RESUMEN
BACKGROUND & AIMS: Identifying metabolic abnormalities that occur before pancreatic ductal adenocarcinoma (PDAC) diagnosis could increase chances for early detection. We collected data on changes in metabolic parameters (glucose, serum lipids, triglycerides; total, low-density, and high-density cholesterol; and total body weight) and soft tissues (abdominal subcutaneous fat [SAT], adipose tissue, visceral adipose tissue [VAT], and muscle) from patients 5 years before the received a diagnosis of PDAC. METHODS: We collected data from 219 patients with a diagnosis of PDAC (patients) and 657 healthy individuals (controls) from the Rochester Epidemiology Project, from 2000 through 2015. We compared metabolic profiles of patients with those of age- and sex-matched controls, constructing temporal profiles of fasting blood glucose, serum lipids including triglycerides, cholesterol profiles, and body weight and temperature for 60 months before the diagnosis of PDAC (index date). To construct the temporal profile of soft tissue changes, we collected computed tomography scans from 68 patients, comparing baseline (>18 months before diagnosis) areas of SAT, VAT, and muscle at L2/L3 vertebra with those of later scans until time of diagnosis. SAT and VAT, isolated from healthy individuals, were exposed to exosomes isolated from PDAC cell lines and analyzed by RNA sequencing. SAT was collected from KRAS+/LSLG12D P53flox/flox mice with PDACs, C57/BL6 (control) mice, and 5 patients and analyzed by histology and immunohistochemistry. RESULTS: There were no significant differences in metabolic or soft tissue features of patients vs controls until 30 months before PDAC diagnosis. In the 30 to 18 months before PDAC diagnosis (phase 1, hyperglycemia), a significant proportion of patients developed hyperglycemia, compared with controls, without soft tissue changes. In the 18 to 6 months before PDAC diagnosis (phase 2, pre-cachexia), patients had significant increases in hyperglycemia and decreases in serum lipids, body weight, and SAT, with preserved VAT and muscle. In the 6 to 0 months before PDAC diagnosis (phase 3, cachexia), a significant proportion of patients had hyperglycemia compared with controls, and patients had significant reductions in all serum lipids, SAT, VAT, and muscle. We believe the patients had browning of SAT, based on increases in body temperature, starting 18 months before PDAC diagnosis. We observed expression of uncoupling protein 1 (UCP1) in SAT exposed to PDAC exosomes, SAT from mice with PDACs, and SAT from all 5 patients but only 1 of 4 controls. CONCLUSIONS: We identified 3 phases of metabolic and soft tissue changes that precede a diagnosis of PDAC. Loss of SAT starts 18 months before PDAC identification, and is likely due to browning. Overexpression of UCP1 in SAT might be a biomarker of early-stage PDAC, but further studies are needed.
Asunto(s)
Caquexia/etiología , Carcinoma Ductal Pancreático/sangre , Carcinoma Ductal Pancreático/diagnóstico , Hiperglucemia/sangre , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/diagnóstico , Adipocitos/metabolismo , Adipocitos/patología , Animales , Glucemia/metabolismo , Temperatura Corporal , Peso Corporal , Carcinoma Ductal Pancreático/complicaciones , Carcinoma Ductal Pancreático/genética , Estudios de Casos y Controles , Células Cultivadas , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Exosomas , Humanos , Hiperglucemia/etiología , Grasa Intraabdominal/diagnóstico por imagen , Grasa Intraabdominal/patología , Ratones , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/genética , ARN Mensajero/metabolismo , Estudios Retrospectivos , Grasa Subcutánea Abdominal/diagnóstico por imagen , Grasa Subcutánea Abdominal/patología , Factores de Tiempo , Tomografía Computarizada por Rayos X , Triglicéridos/sangre , Proteína Desacopladora 1/genética , Regulación hacia ArribaRESUMEN
INTRODUCTION: The majority of patients with pancreatic ductal adenocarcinoma (PC) display either impaired fasting glucose/glucose intolerance or overt diabetes. However, the pathophysiologic basis of this association remains largely unexplained. METHODS: In this case-control study we aimed to study the morphological changes in the islets of patients with PC, compared to control patients with and without type 2 diabetes mellitus (T2DM). T2DM controls and PC cases had a lower ß-cell area and average islet size and density compared to non-T2DM controls (p < 0.05). RESULTS: Compared to both T2DM and non-T2DM controls, mean α-cell area was significantly lower and ß/α-ratio was higher in PC cases (p < 0.05). Furthermore, whereas islets in T2DM controls were characterized by disrupted islet architecture and presence of islet amyloid aggregates, islet composition in PC islets was not significantly different compared to non-T2DM controls (p > 0.05 vs. Control). CONCLUSIONS: Our data shows that PC is associated with a unique pattern of islet pathology characterized by preserved architecture, absence of amyloid aggregates, and relative α-cell loss indicating that distinct mechanisms are likely involved in the pathophysiology of islet failure in PC-induced DM. Insights into the mechanisms mediating ß-cell failure in PC can be important for our understanding of pathophysiology of PC.
