Real-world evidence of adjuvant immunotherapy in resected stage III and IV melanoma patients: CADIM trial final results. Experience from 2 tertiary referral centers. / Evidencia en práctica clínica del tratamiento adyuvante con inmunoterapia en pacientes con melanoma estadio III y IV resecados: Resultados finales del estudio CADIM. Experiencia de dos centros de tercer nivel.

INTRODUCTION: Clinical trials have validated the use of nivolumab and pembrolizumab as adjuvant therapies regarding relapse-free survival (RFS) in patients with resected stage III and IV melanoma. Evidence in real-world patients is currently limited. MATERIAL AND METHOD: The CADIM trial (Characterization of adjuvant immunotherapy in melanoma patients) recruited a total of 81 patients with resected stage III and IV melanoma on nivolumab or pembrolizumab as adjuvant therapy from February 2018 through December 2022. RESULTS: The stage distribution rate was 81.5% (n = 71) for stage III, while 15 patients (18.5%) had resected stage IV. Among stage III patients, 38 were stage IIIC (46.9%). With a median follow-up of 22.8 months, the RFS in the intention-to-treat (ITT) population was 84% at 1 year and 81.5% at 2 years. The overall survival (OS) rate was 99% at 1 year and 91.4% at 2 years. Grade 3-4 treatment-related adverse events were reported in 12.3% of the patients. CONCLUSIONS: This study shows the results of resected stage III and IV melanoma patients on adjuvant therapy with anti-PD-1, and eventually confirmed the safety and efficacy profile described by clinical trials. Comparing clinical trial data with real-world evidence is necessary for a more practical, reliable, and accessible use of these drugs.

S100A12 protein as a porcine health status biomarker when quantified in saliva samples.

The S100A12 protein was validated as a biomarker of health status in porcine saliva samples using a semi-quantitative approach based on Western blotting in four healthy and sixteen diseased animals, and in four animals with severe respiratory disease during three days of antibiotic therapy. Afterwards, a non-competitive sandwich immunoassay was then developed, validated, and used to quantify S100A12 in clinical porcine samples, using 14 healthy and 25 diseased pigs. Finally, the S100A12 concentrations in the saliva of ten pigs with respiratory disease were monitored during antibiotic therapy. Diseased animals showed higher concentrations of S100A12 than healthy animals, and the high concentrations of S100A12 in pigs with respiratory distress were reduced after antimicrobial therapy. The assay developed showed good precision and accuracy, as well as a low limit of detection of 3.19 ng/mL. It was possible to store saliva samples at -20 °C, or even at 4 °C, for two weeks before analysis without losing the validity of the results. The concentrations of S100A12 observed in serum and saliva samples showed a moderately positive association with a correlation coefficient of 0.48. The concentrations of the new validated biomarker S100A12 are highly associated with the novel salivary biomarker of inflammation, adenosine deaminase, and moderately to highly associated with the total oxidant status. The results reported in this study provide a new way of evaluating inflammatory diseases in pigs using saliva samples, which should be further explored for disease prevention and monitoring in the field.

Contracción paradojal del puborrectal como causa de defecación obstructiva: resultados a corto plazo del tratamiento con biofeedback y rehabilitación pelviperineal / Puborectal paradoxical contraction as a cause of obstructive defecation: short-term outcomes of treatment with biofeedback and pelviperineal rehabilitation

