RESUMO
BACKGROUND: Breast conservation therapy is a widely accepted approach in treating breast cancer, yet the average re-excision rates are approximately 25% despite surgical advancements. The Food and Drug Administration (FDA)-approved MarginProbe® device uses radiofrequency spectroscopy for intraoperative margin assessment, potentially reducing re-excision rates. This study evaluated the effectiveness of MarginProbe® in reducing re-excisions compared with standard of care (SOC). METHODS: A prospective cohort with MarginProbe® usage during partial mastectomies from June 2019 to July 2023 (153 patients) was compared with a retrospective control group without the device from January 2015 to May 2019 (300 patients). Both groups underwent partial mastectomies performed by two breast surgeons. Positive margins were defined as tumor on ink for invasive cancers and within 2 mm for ductal carcinoma in situ. RESULTS: When control was used for patient demographics and tumor characteristics, the findings showed that MarginProbe® significantly decreased the probability of re-excision by 58% (p < 0.001), although it led to a higher shave volume, with an average of 9.8 cc additional tissue removed compared with SOC (p < 0.001). Human epidermal growth factor 2 (HER2) positivity was significantly associated with increased odds of re-excision (p = 0.036). MarginProbe® demonstrated a sensitivity of 70.1% and a specificity of 47.5%. CONCLUSIONS: MarginProbe® is an effective adjunct for intraoperative margin assessment to decrease re-excision rates. However, patient selection is paramount. Given its significant increase in shave volume, women with small breasts may be at higher risk for poor cosmesis. Surgeons should exercise clinical judgement when determining the suitability of MarginProbe® use for patients undergoing breast conservation. Further research is necessary to refine MarginProbe®'s specificity and to optimize its clinical application.
Assuntos
Neoplasias da Mama , Margens de Excisão , Mastectomia Segmentar , Reoperação , Humanos , Feminino , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Mastectomia Segmentar/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Seguimentos , Idoso , Carcinoma Intraductal não Infiltrante/cirurgia , Carcinoma Intraductal não Infiltrante/patologia , Prognóstico , Carcinoma Ductal de Mama/cirurgia , Carcinoma Ductal de Mama/patologia , AdultoRESUMO
INTRODUCTION: Patients who undergo surgery for breast cancer are at risk for venous thromboembolism (VTE) and bleeding, which can lead to significant consequences on outcomes. This study examined factors related to VTE and bleeding risk in breast cancer surgery, with and without reconstruction. We also investigated the relationship between operative time and resident involvement on bleeding and VTE risk. METHODS: Using the ACS-NSQIP database, patients who underwent mastectomy, implant, pedicled, or free flap reconstruction from 2005 to 2021 were identified. Resident involvement was available from 2007 to 2010. We fitted two logistic regressions to model the log odds of bleeding occurrence and VTE as linear functions of procedure type, controlling for age, body mass index, and comorbidities. RESULTS: Implant reconstruction had significantly reduced 30-d incidence of bleeding, compared to those who underwent transverse rectus abdominus muscle flap (P < 0.001). Free flap was associated with a significant increase in bleeding but not VTE risk (P < 0.001; P = 0.132). Increase in operative time significantly increased the risk of bleeding and VTE (P < 0.001). For surgeries with resident involvement coded, there was no significantly increased risk of bleeding or VTE (P = 0.600; P = 0.766). CONCLUSIONS: Implant reconstruction remains the procedure with the lowest risk of both bleeding and VTE. Free flap reconstruction did not show a significantly increased risk of VTE, potentially expanding reconstruction options for patients previously excluded from autologous reconstruction. Surgeons should be mindful of operative time, with re-evaluation of risk factors with each additional hour of surgery, irrespective of reconstruction type. Resident involvement in surgeries should continue to be encouraged by faculty.
