RESUMO
OBJECTIVE: Several systematic reviews and meta-analyses have summarized the evidence on the efficacy and safety of various outpatient cervical ripening methods. However, the method with the highest efficacy and safety profile has not been determined conclusively. We performed a systematic review and network meta-analysis of published randomized controlled trials to assess the efficacy and safety of cervical ripening methods currently employed in the outpatient setting. DATA SOURCES: With the assistance of an experienced medical librarian, we performed a systematic search of the literature using MEDLINE, Embase, Scopus, Web of Science, Cochrane Library, and ClinicalTrials.gov. We systematically searched electronic databases from inception to January 14, 2020. STUDY ELIGIBILITY CRITERIA: We considered randomized controlled trials comparing a variety of methods for outpatient cervical ripening. METHODS: We conducted a frequentist random effects network meta-analysis employing data from randomized controlled trials. We performed a direct, pairwise meta-analysis to compare the efficacy of various outpatient cervical ripening methods, including placebo. We employed ranking strategies to determine the most efficacious method using the surface under the cumulative ranking curve; a higher surface under the cumulative ranking curve value implied a more efficacious method. We assessed the following outcomes: time from intervention to delivery, cesarean delivery rates, changes in the Bishop score, need for additional ripening methods, incidence of Apgar scores <7 at 5 minutes, and uterine hyperstimulation. RESULTS: We included data from 42 randomized controlled trials including 6093 participants. When assessing the efficacy of all methods, 25 µg vaginal misoprostol was the most efficacious in reducing the time from intervention to delivery (surface under the cumulative ranking curve of 1.0) without increasing the odds of cesarean delivery, the need for additional ripening methods, the incidence of a low Apgar score, or uterine hyperstimulation. Acupressure (surface under the cumulative ranking curve of 0.3) and primrose oil (surface under the cumulative ranking curve of 0.2) were the least effective methods in reducing the time to delivery interval. Among effective methods, 50 mg oral mifepristone was associated with the lowest odds of cesarean delivery (surface under the cumulative ranking curve of 0.9). CONCLUSION: When balancing efficacy and safety, vaginal misoprostol 25 µg represents the best method for outpatient cervical ripening.
Assuntos
Misoprostol , Ocitócicos , Gravidez , Feminino , Humanos , Misoprostol/uso terapêutico , Ocitócicos/uso terapêutico , Maturidade Cervical , Metanálise em Rede , Pacientes Ambulatoriais , Trabalho de Parto Induzido/métodosRESUMO
Conidia of the airborne human-pathogenic fungus Aspergillus fumigatus are inhaled by humans. In the lung, they are phagocytosed by alveolar macrophages and intracellularly processed. In macrophages, however, conidia can interfere with the maturation of phagolysosomes to avoid their elimination. To investigate whether polymeric particles (PPs) can reach this intracellular pathogen in macrophages, we formulated dye-labeled PPs with a size allowing for their phagocytosis. PPs were efficiently taken up by RAW 264.7 macrophages and were found in phagolysosomes. When macrophages were infected with conidia prior to the addition of PPs, we found that they co-localized in the same phagolysosomes. Mechanistically, the fusion of phagolysosomes containing PPs with phagolysosomes containing conidia was observed. Increasing concentrations of PPs increased fusion events, resulting in 14% of phagolysosomes containing both conidia and PPs. We demonstrate that PPs can reach conidia-containing phagolysosomes, making these particles a promising carrier system for antimicrobial drugs to target intracellular pathogens. KEY POINTS: ⢠Polymer particles of a size larger than 500 nm are internalized by macrophages and localized in phagolysosomes. ⢠These particles can be delivered to Aspergillus fumigatus conidia-containing phagolysosomes of macrophages. ⢠Enhanced phagolysosome fusion by the use of vacuolin1 can increase particle delivery.