Resumen Introducción: En pacientes constipados crónicos por obstrucción de salida, la contracción paradojal del puborrectal (CPP) o "anismo" es frecuente. El tratamiento con Biofeedback y rehabilitación pelviperineal presenta resultados exitosos entre el 40-90%. Objetivo: Evaluar el resultado del tratamiento con Biofeedback y rehabilitación pelviperineal en pacientes con CPP a corto plazo. Materiales y Método: Serie de casos. Datos obtenidos prospectivamente de la Unidad de Piso Pelviano. Se incluyó pacientes entre 2008 y 2015 que cumplían criterios de constipación crónica secundaria a CPP, confirmado por manometría anorrectal y/o defeco-resonancia. Se analizaron datos demográficos, frecuencia de evacuaciones, uso de laxantes, enemas, pujo, Score de Altomare y Score de constipación de Wexner pre y post-tratamiento. Resultados: 43 pacientes, de los cuales 39 son mujeres. Edad media de 40 años (rango: 14-84). Duración de síntomas fue ≥ 5 años en el 72,5%. Mediana de sesiones de Biofeedback de 8 (6-10). El 62,8% presenta ≤ 2 evacuaciones semanales y disminuye a un 29,3% post-tratamiento (p < 0,001). El 76,2% requiere laxantes orales y el 42,9% enemas, disminuyendo a 35,1% (p < 0,001) y 5,4% (p < 0,001) respectivamente post-tratamiento. Sensación de evacuación incompleta/fragmentada en todos los intentos mejoró de 67,4% a 14,6% (p < 0,001) y el pujo excesivo en más de la mitad de intentos mejoró de 76,1% a 10,8% (p < 0,001). Score de Wexner para constipación y Altomare mejoró de 18 a 7 (p < 0,001) y de 16 a 5 (p < 0,001) respectivamente. Conclusión: El biofeedback y la rehabilitación pelviperineal son efectivas en el tratamiento de la CPP.

Introduction: In patients with chronic constipation by obstructive defecation syndrome Paradoxical Puborectalis Contraction or "anismus" is important. Successful results for Biofeedback treatment and Pelviperineal Rehabilitation it described between 40-90%. Aim: To evaluate the outcome of biofeedback and pelviperineal rehabilitation in patients with CPP in the short-term. Materials and Method: Case series. Data was obtained from the prospective database of Pelvic Floor Unit of Universidad Católica de Chile. Patients with anismus were included between 2008 and 2015. Diagnostic criteria were chronic constipation patients by anismus with anorectal manometry and/or defecoresonancy that confirms this disorder and discards other causes of obstruted defecation síndrome. Demographic variables, frequency of bowel movements, use of laxatives, enemas, pushing, Altomare Score and Wexner constipation Score were analyzed pre and post-treatment. Results: Series of 43 patients, 39 of whom where women. Median age: 40 years (range: 14-84). Duration of symptoms ≥ 5 years in 72.5%. Median of Biofeedback sessions: 8 (range 6-10). Pre-treatment, 62.8% had ≤ 2 evacuations weekly and 29.3% post-treatment (p < 0.001). Oral laxatives were required in 76.2% and 42.9% enemas, decreasing to 35.1% (p < 0.001) and 5.4% (p < 0.001) post-treatment respectively. Feeling of incomplete/evacuation fragmented all the time improved from 67.4% to 14.6% (p < 0.001) and excessive pushing in more than half of time improved from 76.1% to 10.8% (p < 0.001). Wexner Score for and Altomare Score improved from 18 to 7 (p < 0.001) and 16 to 5 (p < 0.001) respectively. Conclusion: Adult with chronic constipation by anismus can be treated effectively with Biofeedback and Pelviperineal Rehabilitation.

Mitotic rate as an important prognostic factor in cutaneous malignant melanoma.

BACKGROUND: Recently, the quantification of mitoses in cutaneous melanoma has been discharged from the main prognostic variables of the TNM classification. OBJECTIVE: To investigate the prognostic value of the presence of mitoses in primary cutaneous melanoma and to establish the number of mitoses per mm2 that may have prognostic significance. METHODS: A retrospective observational study was performed on 141 patients treated for cutaneous melanoma, who were assessed by the same pathologist, and who had a minimum follow-up of 2 years. Clinical, epidemiological, histopathological and follow-up variables were gathered and compared with the number of mitoses to distinguish the significance of differences by means of univariate, multivariate, and survival analyses. RESULTS: The cut-off level related to a better sensitivity and specificity was 1.50 mitoses per mm2. The presence of two or more mitoses/mm2 showed a better relationship with prognostic variables and both the overall and disease-free survival than the presence of 1 or more mitoses/mm2. This happens especially in melanomas thicker than 0.8 mm and it could affect the staging in cases with Breslow between 1 and 2 mm. CONCLUSIONS: A mitotic rate of two or more mitoses per mm2 in cutaneous melanoma should be considered as a more accurate prognostic factor than one or more mitoses per mm2, particularly in tumors equal or greater than 0.8 mm in thickness.

Effectiveness and failures of a fast track protocol after cytoreduction and hyperthermic intraoperative intraperitoneal chemotherapy in patients with peritoneal surface malignancies.

