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1.
Obes Surg ; 34(5): 1693-1703, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38499942

RESUMO

PURPOSE: Chronic pain and obesity often co-occur, negatively affecting one another and psychological wellbeing. Pain and psychological wellbeing improve after bariatric metabolic surgery (BMS), however, it is unknown whether psychological wellbeing improves differently after weight loss between patients with and without chronic pain. We investigated whether weight loss is associated with greater psychological wellbeing and functioning change after BMS, comparing patients with and without preoperative pain syndromes. METHODS: Depression, health-related quality of life, self-esteem, self-efficacy to exercise and controlling eating behaviours, physical activity, and food cravings were measured before and 24 months after BMS among 276 patients with obesity. The presence of preoperative chronic pain syndromes was examined as a moderator for the relationship between 24-month weight loss and changes in psychological outcomes. RESULTS: Chronic pain syndromes were present among 46% of patients. Weight loss was associated with greater improvement in health-related quality of life, self-efficacy to exercise and controlling eating behaviours, self-esteem and greater amelioration in food cravings. Pain syndromes only moderated negatively the relationship between the postoperative weight loss and change in self-efficacy to control eating behaviours (b = -0.49, CI [-0.88,-0.12]). CONCLUSION: Patients with and without chronic pain showed similar improvements in weight and psychological wellbeing and behaviours after BMS. The relationship between weight loss and the improvement of self-efficacy to control eating behaviours was weaker among patients with chronic pain syndrome. Further work, measuring pain severity over time, is needed to shed light on the mechanism underlying pain and postoperative change in psychological wellbeing and weight loss.


Assuntos
Cirurgia Bariátrica , Dor Crônica , Obesidade Mórbida , Humanos , Qualidade de Vida/psicologia , Obesidade Mórbida/cirurgia , Cirurgia Bariátrica/psicologia , Obesidade/cirurgia , Redução de Peso
2.
Obes Surg ; 34(3): 940-946, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38321253

RESUMO

BACKGROUND: Glycemic control is an important goal of bariatric surgery in patients with type 2 diabetes mellitus (T2DM) and obesity. The laparoscopic one-anastomosis gastric bypass (OAGB) has potential metabolic benefits over the laparoscopic Roux-en-Y gastric bypass (RYGB). Aim of this study is to examine whether RYGB or OAGB grants better glycemic control 12 months post-surgery. METHODS: For this retrospective cohort study, patients with T2DM and obesity, who underwent primary OAGB between 2008 and 2017 were reviewed. For each OAGB patient, three primary RYGB patients were matched for age, gender and body mass index (BMI). Glycemic control was expressed by the glycated hemoglobin (HbA1c), which was measured pre- and 12 months post-operatively. Weight loss was reported in percentage total weight loss (%TWL). RESULTS: A total of 152 patients, of whom 38 had OAGB and 114 RYGB, were included. Mean (standard deviation (SD)) HbA1c was 7.49 (1.51)% in the OAGB group and 7.56(1.23)% in the RYGB group at baseline. Twelve months after surgery the mean (SD) HbA1c dropped to 5.73 (0.71)% after OAGB and 6.09 (0.76)% after RYGB (adjusted p = 0.011). The mean (SD) BMI was reduced from 42.5(6.3) kg/m2 to 29.6(4.7) kg/m2 after OAGB and 42.3(5.8) kg/m2 to 29.9 (4.5) kg/m2 after RYGB; reflecting 30.3 (6.8) %TWL post-OAGB and 29.0 (7.3) %TWL post-RYGB (p = 0.34). CONCLUSION: This study indicates that OAGB leads to lower HbA1c one year after surgery compared to RYGB, without a difference in weight loss. Prospective (randomized) studies are needed to ascertain the most optimal metabolic treatment for patients with obesity and T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Humanos , Derivação Gástrica/efeitos adversos , Obesidade Mórbida/cirurgia , Hemoglobinas Glicadas , Estudos Retrospectivos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/cirurgia , Estudos Prospectivos , Estudos de Coortes , Obesidade/cirurgia , Obesidade/etiologia , Redução de Peso
3.
J Vasc Res ; 61(2): 68-76, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38219725

