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1.
Surgery ; 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38972770

RESUMEN

BACKGROUND: Cowden syndrome is an autosomal-dominant disorder caused by a germline phosphatase and tensin homolog mutation, giving rise to several tumors with an aggressive clinical course. In the thyroid, there are certain histologic criteria that could be related to this syndrome that could be useful for its early detection. We sought to analyze the loss of phosphatase and tensin homolog in thyroid histologic pieces with certain histologic criteria and to determine the percentage of patients diagnosed with Cowden syndrome with this methodology. METHODS: Five hundred thirty-five thyroid specimens collected were retrospectively analyzed (2017-2020). Those samples that presented certain histologic criteria were studied for loss of phosphatase and tensin homolog expression. Patients with loss of expression underwent a clinical study to rule out dermatologic or other lesions compatible with Cowden syndrome. Patients with positive clinical study were referred for genetic study. RESULTS: The phosphatase and tensin homolog study was performed in 6.7% (n = 36) of the thyroidectomy samples, showing loss of expression in 22% (n = 8); the most frequent histologic finding was the presence of multiple monomorphous adenomatous nodules. The samples with loss of expression showed more diffuse oncocytic changes. Of the 8 patients with loss of expression, 5 showed dermatologic lesions that could be associated with Cowden syndrome and 1 had a history of macrocephaly. These patients were referred for genetic study, being positive for Cowden syndromein in one quarter of the cases (n = 2). CONCLUSION: The immunohistochemical study of phosphatase and tensin homolog in pieces of thyroidectomies with histologic criteria suggestive of Cowden syndrome can help in its early diagnosis.

3.
Surgery ; 175(5): 1291-1298, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38350761

RESUMEN

BACKGROUND: Primary hyperparathyroidism can impact patient quality of life with psychopathological symptoms like mood and sleep disturbances. In the latest recommendations published according to the primary hyperparathyroidism surgical consensus, these neuropsychological symptoms continue to be excluded. This study aims to assess the negative effects of mood and sleep on patients with primary hyperparathyroidism compared to healthy controls and analyze their improvement after surgery. METHODS: Prospective case-control study of patients with primary hyperparathyroidism. The Beck questionnaire and Pittsburgh Sleep Quality Index were used. The control group consisted of healthy people matched by age and sex. Preoperative results were compared with results at 3 and 12 months after surgery and compared with the control group. Statistical analysis consisted of the Kolmogorov-Smirnov test and Student's t test for correlations. RESULTS: Forty-nine patients who underwent parathyroidectomy were analyzed. In relation to depression, differences were observed between the results of the preoperative period and 3 months after surgery, with a significant decrease in depression score (16.80 ± 9.98 vs 13.08 ± 10.76; P = .001). This improvement was maintained after 1 year (P < .001). Regarding the quality of sleep, there were no differences 3 months after the intervention, but there were differences at 12 months (9.48 ± 4.76 vs 8.27 ± 4.38; P = .032). The dimensions of the Pittsburgh Sleep Quality Index were analyzed, observing significant differences only in daytime dysfunction after 3 months and 12 months after surgery (1.02 ± 0.99 vs 0.69 ± 0.82; P = .01 and 1.04 ± 0.98 vs 0.60 ± 0.76; P = .004). CONCLUSION: Mood changes and sleep quality improve after primary hyperparathyroidism surgery, although at different postoperative times, with this improvement being more pronounced in mood. This assessment should be taken into account in the preoperative consultation of patients with primary hyperparathyroidism.


