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1.
Cardiooncology ; 8(1): 19, 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36401304

RESUMO

We report the case of a 59-year-old female patient with no previous cardiovascular disease treated for Breast cancer with Capecitabine. Shortly after starting treatment, she developed recurrent angina. An exercise stress echocardiogram was performed, which induced a type 1 Brugada pattern 12 s of a non-sustained pleomorphic ventricular tachycardia ensued.

2.
Cardiovasc Revasc Med ; 36: 34-40, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33941485

RESUMO

BACKGROUND: There are limited data on influence of body mass index (BMI) on outcomes of acute myocardial infarction-cardiogenic shock (AMI-CS). METHODS: Adult AMI-CS admissions from 2008 to 2017 were identified from the National Inpatient Sample and stratified by BMI into underweight (<19.9 kg/m2), normal-BMI (19.9-24.9 kg/m2) and overweight/obese (>24.9 kg/m2). Outcomes of interest included in-hospital mortality, invasive cardiac procedures use, hospitalization costs, and discharge disposition. RESULTS: Of 339,364 AMI-CS admissions, underweight and overweight/obese constitute 2356 (0.7%) and 46,675 (13.8%), respectively. In 2017, compared to 2008, there was an increase in underweight (adjusted odds ratio [aOR] 6.40 [95% confidence interval {CI} 4.91-8.31]; p < 0.001) and overweight/obese admissions (aOR 2.93 [95% CI 2.78-3.10]; p < 0.001). Underweight admissions were on average older, female, with non-ST-segment-elevation AMI-CS, and higher comorbidity. Compared to normal and overweight/obese admissions, underweight admissions had lower rates of coronary angiography (57% vs 72% vs 78%), percutaneous coronary intervention (40% vs 54% vs 54%), and mechanical circulatory support (28% vs 46% vs 49%) (p < 0.001). In-hospital mortality was lower in underweight (32.9% vs 34.1%, aOR 0.64 [95% CI 0.57-0.71], p < 0.001) and overweight/obese (27.6% vs 38.4%, aOR 0.89 [95% CI 0.87-0.92], p < 0.001) admissions. Higher hospitalization costs were seen in overweight/obese admissions while underweight admissions were discharged more often to skilled nursing facilities. CONCLUSION: Underweight patients received less frequent cardiac procedures and were discharged more often to skilled nursing facilities. Underweight and overweight/obese AMI-CS admissions had lower in-hospital mortality compared to normal BMI.


Assuntos
Infarto do Miocárdio , Intervenção Coronária Percutânea , Adulto , Índice de Massa Corporal , Feminino , Mortalidade Hospitalar , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/efeitos adversos , Choque Cardiogênico/diagnóstico , Choque Cardiogênico/terapia , Estados Unidos/epidemiologia
3.
Ann Intern Med ; 174(11): JC126, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34724397

RESUMO

SOURCE CITATION: Dankiewicz J, Cronberg T, Lilja G, et al. Hypothermia versus normothermia after out-of-hospital cardiac arrest. N Engl J Med. 2021;384:2283-94. 34133859.


Assuntos
Hipotermia Induzida , Hipotermia , Parada Cardíaca Extra-Hospitalar , Adulto , Coma/terapia , Humanos , Parada Cardíaca Extra-Hospitalar/terapia
4.
BMJ ; 373: n379, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846159

RESUMO

Atrial fibrillation is a common chronic disease seen in primary care offices, emergency departments, inpatient hospital services, and many subspecialty practices. Atrial fibrillation care is complicated and multifaceted, and, at various points, clinicians may see it as a consequence and cause of multi-morbidity, as a silent driver of stroke risk, as a bellwether of an acute medical illness, or as a primary rhythm disturbance that requires targeted treatment. Primary care physicians in particular must navigate these priorities, perspectives, and resources to meet the needs of individual patients. This includes judicious use of diagnostic testing, thoughtful use of novel therapeutic agents and procedures, and providing access to subspecialty expertise. This review explores the epidemiology, screening, and risk assessment of atrial fibrillation, as well as management of its symptoms (rate and various rhythm control options) and stroke risk (anticoagulation and other treatments), and offers a model for the integration of the components of atrial fibrillation care.


