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BACKGROUND: Weight regain (WR) post bariatric surgery affects almost 20% of patients. It has been theorized that a complex interplay between physiologic adaptations and epigenetic mechanisms promotes WR in obesity, however, reliable predictors have not been identified. Our study examines the relationship between early postoperative weight loss (WL), nadir weight (NW), and WR following laparoscopic Roux-en-Y gastric bypass (LRYGB) and sleeve gastrectomy (LSG). METHODS: A retrospective review of prospectively collected data was conducted for LRYGB or LSG patients from 2012 to 2016. Demographics, preoperative BMI, procedure type, and postoperative weight at 6, 12, 24, 36, and 48 months were recorded. WR was defined as > 20% increase from NW. Univariate and multivariate linear and logistic regression models were used to determine the association between early postoperative WL with NW and WR at 4 years. RESULTS: Thousand twenty-six adults were included (76.8% female, mean age 44.9 ± 11.9 years, preoperative BMI 46.1 ± 8); 74.6% had LRYGB and 25.3% had LSG. Multivariable linear regression models showed that greater WL was associated with lower NW at 6 months (Coef - 2.16; 95% CI - 2.51, - 1.81), 1 year (Coef - 2.33; 95% CI - 2.58, - 2.08), 2 years (Coef - 2.04; 95% CI - 2.25, - 1.83), 3 years (Coef - 1.95; 95% CI - 2.14, - 1.76), and 4 years (Coef - 1.89; 95% CI - 2.10, - 1.68), p ≤ 0.001. WR was independently associated with increased WL between 6 months and 1 year (Coef 1.59; 95% CI 1.05,2.14; p ≤ 0.001) and at 1 year (Coef 1.24; 95% CI 0.84,1.63;p ≤ 0.001) postoperatively. The multivariable logistic regression model showed significantly increased risk of WR at 4 years for patients with greater WL at 6 months (OR 1.20, 95% CI 1.08,1.33; p = 0.001) and 1 year (OR 1.14; 95% CI 1.06,1.23; p ≤ 0.001). CONCLUSION: Our findings demonstrate that higher WL at 6 and 12 months post bariatric surgery may be risk factors for WR at 4 years. Surgeons may need to follow patients with high early weight loss more closely and provide additional treatment options to maximize their long-term success.
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Derivação Gástrica , Gastroplastia , Laparoscopia , Obesidade Mórbida , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Derivação Gástrica/métodos , Obesidade Mórbida/cirurgia , Gastroplastia/métodos , Índice de Massa Corporal , Gastrectomia/métodos , Laparoscopia/métodos , Estudos Retrospectivos , Aumento de Peso , Redução de Peso/fisiologia , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
INTRODUCTION: Work related injuries in minimally invasive surgery (MIS) are common because of the strains placed on the surgeon's or assistant's body. The objective of this study was to compare specific ergonomic risks among surgeons and surgical trainees performing robotic and laparoscopic procedures. MATERIALS AND METHODS: Ergonomic data and discomfort questionnaires were recorded from surgeons and trainees (fellows/residents) for both robotic and laparoscopic procedures. Perceived discomfort questionnaires were recorded pre/postoperatively. Intraoperatively, biomechanical loads were captured using motion tracking sensors and electromyography (EMG) sensors. Perceived discomfort, body position and muscle activity were compared between robotic and laparoscopic procedures using a linear regression model. RESULTS: Twenty surgeons and surgical trainees performed 29 robotic and 48 laparoscopic procedures. Postoperatively, increases in right finger numbness and right shoulder stiffness and surgeon irritability were noted after laparoscopy and increased back stiffness after robotic surgery. Further, the laparoscopic group saw increases in right hand/shoulder pain (OR 0.8; p = 0.032) and left hand/shoulder pain (0.22; p < 0.001) compared to robotic. Right deltoid and trapezius excessive muscle activity were significantly higher in laparoscopic operations compared to robotic. Demanding and static positioning was similar between the two groups except there was significantly more static neck position required for robotic operations. CONCLUSION: Robotic assisted surgeries led to lower postoperative discomfort and muscle strain in both upper extremities, particularly dominant side of the surgeon, but increased static neck positioning with subjective back stiffness compared with laparoscopy. These recognized ergonomic differences between the two platforms can be used to raise surgeon awareness of their intraoperative posture and to develop targeted physical and occupational therapy interventions to decrease surgeon WMSDs and increase surgeon longevity.