Asunto(s)
Hiperparatiroidismo Primario , Humanos , Hiperparatiroidismo Primario/complicaciones , Hiperparatiroidismo Primario/cirugía , Hiperparatiroidismo Primario/psicología , Calidad del Sueño , Calidad de Vida , Estudios de Casos y Controles , Paratiroidectomía/métodos , Estudios Prospectivos
6.
World J Surg ; 47(9): 2197-2205, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37210692

RESUMEN

BACKGROUND: Improvements in quality of life (QoL) after parathyroidectomy in patients with primary hyperparathyroidism (PHPT) is discussed. It has not been analyzed whether these improvements can be influenced by a specific socio-personal or clinical patient profile. OBJECTIVES: to analyze QoL differences after parathyroidectomy and to determine a socio-personal and clinical profile that influences improvement after parathyroidectomy. METHODS: A longitudinal prospective cohort study in patients with PHPT. SF-36 and PHPQOL questionnaires were completed by the patients. A comparative preoperatory analysis was carried out, at three and twelve months after surgery. Student's t test was used for the correlations. The size of the effect was assessed using G*Power software. A multivariate analysis was performed to evaluate the socio-personal and clinical variables affecting the improvement in QoL after surgery. RESULTS: Forty-eight patients were analyzed. Three months after surgery an improvement was found in physical function, general health, vitality, social function, emotional role, mental health and in the patient's declared health assessment. One year after the intervention a general improvement was observed, with a greater effect on mental health and declared health evolution. Patients with bone pain presented with a higher probability of improvement after surgery. Patients with prior psychological disease had a lower associated probability of an improvement and high levels of PTH related to a greater probability of improvement after surgery. CONCLUSIONS: There is an improvement in the QoL of PHPT patients after parathyroidectomy. Patients with bone pain and high PTH levels prior to the parathyroidectomy present with a greater probability of having a greater improvement in QoL after surgery.


Asunto(s)
Hiperparatiroidismo Primario , Calidad de Vida , Humanos , Hiperparatiroidismo Primario/complicaciones , Hiperparatiroidismo Primario/cirugía , Estudios Prospectivos , Paratiroidectomía , Dolor , Hormona Paratiroidea
7.
Cir Esp (Engl Ed) ; 101(10): 665-677, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37094777

RESUMEN

INTRODUCTION: The effectiveness of the Enhanced Recovery After Surgery (ERAS) protocols in gastric cancer surgery remains controversial. METHODS: Multicentre prospective cohort study of adult patients undergoing surgery for gastric cancer. Adherence with 22 individual components of ERAS pathways were assessed in all patients, regardless of whether they were treated in a self-designed ERAS centre. Each centre had a three-month recruitment period between October 2019 and September 2020. The primary outcome was moderate-to-severe postoperative complications within 30 days after surgery. Secondary outcomes were overall postoperative complications, adherence to the ERAS pathway, 30 day-mortality and hospital length of stay (LOS). RESULTS: A total of 743 patients in 72 Spanish hospitals were included, 211 of them (28.4 %) from self-declared ERAS centres. A total of 245 patients (33 %) experienced postoperative complications, graded as moderate-to-severe complications in 172 patients (23.1 %). There were no differences in the incidence of moderate-to-severe complications (22.3% vs. 23.5%; OR, 0.92 (95% CI, 0.59 to 1.41); P = 0.068), or overall postoperative complications between the self-declared ERAS and non-ERAS groups (33.6% vs. 32.7%; OR, 1.05 (95 % CI, 0.70 to 1.56); P = 0.825). The overall rate of adherence to the ERAS pathway was 52% [IQR 45 to 60]. There were no differences in postoperative outcomes between higher (Q1, > 60 %) and lower (Q4, ≤ 45 %) ERAS adherence quartiles. CONCLUSIONS: Neither the partial application of perioperative ERAS measures nor treatment in self-designated ERAS centres improved postoperative outcomes in patients undergoing gastric surgery for cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03865810.