Assuntos
Neoplasias da Mama , Mamoplastia , Mastectomia , Melhoria de Qualidade , Tromboembolia Venosa , Humanos , Feminino , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/prevenção & controle , Neoplasias da Mama/cirurgia , Pessoa de Meia-Idade , Mastectomia/efeitos adversos , Mamoplastia/efeitos adversos , Idoso , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/epidemiologia , Adulto , Duração da Cirurgia , Fatores de Risco , Incidência , Estudos RetrospectivosRESUMO
Although considered a hallmark in early ontogeny, weaning from breastmilk is difficult to monitor in wild primates and weaning ages remain unknown for wild bonobos (Pan Paniscus). Here, we calculated inter-birth intervals from demographic data and measured the isotopic offsets (Δ15N and Δ13C) between mother (n = 17) and offspring (n = 28) fecal sample pairs (n = 131, total n = 246) in the LuiKotale bonobos to assess nutritional weaning for the first time. We tested the effects of infant age, female parity, and sibling competition on Δ15N and Δ13C values. We found bonobo inter-birth intervals ranging from 2.2 to 7.3 years (xÌ = 4.7 ± 1.3 years) at LuiKotale. The Δ15N and Δ13C values suggested nutritional weaning on average by 6.6 and 7.0 years of age respectively, considerably exceeding weaning ages reported for chimpanzees (P. troglodytes) using the same approach. Our Δ13C data suggested that the number of offspring present affected nursing, with first-time mothers nursing more and possibly longer. The Δ15N and Δ13C values decreased with the arrival of the next sibling, suggesting sibling competition reduces milk access. Nevertheless, offspring may continue nursing 2.5-3 years after the birth of the next sibling, corresponding well with observations on low infant mortality. In conclusion, bonobo mothers provide remarkably enduring materna l support in the form of nursing concurrently to several offspring.
Assuntos
Isótopos de Carbono , Fezes , Isótopos de Nitrogênio , Pan paniscus , Desmame , Animais , Pan paniscus/fisiologia , Feminino , Isótopos de Nitrogênio/análise , Isótopos de Carbono/análise , Fezes/química , Masculino , Irmãos , Intervalo entre Nascimentos , Paridade , Mães , Comportamento CompetitivoRESUMO
Maintaining water balance is essential for organismal health, and lactating females must balance individual needs with milk production and offspring hydration. Primate milk is dilute and presumed to be the primary source for infant hydration for a considerable time period. Few studies have investigated the hydration burden that lactation may place on female primates. In this study, we investigated sources of variation in female and offspring drinking frequency among wild chimpanzees (Pan troglodytes). We hypothesized females would experience seasonal and lactation hydration burdens and adjust their drinking behavior to accommodate these, but this hydration burden would vary between females of different dominance ranks. We also predicted that parity would relate to maternal drinking frequency since primiparous females are still investing in their own growth. Finally, we predicted that offspring would drink more in the dry season and as they aged and lost milk as a water source, but that offspring of high-ranking females would be buffered from these effects. Using 41 years of long-term data on the behavior of mothers and offspring of Gombe National Park, we found that mothers drank more in the dry season, but there was no significant difference between mothers of different ranks during this period. Low-ranking females drank significantly more than mid- and high-ranking females during late lactation. Offspring also drank more in the dry season and as they aged, but there was no evidence of buffering for those with high-ranking mothers. While chimpanzees in our study population drank infrequently, they do demonstrate noticeable shifts in drinking behavior that suggests seasonal and reproductive hydration burdens.
Assuntos
Lactação , Pan troglodytes , Animais , Feminino , Humanos , Mães , Gravidez , Reprodução , ÁguaRESUMO
OBJECTIVES: Existing data on bonobo and chimpanzee dental eruption timing are derived predominantly from captive individuals or deceased wild individuals. However, recent advances in noninvasive photographic monitoring of living, wild apes have enabled researchers to characterize dental eruption in relatively healthy individuals under naturalistic conditions. At present, such data are available for only one population of wild chimpanzees. We report data for an additional population of wild chimpanzees and the first dental eruption data for wild bonobos. MATERIALS AND METHODS: We collected photographs and video footage of teeth from the open mouths of wild bonobos and East African chimpanzees of known age from LuiKotale, Democratic Republic of the Congo, and Gombe National Park, Tanzania, respectively. We scored the presence and absence of deciduous teeth from photographs and video footage to characterize deciduous dental eruption timing in these two populations. RESULTS: Deciduous dental eruption ages in our sample fall within the range of variation previously documented for captive chimpanzees, but eruption ages are later in wild than in captive contexts. We found substantial variation in deciduous canine eruption timing, particularly among bonobos. One bonobo had a deciduous canine present by 227 days old while another did not have a deciduous canine present at 477 days old. DISCUSSION: Our data indicate that deciduous teeth erupt later in wild individuals than in captive individuals. We also found that deciduous dental eruption timing varies considerably between individuals within our study populations, a pattern that is consistent with previous studies. Future studies should consider sources of variation in deciduous canine eruption timing and relationships with other aspects of life history as additional data become available.
