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INTRODUCTION: Laparoscopic cholecystectomy (LC) for gangrenous gallbladders (GGBs) can be challenging and represent a significant number of LC cases, necessitating more efficacious surgical techniques. Currently, the standard treatment for GGBs is blunt dissection which can have high iatrogenic complication rates. To our knowledge, this is the first large retrospective study conducted on the novel application of hydrodissection (HD) in LCs for GGBs. METHODS: In this retrospective study of 386 LCs, data were collected for patient demographics, medical comorbidities, operating time (OT), anesthesia time (AT), length of stay (LOS), estimated blood loss, conversion to open procedures, 30-day readmissions, and mortality. Patients were categorized into four groups: (1) Vyas employing HD for GGBs (VHG), (2) non-Vyas group of five surgeons not employing HD for GGBs (NVG), (3) Vyas treating non-GGBs, and (4) non-Vyas group of five surgeons treating non-GGBs. Control groups were age-matched and sex-matched. Statistical analysis used descriptive statistics, Mann-Whitney U testing, and chi-squared testing (α = 0.05). RESULTS: This study demonstrated significantly decreased (P < 0.05) OT (P = 0.001), AT (P < 0.001), LOS (P = 0.015), and conversion to open procedures (P = 0.047) between the VHG and NVG groups, with HD reducing OT by 35.5% compared to blunt dissection. This study did not demonstrate significantly decreased (P > 0.05) estimated blood loss (P = 0.185) and 30-day readmissions (P = 0.531) between the VHG and NVG groups, but they were trending toward significant. There were no mortalities in this study. CONCLUSIONS: HD is associated with improved surgical outcomes of LCs for GGBs demonstrated by reduced OT, AT, LOS, and conversion to open procedures. Further multi-institutional studies are needed to validate HD implementation and further dissemination.
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Colecistectomia Laparoscópica , Colecistite Aguda , Humanos , Colecistectomia Laparoscópica/métodos , Colecistectomia , Estudos Retrospectivos , Tempo de InternaçãoRESUMO
Triple-Negative Breast Cancer (TNBC) has a poor prognosis due to lack of targeted therapy. Doxorubicin (DOX) has failed for multiple reasons, including development of multi-drug resistance, induction of inflammation (IL-6 secretion) and long-term toxicities. DOX is also known to have off target proteasomal activation, justifying the concept of combining it with a proteasomal inhibitor. Our study investigated the therapeutic potential of an irreversible proteasome inhibitor carfilzomib (CARF) alone or in combination with DOX in two TNBC cell lines (MDA-MB-231 and MDA-MB-468). CARF was as effective in inhibiting mitosis in vitro for both cell lines in comparison to DOX alone. CARF performed similar to DOX in inhibiting apoptosis but had better results in reducing proliferation. Further studies in MDA-MB-231 cells demonstrated that CARF also inhibited pro-inflammatory IL-6 secretion and NF κB transcriptional activity while DOX stimulated both IL-6 and NF kappa-B activity. The reduction of IL-6 while using CARF highlights its therapeutic potential and ability to enhance current clinical drug regimens. Furthermore, exogenous administration of IL-6 potentiated NF Kappa B transcriptional activity, pSTAT3 (Tyr705) and JAK inflammatory signaling as well as cell proliferation in CARF- or DOX-treated MDA-MB-231 cells. In vivo, CARF treatment resulted in reduced serum IL-6 compared to treatment with DOX in female SCID-NOD mice with MDA-MB-231 cell tumor. A combinational approach using DOX and CARF presents a clinical potential for better efficacy, reduced proliferation, apoptosis, anti-angiogenesis, and less cardiac dysfunction when compared to current treatments using standalone DOX.
