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1.
Surg Endosc ; 38(5): 2770-2776, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38580757

RESUMEN

INTRODUCTION: The purpose of this study is to investigate the impact of preoperative comorbidities, including depression, anxiety, type 2 diabetes mellitus, obstructive sleep apnea, hypothyroidism, and the type of surgery on %EBWL (percent estimated body weight loss) in patients 1 year after bariatric surgery. Patients who choose to undergo bariatric surgery often have other comorbidities that can affect both the outcomes of their procedures and the postoperative period. We predict that patients who have depression, anxiety, diabetes mellitus, obstructive sleep apnea, or hypothyroidism will have a smaller change in %EBWL when compared to patients without any of these comorbidities. METHODS AND PROCEDURES: Data points were retrospectively collected from the charts of 440 patients from March 2012-December 2019 who underwent a sleeve gastrectomy or gastric bypass surgery. Data collected included patient demographics, select comorbidities, including diabetes mellitus, obstructive sleep apnea, hypothyroidism, depression, and anxiety, and body weight at baseline and 1 year postoperatively. Ideal body weight was calculated using the formula 50 + (2.3 × height in inches over 5 feet) for males and 45.5 + (2.3 × height in inches over 5 feet) for females. Excess body weight was then calculated by subtracting ideal body weight from actual weight at the above forementioned time points. Finally, %EBWL was calculated using the formula (change in weight over 1 year/excess weight) × 100. RESULTS: Patients who had a higher baseline BMI (p < 0.001), diabetes mellitus (p = 0.026), hypothyroidism (p = 0.046), and who had a laparoscopic sleeve gastrectomy rather than Roux-en-Y gastric bypass (p < 0.001) had a smaller %EBWL in the first year after bariatric surgery as compared to patients without these comorbidities at the time of surgery. Controversially, patients with anxiety or depression (p = 0.73) or obstructive sleep apnea (p = 0.075) did not have a statistically significant difference in %EBWL. CONCLUSION: A higher baseline BMI, diabetes mellitus, hypothyroidism, and undergoing laparoscopic sleeve gastrectomy may lead to lower %EBWL in the postoperative period after bariatric surgery. At the same time, patients' mental health status and sleep apnea status were not related to %EBWL. This study provides new insight into which comorbidities may need tighter control in order to optimize weight loss outcomes after bariatric surgery.


Asunto(s)
Cirugía Bariátrica , Comorbilidad , Apnea Obstructiva del Sueño , Pérdida de Peso , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Adulto , Cirugía Bariátrica/métodos , Apnea Obstructiva del Sueño/cirugía , Apnea Obstructiva del Sueño/epidemiología , Obesidad Mórbida/cirugía , Diabetes Mellitus Tipo 2 , Hipotiroidismo/epidemiología , Hipotiroidismo/etiología , Depresión/epidemiología , Depresión/etiología , Ansiedad/epidemiología , Ansiedad/etiología , Gastrectomía/métodos , Periodo Preoperatorio
2.
World J Surg ; 48(3): 681-691, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38340062

RESUMEN

BACKGROUND: Proximal gastrectomy (PG) has become an increasingly preferred procedure for treating early cancer in the upper third of the stomach. However, advantages of PG in postoperative quality of life (QOL) over total gastrectomy (TG) has not fully proven. METHODS: We conducted a multi-institutional prospective observational study (CCOG1602) of patients who undergo TG or PG for cStage I gastric cancer. We used the PGSAS-37 and EORTC-QLQ-C30 to evaluate the changes in body weight and QOL over a 3-year postoperative period. The primary endpoint was the weight loss rate 3 years after surgery. RESULTS: We enrolled 109 patients from 18 institutions and selected 65 and 19 patients for inclusion in the TG and PG groups, respectively. Mean postoperative weight loss rates were 16.0% and 11.7% for the TG and PG groups, respectively (p = 0.056, Cohen's d 0.656) during postoperative year 1% and 15.0% and 10.8% for TG and PG (p = 0.068, Cohen's d 0.543), respectively, during postoperative year 3, indicating that the PG group achieved a better trend with a moderate effect size. According to the PGSAS-37, the PG group experienced a better trend in the indigestion subscale (p < 0.001, Cohen's d -1.085) and total symptom score (p = 0.050, Cohen's d -0.59) during postoperative year 3 compared with the TG group. In contrast, the EORTC-QLQ-C30 detected no difference between the groups at any time point during 3-year postoperative period. CONCLUSIONS: This prospective study demonstrates that PG tended to be more favorable compared with TG with respect to postoperative weight loss and QOL, particularly regarding indigestion.