Assuntos
Hominidae , Pan troglodytes , Animais , Humanos , Pan paniscus , Tanzânia , Erupção DentáriaRESUMO
Compared with most mammals, postnatal development in great apes is protracted, presenting both an extended period of phenotypic plasticity to environmental conditions and the potential for sustained mother-offspring and/or sibling conflict over resources. Comparisons of cortisol levels during ontogeny can reveal physiological plasticity to species or population specific socioecological factors and in turn how these factors might ameliorate or exaggerate mother-offspring and sibling conflict. Here, we examine developmental patterns of cortisol levels in two wild chimpanzee populations (Budongo and Taï), with two and three communities each, and one wild bonobo population (LuiKotale), with two communities. Both species have similar juvenile life histories. Nonetheless, we predicted that key differences in socioecological factors, such as feeding competition, would lead to interspecific variation in mother-offspring and sibling conflict and thus variation in ontogenetic cortisol patterns. We measured urinary cortisol levels in 1394 samples collected from 37 bonobos and 100 chimpanzees aged up to 12 years. The significant differences in age-related variation in cortisol levels appeared population specific rather than species specific. Both bonobos and Taï chimpanzees had comparatively stable and gradually increasing cortisol levels throughout development; Budongo chimpanzees experienced declining cortisol levels before increases in later ontogeny. These age-related population differences in cortisol patterns were not explained by mother-offspring or sibling conflict specifically; instead, the comparatively stable cortisol patterns of bonobos and Taï chimpanzees likely reflect a consistency in experience of competition and the social environment compared with Budongo chimpanzees, where mothers may adopt more variable strategies related to infanticide risk and resource availability. The clear population-level differences within chimpanzees highlight potential intraspecific flexibility in developmental processes in apes, suggesting the flexibility and diversity in rearing strategies seen in humans may have a deep evolutionary history.
Assuntos
Hidrocortisona/urina , Pan paniscus/metabolismo , Pan troglodytes/metabolismo , Animais , Feminino , Masculino , Pan paniscus/crescimento & desenvolvimento , Pan troglodytes/crescimento & desenvolvimento , Especificidade da EspécieRESUMO
OBJECTIVES: Primates exhibit variation in rates of growth and development. Variation in female growth and development across ape species appears to be explained by the Ecological Risk Aversion Hypothesis (ERAH). Indeed, existing data on variation in somatic growth and reproductive maturation between humans' closest living ape relatives, bonobos and chimpanzees, appear to be consistent with this hypothesis. However, existing data on behavioral maturation between the two species appear to contradict this hypothesis. We present novel behavioral data on infant and juvenile females from wild populations of both species in order to further evaluate predictions of the ERAH as it relates to the speed of behavioral maturation. MATERIALS AND METHODS: We analyzed 3 years of behavioral data on 17 female bonobos (<8 years of age) from LuiKotale, Democratic Republic of the Congo and 40 years of behavioral data on 30 age-matched female chimpanzees from Gombe, Tanzania. We compared the timing of (a) the attainment of independence from mothers and (b) the development of social skills using the following proxies: proximity between females and their mothers and the time that females spent engaged in eating, suckling, social play, social grooming, and riding on their mothers. RESULTS: We did not find species differences in the proportion of time that females spent in contact with their mothers or engaged in eating, suckling, social play, or social grooming. Female bonobos spent more time riding on their mothers than did female chimpanzees. Female bonobos spent more time at distances greater than 5 m from their mothers during the ages of 3-8 years, but females did not differ during the ages of 0-3 years. DISCUSSION: Behavioral maturation is largely similar between females of the two species based on the ages and proxies considered herein. We propose alternative explanations for the differences that we found in proximity and riding that do not invoke differences in underlying rates of maturation.