Asunto(s)
Recuperación Mejorada Después de la Cirugía , Neoplasias Gástricas , Adulto , Humanos , Atención Perioperativa , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/complicaciones
8.
Braz. J. Anesth. (Impr.) ; 73(1): 54-71, Jan.-Feb. 2023. tab, graf
Artículo en Inglés | LILACS | ID: biblio-1420654

RESUMEN

Abstract Background Early mobilization after surgery is a cornerstone of the Enhanced Recovery After Surgery (ERAS) programs in total hip arthroplasty (THA) or total knee arthroplasty (TKA). Our goal was to determine the time to mobilization after this surgery and the factors associated with early mobilization. Methods This was a predefined substudy of the POWER.2 study, a prospective cohort study conducted in patients undergoing THA and TKA at 131 Spanish hospitals. The primary outcome was the time until mobilization after surgery as well as determining those perioperative factors associated with early mobilization after surgery. Results A total of 6093 patients were included. The median time to achieve mobilization after the end of the surgery was 24 hours [16-30]. 4,222 (69.3%) patients moved in ≤ 24 hours after surgery. Local anesthesia [OR = 0.80 (95% confidence interval [CI]: 0.72-0.90); p= 0.001], surgery performed in a self-declared ERAS center [OR = 0.57 (95% CI: 0.55-0.60); p< 0.001], mean adherence to ERAS items [OR = 0.93 (95% CI: 0.92-0.93); p< 0.001], and preoperative hemoglobin [OR = 0.97 (95% CI: 0.96-0.98); p< 0.001] were associated with shorter time to mobilization. Conclusions Most THA and TKA patients mobilize in the first postoperative day, early time to mobilization was associated with the compliance with ERAS protocols, preoperative hemoglobin, and local anesthesia, and with the absence of a urinary catheter, surgical drains, epidural analgesia, and postoperative complications. The perioperative elements that are associated with early mobilization are mostly modifiable, so there is room for improvement.


Asunto(s)
Humanos , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Ambulación Precoz , Complicaciones Posoperatorias/etiología , Hemoglobinas , Estudios Prospectivos , Tiempo de Internación
9.
Transpl Immunol ; 76: 101771, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36473577

RESUMEN

PURPOSE: To describe the evolution of the serum levels of soluble HLA-G (s-HLA-G) during the first 12 months after heart transplantation (HT) and to correlate it with clinical outcomes. METHODS: Observational study based in a single-center cohort of 59 patients who underwent HT between December-2003 and March-2010. Soluble HLA-G levels were measured from serum samples extracted before HT, and 1, 3, 6 and 12 months after HT. The cumulative burden of s-HLA-G expression during the first post-transplant year was assessed by means of the area under the curve (AUC) of s-HLA-G levels over time and correlated with the acute rejection burden -as assessed by a rejection score-, the presence of coronary allograft vasculopathy (CAV) grade ≥ 1 and infections during the first post-transplant year; as well as with long-term patient and graft survival. Mean follow-up was 12.4 years. RESULTS: Soluble HLA-G levels decreased over the first post-transplant year (p = 0.020). The AUC of s-HLA-G levels during the first post-transplant year was higher among patients with infections vs. those without infections (p = 0.006). No association was found between the AUC of s-HLA-G levels and the burden of acute rejection or the development of CAV. Overall long-term survival, long-term survival free of late graft failure and cancer-free survival were not significantly different in patients with an AUC of s-HLA-G levels higher or lower than the median of the study population. CONCLUSIONS: Soluble HLA-G levels decreased over the first year after HT. Higher HLA-G expression was associated with a higher frequency of infections, but not with the burden of acute rejection or the development of CAV, neither with long-term patient or graft survival.


Asunto(s)
Antígenos HLA-G , Evaluación del Resultado de la Atención al Paciente , Receptores de Trasplantes , Humanos , Rechazo de Injerto/metabolismo , Supervivencia de Injerto/fisiología , Trasplante de Corazón/efectos adversos , Antígenos HLA-G/sangre , Antígenos HLA-G/química
10.
Front Cell Dev Biol ; 10: 1005675, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36325358