BACKGROUND: The aim of this study was to analyze the results short term perioperative of patients with peritoneal surface malignancies undergoing cytoreduction with peritonectomy and HIPEC under a controlled fast track protocol and evaluate the factors related to the failure of implementation of the protocol. PATIENTS AND METHOD: We prospectively analyzed a consecutive series of patients (N = 156) with peritoneal surface malignancies treated by cytoreductive surgery with peritonectomy procedures and HIPEC from September 2008 until December 2014, in whom a fast track protocol was implemented. We limited the protocol to patients who had optimal cytoreduction, HIPEC administration, and not more than one digestive anastomosis. All patients signed informed consent for surgery and the perioperative multimodal recovery program. RESULTS: A total of 156 consecutive patients, with a median age of 57 years were included in the study. Median PCI was 8 (IQR: 0-32). Morbidity rate (Clavien-Dindo) was 25.6%, with a major morbidity rate (Clavien-Dindo III-IV) of 11.5%. One hundred and three patients (66%) completed the protocol. Multivariate analysis identified the following independent factors, which were related to failure of the protocol: age over 57 years (OR = 3.159, 95% CI: 1.286-7.758, p < 0.05), the realization of a digestive anastomosis (OR = 3.834, 95% CI: 1.562-9.414, p < 0.005) and occurrence of postoperative complications (OR = 18.704, 95% CI: 6.888-50.790, p < 0.001) CONCLUSIONS: Our data support the idea that in selected patients undergoing cytoreductive surgery and HIPEC, with a low PCI and especially no necessity to perform a digestive anastomosis, the implementation of a fast track program is feasible.

Creencias en salud oral de cuidadores de pacientes discapacitados y adultos mayores institucionalizados de la comuna de Quilaco, Región del Biobío / Oral health beliefs in caregivers of institutionalized disabled and elderly patients of the Quilaco commune, Biobío Region

El envejecimiento demográfico acelerado de la población de Chile supone un aumento en la prevalencia no solo de enfermedades crónicas, sino también de personas con discapacidad, y necesidad de ser cuidadas en forma permanente. En este sentido, tomando como grupo de estudio a los cuidadores de los adultos mayores institucionalizados de la comuna de Quilaco, Región del Biobío, analizamos las creencias en salud oral que los cuidadores poseen al momento de llevar a cabo la atención de los adultos mayores que se encuentran a su cargo.

The rapid aging of the population of Chile will produce an increase not only in the prevalence of chronic diseases, but also of people with disabilities, and their need to be cared for permanently. In this sense, taking the caregivers of the institutionalized elderly population of the Quilaco commune, Biobío Region, as a study group, we analyzed the oral health beliefs that caregivers have at the time of undertaking the care of older adults.

Transplantation for acute liver failure: report of results in the region of Castilla y Leon (Spain) after 10 years of activity.

Acute liver failure is an uncommon disease but its overall mortality rate is still high without liver transplantation, which is the treatment of choice for patients achieving certain criteria. We have reported herein the experience and retrospectively analyzed results of liver transplantation for acute liver failure since the beginning of activity of our group, which is the only one in the region of "Castilla y Leon" (Spain). In 10 years, 14 patients underwent emergency transplantation among an overall series of 325 subjects. The patients were generally young men and women; the average wait list time was 2.14 days. The most common etiology was toxic exposure (no cases were related to acetaminophen overdose), followed by viral infection (all because of acute hepatitis B). Our posttransplant outcomes were: perioperative mortality, 0%; posttransplant in-hospital mortality, 14%; and 1-y, 3-y, and 5-year survival rates of 77.1%, 64.3%, and 64.3% respectively. Retransplantation rate was 7%. A major morbidity occurred in four patients: one primary dysfunction, one hyperacute rejection due to ABO blood group-incompatibility requiring retransplantation, two arterial complications, and two biliary leakages. Our outcomes of emergency transplantation were similar to those reported by both the European and Spanish Liver Transplantation Registries, despite the small number of patients.

Eight years experience with liver transplantation in Rio Hortega hospital.