RESUMO

INTRODUCTION: While multiple factors influence coronary artery bypass graft (CABG) success rates, preserving saphenous vein endothelium during surgery may improve patency. Standard preparations include saphenous vein preparation in heparinized saline (saline) which can result in endothelial loss and damage. Here, we investigated the impact of preparing saphenous graft vessels in heparinized patient blood (blood) versus saline. METHODS: Saphenous vein tissues from a total of 23 patients undergoing CABG were split into 2 groups (1) saline and (2) heparinized patient blood. Excess tissue was fixed for analysis immediately following surgery. Level of endothelial coverage, oxidative stress marker 4-hydroxynonenal (4HNE), and oxidative stress protective marker nuclear factor erythroid 2-related factor 2 (NRF2) were evaluated. RESULTS: In saline patient veins, histological analysis revealed a limited luminal layer, suggesting a loss of endothelial cells (ECs). Immunofluorescent staining of EC markers vascular endothelial cadherin (VE-cadherin) and endothelial nitric oxide identified a significant improvement in EC coverage in the blood versus saline groups. Although both treatment groups expressed 4HNE to similar levels, EC blood samples expressed higher levels of NRF2. CONCLUSION: Our data indicate that use of heparinized patient blood helps preserve the endothelium and promotes vein graft health. This has the potential to improve long-term outcomes in patients.


Assuntos
Células Endoteliais , Veia Safena , Humanos , Veia Safena/patologia , Fator 2 Relacionado a NF-E2 , Endotélio Vascular/patologia , Ponte de Artéria Coronária/efeitos adversos
4.
Gut Pathog ; 16(1): 2, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178245

RESUMO

BACKGROUND: The non-pharmaceutical interventions (NPIs) implemented to curb the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) early in the coronavirus disease 2019 (COVID-19) pandemic, substantially disrupted the activity of other respiratory viruses. However, there is limited data from low-and-middle income countries (LMICs) to determine whether these NPIs also impacted the transmission of common enteric viruses. Here, we investigated the changes in the positivity rate of five enteric viruses among hospitalised children who presented with diarrhoea to a referral hospital in coastal Kenya, during COVID-19 pandemic period. METHODS: A total of 870 stool samples from children under 13 years of age admitted to Kilifi County Hospital between January 2019, and December 2022 were screened for rotavirus group A (RVA), norovirus genogroup II (GII), astrovirus, sapovirus, and adenovirus type F40/41 using real-time reverse-transcription polymerase chain reaction. The proportions positive across the four years were compared using the chi-squared test statistic. RESULTS: One or more of the five virus targets were detected in 282 (32.4%) cases. A reduction in the positivity rate of RVA cases was observed from 2019 (12.1%, 95% confidence interval (CI) 8.7-16.2%) to 2020 (1.7%, 95% CI 0.2-6.0%; p < 0.001). However, in the 2022, RVA positivity rate rebounded to 23.5% (95% CI 18.2%-29.4%). For norovirus GII, the positivity rate fluctuated over the four years with its highest positivity rate observed in 2020 (16.2%; 95% C.I, 10.0-24.1%). No astrovirus cases were detected in 2020 and 2021, but the positivity rate in 2022 was similar to that in 2019 (3.1% (95% CI 1.5%-5.7%) vs. 3.3% (95% CI 1.4-6.5%)). A higher case fatality rate was observed in 2021 (9.0%) compared to the 2019 (3.2%), 2020 (6.8%) and 2022 (2.1%) (p < 0.001). CONCLUSION: Our study finds that in 2020 the transmission of common enteric viruses, especially RVA and astrovirus, in Kilifi Kenya may have been disrupted due to the COVID-19 NPIs. After 2020, local enteric virus transmission patterns appeared to return to pre-pandemic levels coinciding with the removal of most of the government COVID-19 NPIs.

5.
Surg Obes Relat Dis ; 20(1): 29-38, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37696732

RESUMO

BACKGROUND: Abdominal pain after bariatric surgery (BS) is frequently observed. Despite numerous diagnostic tests, the cause of abdominal pain is not always found. OBJECTIVES: To quantify type and number of diagnostic tests performed in patients with abdominal pain after BS and evaluate the burden and their yield in the diagnostic process. SETTING: A bariatric center in the Netherlands. METHODS: In this prospective study, we included patients who presented with abdominal pain after BS between December 1, 2020, and December 1, 2021. All diagnostic tests and reoperations performed during one episode of abdominal pain were scored using a standardized protocol. RESULTS: A total of 441 patients were included; 401 (90.9%) were female, median time after BS was 37.0 months (IQR, 11.0-66.0) and mean percentage total weight loss was 31.41 (SD, 10.53). In total, 715 diagnostic tests were performed, of which 355 were abdominal CT scans, 155 were ultrasounds, and 106 were gastroscopies. These tests yielded a possible explanation for the pain in 40.2% of CT scans, 45.3% of ultrasounds, and 34.7% of gastroscopies. The diagnoses of internal herniation, ileus, and nephrolithiasis generally required only 1 diagnostic test, whereas patients with anterior cutaneous nerve entrapment syndrome, irritable bowel syndrome, and constipation required several tests before diagnosis. Even after several negative tests, a diagnosis was still found in the subsequent test: 86.7% of patients with 5 or more tests had a definitive diagnoses. Reoperations were performed in 37.2% of patients. CONCLUSION: The diagnostic burden in patients with abdominal pain following BS is high. The most frequently performed diagnostic test is an abdominal CT scan, yielding the highest number of diagnoses in these patients.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Laparoscopia , Obesidade Mórbida , Humanos , Feminino , Masculino , Derivação Gástrica/efeitos adversos , Obesidade Mórbida/complicações , Estudos Prospectivos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Cirurgia Bariátrica/efeitos adversos , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Dor Abdominal/cirurgia , Laparoscopia/métodos
7.
Obes Surg ; 33(6): 1773-1781, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37186289

