RESUMEN
Insects evolved various modifications to their mouthparts, allowing for a broad exploration of feeding modes. In ants, workers perform non-reproductive tasks like excavation, food processing, and juvenile care, relying heavily on their mandibles. Given the importance of biting for ant workers and the significant mandible morphological diversity across species, it is essential to understand how mandible shape influences its mechanical responses to bite loading. We employed Finite Element Analysis to simulate biting scenarios on mandible volumetric models from 25 ant species classified in different feeding habits. We hypothesize that mandibles of predatory ants, especially trap-jaw ants, would perform better than mandibles of omnivorous species due to their necessity to subdue living prey. We defined simulations to allow only variation in mandible morphology between specimens. Our results demonstrated interspecific differences in mandible mechanical responses to biting loading. However, we found no evident differences in biting performance between the predatory and the remaining ants, and trap-jaw mandibles did not show lower stress levels than other mandibles under bite loading. These results suggest that ant feeding habit is not a robust predictor of mandible biting performance, a possible consequence of mandibles being employed as versatile tools to perform several tasks.
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Hormigas , Animales , Hormigas/fisiología , Mandíbula/anatomía & histología , Fenómenos BiomecánicosRESUMEN
Acinetobacter baumannii-Acinetobacter calcoaceticus complex (referred to herein as A. baumannii) treatment guidelines contain numerous older antimicrobial agents with susceptibility test interpretive criteria (STIC, also known as susceptibility breakpoints) set using only epidemiological data. We utilized a combination of in vitro surveillance data, preclinical murine thigh and lung infection models, population pharmacokinetics, simulation, and pharmacokinetic/pharmacodynamic (PK/PD) target attainment analyses to evaluate A. baumannii STIC for four commonly recommended antimicrobials from different classes (amikacin, ceftazidime, ciprofloxacin, and minocycline). Antimicrobial in vitro surveillance data were based on 1,647 clinical A. baumannii isolates obtained from 109 centers in the United States and Europe. Among these isolates, 5 were selected for evaluation in murine infection models based on fitness and MIC variability. PK and dose-ranging studies were conducted using neutropenic murine thigh and lung infection models The MIC ranges for the 5 isolates evaluated were as follows: amikacin, 2 to 32 µg/mL; ceftazidime, 4 to 16 µg/mL; ciprofloxacin, 0.12 to 2 µg/mL; minocycline, 0.25 to 4 µg/mL. All organisms grew ≥1.5 log10 CFU in both models in untreated controls. Plasma and epithelial lining fluid (ELF) pharmacokinetics for all drugs were determined in mice using liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods. For each isolate, 5 dose levels of each drug were tested individually in the thigh and lung infection model. The inoculum ranged from 7.9 to 8.4 and 6.8 to 7.7 log10 CFU/mL for the lung and thigh models, respectively. PK/PD targets associated with net bacterial stasis and 1- and 2-log10 CFU reductions from baseline were identified for each organism/infection model using Hill-type models. Population pharmacokinetic models for each agent were identified from the literature. Using demographic variables for simulated patients with hospital-acquired or ventilator-associated bacterial pneumonia or urinary tract infections (including acute pyelonephritis) who were administered maximal dosing regimens of each agent, estimates of protein binding, and ELF penetration ratios based on data from the literature, free-drug plasma and total-drug concentration-time profiles were generated, and PK/PD indices by MIC were calculated. Percent probabilities of attaining median and randomly assigned PK/PD targets associated with the above-described endpoints were determined. Recommended susceptible breakpoints for each agent were those representing the highest MIC at which the percent probabilities of achieving PK/PD targets associated with a 1-log10 CFU reduction from baseline approached or were ≥90%. The following susceptible breakpoints for A. baumannii were identified: amikacin, ≤8 µg/mL for pneumonia; ceftazidime, ≤32 and ≤8 µg/mL for pneumonia; ciprofloxacin, ≤1 µg/mL; and minocycline, ≤0.5/≤1 µg/mL which correspond to the standard and high minocycline dosing regimens of 200 mg per day and 200 mg every 12 h, respectively. Implementation of appropriate STIC will help clinicians optimally use the above-described agents and improve the likelihood of successful patient outcomes.