OBJECTIVES: We sought to evaluate our transplant series in light of the parameters outlined in the quality criteria established by the Spanish Hepatic Transplant Society (Sociedad Española de Trasplante Hepático [SETH]). METHODS: We retrospectively analyzed 240 hepatic transplantations performed in 223 patients from November 2001 to December 2009. RESULTS: Among the series, 57% were in Child class C, 50% had cirrhosis without hepatocellular carcinoma, and 32% had this neoplasm. The most common cause for the illness was alcohol, followed by a virus, namely hepatitis C virus in 76% of cases. The average waiting list time was 45.14 days. The total graft ischemia averaged 460 minutes (range, 265-937). The 4.1% (n = 10), incidence of an urgent retransplantation was mainly due to primary graft failure or arterial thrombosis. During the perioperative period the mortality rate was 2.5% (n = 6) and the 1-month mortality rate was 6.6% (n = 16). The raw survival rates at 1, 3, and 5 years after the operation are 85%, 78%, and 72%, respectively. CONCLUSION: Our perioperative as well as the long-term results fall within the quality standards established by SETH.

[Acute mediastinitis except in a context of cardiac surgery]. / Les médiastinites aiguës en dehors d'un contexte de chirurgie cardiaque.

Acute mediastinitis is a life-threatening complication (20 to 40 % of mortality) secondary to oropharyngeal abscesses, neck infections or oesophageal leak spreading into the mediastium. Early diagnosis and optimal therapeutic approach are crucial for patient survival. CT scanning of the cervical and thoracic area is a useful tool for diagnosis and follow-up. Treatment is based on broad-spectrum antibiotherapy, adequate surgery, mediastinal drainage, and treatment of possible organ failure. There is no surgical standardized attitude. Mini-invasive approach could be satisfactory when prompt diagnosis is established and the thoracic drainage is effective. Repeated postoperative CT scanning and close clinical and laboratory monitoring could make an additional thoracotomy a second-line procedure.

[Respiratory complications after oesophagectomy for cancer]. / Complications respiratoires de l'oesophagectomie pour cancer.

Surgery is the cornerstone of treatment for resectable tumours of the oesophagus. Recent advances of surgical techniques and anaesthesiology have led to a substantial decrease in mortality and morbidity. Respiratory complications affect about 30% of patients after oesophagectomy and 80% of these complications occur within the first five days. Respiratory complications include sputum retention, pneumonia and ARDS. They are the major cause of morbidity and mortality after oesophageal resection and numerous studies have identified the factors associated with these complications. The mechanisms are not very different from those observed after pulmonary resection. Nevertheless, there is an important lack of definition, and evaluation of the incidence is particularly difficult. Furthermore, respiratory complications are related to many factors. Careful medical history, physical examination and pulmonary function testing help to identify the risk factors and provide strategies to reduce the risk of pulmonary complications. Standardized postoperative management and a better understanding of the pathogenesis of pulmonary complications are necessary to reduce hospital mortality. This article discusses preoperative, intraoperative, and postoperative factors affecting respiratory complications and strategies to reduce the incidence of these complications after oesophagectomy.

Impact of blood transfusions on outcome after pneumonectomy for thoracic malignancies.

The aim of the present study was to determine the risk factors and impact on outcome of blood transfusions following pneumonectomy for thoracic malignancies. A retrospective analysis of 432 consecutive patients was carried out, of whom 183 (42.4%) were transfused post-operatively. The associations between blood transfusions and 20 variables were assessed by univariate and multivariate analysis. Survival analysis included log-rank test and Cox regression model. Patient age, neoadjuvant treatment, completion pneumonectomy and extended procedures were independent predictors of transfusion. It was found that 30-day mortality increased significantly from 2.4% (no transfusion) to 10.9 and 21.9% (2 red blood cell packs, respectively). Blood transfusion was the strongest predictor of 30-day mortality (odds ratio (OR) 10; 95% confidence interval (CI): 3.7-27), respiratory failure (OR 19.2; 95% CI 7.4-49.4) and infectious complications (OR 3; 95% CI 1.5-6.2). In the 367 lung cancer patients, a significantly lower 5-yr survival was observed in univariate analysis of transfused patients (27.8+/-5.4% versus 39.4+/-4.5%). In a Cox regression analysis, blood transfusion was no longer found to be significant. A dose-related correlation is suggested between blood transfusion and early mortality through an increase of infectious and respiratory complications. In contrast, blood transfusion had no independent adverse impact on long-term survival.

Effect of small doses of naloxone on the pulsatile secretion of prolactin in the crossbreed ewe during the non-breeding season.