Assuntos
Fibrilação Atrial/diagnóstico , Programas de Rastreamento/normas , Guias de Prática Clínica como Assunto , Atenção Primária à Saúde/normas , Acidente Vascular Cerebral/prevenção & controle , Antiarrítmicos/administração & dosagem , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , Cateterismo Cardíaco , Eletrocardiografia , Carga Global da Doença , Estilo de Vida Saudável , Frequência Cardíaca/efeitos dos fármacos , Frequência Cardíaca/fisiologia , Humanos , Incidência , Programas de Rastreamento/métodos , Prevalência , Atenção Primária à Saúde/métodos , Medição de Risco/métodos , Fatores de Risco , Acidente Vascular Cerebral/etiologia
5.
World J Cardiol ; 13(12): 720-732, 2021 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-35070114

RESUMO

Acute myocardial infarction (AMI) with left ventricular (LV) dysfunction patients, the most common cause of cardiogenic shock (CS), have acutely deteriorating hemodynamic status. The frequent use of vasopressor and inotropic pharmacologic interventions along with mechanical circulatory support (MCS) in these patients necessitates invasive hemodynamic monitoring. After the pivotal Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness trial failed to show a significant improvement in clinical outcomes in shock patients managed with a pulmonary artery catheter (PAC), the use of PAC has become less popular in clinical practice. In this review, we summarize currently available literature to summarize the indications, clinical relevance, and recommendations for use of PAC in the setting of AMI-CS.

6.
FASEB J ; 34(7): 8778-8786, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32946179

RESUMO

Reporting the sex of biological material is critical for transparency and reproducibility in science. This study examined the reporting of the sex of cells used in cardiovascular studies. Articles from 16 cardiovascular journals that publish peer-reviewed studies in cardiovascular physiology and pharmacology in the year 2018 were systematically reviewed using terms "cultured" and "cells." Data were collected on the sex of cells, the species from which the cells were isolated, and the type of cells, and summarized as a systematic review. Sex was reported in 88 (38.6%) of the 228 studies meeting inclusion criteria. Reporting rates varied with Circulation, Cardiovascular Research and American Journal of Physiology: Heart and Circulatory Physiology having the highest rates of sex reporting (>50%). A majority of the studies used cells from male (54.5%) or both male and female animals (32.9%). Humans (31.8%), rats (20.4%), and mice (43.8%) were the most common sources for cells. Cardiac myocytes were the most commonly used cell type (37.0%). Overall reporting of sex of experimental material remains below 50% and is inconsistent among journals. Sex chromosomes in cells have the potential to affect protein expression and molecular signaling pathways and should be consistently reported.


Assuntos
Pesquisa Biomédica , Sistema Cardiovascular/fisiopatologia , Sistema Cardiovascular/citologia , Células Cultivadas , Feminino , Humanos , Masculino , Fatores Sexuais
7.
J Am Heart Assoc ; 9(15): e016893, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32715895

RESUMO

Background Intracerebral hemorrhage (ICH) risk is higher in elderly patients with atrial fibrillation on antithrombotic therapy as well as those with cerebral amyloid angiopathy (CAA). We investigated if mortality among patients with atrial fibrillation on antithrombotic therapy presenting with non-traumatic ICH was influenced by underlying CAA. Methods and Results We used the Rochester Epidemiology Project to identify 6045 patients with atrial fibrillation aged >55 years on anticoagulation or antiplatelet therapy from 1995 to 2016. Seventy-four patients in this cohort presented with non-traumatic ICH. Medical records including imaging data were reviewed to identify those with CAA and record baseline variables and outcomes of interest; 38 of our 74 patients (51.4%) (mean age 81.5 years) met Modified Boston Criteria for possible or probable CAA. Twenty-six of 74 patients (35%) died during the first 30 days while 56 of the 74 (76%) patients died by 10 years follow-up after index ICH. Overall mortality was not significantly different between the CAA and non-CAA groups at any point of time during follow-up (P=0.89) even amongst patients restarted on anticoagulation +/- antiplatelet (n=19) (P=0.46) or those patients restarted only on antiplatelet therapy (n=22) (P=0.66). Three of the 41 patients who restarted on antithrombotic therapy had a recurrent ICH; these 3 patients met criteria for possible or probable CAA. Conclusions Although more than half of our patients with atrial fibrillation on antithrombotic therapy and non-traumatic ICH met Modified Boston Criteria for CAA, CAA did not significantly influence the high mortality seen in this cohort.