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Acinetobacter baumannii , Antiinfecciosos , Neumonía Asociada al Ventilador , Animales , Ratones , Amicacina , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias , Ceftazidima/uso terapéutico , Cromatografía Liquida , Ciprofloxacina/farmacología , Ciprofloxacina/uso terapéutico , Pruebas de Sensibilidad Microbiana , Minociclina/farmacología , Minociclina/uso terapéutico , Neumonía Asociada al Ventilador/tratamiento farmacológico , Espectrometría de Masas en TándemAsunto(s)
Infecciones Comunitarias Adquiridas , Neumonía Bacteriana , Humanos , Bacterias , Antibacterianos/uso terapéutico , Tetraciclinas , Neumonía Bacteriana/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/microbiologíaRESUMEN
Meropenem-vaborbactam is a fixed-dose beta-lactam/beta-lactamase inhibitor with potent in vitro and in vivo activity against Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales. Pharmacokinetic-pharmacodynamic (PK-PD) target attainment analyses were undertaken using population pharmacokinetic models, nonclinical PK-PD targets for efficacy, in vitro surveillance data, and simulation to provide support for 2 g meropenem-2 g vaborbactam every 8 h (q8h) administered as a 3-h intravenous (i.v.) infusion, and dosing regimens adjusted for patients with renal impairment. Simulated patients varying by renal function measure (estimated glomerular filtration rate [eGFR], mL/min/1.73 m2 and absolute eGFR, mL/min) and resembling the clinical trial population (complicated urinary tract infection, including acute pyelonephritis) were generated. The PK-PD targets for meropenem, the percentage of time on day 1 that free-drug plasma concentrations were above the MIC (%T>MIC), and vaborbactam, the ratio of free-drug plasma area under the concentration-time curve (AUC) on day 1 to the MIC (AUC:MIC ratio), were calculated. Percent probabilities of achieving meropenem free-drug plasma %T>MIC and vaborbactam free-drug plasma AUC:MIC ratio targets were assessed. MIC distributions for Enterobacterales, KPC-producing Enterobacterales, and Pseudomonas aeruginosa were considered as part of an algorithm to assess PK-PD target attainment. For assessments of free-drug plasma PK-PD targets associated with a 1-log10 CFU reduction from baseline, percent probabilities of PK-PD target attainment ranged from 81.3 to 100% at meropenem-vaborbactam MIC values of 4 or 8 µg/mL among simulated patients. The results of these PK-PD target attainment analyses provide support for a dosing regimen of 2 g meropenem-2 g vaborbactam q8h administered as a 3-h i.v. infusion, with dosing regimens adjusted for patients with renal impairment and a meropenem-vaborbactam susceptibility breakpoint of ≤8 µg/mL (tested with a fixed vaborbactam concentration of 8 µg/mL) for Enterobacterales and P. aeruginosa based on these dosing regimens.
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Antibacterianos , Infecciones Urinarias , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Inhibidores de beta-Lactamasas/farmacología , Infecciones Urinarias/tratamiento farmacológico , Klebsiella pneumoniae , Administración Intravenosa , Pseudomonas aeruginosa , Pruebas de Sensibilidad MicrobianaRESUMEN
The dissolution of porous materials in a flow field controls the fluid pathways through rocks and soils and shapes the morphology of landscapes. Identifying the dissolution front, the interface between the reactive and the unreactive volumes in a dissolving medium, is a prerequisite for describing dissolution-induced structure emergence and transformation. Despite its fundamental importance, the report on the dynamics of a dissolution front in an evolving natural microstructure is scarce. Here we show an unexpected, spontaneous migration of the dissolution front against the flow direction. This retraction stems from infiltration instability induced surface generation, which leads to an increase in reactive surface area when a porous medium dissolves in an imposing flow field. There is very good agreement between observations made with in situ, X-ray tomography and model predictions. Both show that the value of reactive surface area reflects a balance between flow-dependent surface generation and destruction, i.e. the "dry" geometric surface area of a porous material, measured without a flow field, is not necessarily the upper limit of its reactive surface area when in contact with reactive flow. This understanding also contributes to reconciling the discrepancies between field and laboratory derived solid-fluid reaction kinetics.
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BACKGROUND: The aim of the present study was to create a unique risk adjustment model for surgical site infection (SSI) in patients who underwent colorectal surgery (CRS) at the Cleveland Clinic (CC) with inherent high risk factors by using a nationwide database. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried to identify patients who underwent CRS between 2005 and 2010. Initially, CC cases were identified from all NSQIP data according to case identifier and separated from the other NSQIP centers. Demographics, comorbidities, and outcomes were compared. Logistic regression analyses were used to assess the association between SSI and center-related factors. RESULTS: A total of 70,536 patients met the inclusion criteria and underwent CRS, 1090 patients (1.5%) at the CC and 69,446 patients (98.5%) at other centers. Male gender, work-relative value unit, diagnosis of inflammatory bowel disease, pouch formation, open surgery, steroid use, and preoperative radiotherapy rates were significantly higher in the CC cases. Overall morbidity and individual postoperative complication rates were found to be similar in the CC and other centers except for the following: organ-space SSI and sepsis rates (higher in the CC cases); and pneumonia and ventilator dependency rates (higher in the other centers). After covariate adjustment, the estimated degree of difference between the CC and other institutions with respect to organ-space SSI was reduced (OR 1.38, 95% CI 1.08-1.77). CONCLUSIONS: The unique risk adjustment strategy may provide center-specific comprehensive analysis, especially for hospitals that perform inherently high-risk procedures. Higher surgical complexity may be the reason for increased SSI rates in the NSQIP at tertiary care centers.