Asunto(s)
Dispepsia , Neoplasias Gástricas , Humanos , Calidad de Vida , Estudios Prospectivos , Neoplasias Gástricas/cirugía , Dispepsia/cirugía , Gastrectomía/métodos , Periodo Posoperatorio , Pérdida de Peso , Resultado del Tratamiento
3.
Diabet Med ; 40(5): e15063, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36756713

RESUMEN

AIMS/HYPOTHESIS: To determine the relationship of dementia with preceding body mass index (BMI), changes in body weight and waist circumference in older people with type 2 diabetes. METHODS: In the Edinburgh Type 2 Diabetes Study (1064 men and women with type 2 diabetes, aged 60-75), body weight, waist circumference and BMI were measured at baseline and after 4 years in a subgroup (n = 821). Percentage body weight and waist circumference change over 4 years were calculated. Data on incident dementia was recorded during a median follow-up time of 10.84 years. Survival models considering a range of co-variables and/or death as a competing risk were used to estimate the risks of dementia associated with each weight-related variable. RESULTS: A total of 105 incident dementia events were recorded. When compared with people in the lowest BMI group (<25 kg/m2 ), risk of dementia was lower in intermediate BMI groups (25-29.9 kg/m2 , HR 0.44, p = 0.002; 30-34.9 kg/m2 , HR 0.41, p = 0.001) and the highest BMI group (≧35 kg/m2 , HR 0.35, p = 0.001). In the weight change subgroup, 78 incident dementia events were recorded between years 4 and 10. Body weight loss over 5% (compared with ≦5%) was associated with higher incidence of dementia (HR 2.06, p = 0.010). The association between waist circumference change and dementia was not significant. CONCLUSIONS/INTERPRETATIONS: Both a lower BMI and weight loss over a period of years are indicative of increased dementia risk for older people with type 2 diabetes, while waist circumference changes may be less informative.


Asunto(s)
Diabetes Mellitus Tipo 2 , Masculino , Humanos , Femenino , Anciano , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/epidemiología , Circunferencia de la Cintura , Factores de Riesgo , Peso Corporal
4.
Cancer Control ; 30: 10732748231204719, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37749874

RESUMEN

BACKGROUND: Pancreatic cancer (PC) has a poor prognosis, with body weight loss commonly observed at diagnosis. However, the impact on PC prognosis of weight loss at the time of diagnosis on PC prognosis is unknown. METHODS: This retrospective, single-center study enrolled consecutively patients diagnosed with metastatic or locally advanced PC or resectable PC who were intolerant of or refused surgery. Patients who had lost more than 5% of their body weight or more than 2% and had a body mass index (BMI) of less than 20 kg/m2 at diagnosis were classified as experiencing body weight loss. Patients were subclassified into 2 groups: patients with and without weight loss. The study evaluated patient-related and PC-related factors affecting prognosis. Cox proportional hazards models were used to assess factors affecting prognosis. The primary endpoint was overall survival. Additionally, 1:1 propensity score matching was performed to reduce bias. RESULTS: In total, 220 patients were included in the study. The median age of the patients was 74 years, and 49.1% were male. Weight loss at diagnosis was observed in 43.2% of patients. There were no significant differences in clinical factors, except for anthropometric parameters, between the groups. The median survival time did not differ between the weight loss and no weight loss groups (149 and 173 days, respectively, P = .669). After matching, no significant differences in survival times were observed between the 2 groups. CONCLUSIONS: This study found no association between weight loss at diagnosis and prognosis in patients with advanced PC treated with best supportive care or chemotherapy.


Asunto(s)
Neoplasias Pancreáticas , Humanos , Masculino , Anciano , Femenino , Estudios Retrospectivos , Pronóstico , Neoplasias Pancreáticas/tratamiento farmacológico , Pérdida de Peso , Neoplasias Pancreáticas
5.
Gastric Cancer ; 26(4): 626-637, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37106214

RESUMEN

BACKGROUND: Body weight loss (BWL) is a negative prognostic factor in metastatic gastric or gastroesophageal junction cancer (mGC/GEJC). In the phase III TAGS study, trifluridine/tipiracil improved survival versus placebo in third- or later-line mGC/GEJC. These retrospective analyses examined the association of early BWL with survival outcomes in TAGS. METHODS: Efficacy and safety were assessed in patients who experienced < 3% or ≥ 3% BWL from treatment start until day 1 of cycle 2 (early BWL). The effect of early BWL on overall survival (OS) was assessed by univariate and multivariate analyses. RESULTS: Body weight data were available for 451 of 507 (89%) patients in TAGS. In the trifluridine/tipiracil and placebo arms, respectively, 74% (224/304) and 65% (95/147) experienced < 3% BWL, whereas 26% (80/304) and 35% (52/147) experienced ≥ 3% BWL at cycle 1 end. Median OS was longer in < 3% BWL versus ≥ 3% BWL subgroups (6.5 vs 4.9 months for trifluridine/tipiracil; 6.0 vs 2.5 months for placebo). In univariate analyses, an unadjusted HR of 0.58 (95% CI, 0.46-0.73) for the < 3% vs ≥ 3% BWL subgroup indicated a strong prognostic effect of early BWL. Multivariate analyses confirmed early BWL as both prognostic (P < 0.0001) and predictive (interaction P = 0.0003) for OS. Similar results were obtained for progression-free survival. Any-cause grade ≥ 3 adverse events were reported in 77% and 82% of trifluridine/tipiracil-treated and 45% and 67% of placebo-treated patients with < 3% and ≥ 3% BWL, respectively. CONCLUSIONS: In TAGS, early BWL was a strong negative prognostic factor for OS in patients with mGC/GEJC receiving third- or later-line treatment.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Gástricas , Humanos , Trifluridina/uso terapéutico , Pronóstico , Uracilo/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Estudios Retrospectivos , Combinación de Medicamentos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Pérdida de Peso
6.
Int J Clin Oncol ; 28(12): 1625-1632, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37875767