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Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Cirurgiões , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Dor de Ombro , Ergonomia , Laparoscopia/efeitos adversos , Laparoscopia/métodosRESUMO
INTRODUCTION: Obesity and its associated comorbidities represent a pervasive problem in the United States across all age groups. There are conflicting data regarding the effectiveness and postoperative recovery of bariatric surgery in elderly patients. The aim of this study was to compare outcomes of bariatric surgery across age groups. MATERIALS AND METHODS: After obtaining institutional review board approval, patients with morbid obesity who underwent non-revisional laparoscopic Roux-en-Y gastric bypass (LRYGB) and sleeve gastrectomy (LSG) at our institution between 2011 and 2015 were included in this retrospective study. Patients were subdivided into five age groups: < 30, 30-39, 40-49, 50-59, and ≥ 60 years. Patient baseline demographics and comorbidities were collected. Postoperative outcomes including reinterventions/reoperations, 30-day-readmissions, 90-day-mortality, comorbidities' resolution, and change in BMI (ΔBMI) up to 4 years were recorded and compared. The groups were compared with ANOVA and chi-square tests and multivariable analyses. RESULTS: LRYGB was performed in 74.7% of the 1026 study patients. Patients ≥ 60 years old demonstrated lower preoperative BMI than patients < 50 years (p < 0.001). Patients 50-59 years old had increased length of stay compared to 30-39 (p = 0.003) and a higher prevalence of all comorbidities was found in older patients (p < 0.001). There was no significant difference in 30-day-readmissions; 90-day-mortality; reoperations; and reinterventions among the study groups. The ΔBMI was higher in younger patients and comorbidity resolution was more likely in younger patients with the exception of obstructive sleep apnea. CONCLUSION: Bariatric surgery can be accomplished safely across all age groups with satisfiable postoperative weight loss. However, older age had higher hospital stay and convalescence and lower comorbidity resolution compared to younger patients. Thus, bariatric surgery should be offered earlier in life to allow the patients to reap its benefits.
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Cirurgia Bariátrica , Derivação Gástrica , Obesidade Mórbida , Idoso , Humanos , Recém-Nascido , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
The spatial dissemination of three prevalent taxa of sooty blotch and flyspeck (SBFS) fungi under several levels of precipitation was compared during 2015 and 2016 in an Iowa apple orchard. Overhead irrigation was used to supplement ambient precipitation in order to insure SBFS spore dissemination and colony development. There were five irrigation levels, involving 1-min-long periods of irrigation that were imposed either once or twice per hour at intervals of 3, 6, or 12 h, as well as a nonirrigated control. Preselected apple fruit were inoculated with one of the three SBFS taxa to serve as sources of inoculum. Dissemination from these inoculated apple fruit was assessed at harvest by counting SBFS colonies on water-sprayed and nontreated fruit. As a further control, additional fruit were enclosed in fruit bags throughout the fruit development period. In both 2015 and 2016, the number of colonies of the SBFS fungus Peltaster gemmifer per apple increased sharply as the duration of irrigation increased, whereas the number of colonies of Microcyclosporella mali increased to a lesser extent and Stomiopeltis sp. RS1 showed no increase. In 2015, the linear relationship between the duration of irrigation-imposed precipitation levels and the number of colonies on the water-sprayed apple fruit was similar for P. gemmifer (slope = 0.09), Stomiopeltis sp. RS1 (slope = 0.07), and Microcyclosporella mali (slope = 0.13); whereas, in 2016, the slope was higher for P. gemmifer (0.28) than for Stomiopeltis sp. RS1 (-0.09) or M. mali (0.06). The results indicated that dissemination of P. gemmifer increased sharply in response to increased irrigation-imposed precipitation, and that dissemination patterns differed considerably among the three SBFS taxa. The apparent advantage of P. gemmifer in precipitation-triggered dissemination may stem from its ability to produce spores rapidly by budding. To our knowledge, this is the first article to assess splash dispersal by SBFS fungi in the field and the first to document taxon-specific patterns of dissemination in this pathogen complex.