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Enfermedades del Colon/cirugía , Hospitales de Alto Volumen/estadística & datos numéricos , Enfermedades del Recto/cirugía , Ajuste de Riesgo/métodos , Infección de la Herida Quirúrgica/epidemiología , Centros de Atención Terciaria/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Bases de Datos Factuales , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Factores de Riesgo , Centros de Atención Terciaria/normas , Estados Unidos , Adulto JovenRESUMEN
OBJECTIVE: To compare and contrast three databases, that is, The International Centre for Nephrogenic Systemic Fibrosis Registry (ICNSFR), the Food and Drug Administration Adverse Event Reporting System (FAERS) and a legal data set, through pharmacovigilance and to evaluate international nephrogenic systemic fibrosis (NSF) safety efforts. METHODS: The Research on Adverse Drug events And Reports methodology was used for assessment-the FAERS (through June 2009), ICNSFR and the legal data set (January 2002 to December 2010). Safety information was obtained from the European Medicines Agency, the Danish Medicine Agency and the Food and Drug Administration. RESULTS: The FAERS encompassed the largest number (n = 1395) of NSF reports. The ICNSFR contained the most complete (n = 335, 100%) histopathological data. A total of 382 individual biopsy-proven, product-specific NSF cases were analysed from the legal data set. 76.2% (291/382) identified exposure to gadodiamide, of which 67.7% (197/291) were unconfounded. Additionally, 40.1% (153/382) of cases involved gadopentetate dimeglumine, of which 48.4% (74/153) were unconfounded, while gadoversetamide was identified in 7.3% (28/382) of which 28.6% (8/28) were unconfounded. Some cases involved gadobenate dimeglumine or gadoteridol, 5.8% (22/382), all of which were confounded. The mean number of exposures to gadolinium-based contrast agents (GBCAs) was gadodiamide (3), gadopentetate dimeglumine (5) and gadoversetamide (2). Of the 279 unconfounded cases, all involved a linear-structured GBCA. 205 (73.5%) were a non-ionic GBCA while 74 (26.5%) were an ionic GBCA. CONCLUSION: Clinical and legal databases exhibit unique characteristics that prove complementary in safety evaluations. Use of the legal data set allowed the identification of the most commonly implicated GBCA. ADVANCES IN KNOWLEDGE: This article is the first to demonstrate explicitly the utility of a legal data set to pharmacovigilance research.
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Medios de Contraste/efectos adversos , Gadolinio/efectos adversos , Dermopatía Fibrosante Nefrogénica/inducido químicamente , Farmacovigilancia , Conducta Cooperativa , Bases de Datos Factuales , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Gadolinio DTPA/efectos adversos , Compuestos Heterocíclicos , Humanos , Masculino , Meglumina/efectos adversos , Meglumina/análogos & derivados , Compuestos Organometálicos/efectos adversos , Sistema de Registros , Estados UnidosRESUMEN
AIM: The study aimed to establish a method for the measurement of mesenteric tension after ileal pouch-anal anastomosis (IPAA) and to evaluate the impact of tension on clinical outcome and quality of life. METHODS: All consecutive patients undergoing an open IPAA from July 2008 to October 2009 were prospectively enrolled. After the creation of the anastomosis, mesenteric tension was estimated by the surgeon in the operating room on a 10-point scale (1, least tension; 10, most tension). The association was analysed between mesenteric tension defined as low (1-2), medium (3-7) and high (8-10) and postoperative complications and quality of life (Cleveland Clinic Global Scale). RESULTS: A mesenteric tension score was obtained in 134 patients (71 men, 53.0%). Median age was 38.5 (29.3-47.0) years. Fifty-six patients (41.8%) had a low, 59 (44.0%) a medium and 19 (14.2%) a high degree of mesenteric tension. Patients with a high mesenteric tension had a shorter anal transitional zone, a longer distance from the upper border of the symphysis pubis to the apex of the small bowel loop designated for the ileoanal anastomosis, a thinner abdominal wall at the stoma site and a longer distance from the pouch to the ileostomy. The proportion of patients with high mesenteric tension was less after stapled anastomosis. On long-term follow-up, patients with high mesenteric tension were more likely to suffer from anastomotic stricture and pouch failure. Pouch function was not influenced by mesenteric tension. CONCLUSION: High mesenteric tension after IPAA is adversely associated with postoperative complications and pouch survival.
