ABSTRACT
Pathogenic variation in genes encoding proteins of the cardiac sarcomere is responsible for 30%-40% of cases of hypertrophic cardiomyopathy. The main clinical utility of genetic testing is to provide diagnostic confirmation and facilitation of family screening. It also assists in the detection of aetiologies, which require distinct monitoring and treatment approaches. Other clinical applications, including the use of genetic information to inform risk prediction models, have been limited by the challenge of establishing robust genotype-phenotype correlations with actionable consequences, but new data on the interaction between rare and common genetic variation, as well as the emergence of therapies targeting disease-specific pathogenic mechanisms, herald a new era for genetic testing in routine practice.
Subject(s)
Cardiomyopathy, Hypertrophic , Genetic Testing , Sarcomeres , Humans , Genetic Testing/methods , Cardiomyopathy, Hypertrophic/genetics , Cardiomyopathy, Hypertrophic/diagnosis , Sarcomeres/genetics , Mutation , Genetic Predisposition to Disease/genetics , Genetic Variation/geneticsABSTRACT
BACKGROUND: In hypertrophic cardiomyopathy (HCM), myocyte disarray and microvascular disease (MVD) have been implicated in adverse events, and recent evidence suggests that these may occur early. As novel therapy provides promise for disease modification, detection of phenotype development is an emerging priority. To evaluate their utility as early and disease-specific biomarkers, we measured myocardial microstructure and MVD in 3 HCM groups-overt, either genotype-positive (G+LVH+) or genotype-negative (G-LVH+), and subclinical (G+LVH-) HCM-exploring relationships with electrical changes and genetic substrate. METHODS: This was a multicenter collaboration to study 206 subjects: 101 patients with overt HCM (51 G+LVH+ and 50 G-LVH+), 77 patients with G+LVH-, and 28 matched healthy volunteers. All underwent 12-lead ECG, quantitative perfusion cardiac magnetic resonance imaging (measuring myocardial blood flow, myocardial perfusion reserve, and perfusion defects), and cardiac diffusion tensor imaging measuring fractional anisotropy (lower values expected with more disarray), mean diffusivity (reflecting myocyte packing/interstitial expansion), and second eigenvector angle (measuring sheetlet orientation). RESULTS: Compared with healthy volunteers, patients with overt HCM had evidence of altered microstructure (lower fractional anisotropy, higher mean diffusivity, and higher second eigenvector angle; all P<0.001) and MVD (lower stress myocardial blood flow and myocardial perfusion reserve; both P<0.001). Patients with G-LVH+ were similar to those with G+LVH+ but had elevated second eigenvector angle (P<0.001 after adjustment for left ventricular hypertrophy and fibrosis). In overt disease, perfusion defects were found in all G+ but not all G- patients (100% [51/51] versus 82% [41/50]; P=0.001). Patients with G+LVH- compared with healthy volunteers similarly had altered microstructure, although to a lesser extent (all diffusion tensor imaging parameters; P<0.001), and MVD (reduced stress myocardial blood flow [P=0.015] with perfusion defects in 28% versus 0 healthy volunteers [P=0.002]). Disarray and MVD were independently associated with pathological electrocardiographic abnormalities in both overt and subclinical disease after adjustment for fibrosis and left ventricular hypertrophy (overt: fractional anisotropy: odds ratio for an abnormal ECG, 3.3, P=0.01; stress myocardial blood flow: odds ratio, 2.8, P=0.015; subclinical: fractional anisotropy odds ratio, 4.0, P=0.001; myocardial perfusion reserve odds ratio, 2.2, P=0.049). CONCLUSIONS: Microstructural alteration and MVD occur in overt HCM and are different in G+ and G- patients. Both also occur in the absence of hypertrophy in sarcomeric mutation carriers, in whom changes are associated with electrocardiographic abnormalities. Measurable changes in myocardial microstructure and microvascular function are early-phenotype biomarkers in the emerging era of disease-modifying therapy.
