis (AC) requiring hospitalization using the 2018 National Readmission Database (NRD). Exclusion criteria included age ≥ 18 years and death on index admission. Multivariable logistic regression was performed to identify factors associated with 30-day readmissions. RESULTS: We identified 550 unique index acute cholecystitis admissions. Mean age was 14.6 ± 3.0 years. Majority of patients were female (n = 372, 67.6%). Index cholecystectomy was performed in (n = 435, 79.1%) of cases. Thirty-day readmission rate was 2.8% in patients who underwent index cholecystectomy and 22.6% in those who did not (p < 0.001). On multivariable analysis, patients who did not undergo index cholecystectomy had higher odds of 30-day readmission than those who did not (OR 10.66, 95% CI 5.06-22.45, p < 0.001). Female patients also had higher odds of 30-day readmission compared to males (OR 3.37, 95% CI 1.31-8.69). CONCLUSIONS: Patients who did not undergo index cholecystectomy had over tenfold increase in odds of 30-day readmission. Further research is required to understand the barriers to index cholecystectomy despite society recommendations and clear clinical benefit.


Asunto(s)
Colecistectomía Laparoscópica , Colecistitis Aguda , Adulto , Humanos , Niño , Masculino , Femenino , Adolescente , Readmisión del Paciente , Estudios Retrospectivos , Colecistectomía , Hospitalización , Colecistitis Aguda/etiología , Tiempo de Internación , Colecistectomía Laparoscópica/efectos adversos
9.
Surg Endosc ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38886232

RESUMEN

BACKGROUND: There is little international data on morbidity and mortality of surgery for perforated peptic ulcer (PPU). This study aimed to understand the global 30-day morbidity and mortality of patients undergoing surgery for PPU and to identify variables associated with these. METHOD: We performed an international study of adults (≥ 18 years) who underwent surgery for PPU from 1st January 2022 to 30th June 2022. Patients who were treated conservatively or had an underlying gastric cancer were excluded. Patients were divided into subgroups according to age (≤ 50 and > 50 years) and time from onset of symptoms to hospital presentation (≤ 24 and > 24 h). Univariate and Multivariate analyses were carried out to identify factors associated with higher 30-day morbidity and mortality. RESULTS:  1874 patients from 159 centres across 52 countries were included. 78.3% (n = 1467) of the patients were males and the median (IQR) age was 49 years (25). Thirty-day morbidity and mortality were 48.5% (n = 910) and 9.3% (n = 174) respectively. Median (IQR) hospital stay was 7 (5) days. Open surgery was performed in 80% (n = 1505) of the cohort. Age > 50 years [(OR = 1.7, 95% CI 1.4-2), (OR = 4.7, 95% CI 3.1-7.6)], female gender [(OR = 1.8, 95% CI 1.4-2.3), (OR = 1.9, 95% CI 1.3-2.9)], shock on admission [(OR = 2.1, 95% CI 1.7-2.7), (OR = 4.8, 95% CI 3.2-7.1)], and acute kidney injury [(OR = 2.5, 95% CI 1.9-3.2), (OR = 3.9), 95% CI 2.7-5.6)] were associated with both 30-day morbidity and mortality. Delayed presentation was associated with 30-day morbidity [OR = 1.3, 95% CI 1.1-1.6], but not mortality. CONCLUSIONS: This study showed that surgery for PPU was associated with high 30-day morbidity and mortality rate. Age, female gender, and signs of shock at presentation were associated with both 30-day morbidity and mortality.