RESUMEN

BACKGROUND: Body weight loss (BWL) is a serious complication of gastrectomy in patients with gastric cancer (GC). Nutritional intervention alone is inadequate for preventing BWL, and a new approach is needed. Oral frailty among older adults has recently attracted attention. This study aimed to investigate masticatory ability and BWL after gastrectomy. METHODS: This was a single-center, retrospective study. Functional tooth units (FTU) were used to measure masticatory ability. Patients with FTU < 4 were defined as low FTU group and FTU ≥ 4 as high FTU group. The BWL was compared between the two groups. RESULTS: Sixty patients who underwent distal gastrectomy for GC from March 2022 to January 2023 were enrolled in this study. The median FTU was 3 (range 0-12). The low-FTU group (FTU < 4) included 29 patients, while the high-FTU group (FTU ≥ 4) included 31 patients. The %BWL in the low FTU group was significantly higher than that in the high-FTU group at 1 and 3 months (p = 0.003 and p = 0.017, respectively). The risk factors associated with a %BWL > 5 at 1 and 3 months after gastrectomy were analyzed using logistic regression analysis. Only FTU < 4 was an independent risk factor after gastrectomy for GC in univariate and multivariate analyses (p = 0.028 and p = 0.006, respectively). CONCLUSIONS: Low FTU in patients with preoperative GC was a risk factor for %BWL 1 and 3 months postoperatively. Appropriate oral interventions may be useful in improving the postoperative nutritional status after gastrectomy.


Asunto(s)
Fragilidad , Neoplasias Gástricas , Humanos , Anciano , Estudios Retrospectivos , Pérdida de Peso , Fragilidad/etiología , Fragilidad/cirugía , Gastrectomía/efectos adversos , Factores de Riesgo , Neoplasias Gástricas/cirugía
7.
J Dairy Sci ; 106(7): 4799-4812, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37164861

RESUMEN

After calving, high-yielding dairy cows mobilize body reserves for energy, sometimes to the detriment of health and fertility. This study aimed to estimate the genetic correlation between body weight loss until nadir and daily milk production (MY24) in first- (L1) and second-lactation (L2) Holstein cows. The data set included 859,020 MY24 records and 570,651 daily raw body weight (BWr) phenotypes from 3,989 L1 cows, and 665,361 MY24 records and 449,449 BWr phenotypes from 3,060 L2 cows, recorded on 36 French commercial farms equipped with milking robots that included an automatic weighing platform. To avoid any bias due to change in digestive content, BWr was adjusted for variations in feed intake, estimated from milk production and BWr. Adjusted body weight was denoted BW. The genetic parameters of BW and MY24 in L1 and L2 cows were estimated using a 4-trait random regression model. In this model, the random effects were fitted by second-order Legendre polynomials on a weekly basis from wk 1 to 44. Nadir of BW was found to be earlier than reported in the literature, at 29 d in milk, and BW loss from calving to nadir was also lower than generally assumed, close to 29 kg. To estimate genetic correlations between body weight loss and production, we defined BWL5 as the loss of weight between wk 1 and 5 after calving. Genetic correlations between BWL5 and MY24 ranged from -0.26 to 0.05 in L1 and from -0.11 to 0.10 in L2, according to days in milk. These moderate to low values suggest that it may be possible to select for milk production without increasing early body mobilization.


Asunto(s)
Lactancia , Leche , Femenino , Bovinos , Animales , Leche/metabolismo , Peso Corporal , Lactancia/genética , Pérdida de Peso , Ingestión de Alimentos
8.
Support Care Cancer ; 30(7): 6163-6173, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35426524

RESUMEN

PURPOSE: The purpose of this prospective study was to assess which nutritional impact symptoms (NIS) interfere with oral intake in patients with head and neck cancer (HNC) and how the symptoms interfere with body weight loss, up to 1 year after treatment. METHODS: This was a prospective study of 197 patients with HNC planned for treatment with curative intention. Body weight was measured before the start of treatment, at 7 weeks after the start of treatment, and at 6 and 12 months after completion of treatment. NIS and NIS interfering with oral intake at each follow-up were examined with the Head and Neck Patient Symptom Checklist© (HNSC©). RESULTS: At 7 weeks of follow-up, patients experienced the greatest symptom and interference burden, and 12 months after treatment the NIS scorings had not returned to baseline. One year after treatment, the highest scored NIS to interfere with oral intake was swallowing problems, chewing difficulties, and loss of appetite. At all 3 follow-ups, the total cumulative NIS and NIS interfering with oral intake were associated with body weight loss. Factors increasing the risk for a body weight loss of ≥ 10% at 12 months after treatment were pain, loss of appetite, feeling full, sore mouth, difficulty swallowing, taste changes, and dry mouth. Women scored higher than men in NIS and NIS interfering with oral intake. Furthermore, during the study period about half of the population had a body weight loss > 5%. CONCLUSION: Because both nutritional and clinical factors may affect body weight, this study highlights the importance of a holistic approach when addressing the patients' nutritional issues. TRIAL REGISTRATION: ClinicalTrials.gov NCT03343236, date of registration: November 17, 2017.