RESUMEN

Chemoresistance is one of the most important challenges in cancer therapy. The presence of cancer stem cells within the tumor may contribute to chemotherapy resistance since these cells express high levels of extrusion pumps and xenobiotic metabolizing enzymes that inactivate the therapeutic drug. Despite the recent advances in cancer cell metabolism adaptations, little is known about the metabolic adaptations of the cancer stem cells resistant to chemotherapy. In this study, we have undertaken an untargeted metabolomic analysis by liquid chromatography-high-resolution spectrometry combined with cytotoxicity assay, western blot, quantitative real-time polymerase chain reaction (qPCR), and fatty acid oxidation in a prostate cancer cell line resistant to the antiandrogen 2-hydroxiflutamide with features of cancer stem cells, compared to its parental androgen-sensitive cell line. Metabolic fingerprinting revealed 106 out of the 850 metabolites in ESI+ and 67 out of 446 in ESI- with significant differences between the sensitive and the resistant cell lines. Pathway analysis performed with the unequivocally identified metabolites, revealed changes in pathways involved in energy metabolism as well as posttranscriptional regulation. Validation by enzyme expression analysis indicated that the chemotherapy-resistant prostate cancer stem cells were metabolically dormant with decreased fatty acid oxidation, methionine metabolism and ADP-ribosylation. Our results shed light on the pathways underlying the entry of cancer cells into dormancy that might contribute to the mechanisms of drug resistance.

11.
Br Dent J ; 233(9): 757-764, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36369557

RESUMEN

Malnutrition is prevalent in patients with head and neck cancer (HNC) at diagnosis but can occur at any stage of the treatment pathway. The impact of disease burden and treatment side effects can lead to altered anatomy, compromised quality and quantity of saliva and impaired swallowing function, which can result in deleterious effects on nutritional status. Optimising nutrition status is critical, as malnutrition is adversely associated with treatment tolerance and outcomes, wound healing, morbidity, mortality, quality of life and survival. Dietitians are integral members of the HNC multidisciplinary team and are uniquely qualified in the assessment, management and optimisation of nutritional status across the care pathway. This includes providing informational counselling to patients and carers on the short- and long-term nutritional impact of planned treatments alongside multidisciplinary members. Dietitians lead on the recommendation, provision and monitoring of nutrition support, which can be via the oral, enteral or parenteral route. Oral nutrition support includes dietary counselling, nourishing dietary, food fortification advice and high energy/protein oral nutritional supplements. Enteral nutrition support, or tube feeding, can be required on a short- and/or long-term basis and dietitians support appropriate decision-making for the type of tube and timing of placement across the care pathway.


Asunto(s)
Neoplasias de Cabeza y Cuello , Desnutrición , Nutricionistas , Humanos , Calidad de Vida , Apoyo Nutricional , Desnutrición/etiología , Desnutrición/prevención & control , Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/terapia , Estado Nutricional
12.
Br Dent J ; 233(9): 765-768, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36369558

RESUMEN

Patients treated for head and neck cancer may be susceptible to a higher incidence of dental disease due to long-term sequelae of treatment for head and neck cancer. Most patients with head and neck cancer are discharged from a hospital environment and responsibility for long-term dental care is transferred back from the restorative dentistry team to the dentist and dental care professionals in primary care. Treatment of these patients should be undertaken in a supportive environment, taking into account the physical and psychological repercussions of previous treatment. With the exception of some surgical procedures, routine dental care is not contraindicated in patients after head and neck cancer treatment and it is expected that the dentist and dental care professionals will be responsible for long-term routine dental treatment. Primary dental care practitioners should be aware of the process to refer patients back to the head and neck cancer multidisciplinary team if they note a suspicious change during their routine clinical examinations. Referral to a restorative dentistry consultant for planning and carrying out complex items of care may sometimes be necessary, but patients should always remain under the long-term care of their primary dental care practitioner.