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Canal Anal/cirugía , Reservorios Cólicos/efectos adversos , Íleon/cirugía , Mesenterio , Estrés Mecánico , Adulto , Anastomosis Quirúrgica/efectos adversos , Constricción Patológica/etiología , Femenino , Humanos , Masculino , Mesenterio/cirugía , Persona de Mediana Edad , Proctocolectomía Restauradora , Estudios Prospectivos , Calidad de Vida , Técnicas de Sutura , Resultado del TratamientoRESUMEN
BACKGROUND: Tumour necrosis factor-α inhibitors (TNFαIs) are used for treatment of inflammatory disorders. There is evidence linking these agents with occurrence of malignancies. For four out of five TNFαIs the Food and Drug Administration (FDA) label states, 'melanoma has been reported in patients treated with these agents'. OBJECTIVES: To determine whether a statistically significant association exists between administration of TNFαIs and development of malignant melanoma. METHODS: We searched the FDA Adverse Event Reporting System (FAERS) database for terms related to melanoma and TNFαIs for detection of safety signals. We also searched a large urban academic electronic medical record (EMR) database for which we calculated the relative risk (RR) of melanoma in subjects exposed to TNFαIs vs. nonexposed subjects. RESULTS: There were 972 reports of melanoma associated with a TNFαI identified in the FAERS database, with 69 reports among individuals using more than one TNFαI. A safety signal was detected for infliximab, golimumab, etanercept and adalimumab, but not certolizumab pegol. For TNFαIs as a class of drugs, a safety signal was detectable in the FAERS database, and RR was significant in the EMR database. For the EMR cohort, 6045 patients were exposed to TNFαIs and 35 cases of melanoma were detected. Significance for RR was detected for adalimumab (RR 1·8, P = 0·02) and etanercept (RR 2·35, P = 0·0004 < 0·001). CONCLUSIONS: We identified a significant association between exposure to TNFαIs and malignant melanoma in two different analyses. Our findings add to existing evidence linking these agents with the occurrence of malignant melanoma. Additional investigations are required to explore this association further along with the risk of melanoma with TNFαI therapy.
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Melanoma/inducido químicamente , Neoplasias Cutáneas/inducido químicamente , Factor de Necrosis Tumoral alfa/antagonistas & inhibidores , Sistemas de Registro de Reacción Adversa a Medicamentos , Humanos , Factores de RiesgoRESUMEN
Given the limited understanding about pharmacokinetic-pharmacodynamic (PK-PD) determinants of oseltamivir efficacy, data from two phase 2 influenza virus inoculation studies were evaluated. Healthy volunteers in studies 1 and 2 were experimentally infected with influenza A/Texas (the concentration of neuraminidase inhibitor which reduced neuraminidase activity by 50% [IC(50)] = 0.18 nM) or B/Yamagata (IC(50) = 16.76 nM), respectively. In study 1, 80 subjects received 20, 100, or 200 mg of oral oseltamivir twice daily (BID), 200 mg oseltamivir once daily, or placebo for 5 days. In study 2, 60 subjects received 75 or 150 mg of oral oseltamivir BID or placebo for 5 days. Oseltamivir carboxylate (OC) (active metabolite) PK was evaluated using individual PK data and a population PK model to derive individual values for area under the concentration-time curve from 0 to 24 h (AUC(0-24)), minimum concentration of OC in plasma (C(min)), and maximum concentration of OC in plasma (C(max)). Exposure-response relationships were evaluated for continuous (area under composite symptom score curve [AUCSC], area under the viral titer curve, and peak viral titer) and time-to-event (alleviation of composite symptom scores and cessation of viral shedding) efficacy endpoints. Univariable analyses suggested the existence of intuitive and highly statistically significant relationships between OC AUC(0-24 )evaluated as a 3-group variable and AUCSC, time to alleviation of composite symptom scores, and time to cessation of viral shedding. The upper OC AUC(0-24) threshold (~14,000 ng · h/ml) was similar among these endpoints. Multivariable analyses failed to demonstrate the influence of study/strain on efficacy endpoints. These results provide the first demonstration of exposure-response relationships for efficacy for oseltamivir against influenza and suggest that OC exposures beyond those achieved with the approved oseltamivir dosing regimen will provide enhanced efficacy. The clinical applicability of these observations requires further investigation.