Asunto(s)
Trastornos de Deglución , Neoplasias de Cabeza y Cuello , Peso Corporal , Lista de Verificación , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Femenino , Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/terapia , Humanos , Masculino , Estado Nutricional , Estudios Prospectivos , Pérdida de Peso
9.
Int J Mol Sci ; 23(6)2022 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-35328622

RESUMEN

GCN1 is an evolutionarily-conserved ribosome-binding protein that mediates the amino acid starvation response as well as the ribotoxic stress response. We previously demonstrated that Gcn1 mutant mice lacking the GCN2-binding domain suffer from growth retardation and postnatal lethality via GCN2-independent mechanisms, while Gcn1-null mice die early in embryonic development. In this study, we explored the role of GCN1 in adult mice by generating tamoxifen-inducible conditional knockout (CKO) mice. Unexpectedly, the Gcn1 CKO mice showed body weight loss during tamoxifen treatment, which gradually recovered following its cessation. They also showed decreases in liver weight, hepatic glycogen and lipid contents, blood glucose and non-esterified fatty acids, and visceral white adipose tissue weight with no changes in food intake and viability. A decrease of serum VLDL suggested that hepatic lipid supply to the peripheral tissues was primarily impaired. Liver proteomic analysis revealed the downregulation of mitochondrial ß-oxidation that accompanied increases of peroxisomal ß-oxidation and aerobic glucose catabolism that maintain ATP levels. These findings show the involvement of GCN1 in hepatic lipid metabolism during tamoxifen treatment in adult mice.


Asunto(s)
Proteínas de Saccharomyces cerevisiae , Animales , Lípidos , Hígado/metabolismo , Glucógeno Hepático/metabolismo , Ratones , Ratones Noqueados , Factores de Elongación de Péptidos/metabolismo , Proteínas Serina-Treonina Quinasas , Proteómica , Proteínas de Unión al ARN/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Tamoxifeno/efectos adversos , Tamoxifeno/metabolismo , Transactivadores/metabolismo , Pérdida de Peso
10.
Gastric Cancer ; 24(5): 1150-1159, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33835329

RESUMEN

BACKGROUND: Body weight loss (BWL) after gastrectomy is associated with not only a deteriorated quality of life but also a poor prognosis. Oral nutritional supplements (ONS) may be used to minimize BWL, which is observed in the first 3 months after gastrectomy and becomes stable thereafter, although the results of several randomized trials remain controversial. METHODS: We performed a multicenter, open-label randomized controlled trial including 1003 gastric cancer patients undergoing curative gastrectomy. Patients were assigned to the ONS group or the control group. In the former, 400 ml (400 kcal) per day for 12 weeks as enteral nutrition was planned, and the actual intake amount was recorded daily by patients themselves. The primary endpoint was BWL 1 year after gastrectomy. RESULTS: BWL data were available in 880 patients (ONS 437, control 443). BWL at 3 months was significantly lower in the ONS group than in the control group (7.1 ± 5.6% and 8.5 ± 5.8%, p = 0.0011). However, the difference gradually declined after 6 months and was not significant 1 year after surgery (9.3 ± 8.2% and 9.8 ± 8.7%, p = 0.37). In the ONS group, 50.4% of patients took more than 200 ml/day of ONS (average 301 ml) and showed significantly less BWL (8.2 ± 7.2%) at 1 year than the control (p = 0.0204). CONCLUSION: The administration of ONS for 12 weeks after gastrectomy did not improve BWL at 1 year. However, the improvement in BWL remained until 1 year after surgery in patients who took more than 200 kcal/day of ONS.


Asunto(s)
Calidad de Vida , Neoplasias Gástricas , Dieta , Gastrectomía , Humanos , Neoplasias Gástricas/cirugía , Pérdida de Peso
11.
Future Oncol ; 17(19): 2431-2438, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33764163

RESUMEN

Limited data are available regarding the efficacy of nutrition support in advanced gastric cancer (AGC) patients receiving a standard second-line combination chemotherapy. The BALAST study is conducted as a prospective, multicenter observational study to evaluate the efficacy of nutrition support for patients with AGC treated with ramucirumab plus taxane as second-line treatment. As part of the routine care, patients who are malnourished or at risk of malnutrition will receive nutrition support from dietitians. We will enroll a total of 26 patients to estimate weight control rate at 12 weeks as primary end point. This study will generate valuable data reinforcing the role of nutrition support therapy for AGC patients receiving second-line chemotherapy.