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Neoplasias da Mama/metabolismo , Doxorrubicina/farmacologia , Interleucina-6/metabolismo , NF-kappa B/metabolismo , Oligopeptídeos/farmacologia , Inibidores de Proteassoma/farmacologia , Fator de Transcrição STAT3/metabolismo , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: The trauma pandemic is one of the leading causes of death worldwide but especially in rapidly developing economies. Perhaps, a common cause of trauma-related mortality in these settings comes from the rapid expansion of motor vehicle ownership without the corresponding expansion of national prehospital training in developed countries. The resulting road traffic injuries often never make it to the hospital in time for effective treatment, resulting in preventable disability and death. The current article examines the development of a medical first responder training program that has the potential to reduce this unnecessary morbidity and mortality. METHODS: An intensive training workshop has been differentiated into two progressive tiers: acute trauma training (ATT) and broad trauma training (BTT) protocols. These four-hour and two-day protocols, respectively, allow for the mass education of laypersons-such as police officials, fire brigade, and taxi and/or ambulance drivers-who are most likely to interact first with prehospital victims. Over 750 ATT participants and 168 BTT participants were trained across three Indian educational institutions at Jodhpur and Jaipur. Trainees were given didactic and hands-on education in a series of critical trauma topics, in addition to pretraining and post-training self-assessments to rate clinical confidence across curricular topics. Two-sample t-test statistical analyses were performed to compare pretraining and post-training confidence levels. RESULTS: Program development resulted in recruitment of a variety of career backgrounds for enrollment in both our ATT and BTT workshops. The workshops were run by local physicians from a wide spectrum of medical specialties and previously ATT-trained police officials. Statistically significant improvements in clinical confidence across all curricular topics for ATT and BTT protocols were identified (P < 0.0001). In addition, improvement in confidence after BTT training was similar in Jodhpur compared with Jaipur. CONCLUSIONS: These results suggest a promising level of reliability and reproducibility across different geographic areas in rapidly developing settings. Program expansion can offer an exponential growth in the training rate of medical first responders, which can help curb the trauma-related mortality in rapidly developing economies. Future directions will include clinical competency assessments and further progressive differentiation into higher tiers of trauma expertise.
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Países em Desenvolvimento , Serviços Médicos de Emergência/métodos , Socorristas/educação , Tratamento de Emergência/métodos , Ferimentos e Lesões/terapia , Competência Clínica , Currículo , Serviços Médicos de Emergência/organização & administração , Humanos , Índia , Desenvolvimento de Programas , Avaliação de Programas e Projetos de SaúdeRESUMO
BACKGROUND: A major factor contributing to global trauma mortality and morbidity is the lack of effective prehospital trauma services in developing settings. We developed a 2-d training course for nondoctor first responders featuring high-fidelity simulation and video-assisted debriefing, self-directed learning videos, and native language instruction. MATERIALS AND METHODS: A pilot session was conducted in Jodhpur, Rajasthan. Eighteen local instructors were recruited to train 48 layperson first responders in 10 essential subjects. Didactic sessions of 15-20 min consisting of self-directed learning videos were followed by 30-40 min skill sessions featuring high-fidelity simulation, and concluded with 15-20 min video-debriefing periods. Changes in competence were evaluated using pretraining and posttraining surveys. RESULTS: Results demonstrated that statistically significant competence increases in all areas of trauma management assessed: airway (t[46] = 7.30, P < 0.000), hemorrhage (t[46] = 9.96, P < 0.000), fractures (t[46] = 9.22, P < 0.000), cervical spine injury (t[46] = 12.12, P = 0.000), chest injury (t[46] = 7.84, P < 0.000), IV line placement (t[46] = 4.36, P < 0.000), extrication (t[46] = 2.81, P < 0.005), scene assessment (t[46] = 7.06, P < 0.000), triage (t[46] = 5.92, P < 0.000), and communication (t[46] = 5.56, P < 0.000). Highest increases in competence were observed in cervical spine injury and hemorrhage management, with lowest increases in IV line placement and extrication. CONCLUSIONS: Results suggest this approach may be effective in imparting prehospital trauma management concepts to layperson first responders. This study highlights an innovative educational avenue through which trauma management capacity can be enhanced in developing settings.