Assuntos
Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Angiopatia Amiloide Cerebral/complicações , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/mortalidade , Idoso , Idoso de 80 Anos ou mais , Angiopatia Amiloide Cerebral/diagnóstico por imagem , Feminino , Humanos , Incidência , Imageamento por Ressonância Magnética , Masculino , Minnesota/epidemiologia , Recidiva , Estudos Retrospectivos , Acidente Vascular Cerebral/prevenção & controle , Tomografia Computadorizada por Raios X
8.
Open Forum Infect Dis ; 7(1): ofaa003, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31988969

RESUMO

We performed a case-control study to evaluate an electronic, asynchronous infectious diseases consultative service at 2 rural hospitals within our health system. Patients with consultation via this platform (n = 100) had a significantly decreased odds of death at 30 days compared with propensity-matched controls (n = 300; adjusted odds ratio, 0.3; 95% confidence interval, 0.2-0.7; P = .003).

9.
Pacing Clin Electrophysiol ; 40(3): 310-322, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27943333

RESUMO

BACKGROUND: Echocardiographically detected patent foramen ovale (PFO) has been associated with stroke/transient ischemic attack (TIA) in patients with cardiac implantable electronic devices (CIEDs). We sought to evaluate the relationship between echocardiographic characteristics and risk of stroke/TIA and mortality in CIED patients with PFO. METHODS: In 6,086 device patients, PFO was detected in 319 patients. A baseline echocardiogram was present in 250 patients, with 186 having a follow-up echocardiogram. RESULTS: Of 250 patients with a baseline echocardiogram, 9.6% (n = 24) had a stroke/TIA during mean follow-up of 5.3 ± 3.1 years; and 42% (n = 105) died over 7.1 ± 3.7 years. Atrial septal aneurysm, prominent Eustachian valve, visible shunting across PFO, baseline or change in estimated right ventricular systolic pressure (RVSP)/tricuspid regurgitation (TR), or maximum RVSP were not associated with postimplant stroke/TIA (P > 0.05). An exploratory multivariate analysis using time-dependent Cox models showed increased hazard of death in patients with increase in TR ≥2 grades (hazard ratio [HR] 1.780, 95% confidence interval [CI] 1.447-2.189, P < 0.0001), or increase in RVSP by >10 mm Hg (HR 2.018, 95% CI 1.593-2.556, P < 0.0001), or maximum RVSP in follow-up (HR 1.432, 95% CI 1.351-1.516, P < 0.0001). A significant increase (P < 0.001) in TR was also noted during follow-up. CONCLUSIONS: In patients with CIED and PFO, structural and hemodynamic echocardiographic markers did not predict future stroke/TIA. However, a significantly higher TR or RVSP was associated with higher mortality.


Assuntos
Desfibriladores Implantáveis/estatística & dados numéricos , Ecocardiografia/estatística & dados numéricos , Forame Oval Patente/mortalidade , Ataque Isquêmico Transitório/mortalidade , Marca-Passo Artificial/estatística & dados numéricos , Acidente Vascular Cerebral/mortalidade , Idoso , Causalidade , Comorbidade , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Humanos , Masculino , Minnesota/epidemiologia , Prevalência , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Estatística como Assunto , Taxa de Sobrevida
10.
J Interv Card Electrophysiol ; 46(3): 237-43, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26898212

RESUMO

INTRODUCTION: Cardiac implantable electronic device (CIED) leads frequently develop echogenic masses. However, the nature of these masses is not well understood. In patients in whom atrial fibrillation (AF) catheter ablation is planned, there is concern that transseptal puncture may result in cerebrovascular embolism of these masses. The optimal therapeutic strategy in this setting remains undefined. METHODS: We describe six patients identified over a 6-year period (2008-2014) with device lead-based masses prior to or at the time of AF ablation. We examined the anticoagulation strategy and periprocedural management based on mass identification. RESULTS: In all six patients (age 39-73; four males), the device lead mass was found in the right atrium. The average mass size was 11 ± 1.3 mm. The majority of patients were already on anticoagulation (5/6; 83 %), and an intensified anticoagulation regimen was initiated (INR goal 3.0). In all six patients, the size of the device lead mass decreased on repeat imaging. In two sixths (33 %) patients, the lead-based mass completely resolved within 2 months. The remaining four patients had persistent lead-based masses (average follow-up of 10.9 ± 9.6 months). DISCUSSION: We describe a series of patients with CIED lead-based masses found at the time of ablation. These cases illustrate that lead-based masses can disappear while patients are on high-intensity anticoagulation, most compatible with a thrombotic origin. These early data will need to be assessed in larger cohorts for further validation and evaluation of safety.