10.
Clin Lab ; 70(2)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38345987

RESUMEN

BACKGROUND: A voluntary reporting system (VRS) is still used to detect adverse events (AEs) in health-care services in many countries. We attempted to apply the Global Trigger Tool (GTT) for the first time in our country and searched for an answer to the question of whether there could be new triggers. METHODS: Two hundred and forty inpatient records were selected from total of 1,807 inpatient files in the university obstetrics and gynecology clinic between 2018 and 2020. Twenty files per month were reviewed retrospectively using GTT, an approach developed by the American Institute for Health Development. VRS records of the same period were examined. The data were evaluated according to the National Coordinating Council for Medication Error Reporting and Prevention scale and those in the E, F, G, H, I categories were included. RESULTS: The number of AEs per 1,000 patient days was 47.81, AEs per 1,000 patient hospitalizations was 95.83, and hospitalizations with AEs was 9.58%. In the VRS data, 10 of 85 reporting cases were listed in the E category (Damage is temporary and requires intervention), 6 of them were related to fall of the patient, and 4 of them were related to medical device and material safety. By applying GTT, 45 cases in category E and 35 cases in category F (Damage is temporary and requires hospitalization or prolonged hospitalization) AEs were detected in 23 patients (9.58%). The number of AEs reported was 8.3 times higher in the GTT than with VRS. Healthcare related infection, development of complications from any procedure, APTT>100 Seconds, INR>6, Organ Injury - Repair or Removal, All Kinds of Operative Complications were found to be the most sensitive triggers (PPV = 100). There was no difference between the patients with and without AEs in terms of age and number of hospitalization days (p: 0.707, p: 0.618). The sensitivity rate of vaginal dinoprostone use and CRP elevation (30% and 22%, respectively) was higher than the mean sensitivity rate of GTT triggers (15.6%). CONCLUSIONS: The GTT is more effective than VRS in detecting AEs. Using vaginal dinoprostone (propess) and high CRP levels could be used as a trigger. The GTT is a credible and fruitful instrument for determining AEs when adapted to the departmental practices.


Asunto(s)
Errores Médicos , Seguridad del Paciente , Femenino , Humanos , Errores Médicos/prevención & control , Estudios Retrospectivos , Dinoprostona , Hospitales Universitarios , Voluntarios
11.
Clin Lab ; 70(2)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38345973

RESUMEN

BACKGROUND: Type 2 diabetes mellitus (T2DM) is common in Saudi Arabia and represents a major health concern. Silent information regulator of transcription-1 (SIRT1) positively influences insulin sensitivity and might contribute to the pathogenesis of T2DM. This study aimed to investigate the frequency of two common functional single nucleotide polymorphisms (SNPs) in the promoter region of SIRT1; rs12778366 (T>C) and rs3758391 (T>C) in Saudi Arabian population and examine any association with T2DM. METHODS: A total of 445 volunteers were divided into 224 healthy controls and 221 patients previously diagnosed with T2DM. Genomic DNA was extracted from all samples and genotyped for SIRT1 rs12778366 and rs3758391 SNPs by TaqMan RT-PCR allelic discrimination assay. Logistic regression analysis was used to establish any relationship between these polymorphisms and T2DM. RESULTS: In the total study population, rs12778366 genotype frequencies were TT (89.2%), TC (10.3%), and CC (0.45%) and for the rs3758391 they were TT (16.4%), TC (44.5%), and CC (39.1%). The distribution of these genotypes, in both polymorphisms, were similar among T2DM and controls. Logistic regression analysis confirmed the lack of association between the presence of CC or CT variants and T2DM for rs12778366 and rs3758391 SNP (OR = 0.98 [CI]: 0.55 - 1.75; p = 0.999 and OR= 0.75; [CI]: 0.45 - 1.24; p = 0.313), respectively. CONCLUSIONS: This study revealed the frequency of SIRT1 rs12778366 and rs3758391 SNPs in our population and reported no association between these polymorphisms and the risk for T2DM. This finding might add to the growing body of literature exploring the genetics of T2DM.


Asunto(s)
Diabetes Mellitus Tipo 2 , Sirtuina 1 , Humanos , Arabia Saudita/epidemiología , Sirtuina 1/genética , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Genotipo , Polimorfismo de Nucleótido Simple , Regiones Promotoras Genéticas/genética , Predisposición Genética a la Enfermedad/genética , Estudios de Casos y Controles , Frecuencia de los Genes
12.
J Environ Manage ; 359: 121058, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38714036

RESUMEN

Water pollution remains a pressing environmental issue, with diverse pollutants such as heavy metals, pharmaceuticals, dyes, and aromatic hydrocarbon compounds posing a significant threat to clean water access. Historically, biomass-derived activated carbons (ACs) have served as effective adsorbents for water treatment, owing to their inherent porosity and expansive surface area. Nanocomposites have emerged as a means to enhance the absorption properties of ACs, surpassing conventional AC performance. Biomass-based activated carbon nanocomposites (ACNCs) hold promise due to their high surface area and cost-effectiveness. This review explores recent advancements in biomass-based ACNCs, emphasizing their remarkable adsorption efficiencies and paving the way for future research in developing efficient and affordable ACNCs. Leveraging real-time communication for ACNC applications presents a viable approach to addressing cost concerns.