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Malus , Frutas , Iowa , Filogenia , Doenças das PlantasRESUMO
BACKGROUND: Bariatric clinical calculators have already been implemented in clinical practice to provide objective predictions of complications and outcomes. The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) Surgical Risk/Benefit Calculator is the most comprehensive risk calculator in bariatric surgery. OBJECTIVES: Evaluate the accuracy of the calculator predictions regarding the 30-day complication risk, 1-year weight loss outcomes, and comorbidity resolution. SETTING: MBSAQIP-accredited center. METHODS: All adult patients who underwent primary laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy at our institution between 2012 and 2019 were included. Baseline characteristics were used to generate the individualized outcome predictions for each patient through the bariatric risk calculator and were compared to actual patient outcomes. Statistical analysis was performed using c-statistics, linear regression models, and McNemmar chi-square test. RESULTS: One thousand four hundred fifty-three patients with a median age of 45 (37, 55) and consisting of 80.1% females were included in the study. The c-statistics for the complications and comorbidity resolution ranged from .533 for obstructive sleep apnea remission to .675 for 30-day reoperation. The number of comorbidity resolutions predicted by the calculator was significantly higher than the actual remissions for diabetes, hyperlipidemia, hypertension and obstructive sleep apnea (P < .001). On average, the calculator body mass index (BMI) predictions deviated from the observed BMI measurement by 3.24 kg/m2. The RYGB procedure (Coef -.89; P = .005) and preoperative BMI (Coef -.4; P = .012) were risk factors associated with larger absolute difference between the predicted and observed BMI. CONCLUSIONS: The MBSAQIP Surgical Risk/Benefit Calculator prediction models for 1-year BMI, 30-day reoperation, and reintervention risks were fairly well calibrated with an acceptable level of discrimination except for obstructive sleep apnea remission. The 1-year BMI estimations were less accurate for RYGB patients and cases with very high or low preoperative BMI measurements. Therefore, the bariatric risk calculator constitutes a helpful tool that has a place in preoperative counseling.
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Cirurgia Bariátrica , Obesidade Mórbida , Melhoria de Qualidade , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Medição de Risco , Obesidade Mórbida/cirurgia , Cirurgia Bariátrica/normas , Cirurgia Bariátrica/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Redução de Peso/fisiologia , Derivação Gástrica/efeitos adversos , Acreditação , Gastrectomia/efeitos adversosRESUMO
BACKGROUND: The rising prevalence of insulin resistance (IR), metabolic syndrome, and type 2 diabetes are associated with increases in abdominal mesenteric fat. Adipocytes are sensitive to low temperatures, making cryolipolysis of mesenteric fat an attractive treatment modality to potentially reduce IR. OBJECTIVES: We aimed to determine whether (1) cryolipolysis is safe in reducing the volume of the mesenteric fat and (2) reduction in mesenteric fat volume reduces indices of IR and glycemic dysfunction. SETTING: Indiana University School of Medicine. METHODS: A novel cooling device and method delivered cryolipolysis in a controlled manner to avoid tissue ablative temperatures. Ossabaw pigs (n = 8) were fed a high-fat diet for 9 months to develop visceral obesity, IR, and metabolic syndrome. Following laparotomy, mesenteric fat cryolipolysis (MFC) was performed in 5 pigs, while 3 served as sham surgery controls. The volume of the mesenteric fat was measured by computed tomography and compared with indices of glucose intolerance before and at 3 and 6 months postprocedure. RESULTS: MFC safely reduced mesenteric fat volume by â¼30% at 3 months, which was maintained at 6 months. Body weight did not change in either the MFC or sham surgery control groups. Measure of glycemic control, insulin sensitivity, and blood pressure significantly improved after MFC compared with sham controls. CONCLUSION: MFC reduces the volume of mesenteric fat and improves glycemic control in obese, IR Ossabaw pigs, without adverse effects.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Síndrome Metabólica , Suínos , Animais , Síndrome Metabólica/cirurgia , Síndrome Metabólica/complicações , Diabetes Mellitus Tipo 2/complicações , Obesidade/complicações , Peso CorporalRESUMO
BACKGROUND: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) Bariatric Surgical Risk/Benefit Calculator uses procedure-specific prediction models to generate individualized surgical risk/outcome estimates. This tool helps guide informed consent and operative selection. We hypothesized that calculator use would influence patient procedure choice. OBJECTIVE: To assess patient perspectives on the bariatric surgical calculator. SETTING: A randomized controlled trial at an MBSAQIP-accredited center. METHODS: During the preoperative bariatric surgical office consultation, patients were randomized into 2 groups: the control group received conventional surgeon-led counseling, whereas surgeons used the risk/benefit calculator to guide decision making for the calculator group. Surveys were completed by patients following consultations to evaluate satisfaction and perceived impact of the risk/benefit calculator on operative selection. RESULTS: Between 2020 and 2022, 61 patients were randomized to the calculator group and 68 patients to the control group. The percentage of patients whose procedure of choice changed following consultation was similar in the calculator versus control group (44.3% versus 41.2%; P = .723). However, calculator group patients were less likely to perceive surgeon counseling as very important for their decision making (43.3% versus 76.5%; P < .001). Eighty-five percent of calculator group patients rated the calculator as useful or very useful, and only 1.7% found it not very important. The reasons patients changed procedure choice were similar between the groups (P = .091); the most common cause was to improve their anticipated outcome (48.7% versus 54.8%). CONCLUSIONS: While the risk/benefit calculator was perceived as a helpful tool by most patients, its use did not influence their procedure choice. However, the patient-reported usefulness and importance of the calculator during surgeon counseling suggest that the information provided has weight in patient decision making.