Lay abstract Various guidelines recommend that nutrition support therapy should be considered if cancer patients are malnourished or at risk of malnutrition. Several studies have revealed that body weight loss, which is an important factor in determining the nutrition status, may predict survival during second-line standard chemotherapy with ramucirumab and a taxane for advanced gastric cancer (AGC) patients. However, limited data are available regarding the efficacy of nutrition support in AGC patients receiving ramucirumab and a taxane. This study is conducted as a prospective, multicenter observational study to evaluate the efficacy of nutrition support for Japanese patients with AGC treated with ramucirumab and a taxane. This study will generate valuable data reinforcing the role of nutrition support therapy for AGC patients in second-line treatment. Clinical trial registration: UMIN000037867.


Asunto(s)
Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Desnutrición/terapia , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Mantenimiento del Peso Corporal/efectos de los fármacos , Estudios de Seguimiento , Humanos , Masculino , Desnutrición/diagnóstico , Desnutrición/etiología , Estudios Multicéntricos como Asunto , Estadificación de Neoplasias , Terapia Nutricional , Estado Nutricional/efectos de los fármacos , Estudios Observacionales como Asunto , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Supervivencia sin Progresión , Estudios Prospectivos , Neoplasias Gástricas/complicaciones , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/mortalidad , Ramucirumab
12.
Langenbecks Arch Surg ; 406(3): 659-666, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33611694

RESUMEN

BACKGROUND: Gastric tube reconstruction is a form of esophagogastrostomy performed after laparoscopic proximal gastrectomy (LPG). It is a simple and safe technique, but it may cause reflux esophagitis (RE) and impair postsurgical QOL. For several years, we have developed the gastric tube reconstruction and performed it on more than 100 patients. This study aimed to determine whether gastric tube reconstruction can be a feasible choice after LPG in regard to surgical safety and postoperative nutritional status. METHODS: The subjects consisted of 171 patients who underwent LPG (n = 102) or laparoscopic total gastrectomy (LTG) (n = 69). We compared the two groups in terms of surgical outcomes, incidence rate of RE, and nutritional status including postoperative weight loss and hemoglobin levels. RESULTS: There were no significant differences with regard to the surgical duration and blood loss between the two groups. The incidence of RE was not significantly higher with LPG than with LTG (16.7% vs. 10.1%, respectively; P = 0.07). Later than 2 years and 6 months after surgery, the body weight percentage of preoperative body weight in the LPG group was significantly higher than that in the LTG group. Hemoglobin and ferritin levels in the LPG group were significantly higher than those in the LTG group, later than one after surgery. The overall survival rates were similar between the two groups (5-year survival rates: 97.1% vs. 94.2% in the LPG and LTG groups, respectively; P = 0.69). CONCLUSIONS: Gastric tube reconstruction after LPG is simple and had better outcomes than LTG in terms of postoperative nutritional status.


Asunto(s)
Laparoscopía , Neoplasias Gástricas , Gastrectomía/efectos adversos , Humanos , Complicaciones Posoperatorias/epidemiología , Calidad de Vida , Estudios Retrospectivos , Neoplasias Gástricas/cirugía , Resultado del Tratamiento
13.
Mol Syst Biol ; 15(2): e8636, 2019 02 19.
Artículo en Inglés | MEDLINE | ID: mdl-30782979

RESUMEN

The liver and kidney in mammals play central roles in protecting the organism from xenobiotics and are at high risk of xenobiotic-induced injury. Xenobiotic-induced tissue injury has been extensively studied from both classical histopathological and biochemical perspectives. Here, we introduce a machine-learning approach to analyze toxicological response. Unsupervised characterization of physiological and histological changes in a large toxicogenomic dataset revealed nine discrete toxin-induced disease states, some of which correspond to known pathology, but others were novel. Analysis of dynamics revealed transitions between disease states at constant toxin exposure, mostly toward decreased pathology, implying induction of tolerance. Tolerance correlated with induction of known xenobiotic defense genes and decrease of novel ferroptosis sensitivity biomarkers, suggesting ferroptosis as a druggable driver of tissue pathophysiology. Lastly, mechanism of body weight decrease, a known primary marker for xenobiotic toxicity, was investigated. Combined analysis of food consumption, body weight, and molecular biomarkers indicated that organ injury promotes cachexia by whole-body signaling through Gdf15 and Igf1, suggesting strategies for therapeutic intervention that may be broadly relevant to human disease.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Riñón/efectos de los fármacos , Hígado/efectos de los fármacos , Xenobióticos/toxicidad , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/fisiopatología , Factor 15 de Diferenciación de Crecimiento/genética , Humanos , Riñón/patología , Hígado/patología , Transducción de Señal/efectos de los fármacos , Fenómenos Toxicológicos/genética , Aprendizaje Automático no Supervisado
14.
Support Care Cancer ; 28(9): 4381-4393, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31916008