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Países em Desenvolvimento , Educação Continuada/métodos , Serviços Médicos de Emergência , Socorristas/educação , Ferimentos e Lesões/terapia , Competência Clínica , Simulação por Computador , Serviços Médicos de Emergência/métodos , Serviços Médicos de Emergência/normas , Humanos , Índia , Manequins , Modelos Educacionais , Avaliação de Programas e Projetos de Saúde , Gravação em VídeoRESUMO
The discovery, synthesis, and characterization of 9H-carbazole-1-carboxamides as potent and selective ATP-competitive inhibitors of Janus kinase 2 (JAK2) are discussed. Optimization for JAK family selectivity led to compounds 14 and 21, with greater than 45-fold selectivity for JAK2 over all other members of the JAK kinase family.
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Amidas/química , Janus Quinase 2/antagonistas & inibidores , Inibidores de Proteínas Quinases/química , Amidas/metabolismo , Amidas/farmacologia , Sítios de Ligação , Carbazóis/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Humanos , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 1/metabolismo , Janus Quinase 2/metabolismo , Janus Quinase 3/antagonistas & inibidores , Janus Quinase 3/metabolismo , Simulação de Dinâmica Molecular , Ligação Proteica , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Estrutura Terciária de Proteína , Relação Estrutura-AtividadeRESUMO
Triple negative breast cancer exhibit increased IL-6 expression compared with matched healthy breast tissue and a strong link between inflammation and cancer progression and metastasis has been reported. We investigated whether doxorubicin-hyaluronan-super-paramagnetic iron oxide nanoparticles (DOX-HA-SPION) would show greater therapeutic efficacy in human triple negative breast cancer cells (TNBC) MDA-MB-231, as was recently shown in drug-sensitive and multi-drug-resistant ovarian cancer cells. Therefore, we measured cellular DOX uptake via confocal microscopy; observed morphologic changes: mitochondrial and nuclear changes with electron microscopy, and quantitated apoptosis using FACS analysis after Annexin V and PI staining in MDA-MB-231 cells treated with either DOX alone or DOX-HA-SPION. We also measured both proinflammatory and anti-inflammatory cytokines; IL-6, IL-10 respectively and also measured nitrate levels in the conditioned medium by ELISA. Inaddition, NF-κB activity was measured by luciferase assay. Confocal microscopy demonstrated greater cytoplasmic uptake of DOX-HA-SPION than free DOX. We also demonstrated reduction of Vimentin with DOX-HA-SPION which is significantly less than both control and DOX. DOX-HA-SPION enhanced apoptosis and significantly down regulated both pro-inflammatory mediators IL-6 and NF-κB in comparison to DOX alone. The secretion levels of anti-inflammatory mediators IL-10 and nitrate was not decreased in the DOX or DOX-HA-SPION treatment groups. Our data suggest that DOX-HA-SPION nanomedicine-based drug delivery could have promising potential in treating metastasized and chemoresistant breast cancer by enhancing the drug efficacy and minimizing off-target effects.
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Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Doxorrubicina/farmacocinética , Ácido Hialurônico/química , Interleucina-6/metabolismo , Nanopartículas de Magnetita/química , NF-kappa B/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias da Mama , Linhagem Celular Tumoral , Forma Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacologia , Humanos , Ácido Hialurônico/farmacocinética , Nanopartículas de Magnetita/toxicidadeRESUMO
Worldwide, breast cancer remains as one of the most common cancer diagnosis and cause of cancer related death among women. Fortunately, nanomedicine has brought forth new potential and hope in breast cancer research. The extremely small size of nanoparticles makes it advantageous and potentially superior to use in tumor detection and imaging. One of the more extensively studied particles is quantum dots, semiconductor crystals which are capable of enhanced labeling and imaging of cancer cells. In addition, due to serious toxicity of chemotherapeutic agents, nano-formulations of breast cancer chemotherapy are under investigation and development. This may provide easier administering route and reduced frequency of drugs. With the use of nanoparticles, drug delivery can be carried out in a minimally invasive fashion and treatment regimens can be made much more targeted and specific for each patient. In this review article, we provide an overview on the role nanomedicine has played in breast cancer and mention some of the latest diagnostic and treatment modalities researched to date.