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Cirurgia Bariátrica , Obesidade Mórbida , Cirurgiões , Humanos , Melhoria de Qualidade , Medição de Risco/métodos , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Resultado do Tratamento , Estudos Retrospectivos , Obesidade Mórbida/cirurgia , GastrectomiaRESUMO
Background: Non-technical skills (NTS) are essential for safe surgical patient management. However, assessing NTS involves observer-based ratings, which can introduce bias. Eye tracking (ET) has been proposed as an effective method to capture NTS. The purpose of the current study was to determine if ET metrics are associated with NTS performance. Methods: Participants wore a mobile ET system and participated in two patient care simulations, where they managed a deteriorating patient. The scenarios featured several challenges to leadership, which were evaluated using a 4-point Likert scale. NTS were evaluated by trained raters using the Non-Technical Skills for Surgeons (NOTSS) scale. ET metrics included percentage of fixations and visits on areas of interest. Results: Ten medical students participated. Average visit duration on the patient was negatively correlated with participants' communication and leadership. Average visit duration on the patient's intravenous access was negatively correlated with participants' decision making and situation awareness. Conclusions: Our preliminary data suggests that visual attention on the patient was negatively associated with NTS and may indicate poor comprehension of the patient's status due to heightened cognitive load. In future work, researchers and educators should consider using ET to objectively evaluate and provide feedback on their NTS.
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Tissue injury to skin diminishes miR-200b in dermal fibroblasts. Fibroblasts are widely reported to directly reprogram into endothelial-like cells and we hypothesized that miR-200b inhibition may cause such changes. We transfected human dermal fibroblasts with anti-miR-200b oligonucleotide, then using single cell RNA sequencing, identified emergence of a vasculogenic subset with a distinct fibroblast transcriptome and demonstrated blood vessel forming function in vivo. Anti-miR-200b delivery to murine injury sites likewise enhanced tissue perfusion, wound closure, and vasculogenic fibroblast contribution to perfused vessels in a FLI1 dependent manner. Vasculogenic fibroblast subset emergence was blunted in delayed healing wounds of diabetic animals but, topical tissue nanotransfection of a single anti-miR-200b oligonucleotide was sufficient to restore FLI1 expression, vasculogenic fibroblast emergence, tissue perfusion, and wound healing. Augmenting a physiologic tissue injury adaptive response mechanism that produces a vasculogenic fibroblast state change opens new avenues for therapeutic tissue vascularization of ischemic wounds.