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Antivirales/farmacología , Antivirales/farmacocinética , Gripe Humana/tratamiento farmacológico , Oseltamivir/análogos & derivados , Adulto , Antivirales/administración & dosificación , Área Bajo la Curva , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Subtipo H1N1 del Virus de la Influenza A/enzimología , Virus de la Influenza B/enzimología , Masculino , Análisis Multivariante , Neuraminidasa/antagonistas & inhibidores , Oseltamivir/administración & dosificación , Oseltamivir/farmacocinética , Oseltamivir/farmacología , Factores de Tiempo , Resultado del Tratamiento , Carga Viral , Esparcimiento de Virus , Adulto JovenRESUMEN
AIM: Studies investigating the functional outcome after restorative surgery for rectal cancer have mainly focused on the effect of different surgical techniques on bowel habit or sexual activity at a single time-point. The aim of this study was to assess, longitudinally, the effect of rectal cancer treatment on bowel function, quality of life and sexual activity. METHOD: The study parameters were assessed using self-administered questionnaires, including the Short Form 36 (SF-36), repeatedly, over a 5-year period. Patient details were obtained from the Cleveland Clinic prospective database. RESULTS: There were 260 (186 male) patients. The mean ages of male and female patients at the time of surgery were 60.5 and 57.5 years, respectively. There was no significant difference in comorbidity or stage between the groups. Women had a better overall survival. More women than men had postoperative radiation and perioperative blood transfusions. Men had a higher percentage of hand-sewn anastomoses (23.9%vs 10.8%, P = 0.018), but there was no overall difference in the mean level of anastomosis (2.3 cm vs 1.9 cm, P = 0.38). Men had worse nocturnal bowel function, more incontinence and a poorer mental component score on the SF-36. Pad use increased over time to a greater degree in women. Sexual activity, which was similar in men and women at baseline, had fallen at 5 years in both genders. CONCLUSION: After restorative resection for rectal cancer, bowel function is worse in men than in women, especially night evacuation at 3 and 5 years postoperatively. Sexual function in both genders declines sharply initially within 1 year postoperatively and more gradually over 5 years.
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Incontinencia Fecal/etiología , Complicaciones Posoperatorias/etiología , Calidad de Vida , Neoplasias del Recto/cirugía , Recto/cirugía , Conducta Sexual , Anastomosis Quirúrgica/métodos , Quimioterapia Adyuvante , Reservorios Cólicos , Defecación , Incontinencia Fecal/fisiopatología , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Radioterapia Adyuvante , Neoplasias del Recto/terapia , Factores Sexuales , Encuestas y Cuestionarios , Tasa de SupervivenciaRESUMEN
AIM: Hartmann's procedure for perforated diverticulitis is associated with substantial morbidity and mortality. This study analyses factors associated with morbidity/mortality and possible changes over time. METHOD: Patients treated by urgent Hartmann's procedure for perforated diverticulitis between 1992 and 2010 were studied, and information was collected on age, sex, perioperative details, 30-day morbidity and mortality recorded in an institutional review board approved database supplemented by chart review. Patients were divided into four groups based on the year of surgery. Univariate and multivariate logistic regression analysis was performed to identify risk factors associated with morbidity and mortality. RESULTS: In all, 199 patients (51% female, mean age 65 years, mean body mass index 28 kg/m(2)) were identified. The American Society of Anesthesiologists (ASA) score was 4 in 30% of patients and Hinchey Stage IV in 16%. The mean length of stay was 12.5 ± 10 days. Mortality was 15% and did not change significantly over time. Overall morbidity was 52% and significantly increased over time on univariate analysis (P = 0.007) but not on multivariate analysis (P = 0.11). Independent predictors of morbidity on multivariate analysis were Hinchey IV (P < 0.001) and hypoproteinaemia (P = 0.001). Independent predictors for mortality were ASA > 3 (P = 0.01), abnormal creatinine (P = 0.007), steroid use (P = 0.007), Hinchey IV (P = 0.032), low albumin (P < 0.001) and low body mass index (P = 0.001). CONCLUSION: Mortality after Hartmann's procedure for perforated diverticulitis has not decreased during the last 18 years. Morbidity has actually increased over time although this is related to increased disease severity and comorbidity. Future efforts should focus on the identification of patient subgroups benefiting from earlier elective surgery and alternative surgical approaches when perforated diverticulitis does occur.