RESUMO

BACKGROUND: In addition to the reduction of symptomatic gallstone disease, ursodeoxycholic acid (UDCA) might also have beneficial metabolic effects after bariatric surgery. We examined the impact of UDCA on liver enzymes, hemoglobin A1c (HbA1c), lipids, and inflammation markers. METHODS: Patients in the UPGRADE trial (placebo-controlled, double-blind) were randomized between UDCA 900 mg daily or placebo pills for 6 months after bariatric surgery. Patients without blood measurements pre- or 6 months postoperatively were excluded. The change in liver enzymes, Hba1c, lipids, and inflammation markers after surgery were compared between the UDCA and placebo group, followed by a postoperative cross-sectional comparison. RESULTS: In total, 513 patients were included (age [mean ± SD] 45.6 ± 10.7 years; 79% female). Preoperative blood values did not differ between UDCA (n = 266) and placebo (n = 247) groups. Increase of alkaline phosphatase (ALP) was greater in the UDCA group (mean difference 3.81 U/l [95%CI 0.50 7.12]). Change in other liver enzymes, HbA1c, lipids, and CRP levels did not differ. Postoperative cross-sectional comparison in 316 adherent patients also revealed a higher total cholesterol (mean difference 0.25 mg/dl [95%CI 0.07-0.42]), lower aspartate aminotransferase (mean difference -3.12 U/l [-5.16 - -1.08]), and lower alanine aminotransferase level (mean difference -5.89 U/l [-9.41 - -2.37]) in the UDCA group. CONCLUSION: UDCA treatment leads to a higher, but clinically irrelevant increase in ALP level in patients 6 months after bariatric surgery. No other changes in metabolic or inflammatory markers were observed. Except for the reduction of gallstone formation, UDCA has no effects after bariatric surgery.


Assuntos
Cirurgia Bariátrica , Cálculos Biliares , Obesidade Mórbida , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Masculino , Ácido Ursodesoxicólico/uso terapêutico , Estudos Transversais , Hemoglobinas Glicadas , Obesidade Mórbida/cirurgia , Cálculos Biliares/cirurgia , Inflamação , Lipídeos
8.
Virus Evol ; 9(1): vead023, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37066020

RESUMO

Human enteric adenovirus species F (HAdV-F) is a leading cause of childhood diarrhoeal deaths. The genomic analysis would be key to understanding transmission dynamics, potential drivers of disease severity, and vaccine development. However, currently, there are limited HAdV-F genomic data globally. Here, we sequenced and analysed HAdV-F from stool samples collected in coastal Kenya between 2013 and 2022. The samples were collected at Kilifi County Hospital in coastal Kenya from children <13 years of age who reported a history of three or more loose stools in the previous 24 hours. The genomes were analysed together with the data from the rest of the world by phylogenetic analysis and mutational profiling. Types and lineages were assigned based on phylogenetic clustering consistent with the previously described criteria and nomenclature. Participant clinical and demographic data were linked to genotypic data. Of ninety-one cases identified using real-time Polymerase Chain Reaction, eighty-eight near-complete genomes were assembled, and these were classified into HAdV-F40 (n = 41) and HAdV-F41 (n = 47). These types co-circulated throughout the study period. Three and four distinct lineages were observed for HAdV-F40 (Lineages 1-3) and HAdV-F41 (Lineages 1, 2A, 3A, 3C, and 3D). Types F40 and F41 coinfections were observed in five samples and F41 and B7 in one sample. Two children with F40 and 41 coinfections were also infected with rotavirus and had moderate and severe diseases as defined using the Vesikari Scoring System, respectively. Intratypic recombination was found in four HAdV-F40 sequences occurring between Lineages 1 and 3. None of the HAdV-F41 cases had jaundice. This study provides evidence of extensive genetic diversity, coinfections, and recombination within HAdV-F40 in a rural coastal Kenya that will inform public health policy, vaccine development that includes the locally circulating lineages, and molecular diagnostic assay development. We recommend future comprehensive studies elucidating on HAdV-F genetic diversity and immunity for rational vaccine development.