Assuntos
Aspergillus fumigatus , Fagossomos , Humanos , Esporos Fúngicos , Macrófagos/microbiologia , FagocitoseRESUMO
BACKGROUND: Baveno VI and expanded Baveno VI criteria have been recommended to circumvent the need for endoscopy screening in patients with a very low probability of varices needing treatment (VNT). AIM: To validate these criteria in a Latin American population. METHODS: The ability of Baveno VI criteria (liver stiffness measurement (LSM) <20 kPa and platelet count >150 × 103/µL) and expanded Baveno VI criteria (LSM < 25kPa and platelet count >110 × 103/µL) to exclude the presence of VNT was tested in a prospectively recruited cohort of patients with Child-Pugh A liver cirrhosis and with no previous variceal haemorrhage who attended the liver clinics of three major hospitals in Chile. RESULTS: Three hundred patients were included. The median (IQR) age was 61 [18-86] years, median MELD was 8.0 (6-17), median LSM was 17.2 (10.2-77) kPa and median platelet count was 137 (23-464) × 103 /µL. The main aetiology was non-alcoholic fatty liver disease (67.3%). VNT were present in 18% of patients. The Baveno VI criteria had a sensitivity of 98.1% and a specificity of 38.2%, potentially sparing 31.3% of upper endoscopies with a very low risk of missing VNT (1.1%). The expanded Baveno VI criteria had a sensitivity of 90.7% and a specificity of 61%, potentially sparing 51.3% of upper endoscopies with a risk of missing VNT of 3.6%. Both criteria were independently associated with the absence of VNT. CONCLUSION: We validated the Baveno VI and expanded Baveno VI criteria in Chilean population, potentially sparing 31.3% and 51.3% of endoscopies, respectively, with a very low risk of missing VNT. Fondecyt 1191183.
Assuntos
Técnicas de Imagem por Elasticidade , Varizes Esofágicas e Gástricas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Chile , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/etiologia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Humanos , Cirrose Hepática/complicações , Pessoa de Meia-Idade , Adulto JovemRESUMO
We describe the synthesis of hydrophilic poly(poly(ethylene glycol) methyl ether methacrylate) (PmPEGMA) and hydrophobic poly(methyl methacrylate) (PMMA) caspofungin conjugates by a post-polymerization modification of copolymers containing 10 mol % pentafluorophenyl methacrylate (PFPMA), which were obtained via reversible addition-fragmentation chain transfer copolymerization. The coupling of the clinically used antifungal caspofungin was confirmed and quantified in detail by a combination of 1H-, 19F- and diffusion-ordered NMR spectroscopy, UV-vis spectroscopy, and size exclusion chromatography. The trifunctional amine-containing antifungal was attached via several amide bonds to the hydrophobic PMMA, but sterical hindrance induced by the mPEGMA side chains prohibited intramolecular double functionalization. Both polymer-drug conjugates revealed activity against important human-pathogenic fungi, that is, two strains of Aspergillus fumigatus and one strain of Candida albicans (2.5 mg L-1 < MEC < 8 mg L-1, MIC50 = 4 mg L-1), whereas RAW 264.7 macrophages as well as HeLa cells remained unaffected at these concentrations.
Assuntos
Antifúngicos , Ácidos Polimetacrílicos , Antifúngicos/farmacologia , Caspofungina , Células HeLa , HumanosRESUMO
PURPOSE: Intestinal malrotation is often diagnosed in infancy. The true incidence of malrotation outside of this age is unknown. These patients can present atypically or be asymptomatic and diagnosed incidentally. We evaluate the incidence, clinical presentation, ideal imaging, and intra-operative findings of patients with malrotation over 1 year of age. METHODS: Retrospective review was conducted in patients older than 1 year, treated for malrotation at a single pediatric tertiary care center from 2000 to 2015. Data analyzed included demographics, presentation, imaging, intraoperative findings, and follow-up. Patients predisposed to malrotation were excluded. RESULTS: 246 patients were diagnosed with malrotation, of which 77 patients were older than 1 year of age. The most common presenting symptoms were vomiting (68%) and abdominal pain (57%). The most common method of diagnosis was UGI (61%). In 88%, the UGI revealed malrotation. 73 of 75 were confirmed to have malrotation at surgery. Intra-operatively, 60% were found to have a malrotated intestinal orientation and 33% with a non-rotated orientation. Obstruction was present in 22% with 12% having volvulus. Of those with follow-up, 58% reported alleviation of symptoms. CONCLUSION: Despite age malrotation should be on the differential given a variable clinical presentation. UGI should be conducted to allow for prompt diagnosis and surgical intervention.