Asunto(s)
Carbón Orgánico , Frutas , Nanocompuestos , Verduras , Purificación del Agua , Nanocompuestos/química , Carbón Orgánico/química , Purificación del Agua/métodos , Frutas/química , Adsorción , Verduras/química , Contaminantes Químicos del Agua/química , Biomasa
13.
J Biol Chem ; 298(7): 102018, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35526563

RESUMEN

Hyperekplexia is a rare neurological disorder characterized by exaggerated startle responses affecting newborns with the hallmark characteristics of hypertonia, apnea, and noise or touch-induced nonepileptic seizures. The genetic causes of the disease can vary, and several associated genes and mutations have been reported to affect glycine receptors (GlyRs); however, the mechanistic links between GlyRs and hyperekplexia are not yet understood. Here, we describe a patient with hyperekplexia from a consanguineous family. Extensive genetic screening using exome sequencing coupled with autozygome analysis and iterative filtering supplemented by in silico prediction identified that the patient carries the homozygous missense mutation A455P in GLRB, which encodes the GlyR ß-subunit. To unravel the physiological and molecular effects of A455P on GlyRs, we used electrophysiology in a heterologous system as well as immunocytochemistry, confocal microscopy, and cellular biochemistry. We found a reduction in glycine-evoked currents in N2A cells expressing the mutation compared to WT cells. Western blot analysis also revealed a reduced amount of GlyR ß protein both in cell lysates and isolated membrane fractions. In line with the above observations, coimmunoprecipitation assays suggested that the GlyR α1-subunit retained coassembly with ßA455P to form membrane-bound heteromeric receptors. Finally, structural modeling showed that the A455P mutation affected the interaction between the GlyR ß-subunit transmembrane domain 4 and the other helices of the subunit. Taken together, our study identifies and validates a novel loss-of-function mutation in GlyRs whose pathogenicity is likely to cause hyperekplexia in the affected individual.


Asunto(s)
Hiperekplexia , Receptores de Glicina , Humanos , Hiperekplexia/genética , Recién Nacido , Rigidez Muscular , Mutación , Mutación Missense , Receptores de Glicina/genética
14.
Clin Gastroenterol Hepatol ; 21(5): 1233-1242.e14, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36075501

RESUMEN

BACKGROUND & AIMS: The Cotton Consensus (CC) criteria for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) may not capture post-ERCP morbidity. PAN-PROMISE, a patient-reported outcome measure (PROM), was developed to quantify acute pancreatitis-related morbidity. This study aims to determine the value of PAN-PROMISE in independently defining ERCP-related morbidity. METHODS: We conducted a prospective cohort study of patients undergoing ERCP at 2 academic centers from September 2021 to August 2022. We administered PAN-PROMISE and assessed quality of life and work productivity at baseline, 48 to 72 hours, 7 days, and 30 days following ERCP. PEP was defined by a 3-physician committee using the CC criteria. We defined high morbidity following ERCP (elevated PROM) by an increase of PAN-PROMISE score of >7 at 7 days post-procedure. The McNemar test assessed discordance between PEP and elevated-PROM. RESULTS: A total of 679 patients were enrolled. Choledocholithiasis (30%) and malignant biliary obstruction (29%) were the main indications for ERCP. Thirty-two patients (4.7%) developed PEP. One hundred forty-seven patients (21.6%) had an elevated PROM, whereas only 20 of them (13.4%) had PEP by the CC criteria (P < .001 for discordance). An elevated PROM strongly correlated with lower physical quality of life and increased direct and indirect health care costs ($80 and $25 per point increase in PAN-PROMISE, respectively). Patients with pancreatic cancer (odds ratio, 4.52; 95% confidence interval, 1.68-10.74) and primary sclerosing cholangitis (odds ratio, 1.79; 95% confidence interval, 1.29-2.45) had the highest odds of elevated PROM. CONCLUSIONS: A substantial number of patients experience significant morbidity after ERCP despite not developing PEP or other adverse events. Future studies are needed to characterize better the reasons behind this increase in symptoms and potential interventions to reduce the symptom burden post-ERCP. CLINICALTRIALS: gov number, NCT05310409.