9.
Cell Rep Med ; 4(4): 100993, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37023745

RESUMO

Primary and secondary bile acids (BAs) influence metabolism and inflammation, and the gut microbiome modulates levels of BAs. We systematically explore the host genetic, gut microbial, and habitual dietary contribution to a panel of 19 serum and 15 stool BAs in two population-based cohorts (TwinsUK, n = 2,382; ZOE PREDICT-1, n = 327) and assess changes post-bariatric surgery and after nutritional interventions. We report that BAs have a moderately heritable genetic component, and the gut microbiome accurately predicts their levels in serum and stool. The secondary BA isoursodeoxycholate (isoUDCA) can be explained mostly by gut microbes (area under the receiver operating characteristic curve [AUC] = ∼80%) and associates with post-prandial lipemia and inflammation (GlycA). Furthermore, circulating isoUDCA decreases significantly 1 year after bariatric surgery (ß = -0.72, p = 1 × 10-5) and in response to fiber supplementation (ß = -0.37, p < 0.03) but not omega-3 supplementation. In healthy individuals, isoUDCA fasting levels correlate with pre-meal appetite (p < 1 × 10-4). Our findings indicate an important role for isoUDCA in lipid metabolism, appetite, and, potentially, cardiometabolic risk.


Assuntos
Cirurgia Bariátrica , Ácidos e Sais Biliares , Humanos , Apetite , Cirurgia Bariátrica/efeitos adversos , Fezes , Inflamação
10.
Science ; 380(6642): eadg6518, 2023 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-36996170

RESUMO

Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, arises from survival motor neuron (SMN) protein insufficiency resulting from SMN1 loss. Approved therapies circumvent endogenous SMN regulation and require repeated dosing or may wane. We describe genome editing of SMN2, an insufficient copy of SMN1 harboring a C6>T mutation, to permanently restore SMN protein levels and rescue SMA phenotypes. We used nucleases or base editors to modify five SMN2 regulatory regions. Base editing converted SMN2 T6>C, restoring SMN protein levels to wild type. Adeno-associated virus serotype 9-mediated base editor delivery in Δ7SMA mice yielded 87% average T6>C conversion, improved motor function, and extended average life span, which was enhanced by one-time base editor and nusinersen coadministration (111 versus 17 days untreated). These findings demonstrate the potential of a one-time base editing treatment for SMA.


Assuntos
Edição de Genes , Atrofia Muscular Espinal , Proteína 1 de Sobrevivência do Neurônio Motor , Proteína 2 de Sobrevivência do Neurônio Motor , Animais , Camundongos , Fibroblastos/metabolismo , Neurônios Motores/metabolismo , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/terapia , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Proteína 2 de Sobrevivência do Neurônio Motor/genética
11.
Gut Pathog ; 14(1): 32, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35915480