Assuntos
Volvo Intestinal/diagnóstico , Volvo Intestinal/cirurgia , Dor Abdominal/etiologia , Adolescente , Criança , Pré-Escolar , Endoscopia Gastrointestinal , Feminino , Refluxo Gastroesofágico/etiologia , Humanos , Lactente , Obstrução Intestinal/etiologia , Obstrução Intestinal/cirurgia , Volvo Intestinal/complicações , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Ultrassonografia , Vômito/etiologia , Adulto JovemRESUMO
BACKGROUND: Post-operative intra-abdominal abscess (PIAA) is the most common complication after appendectomy for perforated appendicitis (PA). Typically, intravenous antibiotics by a peripherally inserted venous catheter are utilized to treat the abscess. We sought to evaluate the role of oral antibiotics in this population. METHODS: This is a retrospective review conducted of children between January 2005 and September 2015 with a PIAA. Demographics, clinical course, complications, and follow-up were analyzed using descriptive statistics. Comparative analysis was performed on those who were treated with oral vs IV antibiotics after diagnosis of PIAA. RESULTS: 103 children were included. Days of symptoms prior to admission were 3.2 ± 2.3 days with a WBC of 17.9 ± 6.4. Median time to diagnosis of PIAA from appendectomy was 7 days (7, 10). Mean total length of stay was 10 ± 3.4 days. 42% were treated with oral antibiotics (n = 43) versus 58% IV antibiotics (n = 60) at the time of discharge. We found a significant increase in total length of hospital stay (9.1 vs 10.7, p = 0.02) and number of medical encounters required for treatment (3.4 vs 4.4, p ≤ 0.01) in the IV group. CONCLUSIONS: PIAA treatment after appendectomy for PA can be treated with oral antibiotics with equivalent outcomes as IV antibiotic treatment, but with shorter length of hospitalizations and less medical encounters required.
Assuntos
Abscesso Abdominal/tratamento farmacológico , Antibacterianos/administração & dosagem , Apendicectomia/efeitos adversos , Apendicite/cirurgia , Cuidados Pós-Operatórios/métodos , Infecção da Ferida Cirúrgica/tratamento farmacológico , Criança , Feminino , Humanos , Tempo de Internação/tendências , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Cirrhotic patients have an increased surgical risk due to potential intra and postoperative complications. AIM: To describe the clinical characteristics and surgical complications of cirrhotic patients undergoing surgery in a Chilean university hospital. PATIENTS AND METHODS: Review of medical records of 102 cirrhotic patients aged 60 ± 11 years (52% males) who underwent elective or urgency surgery at an university hospital between 2010 and 2016. General, pre-surgical, and post-surgical complications were recorded. RESULTS: The main etiologies of cirrhosis were non-alcoholic steatohepatitis (31%), and alcoholic cirrhosis (28%). Child-Pugh scores were A, B and C in 50, 28 and 22% of cases respectively. Median MELD (Model for End-stage Liver Disease) score was 11 (interquartile range: 10-15). The surgical procedure was elective in 71% of cases, with predominance of abdominal surgery (86%). The American Society of Anesthesiologists (ASA) score was three or more in 52% of patients. The frequency of any adverse outcome was 62%. The frequency increased along with the severity of cirrhosis and when surgery was urgent. The most common complications were acute renal failure (24%), increased ascites (23%) and encephalopathy (22%). Admission to intensive care unit occurred on 26% of patients, with six hospital deaths. CONCLUSIONS: In these patients, surgical complications were common, although with low mortality.