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Antineoplásicos/administração & dosagem , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , Imagem Molecular/métodos , Terapia de Alvo Molecular/métodos , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Feminino , Humanos , Nanomedicina/métodosRESUMO
Over the past half century, diseases that were predominantly treated surgically have transitioned to less invasive medical therapies. Such diseases that are now effectively treated with medicine are (1) peptic ulcer disease (PUD), (2) coronary artery disease (CAD), and (3) gastrointestinal stromal tumors (GISTs). Likewise, gallstone disease may soon follow this trend. Currently, the gold standard treatment of symptomatic gallstones is laparoscopic cholecystectomies. Though one of the most common surgeries in the United States, certain cases of acute and gangrenous cholecystitis can be some of the most difficult surgeries to perform. Advancements in neutrophil extracellular trap (NET) inhibitor medical therapies will alter gallstone disease management and the mainstream role of surgical interventions. This focus on less invasive therapies will greatly impact the quality of patient care, financial obligations, and even resident training opportunities.
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Inflammation of the gallbladder, also known as acute cholecystitis, may be caused by infection and inflammation of the gallbladder wall due to bile stasis, with or without gallstones. It is one of the most common surgical procedures that are performed laparoscopically. Gangrenous gallbladders are one of the most difficult conditions to treat clinically and surgically, being the cause of many medical malpractice litigations. Gangrenous gallbladders constitute 15% of all laparoscopic surgeries, with the cost of these surgeries being approximately $48,000, compared to other laparoscopic gallbladder surgeries being around $7,000. Dr. Dinesh Vyas and his team have worked together to develop the novel HydroLap, which is a tool that utilizes hydrodissection technology during laparoscopic cholecystectomies to remove the delicate, dead tissue while preserving the healthy tissue of surrounding structures. This decade-long journey began in the operating room and resulted in an innovation that is awaiting Food and Drug Administration (FDA) approval for use in 2023.
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Purpose: Reporting sharps injuries is crucial for healthcare worker occupational safety. However, these incidents are often underreported, thus posing potentially dangerous working environments. Previous small and limited studies have quantified this underreporting in specific groups of healthcare workers. This study aims to expand on these studies by further quantifying sharps injury incidences through a national study, thus better understanding healthcare reporting behaviors and the reasons for underreporting. Patients and Methods: This is a national, multi-center, cross-sectional study conducted via an online anonymous survey distributed through email among United States attending physicians, fellows, residents, medical students, and nurses of all specialties (ie, surgery, medicine, pediatrics). Data analysis used descriptive statistics and regressive modeling with significance defined as p<0.05. Results: Of over 3000 surveys emailed, 460 (15.3%) healthcare workers responded. The most vulnerable cohort to report sharps injuries were medical students (0.87 injuries per year ±0.69, n=92) and Postgraduate Year (PGY) 1 (0.67±0.81, n=71), PGY2 (0.86±-0.82, n=48), and PGY3 (0.92±0.8, n=45) resident physicians. Healthcare workers in surgical fields reported significantly higher likelihoods (odds ratio=4.61, p<0.001, 95% confidence interval 2.83-7.26) of sharps injuries. Medical students reported sharps injuries the least (40%) and nurses reported sharps injuries the most frequently (71%). The three most common reasons for not reporting sharps injuries included (1) healthcare workers perceiving low infection risk based on patient medical history, (2) fear of peer perception, and (3) belief of lack of reporting utility or that reporting is inconsequential. Conclusion: Medical students and physicians early in training, especially those in surgical fields, are more vulnerable to sharps injuries, but are less likely to report, while nurses are the most likely to report. Dedicated sharps training, education to reduce stigma around injury, and implementing a simplified reporting process may help encourage reporting as well as consistency in reporting, leading to improved workplace safety.
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The benign cystic mesothelioma of the peritoneum is a rare lesion and is known for local recurrence. This is first case report of a rapidly developing massive abdominal tumor with histological finding of benign cystic mesothelioma (BCM). We describe a BCM arising in the retroperitoneal tis[sue on the right side, lifting ascending colon and cecum to the left side of abdomen. Patient was an active 58-year-old man who noticed a rapid abdominal swelling within a two month time period with a weight gain of 40 pounds. Patient had no risk factors including occupational (asbestos, cadmium), family history, social (alcohol, smoking) or history of trauma. We will discuss the clinical, radiologic, intra-operative, immunohistochemical, pathologic findings, and imaging six months after surgery. Patient has no recurrence and no weight gain on follow up visits and imaging.