Subject(s)
Cardiomyopathy, Hypertrophic , Hypertrophy, Left Ventricular , Humans , Sarcomeres/genetics , Diffusion Tensor Imaging , Genetic Predisposition to Disease , Mutation , Cardiomyopathy, Hypertrophic/diagnosis , Phenotype , Biomarkers , FibrosisABSTRACT
BACKGROUND: Clinical importance of mitral annulus disjunction (MAD) is not well established. PURPOSE: Characterize a population of MAD all-comers diagnosed by cardiac magnetic resonance imaging (MRI). STUDY TYPE: Retrospective. POPULATION: MAD confirmed in 222 patients, age of 49.2 ± 19.3 years, 126 (56.8%) males. FIELD STRENGTH/SEQUENCE: 1.5 T and 3 T/steady-state free precession and inversion recovery. ASSESSMENT: Clinical history, outcomes, imaging, and arrhythmia data. MAD defined as a separation ≥2 mm between left ventricular myocardium and mitral annulus. Presence and pattern of late gadolinium enhancement (LGE) were analyzed. LGE in the papillary muscles and adjacent to MAD were identified as MAD related. Ventricular arrhythmias (VA) were grouped into non-sustained ventricular arrhythmias (NSVA) or sustained. Cardiovascular death assessed. STATISTICAL TESTS: Differences between baseline characteristics were compared. Univariate regression was used to investigate possible associations between ventricular arrhythmia and cardiovascular death with characteristics associated with the severity of MAD. A multivariable logistic regression included significant variables from the univariate analysis and was performed for MAD-related and global LGE. RESULTS: MAD extent 5.0 ± 2.6 mm. MV annulus expanded during systole for MAD ≥6 mm. Systolic expansion associated with prolapse, billowing, and curling. LGE present in 82 patients (36.9%). Twenty-three patients (10.4%) showed MAD-related LGE by three different observers. No association of LGE with MAD extent (P = 0.545) noted. Follow-up 4.1 ± 2.4 years. No sustained VA observed. In univariable analysis, NSVA was more prevalent in patients with MAD ≥6 mm (33.3% vs. 9.9%), but this was attenuated on multivariate analysis (P = 0.054). The presence of NSVA was associated with global LGE but not MAD-related LGE in isolation (P = 0.750). Three patients died of cardiovascular causes (1.4%) and none had MAD-related LGE. None died of sudden cardiac arrest. CONCLUSION: In patients referred for cardiac MRI, mitral valve dysfunction was associated with MAD severity. Scar was not related to the extent of MAD, but associated with NSVA. The risk of sustained arrhythmias and cardiovascular death was low in this population. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.
ABSTRACT
BACKGROUND: The first 3 years of life are a critical period for the development of socio-emotional skills, highlighting the importance of socio-emotional development in early childhood. This study aimed to evaluate the effectiveness of a health promotion intervention program on the socio-emotional development of children aged 12 to 42 months during the COVID-19 pandemic. METHODS: A total of 344 children from 15 childcare centers participated in this study, with six centers in the intervention group and nine in the control group. Childcare teachers in the intervention group received a 6-month training program aimed at promoting healthy lifestyles, including topics such as diet, sleep, physical activity, and sedentary behavior. Sociodemographic and anthropometric measures were assessed at baseline, and socio-emotional development was assessed using the Bayley Scales of Infant and Toddler Development - Third Edition (Bayley-III) at baseline and post-intervention. RESULTS: After the intervention, a significant difference in socio-emotional development was observed between children with mothers of varying education levels. Specifically, children whose mothers had lower education levels demonstrated significantly greater socio-emotional development (B = 19.000, p = 0.028) compared to the control group. In contrast, there was no significant difference in socio-emotional development among children with mothers from higher education levels. CONCLUSION: These findings suggest that intervention programs for childcare teachers can effectively promote healthy socio-emotional development in children from socioeconomically disadvantaged backgrounds. Future intervention programs should consider tailoring their approaches to target disadvantaged populations. TRIAL REGISTRATION: This cluster randomized controlled trial was registered in the Clinical Trials database/platform on 09/09/2019 (number NCT04082247).