RESUMEN

PURPOSE: Differences in body weight changes and serum liver tests (LTs) in acute myeloid leukemia (AML) patients receiving parenteral nutrition (PN) versus no PN during remission induction (RI) treatment were assessed. METHODS: Retrospectively, differences in body weight changes and serum LTs in AML patients (n = 213) who received PN versus no PN during RI treatment in one of three Dutch hospitals between 2004 and 2015 were assessed. Weekly body weight and serum LT registrations were collected from medical records. Patients' body weight changes were compared between the hospitals where PN is applied upon first indication of inadequate oral intake (PN hospitals) and the hospital where use of PN is limited to severe cases only (no-PN hospital) using repeated measures mixed model analysis. Differences in severity of serum LT elevations, according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, were assessed between patients who did and did not receive PN using chi-square or Fisher's exact tests, and multiple logistic regression analysis. RESULTS: Compared with patients of the PN hospitals, patients of the no-PN hospital experienced significantly more body weight loss during RI treatment (between-group difference 7.2%, 95% CI 4.0-10.3%). Furthermore, PN was associated with transient mild to moderate elevations of liver enzymes, but not with raised median total bilirubin levels nor with occurrence of CTCAE grade 3-4 LT elevations. CONCLUSION: Frequent compared with exceptional use of PN in AML patients during RI treatment better preserved body weight, without clinically relevant (CTCAE grade 3-4) elevations in serum LTs.


Asunto(s)
Peso Corporal/efectos de los fármacos , Leucemia Mieloide Aguda/terapia , Hígado/metabolismo , Nutrición Parenteral/métodos , Inducción de Remisión/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
15.
Eat Weight Disord ; 25(1): 143-150, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29987777

RESUMEN

PURPOSE: To examine associations of patients' attendance to follow-up meetings with a registered dietitian (RD) and physical exercise practices with weight loss during the 1 year following laparoscopic sleeve gastrectomy (SG). METHODS: Of 241 patients with obesity who underwent SG during 2012, 184 (76.3%) participated in a 1-year follow-up telephone interview and had information on number of RD follow-up meetings. Clinical information was available from computerized patient files. Multiple logistic regression analysis, adjusting for propensity score, was computed to reveal factors associated with greater weight loss. RESULTS: The mean %TWL was 31.4 ± 6.1 and the mean number of reported RD meetings during the year following SG was 4.6. The proportion of physically active patients increased by 15% (from 23 to 42) among those who attended at least 3 RD follow-up meetings (n = 123), and by 5% (from 18 to 23) among those who attended fewer than 3 meetings (n = 61) (p = 0.05). Patients conducting physical exercise reported a lower level of pain/discomfort on the EQ5D quality-of-life questionnaire (p = 0.03). The adjusted regression model revealed no association between the number of RD follow-up meetings and weight-reduction success, but physical exercise during the year following SG conferred a 2.6 times greater odds of belonging to the upper two tertiles of the % excess body weight loss ( 95% CI 1.2-5.3). CONCLUSIONS: Patients with better adherence to RD follow-up meetings were also more physically active. Patients on physical exercise also achieved greater weight reduction following SG, and reported less pain or discomfort. Nutritional counselling and physical exercise are necessary to ensure maximal and sustainable benefits from SG.  LEVEL OF EVIDENCE: Level III, Cohort study.


Asunto(s)
Consejo , Ejercicio Físico , Obesidad/cirugía , Cooperación del Paciente , Cuidados Posoperatorios , Pérdida de Peso/fisiología , Adulto , Índice de Masa Corporal , Femenino , Estudios de Seguimiento , Gastrectomía , Humanos , Masculino , Persona de Mediana Edad , Obesidad/fisiopatología , Periodo Posoperatorio , Calidad de Vida
16.
Pak J Med Sci ; 36(6): 1228-1233, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32968385

RESUMEN

OBJECTIVE: The impact of extended antral resection (AR) after laparoscopic sleeve gastrectomy (LSG) on clinical results is still not clearly elucidated with conflicting results. Our study aimed to determine whether AR is superior to antral preservation (AP) regarding clinical results. METHODS: Patients were divided into two groups according to the distance of gastric division as AR group (2cm from pylorus) and AP group (6cm from pylorus). Postoperative excess weight loss percentile (%EWL) and total body weight loss percentiles (%TBWL) at the end of first, 6th and 12 months were compared. Secondly, metabolic parameters and complications were compared. RESULTS: The first 68 patients underwent AP, and the following 43 patients underwent AR. Although statistically not significant, AR achieve more %EWL and %TBWL at the end of the first year, (P>0.05). On the other hand, metabolic parameters were similar at the end of the first year, (P>0.05). Resolution of comorbidities were statistically not different, (P>0.05). Staple line leak occurred in two patients of the AR group (4.7%) and two patients of the AP group (2.9%), (P>0.05). CONCLUSION: Both AR and AP seem to be equally effective in resolution of metabolic response. Although statistically not significant- AR provided more %EWL and %TBWL at the end of 12 months.