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Fibroblastos , Pele , Cicatrização , Animais , Humanos , Camundongos , Antagomirs/farmacologia , Antagomirs/uso terapêutico , Fibroblastos/metabolismo , Fibroblastos/fisiologia , Oligonucleotídeos/farmacologia , Pele/metabolismo , Cicatrização/genética , Cicatrização/fisiologiaRESUMO
The aim of this research paper is to conduct a systematic review of periparturient complications as risk factors of postpartum psychosis. The investigation of risk factors for maternal psychosis following childbirth is complicated by the risk of confounding by a previous psychiatric history; therefore, this systematic review focuses on labor complications as risk factors among women without any previous psychiatric hospitalizations or diagnoses. Articles were collected and analyzed from the PubMed, MEDLINE, and Cochrane Review Library databases, as well as Clinicaltrials.gov, in accordance with the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Article abstracts and article titles of the identified publications were screened independently by all seven authors, and studies were selected if they met the following inclusion criteria: patients were diagnosed with postpartum psychosis per the guidelines in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-V), DSM-IV or World Health Organization's ICD-10 Classification of Mental and Behavioral Disorders; patients presented with no prior psychiatric diagnoses, hospitalizations or history; and the study evaluated the association of periparturient complications to first-onset postpartum psychosis, excluding narrative reviews, systematic reviews, or meta-analyses. Fifteen case-control, cohort, and case report studies, with thousands of patients, were selected to investigate the correlation between perinatal complications and first-onset post-partum psychosis. Obstetric complications during childbirth significantly predisposed for postpartum psychosis in certain individual studies but did not reveal an association in others. More studies must be implemented to elaborate on this limited scope.
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Muscle stem cells (MuSCs) are essential for tissue homeostasis and regeneration, but the potential contribution of MuSC morphology to in vivo function remains unknown. Here, we demonstrate that quiescent MuSCs are morphologically heterogeneous and exhibit different patterns of cellular protrusions. We classified quiescent MuSCs into three functionally distinct stem cell states: responsive, intermediate, and sensory. We demonstrate that the shift between different stem cell states promotes regeneration and is regulated by the sensing protein Piezo1. Pharmacological activation of Piezo1 is sufficient to prime MuSCs toward more responsive cells. Piezo1 deletion in MuSCs shifts the distribution toward less responsive cells, mimicking the disease phenotype we find in dystrophic muscles. We further demonstrate that Piezo1 reactivation ameliorates the MuSC morphological and regenerative defects of dystrophic muscles. These findings advance our fundamental understanding of how stem cells respond to injury and identify Piezo1 as a key regulator for adjusting stem cell states essential for regeneration.
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INTRODUCTION: Survivors of sepsis exhibit persistent immunosuppression. Epigenetic events may be responsible for some of these immunosuppressive changes. During sepsis circulating exosomes contain large quantities of DNA methyltransferase (DNMT) mRNAs. We hypothesized that exosomes directly transfer DNMT mRNAs to recipient monocytes with resultant methylation events and immunosuppression. METHODS: Exosomes containing DNMT mRNA were generated by stimulating monocytes with LPS. Confocal microscopy was used to determine uptake kinetics in the presence of pharmacologic inhibition. Expression and packaging of specific DNMT mRNA was controlled using DNMT siRNAs. Whole genome and gene specific methylation was assessed using bisulfite sequencing. Ingenuity pathway analysis was performed to determine the biological function of significance of differentially methylated regions. RESULTS: Exosomes effectively transferred DNMT mRNA to recipient monocytes. Pharmacologic inhibition of exosome uptake prevented this increase in DNMT mRNA expression. Recipient monocytes exhibited hypermethylation changes and gene suppression. siRNAs decreased the packaging of DNMT mRNAs and prevented TNFα gene suppression, restoring immunocompetence. CONCLUSION: These data support a role for exosome-mediated transfer of DNMT mRNA with resultant methylation and gene silencing. Pharmacologic uptake inhibition or targeted siRNA mediated DNMT gene silencing prevented DNMT mRNA transfer and maintained the cell's ability to express TNFα in response to LPS. This highlights the potential therapeutic value of targeting these exosome-mediated epigenetic events to maintain the host immune response during sepsis.
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DNA (Citosina-5-)-Metiltransferases , Sepse , DNA , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Humanos , Lipopolissacarídeos , Monócitos/metabolismo , Fenótipo , RNA Mensageiro/genética , RNA Interferente Pequeno , Sepse/genética , Transferases/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
Coronavirus disease 2019 (COVID-19) has various neuropsychiatric manifestations, including psychotic, mood, anxiety disorders, trauma-related disorders, and cognitive disorders, such as delirium. Although the psychosocial effects of the COVID-19 pandemic contribute to an increase in psychiatric comorbidities, the COVID-19 virus is also an independent risk factor. Previous studies have revealed that the virus can invade the neural tissue, which causes an imbalance of neurotransmitters that cause neuropsychiatric symptoms. The aim of this article is to conduct a systematic review to determine the patterns of neuropsychiatric manifestations of COVID-19, discussing the frequency and its impact on pre-existing psychiatric disorders. Thirty-nine case reports were collected and analyzed for a systematic review. They were full-text, peer-reviewed journal publications from November 2020 to February 2021. Fifty-three patients were included in our study. The most frequent symptom was abnormal/bizarre behavior (50.9%), followed by agitation/aggression (49.1%), and the third most common was altered mental status and delirium (47.2%). Only 48% of our patients had a pre-existing psychiatric disorder, including three not formally diagnosed but displayed psychiatric symptoms prior to the COVID-19 infection. Findings suggest a positive correlation of new-onset psychiatric symptoms with the SARS-CoV-2 virus. However, the exact pathophysiology of the virus itself causing neuropsychiatric manifestations needs to be investigated further.