Subject(s)
Health Promotion , Pandemics , Female , Infant , Child , Humans , Child, Preschool , Child Day Care Centers , Mothers , EmotionsABSTRACT
BACKGROUND: Natural and synthetic cannabinoids are being used worldwide to treat various symptoms in cancer patients. This study aims to map the therapeutic benefits and adverse effects associated with the use of cannabis-based drugs in these outcomes. METHODS: Following Joanna Briggs Institute guidelines a scoping review was conducted. The study protocol was available in the Open Science Framework public repository. An extensive search strategy involving databases like Cochrane Library, Embase, CINAHL, Medline/PubMed, Lilacs, Google Scholar, and Open Gray for gray literature analysis was executed by a skilled librarian. The inclusion criteria were primary studies (observational and randomized) that evaluated the efficacy and safety of cannabinoids in cancer patients. The review encompassed studies of diverse designs, publication years, and types, as long as they addressed cannabinoids' impact in oncology. RESULTS: Twenty-nine (82.86%) out of total of 35 were randomized and 6 (14.14%) were non-randomized. About 57.1% of studies utilized registered products as interventions, with THC being the most natural cannabinoid cited in variable doses and administration routes. Moreover, 62.85% of studies specified the cancer types (breast, lung, sarcomas, hematological and reproductive system), while only one study detailed cancer staging. The evaluated outcomes encompassed nausea and vomiting (77.14%), appetite (11.43%), pain (8.57%), and tumor regression (2.86%) across different proportions of studies. CONCLUSION: Cannabinoids show promise in managing pain, emesis, and anorexia/cachexia linked to cancer progression. New randomized clinical trials with a larger number of participants and observational studies on long-term safety are crucial to affirm their medicinal utility for cancer patients unresponsive to conventional drugs.
Subject(s)
Cannabinoids , Medical Marijuana , Neoplasms , Humans , Medical Marijuana/therapeutic use , Medical Marijuana/adverse effects , Neoplasms/drug therapy , Cannabinoids/therapeutic use , Cannabinoids/adverse effects , Vomiting/chemically induced , Randomized Controlled Trials as Topic , Nausea/chemically inducedABSTRACT
Myocardial dysfunction is common in patients admitted to the intensive care unit (ICU). Septic disease frequently results in cardiac dysfunction, and sepsis represents the most common cause of admission and death in the ICU. The association between left ventricular (LV) systolic dysfunction and mortality is not clear for critically ill patients. Conversely, LV diastolic dysfunction (DD) seems increasingly recognized as a factor associated with poor outcomes, not only in sepsis but also more generally in critically ill patients. Despite recent attempts to simplify the diagnosis and grading of DD, this remains relatively complex, with the need to use several echocardiographic parameters. Furthermore, the current guidelines have several intrinsic limitations when applied to the ICU setting. In this manuscript, we discuss the challenges in DD classification when applied to critically ill patients, the importance of left atrial pressure estimates for the management of patients in ICU, and whether the study of cardiac dysfunction spectrum during critical illness may benefit from the integration of left ventricular and left atrial strain data to improve diagnostic accuracy and implications for the treatment and prognosis.
Subject(s)
Sepsis , Ventricular Dysfunction, Left , Humans , Critical Illness , Sepsis/complications , Intensive Care Units , Echocardiography/methodsABSTRACT
PURPOSE: We aimed to investigate longitudinal associations between sleep duration and cardiorespiratory fitness, in adolescents. METHODS: Sleep duration was self-reported and cardiorespiratory fitness was assessed by the 20 m shuttle run test, both at baseline and follow-up (2-year follow-up). Participants were 734 Northern Portuguese adolescents (349 girls), aged 14.6 ± 1.8 years, from the LabMed study. RESULTS: Significant decreases were found between baseline and follow-up for sleep duration, whereas for cardiorespiratory fitness there was an increase. Adolescents with short sleep duration at baseline had lower cardiorespiratory fitness at follow-up, comparing to those meeting the sleep guidelines (odds ratio [OR] = 0.506, 95% confidence interval [CI]: 0.326-0.785; p = .002 for whole week; OR = 0.597, 95% CI: 0.407-0.875; p = .008 for weekdays). Girls who were short sleepers at baseline had lower odds of having a healthy cardiorespiratory fitness at follow-up, comparing to those meeting the sleep guidelines (OR = 0.311, 95% CI: 0.158-0.613; p < .001 for whole week; OR = 0.469, 95% CI: 0.262-0.838; p = .011 for weekdays). No significant associations between sleep duration and cardiorespiratory fitness were found for boys. DISCUSSION: There was a significant longitudinal association between short sleep duration and lower cardiorespiratory fitness levels, particularly in girls. Future interventions targeting adolescents' sleep duration should acknowledge behavioral differences between genders, as well as different behaviors adopted by boys ang girls, specifically on weekends.