Assuntos
Doença Hepática Terminal , Idoso , Chile/epidemiologia , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de DoençaRESUMO
Although TEG directs effective resuscitation in adult surgical patients, pediatric data are lacking. We performed a retrospective comparative review of the effect of TEG on blood product utilization and outcomes following pediatric liver transplantation in 38 patients between 2008 and 2014. Diagnoses, laboratory values, fluid and blood product use, and outcomes were examined. Nineteen patients underwent liver transplantation prior to the implementation of TEG, and 19 had perioperative TEG. The most common indications for transplant were BA (n = 14), HB (n = 7), and metabolic disorders (n = 7). Intraoperative blood loss, urine output, fluid and blood product use were similar between groups. However, the use of fresh frozen plasma decreased significantly in TEG patients within the first 24 hours (29 vs 0 mL/kg, P < .01), and between 24 and 48 hours (12 vs 0 mL/kg, P = .01) post-operatively. The total use of fresh frozen plasma during hospitalization was markedly reduced (111 vs 17 mL/kg, P < .01). Four patients in the TEG group had thromboembolic graft complications, including portal vein or hepatic artery thrombosis, and underwent retransplantation. The decreased use of fresh frozen plasma since implementation of TEG is an important finding for resource utilization and patient safety. However, the increased incidence of thromboembolic complications requires further investigation.
Assuntos
Transfusão de Sangue/estatística & dados numéricos , Transplante de Fígado , Ressuscitação/métodos , Tromboelastografia , Adolescente , Transfusão de Sangue/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Avaliação de Resultados em Cuidados de Saúde , Plasma , Estudos RetrospectivosRESUMO
INTRODUCTION: Hepatic dysfunction in patients reliant on total parenteral nutrition (TPN) may benefit from cycled TPN. A concern for neonatal hypoglycemia has limited the use of cycled TPN in neonates less than 1 week of age. We sought to determine both the safety and efficacy of cycled TPN in surgical neonates less than 1 week of age. METHODS: A retrospective chart review was conducted on surgical neonates placed on prophylactic and therapeutic cycled TPN from January 2013 to March 2016. Specific emphasis was placed on identifying incidence of direct hyperbilirubinemia and hypoglycemic episodes. RESULTS: Fourteen neonates were placed on cycled TPN; 8 were prophylactically cycled and 6 were therapeutically cycled. Median gestational age was 36 weeks (34, 37). Sixty-four percent (n = 9) had gastroschisis. There was no difference between the prophylactic and therapeutic groups in incidence of hyperbilirubinemia > 2 mg/dL (3 (37%) vs 5 (83%), p = 0.08) or the length of time to development of hyperbilirubinemia [24 days (4, 26) vs 27 days (25, 67), p = 0.17]. Time on cycling was similar though patients who were prophylactically cycled had a shorter overall time on TPN. Three (21%) infants had documented hypoglycemia, but only one infant became clinically symptomatic. CONCLUSION: Prophylactic TPN cycling is a safe and efficacious nutritional management strategy in surgical neonates less than 1 week of age with low rates of hypoglycemia and a shorter total course of TPN; however, hepatic dysfunction did not appear to be improved compared to therapeutic cycling.
Assuntos
Hiperbilirrubinemia/epidemiologia , Hiperbilirrubinemia/terapia , Hipoglicemia/epidemiologia , Nutrição Parenteral Total/métodos , Enterocolite Necrosante/epidemiologia , Feminino , Gastrosquise/epidemiologia , Doença de Hirschsprung/epidemiologia , Humanos , Recém-Nascido , Atresia Intestinal/epidemiologia , Volvo Intestinal/epidemiologia , Masculino , Íleo Meconial/epidemiologia , Estudos RetrospectivosRESUMO
This study assessed the protective effect of active immunization of cattle to prevent the envenomation induced by B. asper venom. Two groups of oxen were immunized with a bothropic toxoid and challenged by an intramuscular injection of either 10 or 50 mg B. asper venom, to induce moderate or severe envenomations, respectively. Non-immunized oxen were used as controls. It was found that immunized oxen developed local edema similar to those observed in non-immunized animals. However, systemic effects were totally prevented in immunized oxen challenged with 10 mg venom, and therefore antivenom treatment was not required. When immunized oxen were challenged with 50 mg venom, coagulopathy was manifested 3-16 h later than in non-immunized oxen, demonstrating a delay in the onset of systemic envenomation. In these animals, active immunization did not eliminate the need for antivenom treatment, but increased the time lapse in which antivenom administration is still effective. All experimentally envenomed oxen completely recovered after a week following venom injection. Our results suggest that immunization of cattle with a bothropic toxoid prevents the development of systemic effects in moderate envenomations by B. asper, but does not abrogate these effects in severe envenomation.