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Therapeutic vascular endothelial growth factor (VEGF) replenishment has met with limited success for the management of critical limb-threatening ischemia. To improve outcomes of VEGF therapy, we applied single-cell RNA sequencing (scRNA-seq) technology to study the endothelial cells of the human diabetic skin. Single-cell suspensions were generated from the human skin followed by cDNA preparation using the Chromium Next GEM Single-cell 3' Kit v3.1. Using appropriate quality control measures, 36,487 cells were chosen for downstream analysis. scRNA-seq studies identified that although VEGF signaling was not significantly altered in diabetic versus nondiabetic skin, phospholipase Cγ2 (PLCγ2) was downregulated. The significance of PLCγ2 in VEGF-mediated increase in endothelial cell metabolism and function was assessed in cultured human microvascular endothelial cells. In these cells, VEGF enhanced mitochondrial function, as indicated by elevation in oxygen consumption rate and extracellular acidification rate. The VEGF-dependent increase in cell metabolism was blunted in response to PLCγ2 inhibition. Follow-up rescue studies therefore focused on understanding the significance of VEGF therapy in presence or absence of endothelial PLCγ2 in type 1 (streptozotocin-injected) and type 2 (db/db) diabetic ischemic tissue. Nonviral topical tissue nanotransfection technology (TNT) delivery of CDH5 promoter-driven PLCγ2 open reading frame promoted the rescue of hindlimb ischemia in diabetic mice. Improvement of blood flow was also associated with higher abundance of VWF+/CD31+ and VWF+/SMA+ immunohistochemical staining. TNT-based gene delivery was not associated with tissue edema, a commonly noted complication associated with proangiogenic gene therapies. Taken together, our study demonstrates that TNT-mediated delivery of endothelial PLCγ2, as part of combination gene therapy, is effective in diabetic ischemic limb rescue.
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Diabetes Mellitus Experimental , Fator A de Crescimento do Endotélio Vascular , Animais , Diabetes Mellitus Experimental/genética , Células Endoteliais/metabolismo , Membro Posterior/irrigação sanguínea , Isquemia/metabolismo , Camundongos , Músculo Esquelético/metabolismo , Neovascularização Fisiológica/genética , Fosfolipase C gama/genética , Fosfolipase C gama/metabolismo , Fosfolipase C gama/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fatores de Crescimento do Endotélio Vascular/metabolismo , Fatores de Crescimento do Endotélio Vascular/farmacologia , Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Fator de von Willebrand/metabolismo , Fator de von Willebrand/farmacologia , Fator de von Willebrand/uso terapêuticoRESUMO
INTRODUCTION: Gastroschisis feeding practices vary. Standardized neonatal feeding protocols have been demonstrated to improve nutritional outcomes. We report outcomes of infants with gastroschisis that were fed with and without a protocol. MATERIALS AND METHODS: A retrospective study of neonates with uncomplicated gastroschisis at 11 children's hospitals from 2013 to 2016 was performed.Outcomes of infants fed via institutional-specific protocols were compared with those fed without a protocol. Subgroup analyses of protocol use with immediate versus delayed closure and with sutured versus sutureless closure were conducted. RESULTS: Among 315 neonates, protocol-based feeding was utilized in 204 (65%) while no feeding protocol was used in 111 (35%). There were less surgical site infections (SSI) in those fed with a protocol (7 vs. 16%, p = 0.019). There were no differences in TPN duration, time to initial oral intake, time to goal feeds, ventilator use, peripherally inserted central catheter line deep venous thromboses, or length of stay. Of those fed via protocol, less SSIs occurred in those who underwent sutured closure (9 vs. 19%, p = 0.026). Further analyses based on closure timing or closure method did not demonstrate any significant differences. CONCLUSION: Across this multi-institutional cohort of infants with uncomplicated gastroschisis, there were more SSIs in those fed without an institutional-based feeding protocol but no differences in other outcomes.