Asunto(s)
Neoplasias de Cabeza y Cuello , Humanos , Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/terapia , Derivación y Consulta , Atención Odontológica/métodos
13.
Br Dent J ; 233(9): 794-800, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36369570

RESUMEN

Historically, oral and dental issues for head and neck cancer patients were often not considered until after cancer treatment was complete. As a result, outcomes for oral rehabilitation were sometimes suboptimal. Inconsistencies in service delivery models and qualification, training and experience of staff delivering dental care often compounded this problem, making research and audit almost impossible. Collaborative working by consultants in restorative dentistry from all over the UK as part of a Restorative Dentistry-UK (RD UK) subgroup, renamed more recently as the RD-UK Head and Neck Cancer Clinical Excellence Network (CEN), has re-emphasised the importance of specialist restorative dentistry intervention at the outset of the head and neck cancer pathway to optimise outcomes of patient care. The CEN has driven several initiatives, reflecting Getting It Right First Time (GIRFT) principles aimed at reducing unwarranted variation. This improved consistency in approach and optimised collaborative working of the team now presents a better environment for multicentre audit and research. Ultimately, this should result in a continued improvement in patient and carer experience.


Asunto(s)
Neoplasias de Cabeza y Cuello , Ejercicio Preoperatorio , Humanos , Consenso , Neoplasias de Cabeza y Cuello/terapia , Odontología , Reino Unido
14.
Surgery ; 172(6S): S6-S13, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36427932

RESUMEN

BACKGROUND: In recent years, fluorescence imaging-relying both on parathyroid gland autofluorescence under near-infrared light and angiography using the fluorescent dye indocyanine green-has been used to reduce risk of iatrogenic parathyroid injury during thyroid and parathyroid resections, but no published guidelines exist regarding its use. In this study, orchestrated by the International Society for Fluorescence Guided Surgery, areas of consensus and nonconsensus were examined among international experts to facilitate future drafting of such guidelines. METHODS: A 2-round, online Delphi survey was conducted of 10 international experts in fluorescence imaging use during endocrine surgery, asking them to vote on 75 statements divided into 5 modules: 1 = patient preparation and contraindications to fluorescence imaging (n = 11 statements); 2 = technical logistics (n = 16); 3 = indications (n = 21); 4 = potential advantages and disadvantages of fluorescence imaging (n = 20); and 5 = training and research (n = 7). Several methodological steps were taken to minimize voter bias. RESULTS: Overall, parathyroid autofluorescence was considered better than indocyanine green angiography for localizing parathyroid glands, whereas indocyanine green angiography was deemed superior assessing parathyroid perfusion. Additional surgical scenarios where indocyanine green angiography was thought to facilitate surgery are (1) when >1 parathyroid gland requires resection; (2) during redo surgeries, (3) facilitating parathyroid autoimplantation; and (4) for the predissection visualization of abnormal glands. Both parathyroid autofluorescence and indocyanine green angiography can be used during the same procedure and employing the same imaging equipment. However, further research is needed to optimize the dose and timing of indocyanine green administration. CONCLUSION: Though further research remains necessary, using fluorescence imaging appears to have uses during thyroid and parathyroid surgery.


Asunto(s)
Hipoparatiroidismo , Verde de Indocianina , Humanos , Glándula Tiroides/diagnóstico por imagen , Glándula Tiroides/cirugía , Glándulas Paratiroides/diagnóstico por imagen , Glándulas Paratiroides/cirugía , Imagen Óptica/métodos
15.
Eur J Intern Med ; 105: 89-96, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36123281