Assuntos
Doenças dos Bovinos/prevenção & controle , Venenos de Crotalídeos/toxicidade , Mordeduras de Serpentes/veterinária , Toxoides/administração & dosagem , Vacinação , Animais , Antivenenos/imunologia , Antivenenos/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Testes de Coagulação Sanguínea , Bothrops/imunologia , Bovinos , Doenças dos Bovinos/induzido quimicamente , Doenças dos Bovinos/imunologia , Venenos de Crotalídeos/administração & dosagem , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/imunologia , Edema/prevenção & controle , Injeções Intramusculares , Masculino , Substâncias Protetoras/administração & dosagem , Mordeduras de Serpentes/imunologia , Mordeduras de Serpentes/prevenção & controle , Análise de Sobrevida , Fatores de Tempo , Toxoides/imunologia , Resultado do TratamentoRESUMO
PURPOSE: The success of prospective randomized trials relies on voluntary participation, which has been perceived as a barrier for successful trials in children who rely on parental permission. We sought to identify the reasons parents decline child participation to understand potential limitations in the consent process. METHODS: A prospective observational study was conducted in 92 patients asked to participate in prospective randomized trials between 2012 and 2015. Parental reasons for refusal were documented. RESULTS: The 92 refusals were distributed between studies investigating the management of circumcision, gastroschisis, pectus excavatum, appendicitis, pyloric stenosis, undescended testicles, abdominal abscess and gastroesophageal reflux. Reasons for refusal included preference of treatment path (37 %), inability to follow up (21 %), unspecified resistance to participate in research (18 %), preference to maintain independent surgeon decision (16 %), and desire for historically standard treatment (8 %). Of the families who opted to pursue a specific treatment arm rather than randomization, 35 % had prior experience with that treatment, 32 % had researched the procedure, 18 % wished to pursue the minimal intervention and 15 % did not specify. CONCLUSIONS: Parental preference of therapy is the most common reason for refusal of study participation. This variable could be influenced with more effective explanation of study rationale and existing equipoise.
Assuntos
Cirurgia Geral , Ensaios Clínicos Controlados Aleatórios como Assunto/psicologia , Recusa de Participação/psicologia , Pesquisa Biomédica , Compreensão , Humanos , Pais/psicologia , Estudos ProspectivosRESUMO
PURPOSE: In 2011, we established a dedicated center for patients with chest wall deformities. Here, we evaluate the center's effect on patient volume and management. METHODS: A retrospective review of 699 patients with chest wall anomalies was performed. Patients were compared, based on the date of initial consultation, before the pectus center opened (July 2009-June 2011, Group 1) versus after (July 2011-June 2013, Group 2). Analysis was performed utilizing Chi-square and Mann-Whitney U tests. RESULTS: 320 patients were in Group 1 and 379 in Group 2, an 18.4 % increase in patient volume. Excavatum patients increased from 172 (Group 1) to 189 (Group 2). Carinatum patients increased from 125 (Group 1) to 165 (Group 2). Patients undergoing operative repair of carinatum/mixed defects dropped significantly from 15 % (Group 1) to 1 % (Group 2) (p < 0.01), whereas those undergoing nonoperative bracing for carinatum/mixed defects rose significantly from 19 % (Group 1) to 63 % (Group 2) (p < 0.01). Patients traveled 3-1249 miles for a single visit. CONCLUSION: Initiating a dedicated pectus center increased patient volume and provided an effective transition to nonoperative bracing for carinatum patients. The concentrated focus of medical staff dedicated to chest wall deformities has allowed us to treat patients on a local and regional level.