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Neoplasias Abdominais/diagnóstico , Mesotelioma Cístico/diagnóstico , Neoplasias Peritoneais/diagnóstico , Neoplasias Abdominais/cirurgia , Humanos , Masculino , Mesotelioma Cístico/cirurgia , Pessoa de Meia-Idade , Neoplasias Peritoneais/cirurgia , PrognósticoRESUMO
To improve the quality of patient care for cholecystectomies for gangrenous gallbladders, multiple innovations have been introduced including laparoscopic and robotic surgery. However, laparoscopic cholecystectomies for gangrenous gallbladders performed by blunt dissection still represents one of the most technically challenging general surgery procedures, with a high rate of iatrogenic complications and suboptimal measures for key surgical parameters such as length of stay, operating time, and blood loss. For this reason, the novel use of surgical techniques such as hydrodissection, which involves the expulsion of normal saline streams at a predetermined pressure, for cholecystectomies for gangrenous gallbladders are of utmost importance. In this manuscript, we explore the application of hydrodissection in cholecystectomies for gangrenous gallbladders.
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The impact of the recent pandemic on healthcare workers highlights the need to improve the working environment in hospitals. This is especially true in procedural rooms such as the operating and delivery rooms, which inherently require extended exposure to the virus, allows no social distancing, and generates aerosolized virus into the room through the use of the equipment. While reviewing the history of the development of the current Heating, Ventilation, and Air Conditioning Systems (HVAC), we identified inadequacies in the architecture and regulations of the system that resulted in insufficient protection during the current pandemic. Thus, we worked with building/facilities management, the operating room and nursing staff, and learned from research on airplane cabin air circulation to modify HVAC systems to address this issue. The modification includes calculating and implementing appropriate air changes per hour of the HVAC system. Modifying the existing system allows sufficient exchange of air within the procedure room to reduce the amount of exposure to viruses which results in safer working environments for healthcare workers. In the future, there will continue to be more pandemics, thus it is important to start creating safer working environments now, such as revisiting the hospital architecture and HVAC system, so that they can be improved upon and so that we are more prepared for the future.
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In the United States, colorectal cancer (CRC) is the second leading cause of mortality in men and women. We are now seeing an increasing number of patients with advanced-stage diagnosis and mortality from colorectal cancer before 50 years of age, which requires earlier screening. With the increasing need for CRC screening through colonoscopy, and thus endoscopists, easier and simpler techniques are needed to train proficient endoscopists. The most widely used approach by endoscopists is air insufflation colonoscopy, where air distends the colon to allow visualization of the colonic mucosa. This technique is un-comfortable for patients and requires an anesthetist to administer sedation. In addition, patients commonly complain about discomfort post-op as air escapes into the small bowel and cannot be adequately removed. Current research into the use of water insufflation colonoscopies has proved promising in reducing the need for sedation, decreasing discomfort, and increasing the visibility of the colonic mucosa. Future direction into water insufflation colonoscopies which have shown to be simpler and easier to teach may increase the number of proficient endoscopists in training to serve our aging population.
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Adenoma , Neoplasias do Colo , Pólipos do Colo , Neoplasias Colorretais , Insuflação , Idoso , Colonoscopia , Neoplasias Colorretais/diagnóstico por imagem , Feminino , Humanos , Insuflação/efeitos adversos , MasculinoRESUMO
Checkpoint inhibitors are introduced as a therapy for clinical use for various cancers, and clinicians are documenting new adverse effects. This is the first case report to the best of our knowledge of a patient on checkpoint inhibitor presenting with both polyendocrinopathy and gangrenous gallbladder disease with a mass negative for malignancy.71-year-old man presented four years after his initial diagnosis of stage IV, unresectable, non-ulcerated, acryl, lentiginous malignant melanoma. On presentation, he had gangrenous cholecystitis and was treated with laparoscopic cholecystectomy. Incidentally, the patient was diagnosed two years ago with hypothyroidism, hypophysitis, secondary adrenal insufficiency, and pneumonitis, each suspected to be secondary to treatment with pembrolizumab (Keytruda), a monoclonal anti-programmed cell death-1 antibody. He presented to the emergency department for a gallbladder attack and underwent successful laparoscopic cholecystectomy. The intra-operative finding on opening the specimen was an unusual looking exophytic mass but was negative for malignancy on pathology report and reported as gangrenous cholecystitis. His clinical condition before and after surgery was complicated by worsening comorbidities thought to be secondary to pembrolizumab therapy, which required acute care hospitalizations in the weeks before and after his presentation with cholecystitis. The patient had a few admissions from other co-morbidities post-surgery and was doing better. Immunotherapy with pembrolizumab may have secondary and tertiary effects with unusual presentations that are difficult to interpret for the primary oncology team and even tougher to do for community physicians who may subsequently encounter these patients. The relationship of this patient's comorbidities with immune-related adverse events was not apparent until record requests were conducted after surgery and are still not entirely clear after a literature review. More data is needed to guide decision algorithms and to predict which patients may experience these effects.