Assuntos
Comportamento Animal , Pan paniscus/psicologia , Pan troglodytes/psicologia , Comportamento Social , Animais , República Democrática do Congo , Feminino , Pan paniscus/crescimento & desenvolvimento , Pan troglodytes/crescimento & desenvolvimento , TanzâniaAssuntos
Cesárea , Hemorragia Pós-Parto , Humanos , Feminino , Gravidez , Adulto , Oxigênio/sangue , Oximetria , Fatores de RiscoRESUMO
BACKGROUND: Recent studies have highlighted the overall survival (OS) benefit of cytoreductive radical cystectomy (CRC) in metastatic bladder cancer (mBCa). Cytoreductive surgery has been established in other urologic cancers. However, the efficacy of CRC and optimal criteria for patient selection in mBCa is unclear. This study investigated the oncologic efficacy of CRC, particularly emphasizing the location and number of metastasis sites as a predictor of survival and treatment response. METHODS: A retrospective analysis of cT2-4N0-3M1 mBCa patients treated with multiagent chemotherapy between 2004 and 2019 was conducted using the National Cancer Database. Patients were classified by additional treatment with CRC or conservative local treatment (CLT), consisting of transurethral resection of bladder tumor, radiation, or no local treatment and propensity score (PS) matched. Kaplan-Meier analysis and multivariate Cox Proportional Hazards model assessed the effect of CRC or CLT on OS within the matched cohort and in four subgroups (1) patients with only distant lymph node (LN) metastasis vs. any organ metastasis, (2) patients with single metastasis vs. multiple metastases. Sensitivity analysis estimated the influence of unmeasured confounders on CRC OS benefit. RESULTS: Propensity matching yielded 247 and 251 patients treated with CRC and CLT, respectively. Median OS in patients who received CRC was greater than that of patients treated with CLT (20.4 months vs. 12.0 months, P < 0.001). CRC was associated with reduced mortality risk in patients with only distant LN metastases (HRâ¯=â¯0.545, Pâ¯=â¯0.039), any organ metastasis (HRâ¯=â¯0.421, P < 0.001), and single visceral metastasis (HRâ¯=â¯0.483, Pâ¯=â¯0.002). However, CRC did not significantly improve OS in patients with multiple metastases (HRâ¯=â¯0.501, Pâ¯=â¯0.064). CONCLUSION: These findings demonstrate an OS benefit of CRC with multiagent chemotherapy and pinpoint multiple visceral metastases as a potential contraindication for CRC. Although limited by the influence of unmeasured confounders, these findings may inform future prospective investigations into CRC.
Assuntos
Carcinoma de Células de Transição , Cianoacrilatos , Neoplasias da Bexiga Urinária , Humanos , Procedimentos Cirúrgicos de Citorredução , Cistectomia , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/patologia , Metástase Linfática , Resultado do TratamentoRESUMO
OBJECTIVE: There is growing attention toward the implications of race and ethnicity on health disparities within otolaryngology. While race is an established predictor of adverse head and neck oncologic outcomes, there is paucity in the literature on studies employing national, multi-institutional data to assess the impact of race and ethnicity on head and neck autograft surgery. METHODS: Using the National Surgical Quality Improvement Program (NSQIP) database, trends in 30 days outcomes were assessed. Patients with ICD-10 codes for malignant head and neck neoplasms were isolated. Autograft surgeries were selected using Current Procedural Terminology (CPT) codes for free flap and pedicled flap reconstruction. Primary outcomes included surgical complications, reoperation, readmission, extended length of stay and operation time. Each binary categorical variable was compared to racial/ethnic identity via binary logistic regression. RESULTS: The study cohort consisted of 2447 patients who underwent head and neck autograft surgery (80.71% free flap reconstruction and 19.39% pedicled flap reconstruction). Black patients had significantly higher odds of overall surgical complications (odds ratio [OR] 1.583, 95% confidence interval [CI] 1.091, 2.298, p = 0.016) with much higher odds of perioperative blood transfusions (OR 2.291, 95% CI 1.532, 3.426, p = <.001). Hispanic patients were more likely to undergo reoperation within 30 days after surgery and were more likely to be hospitalized for more than 30 days post-operatively (OR 1.566, 95% CI 1.015, 2.418, p = 0.043 and OR 12.224, 95% CI 2.698, 55.377, p = 0.001, respectively). CONCLUSIONS: Race and ethnicity serve as independent predictors of complications in the post-operative period following head and neck autograft surgery. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3595-3603, 2024.