Asunto(s)
Colangiopancreatografia Retrógrada Endoscópica , Pancreatitis , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Pancreatitis/diagnóstico , Pancreatitis/epidemiología , Pancreatitis/etiología , Estudios Prospectivos , Enfermedad Aguda , Calidad de Vida , Morbilidad , Medición de Resultados Informados por el Paciente , Factores de Riesgo , Estudios Retrospectivos
15.
Genet Med ; 25(8): 100885, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37165955

RESUMEN

PURPOSE: Missense variants clustering in the BTB domain region of RHOBTB2 cause a developmental and epileptic encephalopathy with early-onset seizures and severe intellectual disability. METHODS: By international collaboration, we assembled individuals with pathogenic RHOBTB2 variants and a variable spectrum of neurodevelopmental disorders. By western blotting, we investigated the consequences of missense variants in vitro. RESULTS: In accordance with previous observations, de novo heterozygous missense variants in the BTB domain region led to a severe developmental and epileptic encephalopathy in 16 individuals. Now, we also identified de novo missense variants in the GTPase domain in 6 individuals with apparently more variable neurodevelopmental phenotypes with or without epilepsy. In contrast to variants in the BTB domain region, variants in the GTPase domain do not impair proteasomal degradation of RHOBTB2 in vitro, indicating different functional consequences. Furthermore, we observed biallelic splice-site and truncating variants in 9 families with variable neurodevelopmental phenotypes, indicating that complete loss of RHOBTB2 is pathogenic as well. CONCLUSION: By identifying genotype-phenotype correlations regarding location and consequences of de novo missense variants in RHOBTB2 and by identifying biallelic truncating variants, we further delineate and expand the molecular and clinical spectrum of RHOBTB2-related phenotypes, including both autosomal dominant and recessive neurodevelopmental disorders.


Asunto(s)
Epilepsia , Discapacidad Intelectual , Trastornos del Neurodesarrollo , Humanos , Trastornos del Neurodesarrollo/genética , Epilepsia/genética , Epilepsia/patología , Estudios de Asociación Genética , Discapacidad Intelectual/genética , Fenotipo , GTP Fosfohidrolasas/genética , Proteínas de Unión al GTP/genética , Proteínas Supresoras de Tumor/genética
16.
Clin Genet ; 103(2): 156-166, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36224108

RESUMEN

CNOT2 haploinsufficiency underlies a rare neurodevelopmental disorder named Intellectual Developmental disorder with NAsal speech, Dysmorphic Facies, and variable Skeletal anomalies (IDNADFS, OMIM 618608). The condition clinically overlaps with chromosome 12q15 deletion syndrome, suggesting a major contribution of CNOT2 haploinsufficiency to the latter. CNOT2 is a member of the CCR4-NOT complex, which is a master regulator of multiple cellular processes, including gene expression, RNA deadenylation, and protein ubiquitination. To date, less than 20 pathogenic 12q15 microdeletions encompassing CNOT2, together with a single truncating variant of the gene, and two large intragenic deletions have been reported. Due to the small number of affected subjects described so far, the clinical profile of IDNADFS has not been fully delineated. Here we report five unrelated individuals, three of which carrying de novo intragenic CNOT2 variants, one presenting with a multiexon intragenic deletion, and an additional case of 12q15 microdeletion syndrome. Finally, we assess the features of IDNADFS by reviewing published and present affected individuals and reevaluate the clinical phenotype of this neurodevelopmental disorder.


Asunto(s)
Discapacidad Intelectual , Trastornos del Neurodesarrollo , Humanos , Deleción Cromosómica , Haploinsuficiencia/genética , Trastornos del Neurodesarrollo/genética , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Fenotipo , Proteínas Represoras/genética
17.
J Vasc Surg ; 77(3): 891-898.e1, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36368647