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The molecular scalpel of clustered regularly interspersed short palindromic repeats/CRISPR associated protein 9 (CRISPR/Cas9) technology may be sharp enough to begin cutting the genes implicated in inflammatory bowel disease (IBD) and consequently decrease the 6.3 billion dollar annual financial healthcare burden in the treatment of IBD. For the past few years CRISPR technology has drastically revolutionized DNA engineering and biomedical research field. We are beginning to see its application in gene manipulation of sickle cell disease, human immunodeficiency virus resistant embryologic twin gene modification and IBD genes such as Gatm (Glycine amidinotransferase, mitochondrial), nucleotide-binding oligomerization domain-containing protein 2, KRT12 and other genes implicated in adaptive immune convergence pathways have been subjected to gene editing, however there are very few publications. Furthermore, since Crohn's disease and ulcerative colitis have shared disease susceptibility and share genetic gene profile, it is paramount and is more advantageous to use CRISPR technology to maximize impact. Although, currently CRISPR does have its limitations due to limited number of specific Cas enzymes, off-target activity, protospacer adjacent motifs and crossfire between different target sites. However, these limitations have given researchers further insight on how to augment and manipulate enzymes to enable precise gene excision and limit crossfire between target sites.
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Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Terapia Genética/métodos , Doenças Inflamatórias Intestinais/terapia , Imunidade Adaptativa/genética , Edição de Genes/tendências , Terapia Genética/tendências , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologiaRESUMO
Targeted IL-10 therapy improves survival in preclinical models of critical illness, and intestine-specific IL-10 decreases inflammation in models of chronic Inflammatory disease. We therefore sought to determine whether intestine-specific overexpression of IL-10 would improve survival in sepsis. Transgenic mice that overexpress IL-10 in their gut epithelium (Fabpi-IL-10 mice) and wild-type (WT) littermates (n = 127) were subjected to cecal ligation and puncture with a 27-gauge needle. The 7-day survival rate was 45% in transgenic animals and 30% in WT animals (P < or = 0.05). Systemic levels of IL-10 were undetectable in both groups of animals under basal conditions and were elevated to a similar degree in septic animals regardless of whether they expressed the transgene. Local parameter of injury, including gut epithelial apoptosis, intestinal permeability, peritoneal lavage cytokines, and stimulated cytokines from intraepithelial lymphocytes, were similar between transgenic and WT mice. However, in stimulated splenocytes, proinflammatory cytokines monocyte chemoattractant protein 1 (189 +/- 43 vs. 40 +/- 8 pg/mL) and IL-6 (116 +/- 28 vs. 34 +/- 9 pg/mL) were lower in Fabpi-IL-10 mice than WT littermates despite the intestine-specific nature of the transgene (P < 0.05). Cytokine levels were similar in blood and bronchoalveolar lavage fluid between the 2 groups, as were circulating LPS levels. Transgenic mice also had lower white blood cell counts associated with lower absolute neutrophil counts (0.5 +/- 0.1 vs. 1.0 +/- 0.2 10(3)/mm3; P < 0.05). These results indicate that gut-specific overexpression of IL-10 improves survival in a murine model of sepsis, and interactions between the intestinal epithelium and the systemic immune system may play a role in conferring this survival advantage.