RESUMO

BACKGROUND: Kenya introduced Rotarix® (GlaxoSmithKline Biologicals, Rixensart, Belgium) vaccination into its national immunization programme beginning July 2014. The impact of this vaccination program on the local epidemiology of various known enteropathogens is not fully understood. METHODS: We used a custom TaqMan Array Card (TAC) to screen for 28 different enteropathogens in 718 stools from children aged less than 13 years admitted to Kilifi County Hospital, coastal Kenya, following presentation with diarrhea in 2013 (before vaccine introduction) and in 2016-2018 (after vaccine introduction). Pathogen positivity rate differences between pre- and post-Rotarix® vaccination introduction were examined using both univariate and multivariable logistic regression models. RESULTS: In 665 specimens (92.6%), one or more enteropathogen was detected, while in 323 specimens (48.6%) three or more enteropathogens were detected. The top six detected enteropathogens were: enteroaggregative Escherichia coli (EAggEC; 42.1%), enteropathogenic Escherichia coli (EPEC; 30.2%), enterovirus (26.9%), rotavirus group A (RVA; 24.8%), parechovirus (16.6%) and norovirus GI/GII (14.4%). Post-rotavirus vaccine introduction, there was a significant increase in the proportion of samples testing positive for EAggEC (35.7% vs. 45.3%, p = 0.014), cytomegalovirus (4.2% vs. 9.9%, p = 0.008), Vibrio cholerae (0.0% vs. 2.3%, p = 0.019), Strongyloides species (0.8% vs. 3.6%, p = 0.048) and Dientamoeba fragilis (2.1% vs. 7.8%, p = 0.004). Although not reaching statistical significance, the positivity rate of adenovirus 40/41 (5.8% vs. 7.3%, p = 0.444), norovirus GI/GII (11.2% vs. 15.9%, p = 0.089), Shigella species (8.7% vs. 13.0%, p = 0.092) and Cryptosporidium spp. (11.6% vs. 14.7%, p = 0.261) appeared to increase post-vaccine introduction. Conversely, the positivity rate of sapovirus decreased significantly post-vaccine introduction (7.8% vs. 4.0%, p = 0.030) while that of RVA appeared not to change (27.4% vs. 23.5%, p = 0.253). More enteropathogen coinfections were detected per child post-vaccine introduction compared to before (mean: 2.7 vs. 2.3; p = 0.0025). CONCLUSIONS: In this rural Coastal Kenya setting, childhood enteropathogen infection burden was high both pre- and post-rotavirus vaccination introduction. Children who had diarrheal admissions post-vaccination showed an increase in coinfections and changes in specific enteropathogen positivity rates. This study highlights the utility of multipathogen detection platforms such as TAC in understanding etiology of childhood acute gastroenteritis in resource-limited regions.

13.
Drugs Aging ; 39(9): 715-727, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35859228

RESUMO

BACKGROUND: Psoriasis is a common inflammatory disease in any age group, but also in older patients (≥ 65 years of age). Since older patients are often excluded from clinical trials, limited data specifically on this growing population are available, e.g. regarding the safety and performance of biological treatment. AIMS: We aimed to give insight into this specific population by comparing the drug survival and safety of biologics in older patients with that in younger patients. METHODS: In this real-world observational study, data from 3 academic and 15 non-academic centers in The Netherlands were extracted from the prospective BioCAPTURE registry. Biologics included in this study were tumor necrosis factor (TNF)-α, interleukin (IL)-17, IL-12/23, and IL-23 inhibitors. Patients were divided into two age groups: ≥ 65 years and < 65 years. The Charlson Comorbidity Index (CCI) was used to measure comorbid disease status, and all adverse events (AEs) that led to treatment discontinuation were classified according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. All AEs that led to treatment discontinuation were studied to check whether they could be classified as serious AEs (SAEs). Kaplan-Meier survival curves for overall 5-year drug survival and split according to reasons of discontinuation (ineffectiveness or AEs) were constructed. Cox regression models were used to correct for possible confounders and to investigate associations with drug survival in both age groups separately. Psoriasis Area and Severity Index (PASI) scores during the first 2 years of treatment and at the time of treatment discontinuation were assessed and compared between age groups. RESULTS: A total of 890 patients were included, of whom 102 (11.4%) were aged ≥ 65 years. Body mass index, sex, and distribution of biologic classes (e.g. TNFα, IL12/23) were not significantly different between the two age groups. A significantly higher CCI score was found in older patients, indicative of more comorbidity (p < 0.001). The 5-year ineffectiveness-related drug survival was lower for older patients (44.5% vs. 60.5%; p = 0.006), and the 5-year overall (≥ 65 years: 32.4% vs. < 65 years: 42.1%; p = 0.144) and AE-related (≥ 65 years: 82.1% vs. < 65 years: 79.5%; p = 0.913) drug survival was comparable between age groups. Of all AEs (n = 155) that led to discontinuation, 16 (10.3%) were reported as SAEs but these only occurred in younger patients. After correcting for confounders, the same trends were observed in the drug survival outcomes. Linear regression analyses on PASI scores showed no statistical differences at 6, 12, 18, and 24 months of treatment between age groups. CONCLUSIONS: This study in a substantial, well-defined, prospective cohort provides further support that the use of biologics in older patients seems well-tolerated and effective. Biologic discontinuation due to AEs did not occur more frequently in older patients. Older patients discontinued biologic treatment more often due to ineffectiveness, although no clear difference in PASI scores was observed. More real-world studies on physician- and patient-related factors in older patients are warranted.