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Gastrosquise , Criança , Estudos de Coortes , Gastrosquise/cirurgia , Hospitais Pediátricos , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Estudos Retrospectivos , Resultado do TratamentoRESUMO
An extreme chronic wound tissue microenvironment causes epigenetic gene silencing. An unbiased whole-genome methylome was studied in the wound-edge tissue of patients with chronic wounds. A total of 4,689 differentially methylated regions (DMRs) were identified in chronic wound-edge skin compared with unwounded human skin. Hypermethylation was more frequently observed (3,661 DMRs) in the chronic wound-edge tissue compared with hypomethylation (1,028 DMRs). Twenty-six hypermethylated DMRs were involved in epithelial-mesenchymal transition (EMT). Bisulfite sequencing validated hypermethylation of a predicted specific upstream regulator TP53. RNA-Seq analysis was performed to qualify findings from methylome analysis. Analysis of the downregulated genes identified the TP53 signaling pathway as being significantly silenced. Direct comparison of hypermethylation and downregulated genes identified 4 genes, ADAM17, NOTCH, TWIST1, and SMURF1, that functionally represent the EMT pathway. Single-cell RNA-Seq studies revealed that these effects on gene expression were limited to the keratinocyte cell compartment. Experimental murine studies established that tissue ischemia potently induces wound-edge gene methylation and that 5'-azacytidine, inhibitor of methylation, improved wound closure. To specifically address the significance of TP53 methylation, keratinocyte-specific editing of TP53 methylation at the wound edge was achieved by a tissue nanotransfection-based CRISPR/dCas9 approach. This work identified that reversal of methylation-dependent keratinocyte gene silencing represents a productive therapeutic strategy to improve wound closure.
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Metilação de DNA , Transição Epitelial-Mesenquimal , Animais , Ilhas de CpG , DNA , Epigênese Genética , Transição Epitelial-Mesenquimal/genética , Humanos , Camundongos , Ubiquitina-Proteína Ligases/genéticaRESUMO
BACKGROUND: Bariatric surgery is the most effective treatment for obesity; however, its utilization in older patients remains low. There is a dearth of literature on long-term effectiveness and safety of bariatric surgery in septuagenarian patients. The aim of this study was to compare the short- and long-term outcomes of bariatric surgery in this population. METHODS: Patients who underwent primary laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) at our institution between 2011 and 2015 were included. Patients were divided into two age groups: < 70 and ≥ 70 years. Outcomes included postoperative hospital length of stay (LOS), 30-day complications, up to 4-year complications, 90-day mortality, comorbidity resolution, and 4-year weight loss (BMI change-ΔΒΜΙ). The groups were also compared using multivariable analyses adjusting for potential confounders (gender, preoperative BMI, and type of procedure). RESULTS: Twenty-nine septuagenarians who underwent 21 LRYGB (72.4%) and 8 LSG (27.6%) were compared to 1016 patients aged < 70 years operated on during the same time period. Additionally, following the multivariable analyses, the septuagenarians had higher LOS (3 vs 2.3 days, p = 0.01), 4-year complications (38% vs 23%, p = 0.012), and less comorbidities' resolution but similar 4-year ΔBMI (- 8.6 vs - 10, p = 0.421), and 30-day complications (10% vs 6%, p = 0.316). CONCLUSION: Bariatric surgery in carefully selected septuagenarians can be accomplished with acceptable safety and comparable postoperative weight loss at 4 years. Surgeons may consider broadening their selection criteria to include this patient subgroup but may allow the patients to reap its benefits if offered earlier in life.