Assuntos
Tórax em Funil/cirurgia , Modelos Organizacionais , Centros Cirúrgicos/organização & administração , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
PURPOSE: Literature reports worse outcomes for operations performed during off-hours. As this has not been studied in pediatric extracorporeal life support (ECLS), we compared complications based on the timing of cannulation.. METHODS: This is a retrospective review of 176 pediatric ECLS patients between 2004 and 2015. Patients cannulated during daytime hours (7:00 A.M. to 7:00 P.M., M-F) were compared to off-hours (nighttime or weekend) using t-test and Chi-square. RESULTS: The most common indications for ECLS were congenital diaphragmatic hernia (33 %) and persistent pulmonary hypertension (23 %). When comparing regular hours (40 %) to off-hours cannulation (60 %), there were no significant differences in central nervous system complications, hemorrhage (extra-cranial), cannula repositioning, conversion from venovenous to venoarterial, mortality on ECLS, or survival-to-discharge. The overall complication rate was slightly lower in the off-hours group (45.7 % versus 61.9 %, P = 0.034). CONCLUSION: Outcomes were not significantly worse for patients undergoing ELCS cannulation during off-hours compared to normal weekday working hours.
Assuntos
Cateterismo/normas , Anormalidades Congênitas/terapia , Oxigenação por Membrana Extracorpórea/métodos , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de TempoAssuntos
Hemorragia Cerebral Intraventricular/epidemiologia , Parto Obstétrico/métodos , Cordão Umbilical , Hemorragia Cerebral Intraventricular/diagnóstico por imagem , Constrição , Feminino , Humanos , Incidência , Lactente Extremamente Prematuro , Recém-Nascido , Gravidez , Fatores de Risco , Índice de Gravidade de Doença , Fatores de TempoRESUMO
BACKGROUND: Although the safety of same day discharge (SDD) after laparoscopic cholecystectomy (LC) for symptomatic cholelithiasis (SC) and biliary dyskinesia (BD) in adults has been well documented in the literature, the same data in the pediatric population are lacking. We have recently instituted a protocol for SDD after LC for SC and BD, and this study is an analysis of our initial experience. METHODS: A retrospective chart review of all patients who underwent LC for BD and SC in our institution from January 2011-July 2014 was performed. RESULTS: A total of 227 LC were performed for SC and BD during the study period. Approximately 25% (n = 57) of patients were in the SDD group. The remaining 75% (n = 170) of patients were admitted at least overnight stay (ONS) for the following reasons: medical 16.5% (n = 28), surgery ending too late 4.1% (n = 7), or clinical care habits 79.4% (n = 135). Comparing the SDD group with ONS group, no differences were found in the complication rate, readmissions, or follow up before scheduled appointment. Length of stay was significantly less for the SDD group than for the ONS. A trend for more SDDs was observed as time elapsed from initiation of the protocol. Also, earlier completion of surgery trended toward SDD. CONCLUSIONS: SDD appears safe for pediatric patients undergoing LC for BD or SC. The main obstacles to discharge were time of surgery completion and clinical care habits, both of which improved as comfort level with SDD grew among the staff.
Assuntos
Procedimentos Cirúrgicos Ambulatórios , Discinesia Biliar/cirurgia , Colecistectomia Laparoscópica , Colelitíase/cirurgia , Adolescente , Criança , Colecistectomia Laparoscópica/efeitos adversos , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: Chemical fibrinolysis has been shown to be as effective as surgical debridement for the treatment of pediatric empyema. However, no studies effectively evaluate antibiotic treatment. We evaluated antibiotic utilization among different treatments of pediatric empyema. METHODS: This is a retrospective review of 169 empyema patients who underwent chemical and/or mechanical fibrinolysis at a dedicated children's hospital from 2005-2013. Data points included duration of therapy, cultures, presence of necrosis or abscess, and adverse drug reactions. Immunocompromised patients and those with additional foci of infection were excluded. RESULTS: Twenty-seven patients underwent video-assisted thoracoscopic surgery (VATS), 123 had chemical fibrinolysis via tube thoracostomy with tissue plasminogen activator (tPA), and 19 had tPA followed by VATS. The mean (± standard deviation) duration of total antibiotic therapy was 25.7 ± 6.5 d; following a 24 h afebrile period of 19.4 ± 6.3 d. Patients who had tPA had a significantly shorter duration of parenteral antibiotic therapy when compared with primary VATS (9.2 ± 3.6 d versus 11.6 ± 5.5 d, P = 0.04) and VATS following tPA (9.2 ± 3.6 d versus 14.3 ± 8.1 d, P < 0.01). Patients with necrosis or abscess (n = 26) had an increased total duration of antibiotics (29.3 ± 5.7 d versus 25.1 ± 6.4 d, P < 0.01). Seventy patients (41%) had an adverse reaction related to antibiotic use. CONCLUSIONS: Patients with empyema currently receive a protracted variable course of antibiotic therapy influenced by primary treatment and the presence of necrosis or abscess. With a high incidence of adverse reactions, a standardized protocol with truncated treatment duration should be considered.