Subject(s)
Cardiorespiratory Fitness , Humans , Male , Female , Adolescent , Sleep Duration , Self Report , Physical FitnessABSTRACT
77-year-old female with history of cholecystectomy was admitted at emergency department with fever and myalgia, without other complaints. Physical examination revealed fever, and laboratory tests indicated cholestasis (total bilirubin: 1.5xULN, glutamyltransferase: 20xULN, alkaline phosphatase: 5xULN). Computed Tomography revealed common bile duct (CBD) dilation (9mm), with suspected choledocholithiasis. Given the diagnosis of acute cholangitis, antibiotics were started and ERCP was performed. ERCP revealed a short CBD stenosis (< 2mm length), close to surgical clip, with upstream dilation of the CBD; an 8mm stone in the distal CBD was observed and successfully removed. As guidewire advancement failed after multiple attempts, a SpyGlass DS cholangioscopy was performed showing a fibrotic pinehole stenosis. Guidewire was passed through the stenosis under direct visualization, and an 80-mmx10mm fully covered metal stent deployed.
ABSTRACT
Titin is the largest protein found in nature and spans half a sarcomere in vertebrate striated muscle. The protein has multiple functions, including in the organisation of the thick filament and acting as a molecular spring during the muscle contraction cycle. Missense variants in titin have been linked to both cardiac and skeletal myopathies. Titin is primarily composed of tandem repeats of immunoglobulin and fibronectin type III (Fn3) domains in a variety of repeat patterns; however, the vast majority of these domains have not had their high-resolution structure determined experimentally. Here, we present the crystal structures of seven wild type titin Fn3 domains and two harbouring rare missense variants reported in hypertrophic cardiomyopathy (HCM) patients. All domains present the typical Fn3 fold, with the domains harbouring variants reported in HCM patients retaining the wild-type conformation. The effect on domain folding and stability were assessed for five rare missense variants found in HCM patients: four caused thermal destabilization of between 7 and 13 °C and one prevented the folding of its domain. The structures also allowed us to locate the positions of residues whose mutations have been linked to congenital myopathies and rationalise how they convey their deleterious effects. We find no evidence of physiological homodimer formation, excluding one hypothesised mechanism as to how titin variants could exert pathological effects.
Subject(s)
Muscle Proteins , Sarcomeres , Humans , Connectin/genetics , Muscle Proteins/chemistry , Muscle Proteins/genetics , Muscle Proteins/metabolism , Fibronectin Type III Domain , Muscle, SkeletalABSTRACT
BACKGROUND: There is a paucity of data regarding the phenotype of dilated cardiomyopathy (DCM) gene variants in the general population. We aimed to determine the frequency and penetrance of DCM-associated putative pathogenic gene variants in a general adult population, with a focus on the expression of clinical and subclinical phenotype, including structural, functional, and arrhythmic disease features. METHODS: UK Biobank participants who had undergone whole exome sequencing, ECG, and cardiovascular magnetic resonance imaging were selected for study. Three variant-calling strategies (1 primary and 2 secondary) were used to identify participants with putative pathogenic variants in 44 DCM genes. The observed phenotype was graded DCM (clinical or cardiovascular magnetic resonance diagnosis); early DCM features, including arrhythmia or conduction disease, isolated ventricular dilation, and hypokinetic nondilated cardiomyopathy; or phenotype-negative. RESULTS: Among 18 665 individuals included in the study, 1463 (7.8%) possessed ≥1 putative pathogenic variant in 44 DCM genes by the main variant calling strategy. A clinical diagnosis of DCM was present in 0.34% and early DCM features in 5.7% of individuals with putative pathogenic variants. ECG and cardiovascular magnetic resonance analysis revealed evidence of subclinical DCM in an additional 1.6% and early DCM features in an additional 15.9% of individuals with putative pathogenic variants. Arrhythmias or conduction disease (15.2%) were the most common early DCM features, followed by hypokinetic nondilated cardiomyopathy (4%). The combined clinical/subclinical penetrance was ≤30% with all 3 variant filtering strategies. Clinical DCM was slightly more prevalent among participants with putative pathogenic variants in definitive/strong evidence genes as compared with those with variants in moderate/limited evidence genes. CONCLUSIONS: In the UK Biobank, ≈1 of 6 of adults with putative pathogenic variants in DCM genes exhibited early DCM features potentially associated with DCM genotype, most commonly manifesting with arrhythmias in the absence of substantial ventricular dilation or dysfunction.