RESUMEN

AIMS: To assess the incidence of cancer diagnosis and cancer-related mortality in patients with heart failure (HF). METHODS: Observational study based in a prospective cohort of patients with HF referred to a specialized Spanish clinic between 2010 and 2019. The observed incidence of malignancies (excluding non-melanoma skin cancer) was compared to that expected for the general Spanish population according to the Global Cancer Observatory. RESULTS: We studied 1909 consecutive patients with HF. Over a median follow-up of 4.07 years, 165 new cases of malignancy were diagnosed. Observed age-standardized incidence rates of cancer were 861 (95% CI 618.4-2159.4) cases per 100,000 patients-years in men and 728.5 (95% CI 451.1-4308.7) cases per 100,000 patients-years in women; while age-standardized incidence rates of cancer expected for the general Spanish population were 479.4 cases per 100,000 patients-years in men (risk ratio = 1.80) and 295.5 cases per 100,000 patients-years in women (risk ratio = 2.46). Both a history of pre-existing malignancy at baseline and the development of new malignancies during follow-up were associated with reduced survival. Observed age-standardized cancer-related mortality was 344.1 (95% CI 202.1-1675) deaths per 100,000 patient-years in men and 217.0 (95% CI 32.8-3949.3) deaths per 100,000 patient-years in women; while age-standardized cancer-related mortality expected for the general Spanish population was 201.4 deaths per 100,000 patients-years in men (risk ratio = 1.71) and 96.2 deaths per 100,000 patients-years in women (risk ratio = 2.26). CONCLUSION: Patients with HF showed higher incidence rates of cancer diagnosis and cancer-related mortality than those expected for the general population.


Asunto(s)
Insuficiencia Cardíaca , Neoplasias , Masculino , Humanos , Femenino , Incidencia , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Insuficiencia Cardíaca/epidemiología , Neoplasias/epidemiología
16.
N Engl J Med ; 387(11): 967-977, 2022 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-36018037

RESUMEN

BACKGROUND: A polypill that includes key medications associated with improved outcomes (aspirin, angiotensin-converting-enzyme [ACE] inhibitor, and statin) has been proposed as a simple approach to the secondary prevention of cardiovascular death and complications after myocardial infarction. METHODS: In this phase 3, randomized, controlled clinical trial, we assigned patients with myocardial infarction within the previous 6 months to a polypill-based strategy or usual care. The polypill treatment consisted of aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 or 40 mg). The primary composite outcome was cardiovascular death, nonfatal type 1 myocardial infarction, nonfatal ischemic stroke, or urgent revascularization. The key secondary end point was a composite of cardiovascular death, nonfatal type 1 myocardial infarction, or nonfatal ischemic stroke. RESULTS: A total of 2499 patients underwent randomization and were followed for a median of 36 months. A primary-outcome event occurred in 118 of 1237 patients (9.5%) in the polypill group and in 156 of 1229 (12.7%) in the usual-care group (hazard ratio, 0.76; 95% confidence interval [CI], 0.60 to 0.96; P = 0.02). A key secondary-outcome event occurred in 101 patients (8.2%) in the polypill group and in 144 (11.7%) in the usual-care group (hazard ratio, 0.70; 95% CI, 0.54 to 0.90; P = 0.005). The results were consistent across prespecified subgroups. Medication adherence as reported by the patients was higher in the polypill group than in the usual-care group. Adverse events were similar between groups. CONCLUSIONS: Treatment with a polypill containing aspirin, ramipril, and atorvastatin within 6 months after myocardial infarction resulted in a significantly lower risk of major adverse cardiovascular events than usual care. (Funded by the European Union Horizon 2020; SECURE ClinicalTrials.gov number, NCT02596126; EudraCT number, 2015-002868-17.).


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina , Enfermedades Cardiovasculares , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Inhibidores de Agregación Plaquetaria , Inhibidores de la Enzima Convertidora de Angiotensina/efectos adversos , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Aspirina/efectos adversos , Aspirina/uso terapéutico , Atorvastatina/efectos adversos , Atorvastatina/uso terapéutico , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/prevención & control , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Accidente Cerebrovascular Isquémico/prevención & control , Infarto del Miocardio/complicaciones , Infarto del Miocardio/prevención & control , Infarto del Miocardio/terapia , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ramipril/efectos adversos , Ramipril/uso terapéutico , Prevención Secundaria/métodos
17.
Nat Commun ; 13(1): 4663, 2022 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-35945211