Assuntos
Produtos Biológicos , Psoríase , Idoso , Produtos Biológicos/uso terapêutico , Humanos , Estudos Prospectivos , Psoríase/tratamento farmacológico , Sistema de Registros , Resultado do Tratamento
14.
Acta Derm Venereol ; 102: adv00712, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35356990

RESUMO

Real-world evidence, directly comparing the effectiveness of interleukin (IL)17-inhibitors, IL23-inhibitors, tumour necrosis factor alpha (TNF-α)-inhibitors and an IL12/23-inhibitor in psoriasis, is scarce. The aim of this study was to directly compare the first-year effectiveness of biologic therapies for psoriasis, corrected for confounders. This prospective, multicentre cohort study assessed BioCAPTURE data on etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab, and guselkumab in 1,080 treatment episodes of 700 patients with psoriasis. The course of the mean absolute Psoriasis Area and Severity Index (PASI) and the proportion of patients who achieved PASI90/PASI75 were compared using linear mixed models and mixed logistic regression models respectively, corrected for baseline PASI, biologic naivety, and weight. Patients treated with adalimumab, ustekinumab, secukinumab, ixekizumab, or guselkumab all had a significantly lower mean PASI after 12 months compared with etanercept, and significantly higher overall odds of reaching PASI90 than those treated with etanercept. Patients treated with ixekizumab or guselkumab also had higher probabilities of reaching PASI90 than adalimumab, ustekinumab, and secukinumab. Relative to randomized controlled trials, the proportions of patients who reached PASI90/75 were lower in this real-world study.


Assuntos
Produtos Biológicos , Psoríase , Adalimumab/uso terapêutico , Produtos Biológicos/efeitos adversos , Estudos de Coortes , Etanercepte/uso terapêutico , Humanos , Fatores Imunológicos , Estudos Prospectivos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Resultado do Tratamento , Ustekinumab/uso terapêutico
15.
Obes Sci Pract ; 8(1): 56-65, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35127122

RESUMO

AIMS: Visceral adipose tissue inflammation is a fundamental mechanism of insulin resistance in obesity and type 2 diabetes. Translocation of intestinal bacteria has been suggested as a driving factor for the inflammation. However, although bacterial DNA was detected in visceral adipose tissue of humans with obesity, it is unclear to what extent this is contamination or whether the gut microbiota is causally involved. Effects of fecal microbiota transplantation (FMT) on bacterial translocation and visceral adipose tissue inflammation in individuals with obesity and insulin resistance were assessed. MATERIAL AND METHODS: Eight individuals with clinically severe obesity (body mass index [BMI] >35 kg/m2) and metabolic syndrome received lean donor FMT 4 weeks prior to elective bariatric surgery. The participants were age-, sex-, and BMI-matched to 16 controls that underwent no fecal transplantation. Visceral adipose tissue was collected during surgery. Bacterial translocation was assessed by 16S rRNA gene sequencing of adipose tissue and feces. Pro-inflammatory cytokine expression and histopathological analyses of visceral adipose tissue were performed to assess inflammation. RESULTS: Fecal microbiota transplantation significantly altered gut microbiota composition. Visceral adipose tissue contained a very low quantity of bacterial DNA in both groups. No difference in visceral bacterial DNA content between groups was observed. Also, visceral expression of pro-inflammatory cytokines and macrophage infiltration did not differ between groups. No correlation between inflammatory tone and bacterial translocation was observed. CONCLUSIONS: Visceral bacterial DNA content and level of inflammation were not altered upon FMT. Thus, bacterial translocation may not be the main driver of visceral adipose tissue inflammation in obesity.

16.
Nat Commun ; 13(1): 168, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013323

RESUMO

Skeletal muscle serves fundamental roles in organismal health. Gene expression fluctuations are critical for muscle homeostasis and the response to environmental insults. Yet, little is known about post-transcriptional mechanisms regulating such fluctuations while impacting muscle proteome. Here we report genome-wide analysis of mRNA methyladenosine (m6A) dynamics of skeletal muscle hypertrophic growth following overload-induced stress. We show that increases in METTL3 (the m6A enzyme), and concomitantly m6A, control skeletal muscle size during hypertrophy; exogenous delivery of METTL3 induces skeletal muscle growth, even without external triggers. We also show that METTL3 represses activin type 2 A receptors (ACVR2A) synthesis, blunting activation of anti-hypertrophic signaling. Notably, myofiber-specific conditional genetic deletion of METTL3 caused spontaneous muscle wasting over time and abrogated overload-induced hypertrophy; a phenotype reverted by co-administration of a myostatin inhibitor. These studies identify a previously unrecognized post-transcriptional mechanism promoting the hypertrophic response of skeletal muscle via control of myostatin signaling.