Assuntos
Neoplasias de Cabeça e Pescoço , Complicações Pós-Operatórias , Humanos , Feminino , Masculino , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/etnologia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/etnologia , Reoperação/estatística & dados numéricos , Etnicidade/estatística & dados numéricos , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Autoenxertos , Idoso , Grupos Raciais/estatística & dados numéricos , Estados Unidos/epidemiologia , Adulto , Retalhos Cirúrgicos/transplante , Estudos Retrospectivos , Tempo de Internação/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Duração da CirurgiaRESUMO
BACKGROUND: While other otolaryngology subspecialties have established female authorship trends, there is no comprehensive study within head and neck surgery (HNS). METHODS: Five researchers recorded the gender identity of first and senior authors from HNS subspecialty papers (head and neck oncology, endocrine surgery, salivary gland pathology, and microsurgery) derived from 10 journals in otolaryngology and oncology in the years 2013, 2016, 2019, and 2022. RESULTS: From 3457 articles, 6901 unique author identities were analyzed. Female authors represented 32% (N = 1103) of first authors and 20% (N = 690) of senior authors. Female authors were less likely to publish in microvascular and reconstructive surgery. Senior female authors were more likely to publish in higher impact journals than male senior authors, and first female authors had an increased likelihood of funding compared to their male counterparts. CONCLUSIONS: While female authors remain underrepresented in certain literature, we illustrate promising trends in productivity, funding allocation, and impact.
Assuntos
Autoria , Otolaringologia , Humanos , Feminino , Masculino , Médicas/estatística & dados numéricos , Médicas/tendências , Publicações Periódicas como Assunto , Bibliometria , Editoração/estatística & dados numéricos , Editoração/tendências , Fatores SexuaisRESUMO
OBJECTIVE AND DESIGN: The hypothesis that aspiration of gastric fluid drives the anti-ovalbumin response toward a Th2 reaction even in animals not prone to Th2 responses was evaluated. SUBJECTS: Forty-eight male C57BL/6 mice were used. METHODS: Mice were sensitized and challenged with ovalbumin starting 5 weeks prior to the initiation of weekly aspirations of either gastric fluid or normal saline as a control. Weekly aspiration continued during the course of exposure to ovalbumin. TREATMENT: Aspiration consisted of 50 µl of gastric fluid with 50 µl of 0.9 % normal saline used as a control. Antigen exposure consisted of sensitization to ovalbumin via intraperitoneal injection on days 0 and 14 and challenge on day 21 with aerosolized antigen for 30 min. RESULTS: No evidence of a shift toward a Th2 response as a result of gastric fluid aspiration was seen in the Th1-prone strain utilized, although a profound down-regulation of a broad array of T cell-associated cytokines and chemokines and up-regulation of macrophage-associated markers was observed as a result of aspiration. CONCLUSIONS: These data provide support for the hypothesis that the clinical association between asthma and gastroesophageal reflux disease (GERD) does not involve an exacerbation of asthma by GERD-associated aspiration of gastric fluid, but may cause immune reactions unrelated to the asthma pathology.
Assuntos
Asma/imunologia , Suco Gástrico , Aspiração Respiratória , Imunidade Adaptativa , Animais , Antígenos/imunologia , Asma/patologia , Citocinas/imunologia , Modelos Animais de Doenças , Refluxo Gastroesofágico/imunologia , Células Gigantes/patologia , Imunidade Inata , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina/imunologiaRESUMO
In animals with slow ontogeny and long-term maternal investment, immatures are likely to experience the birth of a younger sibling before reaching maturity. In these species, the birth of a sibling marks a major event in an offspring's early life as the older siblings experience a decrease in maternal support. The transition to siblinghood (TTS) is often considered to be stressful for the older offspring, but physiological evidence is lacking. To explore the TTS in wild bonobos, we investigated physiological changes in urinary cortisol (stress response), neopterin (cell-mediated immunity), and total triiodothyronine (T3, metabolic rate), as well as changes in behaviors that reflect the mother-offspring relationship. Following a sibling's birth, urinary cortisol levels of the older offspring increased fivefold, independent of their age, and remained elevated for 7 months. The cortisol level increase was associated with declining neopterin levels; however, T3 levels and behavioral measures did not change. Our results indicate that the TTS is accompanied by elevated cortisol levels and that this change does not coincide with nutritional weaning and attainment of physical independence. Our results suggest that bonobos and humans experience TTS in similar ways and that this developmental event may have emerged in the last common ancestor.