Asunto(s)
Carcinoma Ductal Pancreático/complicaciones , Diabetes Mellitus Tipo 2 , Enfermedades Pancreáticas/etiología , Neoplasias Pancreáticas/complicaciones , Factores de Edad , Anciano , Amiloide/metabolismo , Autopsia , Índice de Masa Corporal , Estudios de Casos y Controles , Bases de Datos Factuales , Femenino , Células Secretoras de Glucagón/patología , Humanos , Células Secretoras de Insulina/patología , Islotes Pancreáticos/patología , Masculino , Persona de Mediana Edad , Enfermedades Pancreáticas/patología , Factores SexualesRESUMEN
BACKGROUND: The frequency, nature and timeline of changes on thin-slice (≤3 mm) multi-detector computerized tomography (CT) scans in the pre-diagnostic phase of pancreatic ductal adenocarcinoma (PDAC) are unknown. It is unclear if identifying imaging changes in this phase will improve PDAC survival beyond lead time. METHODS: From a cohort of 128 subjects (Cohort A) with CT scans done 3-36 months before diagnosis of PDAC we developed a CTgram defining CT Stages (CTS) I through IV in the radiological progression of pre-diagnostic PDAC. We constructed Cohort B of PDAC resected at CTS I and II and compared survival in CTS I and II in Cohort A (n = 22 each; control natural history cohort) vs Cohort B (n = 33 and 72, respectively; early interception cohort). RESULTS: CTs were abnormal in 16% and 85% at 24-36 and 3-6 months respectively, before PDAC diagnosis. The PDAC CTgram stages, findings and median lead times (months) to clinical diagnosis were: CTS I: Abrupt duct cut-off/duct dilatation (-12.8); CTS II: Low density mass confined to pancreas (-9.5), CTS III: Peri-pancreatic infiltration (-5.8), CTS IV: Distant metastases (only at diagnosis). PDAC survival was better in cohort B than in cohort A despite inclusion of lead time in Cohort A: CTS I (36 vs 17.2 months, p = 0.03), CTS II (35.2 vs 15.3 months, p = 0.04). CONCLUSION: Starting 12-18 months before PDAC diagnosis, progressive and increasingly frequent changes occur on CT scans. Resection of PDAC at the time of pre-diagnostic CT changes is likely to provide survival benefit beyond lead time.
Asunto(s)
Carcinoma Ductal Pancreático/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Anciano , Anciano de 80 o más Años , Carcinoma Ductal Pancreático/cirugía , Estudios de Cohortes , Progresión de la Enfermedad , Diagnóstico Precoz , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada Multidetector , Estadificación de Neoplasias , Neoplasias Pancreáticas/cirugía , Valor Predictivo de las Pruebas , Pronóstico , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
BACKGROUND & AIMS: Of patients with new-onset diabetes (NOD; based on glycemic status) older than 50 years, approximately 1% are diagnosed with pancreatic cancer (PC) within 3 years. We aimed to develop and validate a model to determine risk of PC in patients with NOD. METHODS: We retrospectively collected data from 4 independent and nonoverlapping cohorts of patients (N = 1,561) with NOD (based on glycemic status; data collected at date of diagnosis and 12 months previously) in the Rochester Epidemiology Project from January 1, 2000 through December 31, 2015 to create our model. The model weighed scores for 3 factors identified in the discovery cohort to be most strongly associated with PC (64 patients with PC and 192 with type 2 diabetes): change in weight, change in blood glucose, and age at onset of diabetes. We called our model Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC). We validated the locked-down model and cutoff score in an independent population-based cohort of 1,096 patients with diabetes; of these, 9 patients (82%) had PC within 3 years of meeting the criteria for NOD. RESULTS: In the discovery cohort, the END-PAC model identified patients who developed PC within 3 years of diabetes onset (area under receiver operating characteristic curve 0.87); a score of at least 3 identified patients who developed PC with 80% sensitivity and specificity. In the validation cohort, a score of at least 3 identified 7 of 9 patients with PC (78%) with 85% specificity; the prevalence of PC in patients with a score of at least 3 (3.6%) was 4.4-fold greater than in patients with NOD. A high END-PAC score in patients who did not have PC (false positives) was often due to such factors as recent steroid use or different malignancy. An ENDPAC score no higher than 0 (in 49% of patients) meant that patients had an extremely low risk for PC. An END-PAC score of at least 3 identified 75% of patients in the discovery cohort more than 6 months before a diagnosis of PC. CONCLUSIONS: Based on change in weight, change in blood glucose, and age at onset of diabetes, we developed and validated a model to determine risk of PC in patients with NOD based on glycemic status (END-PAC model). An independent prospective study is needed to further validate this model, which could contribute to early detection of PC.
Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Neoplasias Pancreáticas/etiología , Modelación Específica para el Paciente , Medición de Riesgo/métodos , Factores de Edad , Anciano , Glucemia/análisis , Peso Corporal , Diabetes Mellitus Tipo 2/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/epidemiología , Prevalencia , Estudios Prospectivos , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
Cardiac masses are highly heterogeneous and vary widely in their clinical presentation, imaging features, and survival outcomes. Our understanding is limited by their rarity and the fact that few are confirmed based on surgical pathology. We set out to provide a comprehensive analysis of all cardiac masses resected at our institution from 1999 to 2015, including imaging methods and histopathologic findings. We found papillary fibroelastomas (PFEs) to be the most commonly resected benign cardiac masses, followed by myxomas. Patients with PFEs most frequently presented with cerebrovascular accidents and transient ischemic attacks, whereas those with myxomas were more likely to present with arrhythmias and palpitations. In contrast, primary malignant cardiac masses were much rarer; angiosarcoma was the predominant subtype with a poor prognosis. Renal cell carcinomas were the most commonly discovered primary cancer for metastatic cardiac masses, and calcified amorphous tumors were the most prevalent non-neoplastic masses. For the detection of cardiac masses, transthoracic echocardiography was the most frequently used but least sensitive of the imaging methods analyzed. Transesophageal echocardiography (TEE) was the most sensitive imaging method. Fluorodeoxyglucose Positron Emission Tomography had similar sensitivity to TEE but was the least frequently used imaging method. Computed tomography and magnetic resonance imaging performed well in detecting most masses; PFEs, for which TEE was the most sensitive, was the exception. In conclusion, we found that PFEs were the most commonly resected benign cardiac masses, and TEE was the most accurate imaging method for the detection of all surgically removed masses at our institution.
Asunto(s)
Neoplasias Cardíacas , Mixoma , Humanos , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/epidemiología , Neoplasias Cardíacas/cirugía , Ecocardiografía Transesofágica/métodos , Ecocardiografía , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To evaluate the outcomes, safety, and efficacy of dual antiplatelet therapy (DAPT) with newer P2Y12 inhibitors compared with clopidogrel in patients with acute myocardial infarction (AMI) complicated by cardiac arrest (CA) or cardiogenic shock (CS). PATIENTS AND METHODS: MEDLINE, EMBASE, and the Cochrane Library were queried systematically from inception to January 2021 for comparative studies of adults (≥18 years) with AMI-CA/CS receiving DAPT with newer P2Y12 inhibitors as opposed to clopidogrel. We compared outcomes (30-day or in-hospital and 1-year all-cause mortality, major bleeding, and definite stent thrombosis) of newer P2Y12 inhibitors and clopidogrel in patients with AMI-CA/CS. RESULTS: Eight studies (1 randomized trial and 7 cohort studies) comprising 1100 patients (695 [63.2%] receiving clopidogrel and 405 [36.8%] receiving ticagrelor or prasugrel) were included. The population was mostly male (68.5%-86.7%). Risk of bias was low for these studies, with between-study heterogeneity and subgroup differences not statistically significant. Compared with the clopidogrel cohort, the newer P2Y12 cohort had lower rates of early mortality (odds ratio [OR], 0.60; 95% CI, 0.45 to 0.81; P=.001) (7 studies) and 1-year mortality (OR, 0.51; 95% CI, 0.36 to 0.71; P<.001) (3 studies). We did not find a significant difference in major bleeding (OR, 1.21; 95% CI, 0.71 to 2.06; P=.48) (6 studies) or definite stent thrombosis (OR, 2.01; 95% CI, 0.63 to 6.45; P=.24) (7 studies). CONCLUSION: In patients with AMI-CA/CS receiving DAPT, compared with clopidogrel, newer P2Y12 inhibitors were associated with lower rates of early and 1-year mortality. Data on major bleeding and stent thrombosis were inconclusive.
Asunto(s)
Paro Cardíaco , Infarto del Miocardio , Intervención Coronaria Percutánea , Trombosis , Clopidogrel/uso terapéutico , Femenino , Hemorragia/inducido químicamente , Humanos , Masculino , Infarto del Miocardio/complicaciones , Infarto del Miocardio/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Clorhidrato de Prasugrel/uso terapéutico , Antagonistas del Receptor Purinérgico P2Y/uso terapéutico , Choque Cardiogénico/tratamiento farmacológico , Choque Cardiogénico/etiología , Trombosis/complicaciones , Resultado del TratamientoRESUMEN
Actinotignum schaalii, a Gram-positive rod residing in the urinary tract, is responsible for urinary tract infections and their complications including but not limited to bacteremia and sepsis. A. schaalii is increasingly being detected in body fluid specimens owing to advancements in PCR techniques. This report describes an interesting case of an adult diabetic patient managed for Fournier's gangrene. A. schaalii was detected in the PCR of his wound cultures. To the best of our knowledge, this is the second case of A. schaalii as the causative agent for Fournier's gangrene.
RESUMEN
Wernicke's encephalopathy (WE) is a neurological complication of thiamine deficiency characterized by a triad of acute confusion, ataxia, and ophthalmoplegia. Even though it is most common in chronic alcoholism, an increase in prevalence has been reported recently due to the increased popularity of bariatric surgeries. WE is a known neurological complication after gastric bypass surgery but rarely reported after sleeve gastrectomy. We present a unique case of WE in pregnant women four months after sleeve gastrectomy.