Assuntos
Antibacterianos/uso terapêutico , Empiema Pleural/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
An important host defence mechanism against pathogens is intracellular killing, which is achieved through phagocytosis, a cellular process for engulfing and neutralizing extracellular particles. Phagocytosis results in the formation of matured phagolysosomes, which are specialized compartments that provide a hostile environment and are considered the end point of the degradative pathway. However, all fungal pathogens studied to date have developed strategies to manipulate phagosomal function directly and also indirectly by redirecting phagosomes from the degradative pathway to a non-degradative pathway with the expulsion and even transfer of pathogens between cells. Here, using the major human fungal pathogens Aspergillus fumigatus, Candida albicans, Cryptococcus neoformans and Histoplasma capsulatum as examples, we discuss the processes involved in host phagosome-fungal pathogen interactions, with a focus on fungal evasion strategies. We also discuss recent approaches to targeting intraphagosomal pathogens, including the redirection of phagosomes towards degradative pathways for fungal pathogen eradication.
RESUMO
BACKGROUND: Exercise-induced rhinitis (EIR) is a poorly understood phenomenon that may be related to increased inspiratory airflow. Characterization of the development of EIR is important to understand contributing factors. OBJECTIVE: To characterize how different nasal morphologies respond to airflow-related variables during rapid/deep inspiratory conditions. METHODS: Subject-specific nasal airways were reconstructed from radiographic images. Unilateral airways were classified as Standard, Notched, or Elongated accord to their distinct nasal vestibule morphology. Computational fluid dynamics simulations were performed at various airflow rates. RESULTS: For all simulated flow rates, average resistance at the nasal vestibule, airflow velocity and wall sheer stress were highest in Notched. Average mucosal heat flux was highest in Standard. Notched phenotypes showed lower mean percent increases from 10 L/min to 50 L/min in all computed variables. CONCLUSION: Resistance values and airflow velocities depicted a more constricted nasal vestibule in the Notched phenotypes, while perception of nasal mucosal cooling (heat flux) favored the Standard phenotypes. Different nasal phenotypes may predispose to EIR.
Assuntos
Obstrução Nasal , Rinite , Humanos , Simulação por Computador , Cavidade Nasal/diagnóstico por imagem , Cavidade Nasal/anatomia & histologia , Mucosa Nasal , HidrodinâmicaRESUMO
The mechanism(s) underlying obesity-related postmenopausal (PM) breast cancer (BC) are not clearly understood. We hypothesized that the increased local presence of 'obese' mammary adipocytes within the BC microenvironment promotes the acquisition of an invasive and angiogenic BC cell phenotype and accelerates tumor proliferation and progression. BC cells, treated with primary mammary adipocyte secretome from premenopausal (Pre-M) and PM obese women (ObAdCM; obese adipocyte conditioned-media) upregulated the expression of several pro-tumorigenic factors including VEGF, lipocalin-2 and IL-6. Both Pre-M and PM ObAdCM stimulated endothelial cell recruitment and proliferation and significantly stimulated BC cell proliferation, migration and invasion. IL-6 and LCN2 induced STAT3/Akt signaling in BC cells and STAT3 inhibition abrogated the ObAdCM-stimulated BC cell proliferation and migration. Expression of proangiogenic regulators including VEGF, NRP1, NRP2, IL8RB, TGFß2, and TSP-1 were found to be differentially regulated in mammary adipocytes from obese PM women. Comparative RNAseq indicated an upregulation of PI3K/Akt signaling, ECM-receptor interactions and lipid/fatty acid metabolism in PM versus Pre-M mammary adipocytes. Our results demonstrate that irrespective of menopausal status, cross-talk between obese mammary adipocytes and BC cells promotes tumor aggressiveness and suggest that targeting the LCN2/IL-6/STAT3 signaling axis may be a useful strategy in obesity-driven breast tumorigenesis.