Assuntos
Anticoagulantes/administração & dosagem , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Eletrodos Implantados/efeitos adversos , Trombose/etiologia , Trombose/prevenção & controle , Adulto , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Estudos de Casos e Controles , Desfibriladores Implantáveis/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Marca-Passo Artificial/efeitos adversos , Assistência Perioperatória/métodos , Pré-Medicação/métodos , Resultado do Tratamento
11.
J Interv Card Electrophysiol ; 46(2): 137-43, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26768434

RESUMO

BACKGROUND: Bileaflet mitral valve prolapse (MVP) can be associated with malignant ventricular arrhythmias. It is unknown whether surgical correction alone of this mitral valve pathology leads to a reduction in ventricular dysrhythmias. METHODS: We retrospectively analyzed 4477 patients who underwent mitral valve surgery from 1993-2013 at Mayo Clinic in Rochester, MN. Among these, eight patients with bileaflet MVP who had an internal cardioverter defibrillator (ICD) in place both pre- and post-surgery were identified. ICD interrogation records were evaluated for episodes of ventricular tachycardia (VT), ventricular fibrillation (VF), and appropriate ICD shock therapy. RESULTS: Of these eight patients, five had a malignant ventricular arrhythmia prior to surgery. Data was available 4.6 ± 2.9 years before versus 6.6 ± 4.2 years following surgical intervention. Among these patients, there was a reduction in VF (0.6 versus 0.14 events per-person-year pre- and post-surgery, respectively), VT (0.4 versus 0.05 events per-person-year pre- and post-surgery, respectively), and ICD shocks (0.95 versus 0.19 events per-person-year pre- and post-surgery) following mitral valve surgery. CONCLUSIONS: We report a series of cases where the surgical correction of bileaflet MVP alone was associated with a reduction in malignant arrhythmia and appropriate shocks. These early observations merit further investigation involving larger cohorts to further evaluate the association between abnormal mechanical forces in degenerative mitral valve disease and ventricular dysrhythmias.


Assuntos
Desfibriladores Implantáveis/estatística & dados numéricos , Traumatismos por Eletricidade/mortalidade , Anuloplastia da Valva Mitral/estatística & dados numéricos , Prolapso da Valva Mitral/mortalidade , Prolapso da Valva Mitral/cirurgia , Taquicardia Ventricular/mortalidade , Causalidade , Terapia Combinada/mortalidade , Terapia Combinada/estatística & dados numéricos , Comorbidade , Traumatismos por Eletricidade/prevenção & controle , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Anuloplastia da Valva Mitral/mortalidade , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Taquicardia Ventricular/prevenção & controle , Resultado do Tratamento , Fibrilação Ventricular
12.
Europace ; 18(2): 246-52, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25767086

RESUMO

BACKGROUND: Cardiac implantable electronic devices (CIEDs) are commonly associated with transvenous lead-related thrombi that can cause pulmonary embolism (PE). METHODS AND RESULTS: We retrospectively evaluated all patients with transvenous CIED leads implanted at Mayo Clinic Rochester between 1 January 2000, and 25 October 2010. Pulmonary embolism outcomes during follow-up were screened using diagnosis codes and confirmed with imaging study reports. Of 5646 CIED patients (age 67.3 ± 16.3 years, 64% men, mean follow-up 4.69 years) 88 developed PE (1.6%), incidence 3.32 [95% confidence interval (CI) 2.68-4.07] per 1000 person-years [men: 3.04 (95% CI 2.29-3.96) per 1000 person-years; women: 3.81 (95% CI 2.72-5.20) per 1000 person-years]. Other than transvenous CIED lead(s), 84% had another established risk factor for PE such as deep vein thrombosis (28%), recent surgery (27%), malignancy (25%), or prior history of venous thromboembolism (15%). At the time of PE, 22% had been hospitalized for ≥ 48 h, and 59% had been hospitalized in the preceding 30 days. Pulmonary embolism occurred in 22% despite being on systemic anticoagulation therapy. Out of 88 patients with PE, 45 subsequently died, mortality rate 93 (95% CI 67-123) per 1000 person-years (hazard ratio 2.0, 95% CI 1.5-2.7, P < 0.0001). CONCLUSIONS: Though lead-related thrombus is commonly seen in patients with transvenous CIED leads, clinical PE occurs with a low incidence. It is possible that embolism of lead thrombus is uncommon or emboli are too small to cause consequential pulmonary infarction.