Subject(s)
Cardiomyopathies , Cardiomyopathy, Dilated , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/epidemiology , Arrhythmias, Cardiac/genetics , Biological Specimen Banks , Cardiomyopathies/complications , Cardiomyopathy, Dilated/diagnosis , Cardiomyopathy, Dilated/epidemiology , Cardiomyopathy, Dilated/genetics , Humans , Penetrance , United Kingdom/epidemiologyABSTRACT
BACKGROUND: The costs of developing new treatments and bringing them to the market are substantial. The pharmaceutical industry uses drug promotion to gain a competitive market share, and drive sale volumes and industry profitability. This involves disseminating information about new treatments to relevant targets. However, conflicts of interest can arise when profits are prioritised over patient care and its benefits. Drug promotion regulations are complex interventions that aim to prevent potential harm associated with these activities. OBJECTIVES: To assess the effects of policies that regulate drug promotion on drug utilisation, coverage or access, healthcare utilisation, patient outcomes, adverse events and costs. SEARCH METHODS: We searched Epistemonikos for related reviews and their included studies. To find primary studies we searched MEDLINE, CENTRAL, Embase, EconLit, Global Index Medicus, Virtual Health Library, INRUD Bibliography, two trial registries and two sources of grey literature. All databases and sources were searched in January 2023. SELECTION CRITERIA: We planned to include studies that assessed policies regulating drug promotion to consumers, healthcare professionals or regulators and third-party payers, or any combination of these groups.In this review we defined policies as laws, rules, guidelines, codes of practice, and financial or administrative orders made by governments, non-government organisations or private insurers. One of the following outcomes had to be reported: drug utilisation, coverage or access, healthcare utilisation, patient health outcomes, any adverse effects (unintended consequences), and costs. The study had to be a randomised or non-randomised trial, an interrupted time series analysis (ITS), a repeated measures (RM) study or a controlled before-after (CBA) study. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed eligibility for inclusion of studies. When consensus was not reached, any disagreements were discussed with a third review author. We planned to use the criteria suggested by Cochrane Effective Practice and Organisation of Care (EPOC) to assess the risk of bias of included studies. For randomised trials, non-randomised trials, and CBA studies, we planned to estimate relative effects, with 95% confidence intervals (CI). For dichotomous outcomes, we planned to report the risk ratio (RR) when possible and adjusted for baseline differences in the outcome measures. For ITS and RM, we planned to compute changes along two dimensions: change in level and change in slope. We planned to undertake a structured synthesis following EPOC guidance. MAIN RESULTS: The search yielded 4593 citations, and 13 studies were selected for full-text review. No study met the inclusion criteria. AUTHORS' CONCLUSIONS: We sought to assess the effects of policies that regulate drug promotion on drug use, coverage or access, use of health services, patient outcomes, adverse events, and costs, however we did not find studies that met the review's inclusion criteria. As pharmaceutical policies that regulate drug promotion have untested effects, their impact, as well as their positive and negative influences, is currently only a matter of opinion, debate, informal or descriptive reporting. There is an urgent need to assess the effects of pharmaceutical policies that regulate drug promotion using well-conducted studies with high methodological rigour.