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Interleucina-10/metabolismo , Mucosa Intestinal/metabolismo , Sepse/metabolismo , Animais , Apoptose/efeitos dos fármacos , Endotoxinas/farmacologia , Genótipo , Imuno-Histoquímica , Interleucina-10/genética , Interleucina-6/metabolismo , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Sepse/genética , Sepse/microbiologia , Baço/citologia , Baço/metabolismo , Análise de Sobrevida , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Biosimilars are a growing drug class designed to be used interchangeably with biologics. Biologics are created in living cells and are typically large, complex proteins that may have a variety of uses. Within the field of gastroenterology alone, biologics are used to treat inflammatory bowel diseases, cancers, and endocrine disorders. While biologics have proven to be effective in treating or managing many diseases, patient access is often limited by high costs. The development of biosimilars is an attempt to reduce treatment costs. Biosimilars must be nearly identical to their reference biologics in terms of efficacy, side effect risk profile, and immunogenicity. Although the manufacturing process still involves production within living cells, biosimilars undergo fewer clinical trials than do their reference biologics. This ultimately reduces the cost of production and the cost of the biosimilar drug compared to its reference biologic. Currently, seven biosimilars have been approved by the United States Food and Drug Administration (FDA) for use in Crohn's disease, ulcerative colitis, and colorectal cancer. There are other biologics involved in treating gastroenterologic diseases for which there are no FDA approved biosimilars. Although biosimilars have the potential to reduce healthcare costs in chronic disease management, they face challenges in establishing a significant market share. Physician comfort in prescribing reference biologics instead of biosimilars and patient reluctance to switch from a biologic to a biosimilar are two common contributing factors to biosimilars' slow increase in use. More time will be needed for biosimilars to establish a larger and more consistent market share compared to their reference biologics. Additional data confirming the safety and efficacy of biosimilars, increased number of available biosimilars, and further cost reduction of biosimilars will all be necessary to improve physician confidence in biosimilars and patient comfort with biosimilars.
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Since the 1960s simple inexpensive cold lactated Ringers with additives has been used for short-term cold preservation of kidneys from living donors. We performed 266 living donor kidney transplantations from January 22, 2003 to October 30, 2006. Donor allografts were recovered laparoscopically and flushed with cold heparin, lactated Ringer's and procaine (HeLP) solution. Warm and cold ischemic times were typically <45 min and <90 min, respectively. The mean follow up was 21.6+/-12.2 months. There was no delayed graft function. Actuarial 1-year patient and graft survival were 98.6% and 98.1%, respectively. The creatinine at 1 year was 1.46+/-0.51 mg/dL. The cumulative incidences of acute cellular rejection at 6, 12, 18, and 24 months were 3.0%, 7.1%, 10.2%, and 11.7%. There were no identifiable side effects attributed to the HeLP solution. This study documents the effectiveness of cold HeLP as a flushing and short-term preservation fluid for living donor kidney transplantation with excellent results and significant cost benefit because of its low cost.
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Temperatura Baixa , Heparina/farmacologia , Soluções Isotônicas/farmacologia , Transplante de Rim/métodos , Doadores Vivos , Preservação de Órgãos/métodos , Procaína/farmacologia , Asparaginase , Seguimentos , Humanos , Rim/efeitos dos fármacos , Lactato de RingerRESUMO
The field of medical and surgical weight loss is undergoing an explosion of new techniques and devices. A lot of these are geared towards endoscopic approaches rather than the conventional and more invasive laparoscopic or open approach. One such recent advance is the introduction of intrgastric balloons. In this article, we discuss the recently Food and Drug Administration approved following balloons for weight loss: the Orbera™ Intragastric Balloon System (Apollo Endosurgery Inc, Austin, TX, United States), the ReShape® Integrated Dual Balloon System (ReShape Medical, Inc., San Clemente, CA, United States), and the Obalon (Obalon® Therapeutics, Inc.). The individual features of each of these balloons, the method of introduction and removal, and the expected weight loss and possible complications are discussed. This review of the various balloons highlights the innovation in the field of weight loss.