Assuntos
Arritmias Cardíacas/terapia , Desfibriladores Implantáveis/efeitos adversos , Marca-Passo Artificial/efeitos adversos , Embolia Pulmonar/epidemiologia , Trombose/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/mortalidade , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Modelos de Riscos Proporcionais , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Trombose/diagnóstico por imagem , Trombose/mortalidade , Fatores de Tempo , Adulto Jovem
13.
Indian Pacing Electrophysiol J ; 16(6): 187-191, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28401865

RESUMO

BACKGROUND: Bileaflet mitral valve prolapse (biMVP) is associated with frequent ventricular ectopy (VE) and malignant ventricular arrhythmia. We examined the effect of mitral valve (MV) surgery on VE burden in biMVP patients. METHODS: We included 32 consecutive patients undergoing MV surgery for mitral regurgitation secondary to biMVP between 1993 and 2012 at Mayo Clinic who had available pre- and post-operative Holter monitoring data. Characteristics of patients with a significant reduction in postoperative VE (group A, defined as >10% reduction in VE burden compared to baseline) were compared with the rest of study patients (group B). RESULTS: In the overall cohort, VE burden was unchanged after the surgery (41 interquartile range [16, 196] pre-surgery vs. 40 interquartile range [5186] beats/hour [bph] post-surgery; P = 0.34). However, in 17 patients (53.1%), VE burden decreased by at least 10% after the surgery. These patients (group A) were younger than the group B (59 ± 15 vs. 68 ± 7 years; P = 0.04). Other characteristics including pre- and postoperative left ventricular function and size were similar in both groups. Age <60 years was associated with a reduction in postoperative VE (odds ratio 5.8; 95% confidence interval, 1.1-44.7; P = 0.03). Furthermore, there was a graded relationship between age and odds of VE reduction with surgery (odds ratio 1.9; 95% confidence interval 1.04-4.3 per 10-year; P = 0.04). CONCLUSIONS: MV surgery does not uniformly reduce VE burden in patients with biMVP. However, those patients who do have a reduction in VE burden are younger, perhaps suggesting that early surgical intervention could modify the underlying electrophysiologic substrate.

14.
J Cardiovasc Dev Dis ; 3(1)2016 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-29367555

RESUMO

Takotsubo cardiomyopathy (TC) or stress-induced cardiomyopathy is also popularly referred to as "broken heart syndrome" or "apical ballooning syndrome". [...].

15.
Clin Sports Med ; 34(3): 473-87, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26100423

RESUMO

Athletes with an implantable cardioverter defibrillator (ICD) represent a diverse group of individuals who may be at an increased risk of sudden cardiac death when engaging in vigorous physical activity. Therefore, they are excluded by the current guidelines from participating in most competitive sports except those classified as low intensity, such as bowling and golf. The lack of substantial data on the natural history of the cardiac diseases affecting these athletes as well as the unknown efficacy of ICDs in terminating life-threatening arrhythmias occurring during intense exercise has resulted in the restrictive nature of these now decade old guidelines.


Assuntos
Arritmias Cardíacas/terapia , Atletas , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Esportes para Pessoas com Deficiência/fisiologia , Exercício Físico/fisiologia , Humanos , Fatores de Risco
16.
Int J Cardiol Heart Vasc ; 8: 103-107, 2015 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-26925456

RESUMO

INTRODUCTION: Fibrosing mediastinitis (FM) is a rare but fatal disease characterized by an excessive fibrotic reaction in the mediastinum, which can lead to life-threatening stenosis of the pulmonary veins (PV). Catheter-based intervention is currently the only viable option for therapy. However, the current literature on how best to manage these difficult cases, especially in regards to sequential interventions and their potential complications is very limited. METHODS: We searched through a database of all patients who have undergone PV interventions at the Earl H. Wood Cardiac Catheterization Laboratory in Mayo Clinic, Rochester. From this collection, we selected patients that underwent PV intervention to relieve stenosis secondary to FM. RESULTS: Eight patients were identified, with a mean age of 41 years (24-59 years). Five were men, and three were women. Three patients underwent balloon angioplasty alone, and five patients had stents placed. The majority of patients had acute hemodynamic and symptomatic improvement. More than one intervention was required in five patients, four patients had at least one episode of restenosis, and four patients died within four weeks of their first PV intervention. CONCLUSIONS: We describe the largest reported case series of catheter-based intervention for PV stenosis in FM. Although catheter-based therapy improved hemodynamics, short-term vascular patency, and patient symptoms, the rate of life-threatening complications, restenosis, and mortality associated with these interventions was found to be high. Despite these associated risks, catheter-based intervention is the only palliative option available to improve quality of life in severely symptomatic patients with PV stenosis and FM. Patients with PV stenosis and FM (especially those with bilateral disease) have an overall poor prognosis in spite of undergoing these interventions due to the progressive and recalcitrant nature of the disease. This underscores the need for further innovative approaches to manage this disease.

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