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Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Diverticulitis del Colon/cirugía , Perforación Intestinal/cirugía , Anciano , Procedimientos Quirúrgicos del Sistema Digestivo/mortalidad , Diverticulitis del Colon/complicaciones , Diverticulitis del Colon/mortalidad , Femenino , Humanos , Perforación Intestinal/etiología , Perforación Intestinal/mortalidad , Tiempo de Internación/estadística & datos numéricos , Modelos Logísticos , Masculino , Complicaciones Posoperatorias/mortalidad , Factores de Riesgo , Resultado del TratamientoRESUMEN
Circulating cardiac troponins are markers of myocardial injury. We sought to determine whether cardiac troponin I (cTnI), measured by a sensitive assay, is associated with disease severity and prognosis in pulmonary arterial hypertension (PAH). cTnI was measured in 68 patients with PAH diagnostic category 1 in a research-based sensitive immunoanalyser with a lower limit of detection of 0.008 ng · mL(-1). The associations between cTnI and PAH severity and clinical outcomes were assessed using Chi-squared and Wilcoxon rank sum tests, Kaplan-Meier analysis and Cox regression models. cTnI was detected in 25% of patients. Patients with detectable cTnI had more advanced functional class symptoms, a shorter 6-min walk distance, more pericardial effusions, larger right atrial area, and higher B-type natriuretic peptide and C-reactive protein levels. 36-month transplant-free survival was 44% in patients with detectable cTnI versus 85% in those with undetectable cTnI. cTnI was associated with a 4.7-fold increased risk of death related to right ventricular failure or transplant (hazard ratio 4.74, 95% CI 1.89-11.89; p<0.001), even when adjusted individually for known parameters of PAH severity. Elevated plasma cTnI, even at subclinically detectable levels, is associated with more severe disease and worse outcomes in patients with PAH.
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Hipertensión Pulmonar , Índice de Severidad de la Enfermedad , Troponina I/sangre , Adulto , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Hipertensión Pulmonar Primaria Familiar , Femenino , Humanos , Hipertensión Pulmonar/sangre , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/mortalidad , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Derrame Pericárdico/sangre , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/mortalidad , Valor Predictivo de las Pruebas , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Sensibilidad y EspecificidadRESUMEN
AIM: We reviewed the functional results and quality of life (QOL) of patients who had had an ileoanal pouch (IPAA) for at least 15 years. METHOD: Retrospective analysis was undertaken of data accrued prospectively into a pouch database since 1983. Patients who had retained an IPAA for at least 15 years were identified. Trends in IPAA function and QOL of the patients were determined over a time-period of 15 years after formation of the IPAA. Data were compared for patients who were < 35, 35-55 and > 55 years of age when the IPAA was formed. RESULTS: Three hundred and ninety-six of a total of 3276 patients in the database (53% men, median age 36 years and median follow-up 17.1 years) underwent IPAA with at least 15 years of follow-up. The final pathology was ulcerative colitis in 78%; 66.4% of patients had a restorative proctocolectomy, 91.4% underwent temporary diversion, 59% had a J-pouch configuration and 63.1% a stapled anastomosis. The frequency of bowel movements remained the same over the follow-up period. There was an increase in the incidence of incontinence and urgency after 15 years with no significant change in dietary, social, work and sexual restrictions during follow-up. Patients in all three age groups experienced deterioration in pouch function at 15 years of follow up compared with the function at 5 years. The QOL of the patients remained high and stable. CONCLUSION: There is a deterioration of pouch function after 15 years, irrespective of the age of the patient when the IPAA was formed. Despite this, QOL appears to be high for all patients who retain their pouch.
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Reservorios Cólicos , Adulto , Factores de Edad , Colitis Ulcerosa/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Proctocolectomía Restauradora , Calidad de Vida , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
OBJECTIVE: In women, rectal prolapse is often accompanied by other signs of generalized pelvic floor weakness including uterine and bladder prolapse. The purpose of this study was to compare whether there are differences in outcomes of rectal prolapse surgery between women having combined pelvic organ prolapse (POP) surgery with a urologist or urogynecologist (CS) vs those having abdominal rectal prolapse surgery alone (RP). METHOD: Charts were reviewed to collect perioperative data on those having surgery from 1995 to 2001. Phone surveys were conducted to obtain Cleveland Clinic Foundation (CCF) Incontinence score, Knowles-Eccersley-Scott-Symptom (KESS) Constipation Score, Short Form 36 (SF-36) quality of life score and recurrence rate. Appropriate statistical analysis was performed. RESULTS: Ninety-four operations were performed (23 CS and 71 RP). Forty-six (49%) could be contacted by phone. Mean follow-up was similar in both groups (CS 4.1 vs RP 3.6 years; P = 0.796). There were no significant differences between both groups regarding age, American Society of Anesthesiology classification Score, complications, length of hospital stay, CCF Incontinence score, KESS Constipation Score, SF-36 Score and recurrence rate of rectal prolapse. The operative time (CS 226 vs RP 122 min; P < 0.001) and blood loss (CS 377 vs RP 183 ml; P < 0.001) were significantly increased in the CS group. CONCLUSION: Combined surgery for POP is safe and effective when considering outcomes of rectal prolapse surgery. Therefore surgeons should not hesitate to address all pelvic floor issues during the same operation by working in partnership with the anterior pelvic floor colleagues.