RESUMEN

BACKGROUND: Upper extremity hemodialysis arteriovenous fistulas (AVFs) can become aneurysmal over time due to repeated cannulation and/or outflow steno-occlusive disease. The optimal surgical management of aneurysmal AVFs (aneurysmorrhaphy vs interposition graft) has remained unclear. METHODS: We performed a retrospective review in which current procedural terminology codes were used to screen for patients who had undergone surgical treatment of aneurysmal AVFs between 2016 and 2021 at a single hospital system. The patients were included after a review of the operative reports. The cases were divided by surgical procedure (aneurysmorrhaphy vs interposition graft placement). The patients who had undergone primary AVF ligation or other types of repair were excluded. The primary outcomes were primary assisted and secondary patency, and the secondary outcome was dialysis access abandonment. Multivariable Cox proportional hazards regression was used to test the association between the type of AVF aneurysm repair and the primary and secondary outcomes. RESULTS: From 2016 to 2021, 6951 patients had undergone 16,190 dialysis access procedures. Of these procedures, 381 (2.4%) were related to surgical treatment of an aneurysmal AVF. We excluded 58 primary AVF ligation cases and 20 cases involving other types of repair, leaving 303 cases for analysis. These were divided into two groups: aneurysmorrhaphy (n = 123; 41%) and interposition graft (n = 180; 59%). No differences were found between the groups in male gender (68% vs 63%), hypertension (98% vs 98%), or central stenosis (14% vs 22%). The patients who had undergone aneurysmorrhaphy were younger (median age, 54 years vs 59 years); had had a lower rate of diabetes (41% vs 59%), coronary artery disease (41% vs 58%), and congestive heart failure (41% vs 55%); and were less likely to have undergone upper arm access (72% vs 92%). The median follow-up was 11.1 months (interquartile range, 3.6-25.2 months). No differences were found in the incidence of 30-day wound complications (1% vs 3%) or surgical site infections (4% vs 6%). On multivariable Cox regression, interposition graft placement was associated with the loss of primary assisted patency (adjusted hazard ratio [aHR], 2.42; 95% confidence interval [CI], 1.18-4.95), loss of secondary patency (aHR, 3.10; 95% CI, 1.21-7.94), and abandonment of dialysis access (aHR, 3.07; 95% CI, 1.61-5.87; P < .05 for all) at 2 years. CONCLUSIONS: AVF aneurysmorrhaphy was associated with improved primary assisted and secondary patency and decreased abandonment of dialysis access. We suggest using aneurysmorrhaphy when AVF aneurysms are indicated for repair. However, individual factors such as patient comorbidities, AVF anatomy, remaining dialysis access options, and patient preference should be considered when planning the surgical approach.


Asunto(s)
Fístula Arteriovenosa , Derivación Arteriovenosa Quirúrgica , Humanos , Masculino , Persona de Mediana Edad , Derivación Arteriovenosa Quirúrgica/efectos adversos , Oclusión de Injerto Vascular/etiología , Grado de Desobstrucción Vascular , Resultado del Tratamiento , Factores de Riesgo , Diálisis Renal/efectos adversos , Estudios Retrospectivos , Fístula Arteriovenosa/complicaciones
18.
Cytokine ; 171: 156368, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37716188

RESUMEN

Recent evidence has indicated that interleukin 37 (IL-37) shows down-regulated expression in patients with acute myeloid leukemia (AML), but its association with immunophenotypic markers has not been explored. In the current study, IL37 mRNA expression was analyzed in the peripheral blood of 131 AML patients and 100 controls using the 2-ΔΔCt method (fold change), which was based on the principles of quantitative real-time polymerase chain reaction. AML patients were characterized in terms of gender, therapy, fms-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) and nucleophosmin 1 (NPM1) mutations, French-American-British classification (FAB), World Health Organization (WHO) classification, and immunophenotypes of 25 cytoplasmic and surface markers. IL37 mRNA expression was given as median and interquartile range. Low expression of IL37 mRNA (0.273 [0.062-0.456]) was found in AML patients. This reduced expression was more pronounced in females than in males but the difference was significant before the Bonferroni correction (0.196 [0.045-0.411] vs. 0.4 [0.153-0.466]; probability [p] = 0.008; corrected p = 0.064). In addition, the FAB M4 type (0.109 [0.031-0.269]) and the WHO PML-RARA type (0.171 [0.061-0.482]) had the lowest expression of IL37 mRNA among the other types. For immunophenotypes, only two significant differences were found. First, CD14-positive patients showed a lower level of expression than CD14-negative patients (0.146 [0.033-0.413] vs. 0.323 [0.108-0.468]; p = 0.02). Second, HLA-DR-positive patients showed a higher level of expression than HLA-DR-negative patients (0.325 [0.163-0.474] vs. 0.214 [0.045-0.42]; p = 0.04). However, the corrected p-value was not significant in both cases (p > 0.05). In conclusion, IL37 mRNA expression was down-regulated in AML patients, especially females, and those with the FAB M4 type and the WHO PML-RARA type. This expression may be affected by the immunophenotypic markers CD14 and HLA-DR.