Assuntos
Hidrocortisona , Pan paniscus , Animais , Hidrocortisona/urina , Neopterina , Irmãos , Tri-IodotironinaRESUMO
Fission-fusion dynamics have evolved in a broad range of animal taxa and are thought to allow individuals to mitigate feeding competition. While this is the principal benefit of fission-fusion, few studies have evaluated its costs. We compared gregariousness, foraging budgets, and social budgets between lactating bonobos and chimpanzees from wild populations to evaluate potential costs. Both species exhibit fission-fusion dynamics, but chimpanzees, particularly in East African populations, appear to experience higher feeding competition than bonobos. We expected lactating chimpanzees to be less gregarious than lactating bonobos; reduced gregariousness should allow lactating chimpanzees to mitigate the costs of higher feeding competition without requiring more foraging effort. However, we expected the reduced gregariousness of lactating chimpanzees to limit their time available for affiliative interactions. Using long-term data from LuiKotale bonobos and Gombe chimpanzees, we found that lactating chimpanzees were indeed less gregarious than lactating bonobos, while feeding and travel time did not differ between species. Contrary to our predictions, lactating females did not differ in social interaction time, and lactating chimpanzees spent proportionately more time interacting with individuals other than their immature offspring. Our results indicate that lactating chimpanzees can maintain social budgets comparable to lactating bonobos despite reduced gregariousness and without incurring additional foraging costs. We discuss potential explanations for why lactating bonobos are more gregarious.
RESUMO
Although mice associated with a single bacterial species have been used to provide a simple model for analysis of host-bacteria relationships, bacteria have been shown to display adaptability when grown in a variety of novel environments. In this study, changes associated with the host-bacterium relationship in mice monoassociated with Escherichia coli K-12 over a period of 1,031 days were evaluated. After 80 days, phenotypic diversification of E. coli was observed, with the colonizing bacteria having a broader distribution of growth rates in the laboratory than the parent E. coli. After 1,031 days, which included three generations of mice and an estimated 20,000 generations of E. coli, the initially homogeneous bacteria colonizing the mice had evolved to have widely different growth rates on agar, a potential decrease in tendency for spontaneous lysis in vivo, and an increased tendency for spontaneous lysis in vitro. Importantly, mice at the end of the experiment were colonized at an average density of bacteria that was more than 3-fold greater than mice colonized on day 80. Evaluation of selected isolates on day 1,031 revealed unique restriction endonuclease patterns and differences between isolates in expression of more than 10% of the proteins identified by two-dimensional electrophoresis, suggesting complex changes underlying the evolution of diversity during the experiment. These results suggest that monoassociated mice might be used as a tool for characterizing niches occupied by the intestinal flora and potentially as a method of targeting the evolution of bacteria for applications in biotechnology.