Subject(s)
Drug and Narcotic Control , Health Services , Humans , Health Expenditures , Health Personnel , MarketingABSTRACT
BACKGROUND: Variants in the cardiac myosin-binding protein C gene (MYBPC3) are a common cause of hypertrophic cardiomyopathy (HCM) in adults and have been associated with late-onset disease, but there are limited data on their role in paediatric-onset HCM. The objective of this study was to describe natural history and clinical outcomes in a large cohort of children with HCM and pathogenic/likely pathogenic (P/LP) MYBPC3 variants. METHODS AND RESULTS: Longitudinal data from 62 consecutive patients diagnosed with HCM under 18 years of age and carrying at least one P/LP MYBPC3 variant were collected from a single specialist referral centre. The primary patient outcome was a major adverse cardiac event (MACE). Median age at diagnosis was 10 (IQR: 2-14) years, with 12 patients (19.4%) diagnosed in infancy. Forty-seven (75%) were boy and 31 (50%) were probands. Median length of follow-up was 3.1 (IQR: 1.6-6.9) years. Nine patients (14.5%) experienced an MACE during follow-up and five (8%) died. Twenty patients (32.3%) had evidence of ventricular arrhythmia, including 6 patients (9.7%) presenting with out-of-hospital cardiac arrest. Five-year freedom from MACE for those with a single or two MYBPC3 variants was 95.2% (95% CI: 78.6% to 98.5%) and 68.4% (95% CI: 40.6% to 88.9%), respectively (HR 4.65, 95% CI: 1.16 to 18.66, p=0.03). CONCLUSIONS: MYBPC3 variants can cause childhood-onset disease, which is frequently associated with life-threatening ventricular arrhythmia. Clinical outcomes in this cohort vary substantially from aetiologically and genetically mixed paediatric HCM cohorts described previously, highlighting the importance of identifying specific genetic subtypes for clinical management of childhood HCM.
Subject(s)
Cardiomyopathy, Hypertrophic , Carrier Proteins , Adolescent , Cardiac Myosins/genetics , Cardiomyopathy, Hypertrophic/diagnosis , Cardiomyopathy, Hypertrophic/genetics , Carrier Proteins/genetics , Child , Child, Preschool , Cytoskeletal Proteins/genetics , Female , Heart , Humans , Infant , Male , MutationABSTRACT
AIMS: To study the impact of genotype on the performance of the 2019 risk model for arrhythmogenic right ventricular cardiomyopathy (ARVC). METHODS AND RESULTS: The study cohort comprised 554 patients with a definite diagnosis of ARVC and no history of sustained ventricular arrhythmia (VA). During a median follow-up of 6.0 (3.1,12.5) years, 100 patients (18%) experienced the primary VA outcome (sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator intervention, aborted sudden cardiac arrest, or sudden cardiac death) corresponding to an annual event rate of 2.6% [95% confidence interval (CI) 1.9-3.3]. Risk estimates for VA using the 2019 ARVC risk model showed reasonable discriminative ability but with overestimation of risk. The ARVC risk model was compared in four gene groups: PKP2 (n = 118, 21%); desmoplakin (DSP) (n = 79, 14%); other desmosomal (n = 59, 11%); and gene elusive (n = 160, 29%). Discrimination and calibration were highest for PKP2 and lowest for the gene-elusive group. Univariable analyses revealed the variable performance of individual clinical risk markers in the different gene groups, e.g. right ventricular dimensions and systolic function are significant risk markers in PKP2 but not in DSP patients and the opposite is true for left ventricular systolic function. CONCLUSION: The 2019 ARVC risk model performs reasonably well in gene-positive ARVC (particularly for PKP2) but is more limited in gene-elusive patients. Genotype should be included in future risk models for ARVC.
Subject(s)
Arrhythmogenic Right Ventricular Dysplasia , Arrhythmias, Cardiac , Arrhythmogenic Right Ventricular Dysplasia/genetics , Death, Sudden, Cardiac/epidemiology , Death, Sudden, Cardiac/etiology , Death, Sudden, Cardiac/prevention & control , Genotype , Humans , Risk Assessment , Risk FactorsABSTRACT
We report a case of a 54-year-old female that underwent sigmoidectomy for stage IIA adenocarcinoma. After 5 years of follow-up, despite normal colonoscopy and CEA and CA-19.9 levels, abdominal CT revealed a 3 cm perianastomotic peritoneal lesion and suspected liver metastasis. Although liver biopsy was negative for malignancy, the perianastomotic lesion was confirmed to be metastasis of colonic adenocarcinoma. After chemotherapy, a mild elevation of alkaline phosphatase and γ-GT was evident. MRCP revealed dilation of intrahepatic bile ducts in segment VIII due to an intraluminal lesion in the right hepatic duct, suggestive of intraductal cholangiocarcinoma.