RESUMEN

Kiss1 neurons, producing kisspeptins, are essential for puberty and fertility, but their molecular regulatory mechanisms remain unfolded. Here, we report that congenital ablation of the microRNA-synthesizing enzyme, Dicer, in Kiss1 cells, causes late-onset hypogonadotropic hypogonadism in both sexes, but is compatible with pubertal initiation and preserved Kiss1 neuronal populations at the infantile/juvenile period. Yet, failure to complete puberty and attain fertility is observed only in females. Kiss1-specific ablation of Dicer evokes disparate changes of Kiss1-cell numbers and Kiss1/kisspeptin expression between hypothalamic subpopulations during the pubertal-transition, with a predominant decline in arcuate-nucleus Kiss1 levels, linked to enhanced expression of its repressors, Mkrn3, Cbx7 and Eap1. Our data unveil that miRNA-biosynthesis in Kiss1 neurons is essential for pubertal completion and fertility, especially in females, but dispensable for initial reproductive maturation and neuronal survival in both sexes. Our results disclose a predominant miRNA-mediated inhibitory program of repressive signals that is key for precise regulation of Kiss1 expression and, thereby, reproductive function.


Asunto(s)
ARN Helicasas DEAD-box/metabolismo , Kisspeptinas , Ribonucleasa III/metabolismo , Animales , Femenino , Fertilidad , Kisspeptinas/genética , Kisspeptinas/metabolismo , Masculino , Ratones , MicroARNs/genética , MicroARNs/metabolismo , Neuronas/metabolismo , Ribonucleasa III/genética , Maduración Sexual/genética
18.
Mol Psychiatry ; 27(10): 4335-4342, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35858992

RESUMEN

Amyloid-beta (Aß) deposition is common in cognitively unimpaired (CU) elderly >85 years. This study investigated amyloid distribution and evaluated three published in vivo amyloid-PET staging schemes from a cognitively unimpaired (CU) cohort aged 84.9 ± 4.3 years (n = 75). SUV-based principal component analysis (PCA) was applied to 18F-flutemetamol PET data to determine an unbiased regional covariance pattern of tracer uptake across grey matter regions. PET staging schemes were applied to the data and compared to the PCA output. Concentration of p-tau181 was measured in blood plasma. The PCA revealed three distinct components accounting for 91.2% of total SUV variance. PC1 driven by the large common variance of uptake in neocortical and striatal regions was significantly positively correlated with global SUVRs, APOE4 status and p-tau181 concentration. PC2 represented mainly non-specific uptake in typical amyloid-PET reference regions, and PC3 the occipital lobe. Application of the staging schemes demonstrated that the majority of the CU cohort (up to 93%) were classified as having pathological amount and distribution of Aß. Good correspondence existed between binary (+/-) classification and later amyloid stages, however, substantial differences existed between schemes for low stages with 8-17% of individuals being unstageable, i.e., not following the sequential progression of Aß deposition. In spite of the difference in staging outcomes there was broad spatial overlap between earlier stages and PC1, most prominently in default mode network regions. This study critically evaluated the utility of in vivo amyloid staging from a single PET scan in CU elderly and found that early amyloid stages could not be consistently classified. The majority of the cohort had pathological Aß, thus, it remains an open topic what constitutes abnormal brain Aß in the oldest-old and what is the best method to determine that.


Asunto(s)
Enfermedad de Alzheimer , Amiloidosis , Anciano , Humanos , Anciano de 80 o más Años , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Tomografía de Emisión de Positrones
19.
J Clin Anesth ; 80: 110752, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35405517