Asunto(s)
Leucemia Mieloide Aguda , Proteínas Nucleares , Masculino , Femenino , Humanos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Nucleofosmina , Leucemia Mieloide Aguda/genética , Mutación , Antígenos HLA-DR , Expresión Génica , ARN Mensajero/genética , Interleucinas/genética , Pronóstico , Interleucina-1/genética
19.
Gastrointest Endosc ; 98(3): 348-359.e30, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37004816

RESUMEN

BACKGROUND AND AIMS: Palliation of malignant gastric outlet obstruction (mGOO) allows resumption of peroral intake. Although surgical gastrojejunostomy (SGJ) provides durable relief, it may be associated with a higher morbidity, interfere with chemotherapy, and require an optimum nutritional status. EUS-guided gastroenterostomy (EUS-GE) has emerged as a minimally invasive alternative. We aimed to conduct the largest comparative series to date between EUS-GE and SGJ for mGOO. METHODS: This multicenter retrospective study included consecutive patients undergoing SGJ or EUS-GE at 6 centers. Primary outcomes included time to resumption of oral intake, length of stay (LOS), and mortality. Secondary outcomes included technical and clinical success, reintervention rates, adverse events (AEs), and resumption of chemotherapy. RESULTS: A total of 310 patients were included (EUS-GE, n = 187; SGJ, n = 123). EUS-GE exhibited significantly lower time to resumption of oral intake (1.40 vs 4.06 days, P < .001), at lower albumin levels (2.95 vs 3.33 g/dL, P < .001), and a shorter LOS (5.31 vs 8.54 days, P < .001) compared with SGJ; there was no difference in mortality (48.1% vs 50.4%, P = .78). Technical (97.9% and 100%) and clinical (94.1% vs 94.3%) success was similar in the EUS-GE and SGJ groups, respectively. EUS-GE had lower rates of AEs (13.4% vs 33.3%, P < .001) but higher reintervention rates (15.5% vs 1.63%, P < .001). EUS-GE patients exhibited significantly lower interval time to resumption of chemotherapy (16.6 vs 37.8 days, P < .001). Outcomes between the EUS-GE and laparoscopic (n = 46) surgical approach showed that EUS-GE had shorter interval time to initiation/resumption of oral intake (3.49 vs 1.46 days, P < .001), decreased LOS (9 vs 5.31 days, P < .001), and a lower rate of AEs (11.9% vs 17.9%, P = .003). CONCLUSIONS: This is the largest study to date showing that EUS-GE can be performed among nutritionally deficient patients without affecting the technical and clinical success compared with SGJ. EUS-GE is associated with fewer AEs while allowing earlier resumption of diet and chemotherapy.


Asunto(s)
Derivación Gástrica , Obstrucción de la Salida Gástrica , Humanos , Estudios Retrospectivos , Endosonografía , Stents , Gastroenterostomía , Obstrucción de la Salida Gástrica/etiología , Obstrucción de la Salida Gástrica/cirugía
20.
Scand J Rheumatol ; 52(6): 696-702, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37584636

RESUMEN

OBJECTIVE: This study assessed the relationship between anti-thrombotics and major adverse cardiovascular events (MACE) in patients with anti-phospholipid syndrome (APS). METHOD: We included 13 947 subjects with APS from the National (Nationwide) Inpatient Sample (NIS) database for 2016-2018, and collected relevant covariates and demographic data using ICD-10 codes. Our two primary outcomes were MACE and death. We performed multivariate logistic regression analysis to assess the impact of various anti-thrombotic regimens on MACE/death in our primary cohort and high-risk subgroups. RESULTS: Patients on anti-coagulants had significantly reduced odds of MACE [odds ratio (OR) 0.68, 95% confidence interval (CI) 0.62-0.76, p < 0.001] as well as each of its subcomponents. Those not on any anti-coagulants had significantly increased odds of MACE (OR 1.47, 95% CI 1.24-1.72, p < 0.001). No significant association was found between anti-platelet use and the odds of MACE (p > 0.05). Patients on anti-coagulants were the only class that appeared to have a mortality benefit with reduced odds for death (OR 0.64, 95% CI 0.49-0.84, p = 0.001). In the subgroups at higher risk for MACE (those with atrial fibrillation and thrombocytopenia), full anti-coagulation therapy was also the only anti-thrombotic class that significantly affected the odds of MACE, with a protective effect on MACE, but had no mortality benefit. CONCLUSION: Patients with APS are most likely to benefit from anti-coagulant therapy in reducing MACE. Furthermore, anti-platelets alone or in combination with anti-coagulants are probably not beneficial in MACE reduction and may even increase risk.


Asunto(s)
Síndrome Antifosfolípido , Enfermedades Cardiovasculares , Humanos , Estudios Transversales , Pacientes Internos , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/tratamiento farmacológico , Síndrome Antifosfolípido/epidemiología , Factores de Riesgo , Enfermedades Cardiovasculares/epidemiología
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