Assuntos
Receptores de Activinas Tipo II/genética , Hipertrofia/genética , Metiltransferases/genética , Músculo Esquelético/metabolismo , Atrofia Muscular/genética , Miostatina/genética , Receptores de Activinas Tipo II/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Animais , Dependovirus/genética , Dependovirus/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Estudo de Associação Genômica Ampla , Hipertrofia/metabolismo , Hipertrofia/patologia , Hipertrofia/prevenção & controle , Masculino , Metiltransferases/deficiência , Camundongos , Desenvolvimento Muscular/genética , Músculo Esquelético/patologia , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Miostatina/metabolismo , Transdução de Sinais
17.
Br J Health Psychol ; 27(1): 96-115, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33982392

RESUMO

OBJECTIVE: To investigate whether patients' psychological well-being (depression, quality of life, body image satisfaction) and functioning (self-efficacy for eating and exercising behaviours and food cravings) improve 12 months after bariatric surgery and whether self-compassion is associated with better psychological outcomes and lower weight after bariatric surgery. DESIGN: Longitudinal, prospective observational study. METHODS: Bariatric patients (n = 126, 77.8% female, 46.4 ± 10.8 years) completed the Self-compassion Scale, Center for Epidemiology Studies Depression Scale, Impact of Weight on Quality-of-Life questionnaire, Body Image Scale, Weight Efficacy Lifestyle Questionnaire, Spinal Cord Injury Exercise Self-Efficacy Scale, and G-Food Craving Questionnaire pre-operatively and 12 months post-operatively. A medical professional measured patients' weight during each assessment. Data were analysed using repeated measures t-tests and multivariate regression analyses with Benjamini-Hochberg correction for multiple testing. RESULTS: Patients' BMI, depression, and food cravings decreased significantly after surgery while quality of life, body image satisfaction, and self-efficacy to exercise improved. Higher self-compassion was associated with lower post-operative depression, greater quality of life, higher body image satisfaction, and better self-efficacy for eating behaviours (p-values <.05) but not with post-operative BMI, self-efficacy to exercise, or food cravings. CONCLUSIONS: Even though pre-operative self-compassion was not directly associated with a lower 12-month post-operative BMI, it had a positive relationship with patients' post-operative well-being and self-efficacy for controlling eating behaviour. In turn, this could help patients to manage their health long after bariatric surgery. Further work regarding the role of self-compassion on long-term health outcomes would be worthwhile.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida , Cirurgia Bariátrica/psicologia , Imagem Corporal , Fissura , Comportamento Alimentar/psicologia , Feminino , Humanos , Masculino , Obesidade Mórbida/psicologia , Obesidade Mórbida/cirurgia , Qualidade de Vida
18.
J Laryngol Otol ; 136(3): 248-251, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34158135

RESUMO

BACKGROUND: The impact of coronavirus disease 2019 extends far beyond the immediate burden on healthcare systems caused by hospitalisation of patients with the disease itself. OBJECTIVE: To investigate the impact of the coronavirus disease 2019 pandemic on the referral rate of patients to the suspected head and neck cancer two-week-wait clinic. METHODS: A multicentre retrospective study was performed investigating data collected for all patients attending the suspected head and neck cancer two-week-wait clinic in ENT departments in the West Midlands. RESULTS: A total of 509 fast-track referrals were received from February to April in 2019, compared to 399 referrals in 2020. April 2020 saw a 62.4 per cent reduction in referral rate compared to April 2019. CONCLUSION: The coronavirus disease 2019 pandemic has resulted in changes to health-seeking behaviours, and healthcare provision and delivery. Urgent policy interventions may be required to compensate for the hidden impact that the coronavirus disease 2019 pandemic has had on those with cancer.


Assuntos
COVID-19/epidemiologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Encaminhamento e Consulta/estatística & dados numéricos , Listas de Espera , Adulto , COVID-19/prevenção & controle , COVID-19/transmissão , Controle de Doenças Transmissíveis , Diagnóstico Tardio , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Estudos Retrospectivos , Fatores de Tempo , Reino Unido
19.
Lancet Gastroenterol Hepatol ; 6(12): 993-1001, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34715031