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Cirurgia Bariátrica , Obesidade Mórbida , Idoso , Gastrectomia , Derivação Gástrica , Humanos , Laparoscopia , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: The global coronavirus disease 2019 (COVID-19) pandemic is wreaking havoc on society. Bariatric patients are more prone to severe infection due to their high body mass index (BMI) and are more vulnerable to the effects of isolation, such as depression or disruption of their health habits. OBJECTIVES: To quantify the impact of self-quarantine on bariatric patients and self-quarantine's relationship with weight gain. SETTING: Academic hospital, United States. METHODS: A 30-item survey examining several known contributors to weight regain was distributed among the postoperative bariatric patients of our clinic. Changes in eating habits, exercise, depression, social support, loneliness, and anxiety were studied, among others. RESULTS: A total of 208 patients completed the survey (29.3% response rate). A large percentage of patients reported increases in their depression (44.2%), loneliness (36.2%), nervousness (54.7%), snacking (62.6%), loss of control when eating (48.2%), and binge eating (19.5%) and decreases in their social support (23.2%), healthy food eating (45.5%), and activity (55.2%). Difficulty in accessing vitamins was reported by 13%. Patients more than 18 months out of surgery regained more than 2 kg during an average of 47 days. Risk factors for weight regain were found to be loss of control when eating, increases in snacking and binge eating, reduced consumption of healthy food, and reduced physical activity. CONCLUSION: Bariatric patients are negatively affected by the COVID-19 pandemic and subsequent social isolation on many levels. This patient population is vulnerable to crisis situations; thus, additional intervention is needed to address behaviors that lead to weight regain.
Assuntos
Adaptação Psicológica , Cirurgia Bariátrica , COVID-19/psicologia , Comportamento Alimentar , Obesidade Mórbida/psicologia , Aumento de Peso , Adulto , Ansiedade , Depressão , Exercício Físico , Feminino , Humanos , Solidão , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Pandemias , Fatores de Risco , Isolamento Social , Apoio Social , Estados UnidosRESUMO
BACKGROUND: Studies of patients who have undergone surgery while infected with COVID-19 have shown increased risks for adverse outcomes in both pulmonary complications and mortality. It has become clear that the risk of complications from perioperative COVID-19 infection must be weighed against the risk from delayed surgical treatment. Studies have also shown that prior bariatric surgery conveys protection against mortality from COVID-19 and that obesity is the biggest risk factor for mortality from COVID-19 infection in adults under 45 years of age. Studies in patients who have fully recovered from COVID-19 and underwent elective surgery have not become widely available yet. OBJECTIVES: This multi-institutional case series is presented to highlight patients who developed COVID-19, fully recovered, and subsequently underwent elective bariatric surgery with 30-day outcomes available. SETTING: Nine bariatric surgery centers located across the United States. METHODS: This multicenter case series is a retrospective chart review of patients who developed COVID-19, recovered, and subsequently underwent bariatric surgery. Fifty-three patients are included, and 30-day morbidity and mortality were analyzed. RESULTS: Thirty-day complications included esophageal spasm, dehydration, and ileus. There were no cardiovascular, venous thromboembolism (VTE) or respiratory events reported. There were no 30- day mortalities. CONCLUSIONS: Bariatric surgery has been safely performed in patients who made a full recovery from COVID-19 without increased complications due to cardiovascular, pulmonary, venous thromboembolism, or increased mortality rates.
Assuntos
Cirurgia Bariátrica , COVID-19 , Obesidade Mórbida , Tromboembolia Venosa , Adulto , Cirurgia Bariátrica/efeitos adversos , Humanos , Obesidade Mórbida/cirurgia , Complicações Pós-Operatórias , Estudos Retrospectivos , SARS-CoV-2 , Estados Unidos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controleRESUMO
OBJECTIVE: To provide generalizable estimates for expected outcomes of simple gastroschisis (SG) and complex gastroschisis (CG) patients from a large multi-institutional cohort for use during counseling. STUDY DESIGN: A retrospective study of 394 neonates with gastroschisis at 11 children's hospitals from January 2013 to March 2017 was performed. Analysis by Fisher's exact tests and Wilcoxon rank sum tests were performed. Outcomes of complex and simple gastroschisis are reported. RESULT: There were 315 (80%) SG and 79 (20%) CG. CG had increased time from birth to closure (6 vs 4.4 days), closure to goal feeds (69 vs 23 days), ventilator use (90% vs 73%), SSIs (31% vs 11%), NEC (14% vs 6%), PN use (71 vs 24 days), LOS (104.5 vs 33 days), and mortality (11% vs 0%). CONCLUSION: This study provides generalizable estimates for expected outcomes of patients with both SG and CG that can be utilized during counseling. CG has significantly worse in-hospital outcomes.