RESUMEN

STUDY OBJECTIVE: Assess the relationship between the Enhanced Recovery After Surgery (ERAS®) pathway and routine care and 30-day postoperative outcomes. DESIGN: Prospective cohort study. SETTING: European centers (185 hospitals) across 21 countries. PATIENTS: A total of 2841 adult patients undergoing elective colorectal surgery. Each hospital had a 1-month recruitment period between October 2019 and September 2020. INTERVENTIONS: Routine perioperative care. MEASUREMENTS: Twenty-four components of the ERAS pathway were assessed in all patients regardless of whether they were treated in a formal ERAS pathway. A multivariable and multilevel logistic regression model was used to adjust for baseline risk factors, ERAS elements and country-based differences. RESULTS: A total of 1835 patients (65%) received perioperative care at a self-declared ERAS center, 474 (16.7%) developed moderate-to-severe postoperative complications, and 63 patients died (2.2%). There was no difference in the primary outcome between patients who were or were not treated in self-declared ERAS centers (17.1% vs. 16%; OR 1.00; 95%CI, 0.79-1.27; P = 0.986). Hospital stay was shorter among patients treated in self-declared ERAS centers (6 [5-9] vs. 8 [6-10] days; OR 0.82; 95%CI, 0.78-0.87; P < 0.001). Median adherence to 24 ERAS elements was 57% [48%-65%]. Adherence to ERAS-pathway quartiles (≥65% vs. <48%) suggested that patients with the highest adherence rates experienced a lower risk of moderate-to-severe complications (15.9% vs. 17.8%; OR 0.71; 95%CI, 0.53-0.96; P = 0.027), lower risk of death (0.3% vs. 2.9%; OR 0.10; 95%CI, 0.02-0.42; P = 0.002) and shorter hospital stay (6 [4-8] vs. 7 [5-10] days; OR 0.74; 95%CI, 0.69-0.79; P < 0.001). CONCLUSIONS: Treatment in a self-declared ERAS center does not improve outcome after colorectal surgery. Increased adherence to the ERAS pathway is associated with a significant reduction in overall postoperative complications, lower risk of moderate-to-severe complications, shorter length of hospital stay and lower 30-day mortality.


Asunto(s)
Cirugía Colorrectal , Recuperación Mejorada Después de la Cirugía , Adulto , Cirugía Colorrectal/efectos adversos , Procedimientos Quirúrgicos Electivos/efectos adversos , Humanos , Tiempo de Internación , Estudios Observacionales como Asunto , Atención Perioperativa/métodos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Prospectivos
20.
Obes Surg ; 32(4): 1289-1299, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35143011

RESUMEN

PURPOSE: The effectiveness of enhanced recovery after surgery (ERAS) pathways in patients undergoing bariatric surgery remains unclear. Our objective was to determine the effect of the ERAS elements on patient outcomes following elective bariatric surgery. MATERIALS AND METHODS: Prospective cohort study in adult patients undergoing elective bariatric surgery. Each participating center selected a single 3-month data collection period between October 2019 and September 2020. We assessed the 24 individual components of the ERAS pathways in all patients. We used a multivariable and multilevel logistic regression model to adjust for baseline risk factors, ERAS elements, and center differences RESULTS: We included 1419 patients. One hundred and fourteen patients (8%) developed postoperative complications. There were no differences in the incidence of overall postoperative complications between the self-designated ERAS and non-ERAS groups (54 (8.7%) vs. 60 (7.6%); OR, 1.14; 95% CI, 0.73-1.79; P = .56), neither for moderate-to-severe complications, readmissions, re-interventions, mortality, or hospital stay (2 [IQR 2-3] vs. 3 [IQR 2-4] days, 0.85; 95% CI, 0.62-1.17; P = .33) Adherence to the ERAS elements in the highest adherence quartile (Q1) was greater than 72.2%, while in the lowest adherence quartile (Q4) it was less than 55%. Patients with the highest adherence rates had shorter hospital stay (2 [IQR 2-3] vs. 3 [IQR 2-4] days, 1.54; 95% CI, 1.09-2.17; P = .015), while there were no differences in the other outcomes CONCLUSIONS: Higher adherence to ERAS Society® recommendations was associated with a shorter hospital stay without an increase in postoperative complications or readmissions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03864861.


Asunto(s)
Cirugía Bariátrica , Recuperación Mejorada Después de la Cirugía , Obesidad Mórbida , Adulto , Cirugía Bariátrica/efectos adversos , Humanos , Tiempo de Internación , Obesidad Mórbida/cirugía , Readmisión del Paciente , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Prospectivos
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