17.
BMC Cancer ; 19(1): 416, 2019 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-31046709

RESUMEN

BACKGROUND: Postoperative chemotherapy is beneficial for many pancreatic cancer patients. However, some patients require dose reduction or the discontinuation of adjuvant chemotherapy because of adverse treatment-related effects. In this study, we aimed to evaluate two main outcomes. First, we evaluated the clinicopathological factors affecting patient disease-free survival (DFS) and overall survival (OS) following upfront surgery. Second, we evaluated the factors that influence the continuity of adjuvant chemotherapy. METHODS: Fifty-four patients with resected pancreatic cancer were enrolled. First, we evaluated the clinicopathological factors affecting postoperative survival using the Kaplan-Meier method and Cox regression method. Next, factors affecting the continuity of adjuvant chemotherapy were analyzed using multiple logistic regression analysis. RESULTS: Univariate and multivariate analyses revealed that positive LN metastasis (HR (95% CI) 6.329 (2.381-16.95); p < 0.001) and relative dose intensity (RDI) < 80% for adjuvant chemotherapy (HR (95% CI) 5.154 (1.761-15.15); p = 0.003) were independent predictive factors for DFS. Regarding OS, extended dissection of the nerve plexus around the superior mesenteric artery (SMA) (HR (95% CI) 4.504 (1.721-11.76); p = 0.002), positive microscopic surgical margin (HR (95% CI) 5.565 (1.724-17.96); p = 0.004), and adjuvant chemotherapy of RDI < 80% (HR (95% CI) 3.534 (1.135-2.667); p = 0.029) were also independent predictive factors. Moreover, the level of RDI significantly correlated with DFS and OS. Multiple logistic regression analysis revealed that low RDI was significantly associated with postoperative body weight loss (BWL) ≥ 10%. CONCLUSIONS: The following factors were significantly associated with poor survival: extended dissection of the nerve plexus around the SMA, lymph node metastasis, residual tumor, and RDI of the adjuvant chemotherapy. Patient's prognosis with adjuvant chemotherapy of RDI < 80% was worse. BWL ≥10% was the most important factor affecting the continuity of adjuvant chemotherapy. Perioperative nutritional intervention is necessary for patients who receive adjuvant chemotherapy for advanced pancreatic cancer.


Asunto(s)
Desoxicitidina/análogos & derivados , Ácido Oxónico/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Tegafur/uso terapéutico , Pérdida de Peso , Anciano , Quimioterapia Adyuvante , Desoxicitidina/uso terapéutico , Combinación de Medicamentos , Femenino , Humanos , Modelos Logísticos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/cirugía , Pronóstico , Análisis de Supervivencia , Resultado del Tratamiento , Gemcitabina
18.
Diabetes Obes Metab ; 21(2): 293-302, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30187620

RESUMEN

AIMS: To evaluate if glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce antipsychotic-associated body weight gain in patients with schizophrenia, when compared to controls. MATERIALS AND METHODS: We systematically searched PubMed/EMBASE/PsycINFO/Cochrane using the search terms '(antipsychotic and GLP-1RA)'. Individual participant data from studies randomizing patients to GLP-1RA or control were meta-analysed. The primary outcome was difference in body weight between GLP-1RA and control; secondary outcomes included cardio-metabolic variables and adverse drug reactions (ADRs). Multiple linear regression was conducted including sex, age, psychosis severity, metabolic variable, ADRs, and GLP-1RA agent. RESULTS: Three studies (exenatide once-weekly = 2; liraglutide once-daily = 1) provided participant-level data (n = 164, age = 40.0 ± 11.1 years, body weight = 105.8 ± 20.8 kg). After 16.2 ± 4.0 weeks of treatment, body weight loss was 3.71 kg (95% CI = 2.44-4.99 kg) greater for GLP-1RA versus control (p < 0.001), number-needed-to-treat ≥5% body weight loss = 3.8 (95% CI = 2.6-7.2). Waist circumference, body mass index, HbA1c, fasting glucose and visceral adiposity were each significantly lower with GLP-1RA. Sex, age, psychosis severity, nausea, any ADR, and GLP-1RA agent did not significantly impact outcomes. Body weight loss with GLP-1RAs was greater for clozapine/olanzapine-treated patients (n = 141) than other antipsychotics (n = 27) (4.70 kg, 95% CI = 3.13-6.27 vs. 1.5 kg, 95% CI = -1.47-4.47) (p < 0.001). Nausea was more common with GLP-1RAs than control (53.6% vs. 27.5%, p = 0.002, number-needed-to-harm = 3.8). CONCLUSION: GLP-1RAs are effective and tolerable for antipsychotic-associated body weight gain, particularly clozapine/olanzapine-treated patients. With few included patients, further studies are required before making routine use recommendations for GLP-1RAs.