Subject(s)
Adenocarcinoma , Bile Duct Neoplasms , Cholangiocarcinoma , Colorectal Neoplasms , Liver Neoplasms , Female , Humans , Middle Aged , Bile Duct Neoplasms/surgery , Colorectal Neoplasms/pathology , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/surgery , Adenocarcinoma/pathology , Liver/pathology , Bile Ducts, Intrahepatic/pathology , Cholangiocarcinoma/pathology , Liver Neoplasms/pathologyABSTRACT
A 50-year-old woman with a history of bicuspid aortic valve (BAV) and ascending aorta dissection was referred for endoscopic ultrasound (EUS) for suspected choledocholithiasis. Twelve years earlier she had undergone a Bentall-de Bone procedure and 7 years earlier a thoracic aorta aneurysm (TAA) was repaired with an endovascular prosthesis. EUS confirmed choledocholithiasis, however a large aneurysm (60 mm of diameter), was incidentally detected at the distal end of the aortic endoprosthesis. Computed tomography (CT) later confirmed the aneurysm, extending 4.5 cm above the renal arteries. The patient underwent a successful new endovascular repair. This rare incidental finding underscores the usefulness of a systematic approach when performing EUS, enabling the detection of significant abnormalities beyond the initial indication and allowing for early intervention in TTA patients.
ABSTRACT
A 49-year-old man presented with a three-week history of abdominal pain, bloody diarrhoea and fever. Reported oral ulcers, weight loss and asthenia, as well as papulo-pustular lesions on his limbs and a recurrent ulcer in the lip (Fig.1) in the previous year. During hospitalization, he developed pathergy at venipuncture sites and painful scrotum ulcers. Laboratory showed pancytopenia and elevated CRP. Viral and autoimmune tests were negative. Abdominal CT revealed thickening of the ileocecal region with adenopathies. Blood smear and myelogram were compatible with Chronic Myeloid Leukemia (CML). Bone marrow culture and BK were negative. Karyotype revealed no changes, namely, no trisomy of the 8th. Ileocolonoscopy revealed aphthoid erosions of the ileocecal mucosa and ovoid punched-out cecal ulcers. Biopsies showed intense chronic inflammation in the lamina propria and submucosa with erosions and ulcers. Thus, presenting 5 points in the International Criteria for Behçet's Disease, this diagnosis was assumed as a paraneoplastic manifestation of CML. Corticosteroids improved symptoms, but the patient died three weeks later due to a blastic crisis. BS has been reported in association with CML, some concurrent with, or following treatment with interferon-a or hydroxyurea. Although the pathogenesis remains unclear, there is increasing awareness of its link to hematological malignancies, and trisomy of the 8th.
ABSTRACT
An 82-year-old man was admitted for acute cholangitis. He presented with jaundice and elevated hepatic cholestasis enzymes and C-reactive protein. Abdominal ultrasound and CT scan showed no evidence of gallstones and the main bile duct had 6 mm of diameter. Broad-spectrum antibiotic therapy was initiated and the patient was referred for Endoscopic Retrograde Cholangiopancreatography. During duodenoscopy, a pedunculated subepithelial lesion, measuring approximately 20-30 mm, and suggestive of being a lipoma was found, obstructing the papillary orifice and preventing its access. It was then removed using a diathermic snare. Subsequent cholangiography confirmed the absence of gallstones or any other cause of biliary obstruction. Histopathological analysis confirmed that the lesion was a duodenal lipoma. The patient evolved favorably and had no subsequent episodes of jaundice or cholangitis during follow-up.
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Background and Aims: Sugammadex (SUG) has been associated with changes in coagulation studies. Most reports have concluded a lack of clinical significance based on surgical blood loss with SUG use at the end of surgery. Previous reports have not measured its use intraoperatively during ongoing blood loss. Our hypothesis was that the use of SUG intraoperatively may increase bleeding. Material and Methods: This was a single site retrospective study. Inclusion criteria were patients undergoing a primary posterior cervical spine fusion, aged over 18 years, between July 2015 and June 2021. The primary outcomes compared were intraoperative estimated blood loss (EBL) and postoperative drain output (PDO) between patients receiving SUG, neostigmine (NEO) and no NMB reversal agent. The objective was to determine if there was a difference in primary endpoints between patients administered SUG, NEO or no paralytic reversal agent. Primary endpoints were compared using analysis of variance with a P value of 0.05 used to determine statistical significance. Groups were compared using the Chi-squared test, rank sum or student's t test. A logistic regression model was constructed to account for differences between the groups. Results: There was no difference in median EBL or PDO between groups. The use of SUG was not associated with an increase in odds for >500 milliliters (ml) of EBL. Increasing duration of surgery and chronic kidney disease were both associated with an increased risk for EBL >500 ml. Conclusion: Intraoperative use of SUG was not associated with increased bleeding. Any coagulation laboratory abnormalities previously noted did not appear to have an associated clinical significance.