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Procedimientos Quirúrgicos Ginecológicos/métodos , Prolapso de Órgano Pélvico/cirugía , Calidad de Vida , Prolapso Rectal/cirugía , Procedimientos Quirúrgicos Urológicos/métodos , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Entrevistas como Asunto , Estimación de Kaplan-Meier , Persona de Mediana Edad , Estudios Retrospectivos , Prevención SecundariaRESUMEN
PURPOSE: Parastomal hernia is a common late complication after stoma creation. The management options are many; unfortunately, most literature suggests unsatisfactory results. There are few studies comparing the outcomes after repair of parastomal hernias especially in recurrent cases, and the results are controversial. The aim of this study was to compare outcomes after repair of recurrent parastomal hernias between direct repair (DR) and relocation (RL). METHOD: We performed a retrospective chart review of patients who underwent direct repair or RL for recurrent parastomal hernia during the period between 1990 and 2005. Perioperative data and re-recurrence rates were obtained and analysed with appropriate statistical methods. RESULTS: With mean follow-up time of 2 years, 50 operations were available for evaluation; 27 (54%) DR and 23 (46%) RL [five same-side RL (SSRL) and 18 opposite-side RL (OSRL)]. There were no deaths and there were similar complication rates between groups. Four of five (80%) SSRL had a re-recurrent parastomal hernia. Considering only DR with OSRL, although OSRL had longer operative time and hospital stay than DR, the re-recurrence rate was lower (38%vs 74%; P = 0.02). However, with Kaplan-Meier calculated and longer predicted follow-up time, re-recurrence rates were similar (Log rank P = 0.09). CONCLUSION: Recurrent parastomal hernia repair is associated with high re-recurrence rates.OSRL seems to have promising short-term outcomes; however, whether these results hold up long-term remains unclear. Therefore, larger cohorts of patients with longer follow-up or prospective randomized trials are needed.
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Hernia Ventral/cirugía , Colgajos Quirúrgicos , Mallas Quirúrgicas , Estomas Quirúrgicos/efectos adversos , Femenino , Estudios de Seguimiento , Hernia Ventral/etiología , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Recurrencia , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an increasingly common cause of bacteremia and endocarditis. The cost-effectiveness (CE) of daptomycin was compared with that of vancomycin-gentamicin in patients with MRSA bacteremia with or without endocarditis. METHODS: With use of data from an open-label, randomized study comparing daptomycin with vancomycin-gentamicin in the aforementioned patient population, 3 cost strata were considered: (1) study drug acquisition (daptomycin, $0.37/mg; vancomycin, $7/g; and gentamicin, $0.12/mg); (2) stratum 1 plus the cost of therapy for treatment failures and adverse events, therapeutic drug monitoring, and preparation and administration of all medications; and (3) stratum 2 plus hospital bed costs. Drug costs were based on mean wholesale price, with other costs based on those for a typical community hospital. Cost-effectiveness ratios were calculated as cost divided by proportion of successes. Sensitivity analyses were performed by varying the study drug cost. RESULTS: Forty-five (20 successes) and 44 (14 successes) patients received daptomycin and vancomycin-gentamicin, respectively. The respective median cost-effectiveness ratios for daptomycin and vancomycin-gentamicin for each cost stratum were as follows: $4082 (range, $1062-$13,893) and $560 (range, $66-$1649) for stratum 1 (P < .001); $4582 (range, $1109-$21,882) and $1635 (range, $163-$33,444) for stratum 2 (P = .026); $23,639 (range, $6225-$141,132) and $26,073 (range, $5349-$187,287) for stratum 3 (P = .82). Sensitivity analyses indicated that if the cost of vancomycin was $0, strata 3 cost-effectiveness ratios did not differ ($23,639 and $25,668, respectively; P = .85). Similar results between groups were seen among patients with bacteremia. CONCLUSIONS: When all costs of therapy were considered, the cost-effectiveness of daptomycin and vancomycin-gentamicin was similar, even if the cost of vancomycin was $0.