Assuntos
Escherichia coli K12/crescimento & desenvolvimento , Trato Gastrointestinal/microbiologia , Animais , Escherichia coli K12/genética , Estudos Longitudinais , Camundongos , Mapeamento por RestriçãoRESUMO
BACKGROUND: A large number of studies point toward chronic aspiration associated with gastroesophageal reflux disease (GERD) as an important factor involved in the development of asthma, the incidence of which has increased dramatically in industrially developed countries. Recent work suggests that medical intervention aimed at acid blockade is not sufficient to relieve the effects of chronic aspiration on asthma pathology, leaving surgical treatment of the disease as one of the few remaining options. This study examined the effect of chronic aspiration on the airway-associated immune response to allergens using a model of experimentally induced airway hypersensitivity in Balb/c mice. METHODS: The mice received aspiration of gastric fluid on days 1, 8, 15, 22, 29, 36, 43, and 50 and were sensitized to ovalbumin by intraperitoneal (IP) injection on days 33 and 47, challenged with aerosolized ovalbumin on day 54, and killed on day 56. Control mice received sham gastric fluid aspirations, sham induction of airway hypersensitivity, or both. RESULTS: Chronic aspiration of 50 microl murine gastric fluid once per week for 8 weeks had a profound effect on the immune system in the lung, with upregulation of the macrophage/monocyte-associated cytokines tumor necrosis factor-alpha (TNF-alpha) and interleukin-12 (IL-12) and profound downregulation of a broad array of T-cell-associated cytokines including interleukins 2, 4, 5, 6, 10, 13, and 23, as well as interferon-gamma. The aspiration-induced depression of IL-5 production in particular was found only in mice with airway hypersensitivity and not in control mice without airway hypersensitivity. CONCLUSIONS: The results indicate that chronic aspiration of gastric fluid has a profound effect on the nature of the allergic response to aerosolized allergens, suggesting that the aspiration may be an important factor affecting the pathogenesis of asthma.
Assuntos
Asma/imunologia , Ácido Gástrico/metabolismo , Refluxo Gastroesofágico/complicações , Imunidade Celular , Pulmão/imunologia , Macrófagos Alveolares/imunologia , Linfócitos T/imunologia , Animais , Asma/etiologia , Modelos Animais de Doenças , Progressão da Doença , Ensaio de Imunoadsorção Enzimática , Seguimentos , Refluxo Gastroesofágico/metabolismo , Interleucina-12/imunologia , Interleucina-5/biossíntese , Pulmão/metabolismo , Macrófagos Alveolares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fator de Necrose Tumoral alfa/imunologiaRESUMO
BACKGROUND: Although chronic aspiration has been associated with several pulmonary diseases, the inflammatory response has not been characterized. A novel rodent model of chronic aspiration was therefore developed in order to investigate the resulting innate immune response in the lung. METHODS: Gastric fluid or normal saline was instilled into the left lung of rats (n = 48) weekly for 4, 8, 12, or 16 weeks (n = 6 each group). Thereafter, bronchoalveolar lavage specimens were collected and cellular phenotypes and cytokine concentrations of IL-1alpha, IL-1beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma, TNF-alpha, and TGF-beta were determined. RESULTS: Following the administration of gastric fluid but not normal saline, histologic specimens exhibited prominent evidence of giant cells, fibrosis, lymphocytic bronchiolitis, and obliterative bronchiolitis. Bronchoalveolar lavage specimens from the left (treated) lungs exhibited consistently higher macrophages and T cells with an increased CD4:CD8 T cell ratio after treatment with gastric fluid compared to normal saline. The concentrations of IL-1alpha, IL-1beta, IL-2, TNF-alpha and TGF-beta were increased in bronchoalveolar lavage specimens following gastric fluid aspiration compared to normal saline. CONCLUSION: This represents the first description of the pulmonary inflammatory response that results from chronic aspiration. Repetitive aspiration events can initiate an inflammatory response consisting of macrophages and T cells that is associated with increased TGF-beta, TNF-alpha, IL-1alpha, IL-1beta, IL-2 and fibrosis in the lung. Combined with the observation of gastric fluid-induced lymphocyitic bronchiolitis and obliterative bronchiolitis, these findings further support an association between chronic aspiration and pulmonary diseases, such as obliterative bronchiolitis, pulmonary fibrosis, and asthma.
Assuntos
Bronquiolite/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Modelos Animais de Doenças , Imunidade Inata/imunologia , Macrófagos Alveolares/imunologia , Fibrose Pulmonar/imunologia , Aspiração Respiratória/complicações , Animais , Bronquiolite/etiologia , Bronquiolite/patologia , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/patologia , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Ácido Gástrico , Refluxo Gastroesofágico/complicações , Macrófagos Alveolares/patologia , Masculino , Fibrose Pulmonar/etiologia , Fibrose Pulmonar/patologia , Ratos , Ratos Endogâmicos F344RESUMO
The immune systems of wild rats and of laboratory rats can been utilized as models of the human immune system in pre-industrial and post-industrial societies, respectively. In this study, lymphocyte phenotypes in wild rats were broadly characterized, and the results were compared to those obtained by us and by others using cells derived from various strains of laboratory rats. Although not expected, the production of regulatory T cells was not apparently different in wild rats compared to laboratory rats. On the other hand, differences in expression of markers involved in complement regulation, adhesion, signaling and maturation suggest increased complement regulation and decreased sensitivity in wild-caught rats compared to laboratory rats, and point toward complex differences between the maturation of T cells. The results potentially lend insight into the pathogenesis of post-industrial epidemics of allergy and autoimmune disease.