Asunto(s)
Antipsicóticos/efectos adversos , Enfermedades Cardiovasculares/prevención & control , Receptor del Péptido 1 Similar al Glucagón/agonistas , Hipoglucemiantes/uso terapéutico , Enfermedades Metabólicas/prevención & control , Aumento de Peso/efectos de los fármacos , Adolescente , Adulto , Anciano , Peso Corporal/efectos de los fármacos , Enfermedades Cardiovasculares/inducido químicamente , Esquema de Medicación , Exenatida/administración & dosificación , Exenatida/uso terapéutico , Femenino , Humanos , Hipoglucemiantes/administración & dosificación , Liraglutida/administración & dosificación , Liraglutida/uso terapéutico , Masculino , Enfermedades Metabólicas/inducido químicamente , Persona de Mediana Edad , Obesidad/inducido químicamente , Obesidad/prevención & control , Factores de Riesgo , Esquizofrenia/tratamiento farmacológico , Adulto Joven
19.
BMC Gastroenterol ; 19(1): 104, 2019 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-31238878

RESUMEN

BACKGROUND: Our aim was to clarify the incidence of bowel obstruction associated with a feeding jejunostomy (BOFJ) after thoracoscopic esophagectomy and its association to characteristics and postoperative change in body weight. METHODS: We reviewed 100 consecutive patients who underwent thoracoscopic esophagectomy with gastric tube reconstruction and placement of a jejunostomy feeding catheter for esophageal cancer. The incidence of BOFJ was evaluated and the change in body weight after surgery was compared between patients with and without BOFJ. RESULTS: BOFJ developed in 17 patients. Compared to patients without BOFJ, those with BOFJ had a higher preoperative body mass index (23.3 kg/m2 versus 20.9 kg/m2, P = 0.022), and greater postoperative body weight loss rate: 3 month, decrease to 84.2% of initial body weight versus 89.3% (P = 0.002). Patients with BOFJ had shorter distance between the jejunostomy and midline (40 mm versus 48 mm, P = 0.011) compared to patients without BOFJ. On multivariate analysis, higher preoperative body mass index (odds ratio (OR) = 9.248; 95% confidence interval (CI) = 1.344-63.609; p = 0.024), higher postoperative weight loss at 3 months (OR = 8.490; 95% CI = 1.765-40.837, p = 0.008), and shorter distance between the jejunostomy and midline (OR = 8.160; 95% CI = 1.675-39.747, p = 0.009) were independently associated with BOFJ. CONCLUSION: Patients of BOFJ had greater preoperative body mass, shorter distance between jejunostomy and midline, and greater postoperative weight loss.


Asunto(s)
Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Obstrucción Intestinal/etiología , Enfermedades del Yeyuno/etiología , Yeyunostomía/efectos adversos , Pérdida de Peso , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Nutrición Enteral , Femenino , Humanos , Obstrucción Intestinal/diagnóstico por imagen , Enfermedades del Yeyuno/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Periodo Preoperatorio , Estudios Retrospectivos , Factores de Riesgo , Toracoscopía
20.
Lipids Health Dis ; 18(1): 36, 2019 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-30704490

RESUMEN

BACKGROUND: The study aimed to examine the relationship between levels of serum eicosapentaenoic acid (EPA), arachidonic acid (AA), as well as EPA/AA ratio and weight loss during hospitalization in participants considered to be overweight, with type 2 diabetes. METHODS: The study participants included 142 patients who were hospitalized for treatment of type 2 diabetes. We divided the participants into two groups depending on the achievenemt in reduction of bodyweight 3% or more during hospitalization and examined the relationship between serum levels of EPA and AA, as well as ratio of EPA/AA on admission and effectiveness of weight loss under strict dietary therapy during hospitalization, using Cox proportional hazard models. RESULTS: After adjustment was made for several confounders, the hazard ratio of effective weight loss for logarithmical serum EPA was 1.59 (95% CI 1.02-2.49, P = 0.04) and for logarithmical EPA/AA ratio 1.64 (1.03-2.61, P = 0.04), whereas the hazard ratio for effective weight loss for logarithmical serum AA was 1.11 (0.45-2.78, P = 0.82). In addition, after dividing EPA/AA ratio and serum EPA into quartiles based on participant number, the hazard ratio for the highest quartile of EPA/AA ratio was 2.33 (1.14-4.77, P = 0.02), and for the highest quartile of serum EPA 1.60 (0.80-3.19, P = 0.18) compared with the lowest quartile. CONCLUSION: These results suggest the possibility that EPA is involved in bodyweight change under a caloric-restriction regimen. In addition, EPA/AA ratio was found to be a better predictor of medical intervention for weight loss among overweight patients with type 2 diabetes, compared with serum EPA level.


Asunto(s)
Ácido Araquidónico/sangre , Diabetes Mellitus Tipo 2/sangre , Ácido Eicosapentaenoico/sangre , Sobrepeso/complicaciones , Pérdida de Peso , Anciano , Glucemia/análisis , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapia , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Sobrepeso/sangre , Modelos de Riesgos Proporcionales , Pérdida de Peso/fisiología
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