RESUMO

BACKGROUND: Rapid weight loss is a major risk factor for the formation of cholesterol gallstones. Consequently, patients with morbid obesity undergoing bariatric surgery frequently develop symptomatic gallstone disease. This trial assessed the efficacy of ursodeoxycholic acid versus placebo for the prevention of symptomatic gallstone disease after bariatric surgery. METHODS: This multicentre, double-blind, randomised, placebo-controlled superiority trial enrolled patients with an intact gallbladder scheduled for laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy in three hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module to receive 900 mg ursodeoxycholic acid daily for 6 months or matched placebo. Randomisation was stratified by the presence of asymptomatic gallstones at baseline and type of surgery. Patients, clinicians, and study staff were masked to treatment allocation. The primary endpoint was symptomatic gallstone disease within 24 months, assessed in the modified intention-to-treat population (all randomly assigned eligible patients with any post-randomisation measurement). Prespecified subgroup analyses were done based on the stratification groups. Safety was assessed in all patients who took at least one dose of the study drug. This trial is registered with the Netherlands Trial Register, NL5954. FINDINGS: Between Jan 11, 2017, and Oct 22, 2018, 985 patients were randomly assigned to receive either ursodeoxycholic acid (n=492) or placebo (n=493). 967 patients were included in the modified intention-to-treat population, of whom 959 had data available for primary endpoint assessment. 189 (20%) patients had asymptomatic gallstones at baseline and 78 (8%) received a sleeve gastrectomy. Symptomatic gallstone disease occurred in 31 (6·5%) of 475 patients in the ursodeoxycholic acid group and in 47 (9·7%) of 484 patients in the placebo group (relative risk 0·67, 95% CI 0·43-1·04, p=0·071). Logistic regression showed a significant interaction between ursodeoxycholic acid and the presence of asymptomatic gallstones at baseline (p=0·046), with an effect of ursodeoxycholic acid in patients without (0·47, 0·27-0·84, p=0·0081), and no effect in patients with asymptomatic gallstones at baseline (1·22, 0·61-2·47, p=0·57). The effect was stronger in patients without gallstones at baseline undergoing RYGB (0·37, 0·20-0·71, p=0·0016), whereas the subgroup of patients undergoing sleeve gastrectomy was too small to draw clear conclusions. Adverse events were rare. In the ursodeoxycholic acid group, diarrhoea occurred in four (0·9%) of 444 patients and skin rash in two (0·5%) patients. In the placebo group, diarrhoea occurred in two (0·4%) of 453 patients and skin rash in two (0·4%) patients. The total number of serious adverse events did not significantly differ between the trial groups (75 [17%] in 444 patients in the ursodeoxycholic acid group and 102 [23%] in 453 patients in the placebo group). The most common serious adverse events were abdominal pain and internal hernia. No serious adverse event was attributed to the study drug. INTERPRETATION: Ursodeoxycholic acid prophylaxis did not significantly reduce the occurrence of symptomatic gallstone disease in all patients after bariatric surgery. In patients without gallstones before RYGB surgery, ursodeoxycholic acid treatment reduced the occurrence of symptomatic gallstone disease compared with placebo. Further research is needed to assess the efficacy of ursodeoxycholic acid after sleeve gastrectomy. FUNDING: The Netherlands Organization for Health Research and Development, Zambon Netherlands BV, Foundation for Clinical Research of the Slotervaart Hospital, the Spaarne Gasthuis Academy, and Amsterdam Gastroenterology Endocrinology Metabolism.


Assuntos
Colagogos e Coleréticos/uso terapêutico , Colelitíase/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Ácido Ursodesoxicólico/uso terapêutico , Adulto , Cirurgia Bariátrica/efeitos adversos , Estudos de Casos e Controles , Colagogos e Coleréticos/administração & dosagem , Colagogos e Coleréticos/efeitos adversos , Colelitíase/epidemiologia , Colelitíase/etiologia , Método Duplo-Cego , Feminino , Gastrectomia/efeitos adversos , Derivação Gástrica/efeitos adversos , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Obesidade Mórbida/complicações , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Avaliação de Resultados em Cuidados de Saúde , Placebos/administração & dosagem , Segurança , Resultado do Tratamento , Ácido Ursodesoxicólico/administração & dosagem , Ácido Ursodesoxicólico/efeitos adversos
20.
Obes Surg ; 31(10): 4607-4611, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34283377

RESUMO

Prevailing recommendations on reporting weight loss after bariatric and metabolic surgery are not evidence-based. They promote the outcome metric percentage excess weight loss (%EWL), sometimes indicated as percentage excess body mass index loss (%EBMIL). Many studies proved that this popular outcome measure, in contrast to other weight loss metrics, is inaccurate and error-sensitive when comparing weight loss within and between studies. It is inappropriate for assessing poor weight loss response and weight regain as well. The percentage (total) weight loss metric is the best alternative. The Dutch Society for Metabolic and Bariatric Surgery (DSMBS) recommends to stop using the %EWL (or %EBMIL) metric as primary outcome measure in all cases and calls on the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) to propagate this evidence-based recommendation.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Obesidade Mórbida , Índice de Massa Corporal , Humanos , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Redução de Peso
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