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Antibacterianos/economía , Antibacterianos/uso terapéutico , Daptomicina/economía , Daptomicina/uso terapéutico , Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/tratamiento farmacológico , Bacteriemia/economía , Análisis Costo-Beneficio , Costos y Análisis de Costo , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis Bacteriana/economía , Femenino , Gentamicinas/economía , Gentamicinas/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Infecciones Estafilocócicas/economía , Resultado del Tratamiento , Vancomicina/economía , Vancomicina/uso terapéutico , Adulto JovenRESUMEN
PURPOSE: Little data exist regarding infliximab use in surgical decision making and postoperative complications in ulcerative colitis. Our goals were to determine the rate of postoperative complications in infliximab-treated ulcerative colitis patients undergoing restorative proctocolectomy and to determine whether three-stage procedures are more often necessary. METHODS: We studied a group of infliximab-treated patients and matched control subjects who underwent two-stage restorative proctocolectomy between 2000 and 2006. Postoperative complications were compared. In addition, the rate of three-stage procedures was compared between all infliximab- and noninfliximab-treated patients. RESULTS: A total of 523 restorative proctocolectomies were performed. In the infliximab group, there were 46 two-stage and 39 three-stage procedures. Covariate-adjusted odds of early complication for the infliximab group was 3.54 times that of controls (P = 0.004; 95 percent confidence interval (CI), 1.51-8.31). The odds of sepsis were 13.8 times greater (P = 0.011; 95 percent CI, 1.82-105) and the odds of late complication were 2.19 times greater (P = 0.08; 95 percent CI, 0.91-5.28) for infliximab. The odds of requirement for three-stage procedures was 2.07 times greater in the infliximab group (P = 0.011; 95 percent CI, 1.18-3.63). CONCLUSIONS: Infliximab increases the risk of postoperative complications after restorative proctocolectomy and has altered the surgical approach to ulcerative colitis. Potential benefits of infliximab should be balanced against these risks.
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Anticuerpos Monoclonales/efectos adversos , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/cirugía , Fármacos Gastrointestinales/efectos adversos , Complicaciones Posoperatorias/etiología , Proctocolectomía Restauradora , Adulto , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Terapia Combinada , Femenino , Humanos , Infliximab , Modelos Logísticos , Masculino , Estudios Retrospectivos , Riesgo , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
PURPOSE: This study was designed to evaluate the yield and cost of fever evaluations in average-risk inpatients after elective colorectal surgery. METHODS: A 12-month, retrospective study was performed on patients who developed a postoperative fever > or = 38 degrees C after elective colorectal surgery. A positive fever evaluation was defined as a blood culture, urine culture, chest x-ray, or abdominal CT result that led to a change in patient management. Logistic regression, Fisher's exact test, and chi-squared test were used; odds ratios were calculated. RESULTS: Of 133 patients, 26 percent had a positive evaluation. Blood culture, urine culture, chest x-ray, and CT were positive in 3, 8, 7, and 46 percent, respectively. Risk factors for a positive fever evaluation were temperature > or = 38.5 degrees C, fever evaluation after postoperative Day 6, and a clinical manifestation of systemic inflammatory response syndrome other than fever (all, P < 0.01). The cost per positive fever evaluation for the entire group, patients with 2 risk factors, or patients with 3 risk factors was $5,600, $4,200, and $2,140, respectively. CONCLUSIONS: The current approach to fever evaluation after elective colorectal surgery is low yield and costly. High fever, late postoperative fever, and systemic inflammatory response syndrome are risk factors for a positive fever evaluation after colorectal surgery.
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Enfermedades del Colon/cirugía , Fiebre/economía , Intestino Delgado/cirugía , Complicaciones Posoperatorias/economía , Enfermedades del Recto/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Femenino , Fiebre/epidemiología , Costos de Hospital , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
AIM: As healthcare providers for Crohn's disease, we assume that we have a good understanding of the disease progression and its symptoms. The aim of this study was to gather information about what patients with Crohn's disease think are relevant to their symptoms and what helps them cope with this lifelong benign disease. MATERIALS AND METHODS: A questionnaire was sent to all patients with a diagnosis of Crohn's disease seen in the Digestive Disease Center in the last 5 years. The returned forms were downloaded into a database and sent for analysis. RESULTS: Sixty-two percent of respondents were female. One third were between the ages of 35 and 50 years. Seventy percent were married. Thirty-eight percent had a graduate degree, 19% were unemployed. Fifty percent still smoked, half of them less than one pack a day. Sixty-eight percent said that their symptoms affected work, and one fourth changed jobs due to this. Foods worsened symptoms in 60%, with a decrease in symptoms while on low fiber foods and white meats. Lifestyle change worsened symptoms in 66%. A change in the caregiver was not a significant stressor. More than half used Remicade, with one third stating that it was helpful. Eight percent had never used steroids. Alcohol increased symptoms in 40%. Factors that did not cause a significant change were children at any age, pregnancy, menopause, and hormone replacement therapy. Surgery caused half the patients to improve for many years, although one third felt a lowered self-esteem postoperatively. CONCLUSION: Patients with Crohn's disease should be managed in a more comprehensive manner to provide optimal care. Thus, a team approach that includes a dietician and counselor should be considered as an integral part of this team. This will allow patients to have enhanced skills to cope with changes in their symptoms, whether they are due to the disease itself or the changes in their routine.