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BACKGROUND: Measurement of cardiac structure and function from images (e.g. volumes, mass and derived parameters such as left ventricular (LV) ejection fraction [LVEF]) guides care for millions. This is best assessed using cardiovascular magnetic resonance (CMR), but image analysis is currently performed by individual clinicians, which introduces error. We sought to develop a machine learning algorithm for volumetric analysis of CMR images with demonstrably better precision than human analysis. METHODS: A fully automated machine learning algorithm was trained on 1923 scans (10 scanner models, 13 institutions, 9 clinical conditions, 60,000 contours) and used to segment the LV blood volume and myocardium. Performance was quantified by measuring precision on an independent multi-site validation dataset with multiple pathologies with n = 109 patients, scanned twice. This dataset was augmented with a further 1277 patients scanned as part of routine clinical care to allow qualitative assessment of generalization ability by identifying mis-segmentations. Machine learning algorithm ('machine') performance was compared to three clinicians ('human') and a commercial tool (cvi42, Circle Cardiovascular Imaging). FINDINGS: Machine analysis was quicker (20 s per patient) than human (13 min). Overall machine mis-segmentation rate was 1 in 479 images for the combined dataset, occurring mostly in rare pathologies not encountered in training. Without correcting these mis-segmentations, machine analysis had superior precision to three clinicians (e.g. scan-rescan coefficients of variation of human vs machine: LVEF 6.0% vs 4.2%, LV mass 4.8% vs. 3.6%; both P < 0.05), translating to a 46% reduction in required trial sample size using an LVEF endpoint. CONCLUSION: We present a fully automated algorithm for measuring LV structure and global systolic function that betters human performance for speed and precision.
Subject(s)
Machine Learning , Magnetic Resonance Imaging , Humans , Magnetic Resonance Imaging, Cine/methods , Magnetic Resonance Spectroscopy , Predictive Value of Tests , Reproducibility of Results , Stroke Volume , Ventricular Function, LeftABSTRACT
BACKGROUND: Peroral cholangioscopy (POC)-guided lithotripsy is an effective treatment for difficult biliary stones. A clear definition of factors associated with the efficacy of POC-guided lithotripsy in one session and the performance of electrohydraulic lithotripsy (EHL) and laser lithotripsy (LL) have not clearly emerged. METHODS: This was a non-randomized prospective multicenter study of all consecutive patients who underwent POC lithotripsy (using EHL and/or LL) for difficult biliary stones. The primary endpoint of the study was the number of sessions needed to achieve complete ductal clearance and the factors associated with this outcome. Secondary endpoints included the evaluated efficacies of LL and EHL. RESULTS: Ninety-four patients underwent 113 procedures of EHL or LL. Complete ductal clearance was obtained in 93/94 patients (98.94%). In total, 80/94 patients (85.11%) achieved stone clearance in a single session. In the multivariate analysis, stone size was independently associated with the need for multiple sessions to achieve complete ductal clearance (odds ratio = 1.146, 95% confidence interval: 1.055-1.244; p = 0.001). Using ROC curves and the Youden index, 22 mm was found to be the optimal cutoff for stone size (95% confidence interval: 15.71-28.28; p < 0.001). The majority of the patients (62.8%) underwent LL in the first session. Six patients failed the first session with EHL after using two probes and therefore were crossed over to LL, obtaining ductal clearance in a single additional session with a single LL fiber. EHL was significantly associated with a larger number of probes (2.0 vs. 1.02) to achieve ductal clearance (p < 0.01). The mean procedural time was significantly longer for EHL than for LL [72.1 (SD 16.3 min) versus 51.1 (SD 10.5 min)] (p < 0.01). CONCLUSIONS: POC is highly effective for difficult biliary stones. Most patients achieved complete ductal clearance in one session, which was significantly more likely for stones < 22 mm. EHL was significantly associated with the need for more probes and a longer procedural time to achieve ductal clearance.