Assuntos
Animais Selvagens , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo , Animais , Adesão Celular , Diferenciação Celular , Separação Celular , Ativação do Complemento , Citometria de Fluxo , Imunização , Imunofenotipagem , Indústrias , Ratos , Ratos Endogâmicos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/patologiaRESUMO
Bariatric surgery is a field in rapid evolution, and the speed of this evolution has been accelerating over the last several decades. A thorough understanding of past developments is crucial to anticipating the future intelligently. The trends that have driven evolution historically often persist, and continue to be influential in the future. With this in mind, this article briefly outlines the historical and current trends in bariatric surgery, and follows the trajectory of these trends into the future to anticipate the technologies and techniques that will be most important to the field in the coming years.
Assuntos
Cirurgia Bariátrica/tendências , Cirurgia Bariátrica/métodos , Cirurgia Bariátrica/estatística & dados numéricos , Desenho de Equipamento , Balão Gástrico , Humanos , Laparoscopia , Cirurgia Endoscópica por Orifício Natural/tendências , Obesidade Mórbida , Robótica/tendênciasRESUMO
BACKGROUND: Most studies of thoracic endovascular aortic repair (TEVAR) published since the technology gained US Food and Drug Administration (FDA) approval in March 2005 have included multiple applications including dissection, trauma, and "hybrid" approaches, all of which are currently "off-label." However, little post-approval data exist for the only FDA-approved application, namely descending thoracic aneurysm (DTA). The purpose of this study was to examine our experience with TEVAR for aneurysms limited to the descending thoracic aorta. METHODS: Between March 23, 2005 (date of initial FDA approval) and April 6, 2009, 210 TEVAR procedures were performed at our institution. Of these, 79 (38%) were for saccular (n = 31) or fusiform (n = 48) DTA and form the basis of this report. Patients requiring "hybrid" approaches other than carotid-subclavian bypass were excluded. Devices utilized were Gore TAG (W. L. Gore Associates, Flagstaff, AZ) (n = 67; 85%), Zenith TX2 (Cook Medical Incorporated, Bloomington, IN) (n = 10; 13%), and Medtronic Talent (Medtronic, Inc, Santa Rosa, CA) (n = 5; 6%); 3 (4%) patients received more than one type of device. RESULTS: Median patient age was 73 +/- 4 years; 35 (44%) were female. Mean aortic diameter was 5.8 +/- 1.8 cm. Twenty-four (30%) procedures were urgent-emergent. Thirty-day in-hospital rates of death, stroke, and permanent paraplegia-paresis were 5.1% (n = 4; 1.9% elective mortality), 2.5% (n = 2), and 1.3% (n = 1), respectively. The median postoperative length of stay was 3.0 days (25th and 75th percentiles = 2 and 6, respectively). At a mean follow-up of 23 +/- 17 months (range, 6 to 55), there were 2 (2.5%) late aortic deaths from graft infection (n = 1) and aneurysm rupture (n = 1). Overall actuarial midterm survival is 73% at 55 months, with an aorta-specific actuarial survival of 86% during this same time interval. Five patients (6.3%) required late (>30 days) secondary endovascular re-intervention for type I (n = 4) or type II (n = 1) endoleak; re-intervention was successful in 4 of 5. CONCLUSIONS: Despite the advanced age, comorbid conditions, and significant incidence of urgent-emergent status of patients presenting with DTA, on-label application of TEVAR yields excellent 30-day and midterm outcomes, especially when compared with historic rates of morbidity and mortality with open repair. However, "on-label" applications represent a minority of current TEVAR use, likely due to the relative scarcity of DTA. These data appear to support the increasing utilization of TEVAR as a treatment strategy for this pathology.