The objective of this work was to study the effect of small doses of naloxone (Nx) on the pulsatile secretion of prolactin (Pr). For this purpose 12 crossbreed ewes were selected and allocated to three groups of four. Group 1 was treated with two injections (at 7 and 19 h) of 40 microg of GnRH. Group 2 was treated with two i.m. injections (at 7 and 19 h) of 0.5mg of naloxone. And the control group 3 was sham treated with injections of 3 ml saline. Blood samples were taken at 20 min intervals during six consecutive hours after injections. When ewes were treated at 7h no significant changes were observed in concentrations of prolactin following treatment with GnRH. Values fluctuated between 200 and 210 ng/ml. In group 2 treated with naloxone there was no change in plasma Pr concentrations during the first 100 min of sampling, however 60 min after Nx treatment Pr decreased significantly (p<0.01) and thereafter Pr plasma levels were consistently less (p<0.001) than control and GnRH treated ewes for the duration of the experiment. The response of the three groups after the second injection (19 h): After the injection of GnRH plasma Pr levels followed much the same pattern observed after the initial treatment, Pr concentrations were similar to those of control ewes. Ewes treated with a second small dose of naloxone (0.5mg i.m.) however, showed a decrease in plasma Pr 60 min after the administration of the endogenous opioid antagonist. Thereafter Nx treated ewes had lesser (p<0.001) plasma Pr levels until the termination of the experiment. It was concluded that Nx an opioid antagonist administered in small intermittent doses can alter Pr plasma concentrations in the ewe, showing that endogenous opioids are important modulators of endocrine function and that the administration of small intermittent doses of opioid antagonists produce significant endocrine changes in ewes.

Inhibition of in vitro gamete adhesion and in vivo fertility in mice by immunization with a synthetic peptide.

PROBLEM: To evaluate the contraceptive ability of a synthetic peptide in in vitro and in vivo fertility in the mouse. METHOD OF STUDY: A synthetic peptide segment: GELRERAPGQGTNG (SP) was used to immunize female B6CF1 (C57BL/6 x BALB/c) mice. A peptide with an amino acid sequence QQPLSIQQHERG (p2control) was used as control. Anti-SP and anti-p2control antisera were used to evaluate sperm function inhibition in vitro. Fertility of immunized mice was determined by microscopic evaluation of the number and state of preimplantation embryos (8-16 cell stage). RESULTS: In the mouse, anti-SP antisera recognized surface antigens in the acrosome region of mature and capacitated sperm. Anti-SP antisera inhibited in vitro sperm binding to zona pellucida. In vivo, immune response against SP in Freund's adjuvant resulted in a significant increase (P < 0.01) in the number of dead embryos and eggs (a mean of 66%, in contrast with < 25% in control mice). Fertility inhibition in vivo and in vitro was not observed when the p2control peptide was used in the immunizations. CONCLUSIONS: These results would suggest that the SP sequence is involved in gamete adhesion, and an antifertility vaccine against the SP peptide segment could be feasible.

Late pulmonary artery stump thrombosis with post embolic pulmonary hypertension after pneumonectomy.

Ten years after right pneumonectomy for primary lung cancer, a 51 year old man developed a pulmonary artery stump thrombosis which produced microemboli in the remaining lung and, in turn, led to chronic pulmonary hypertension. This case strongly suggests that prolonged postoperative thromboembolic prophylaxis should be considered in patients undergoing right pneumonectomy.

[Bronchial fistula postpneumonectomy: predictive factors]. / Fistule bronchiques postpneumonectomies: facteurs prédictifs.

OBJECTIVE: To determine predictive factors of bronchial fistula following pneumonectomy. PATIENTS AND METHODS: In 14 years (1989-2003), we collect 58 cases of bronchial fistula following 725 consecutive pneumonectomy in the service of thoracic surgery of the Sainte Marguerite Hospital in Marseilles. There were 53 cases (91.4%) of cancers and 5 cases (8.6%) of various pathology. The average age of the patients was of 61 +/- 10 years (range 24 to 80 years). The sex ratio M/F was 8.7. The software of regression SPSS (version11.5) was used to identify the factors risk of a bronchial fistula after a univariate and multivariate analysis. RESULTS: The prevalence of the bronchial fistula after a pneumonectomy was 8%.The preoperative factors which increased to a significant degree the incidence of the bronchial dent to the univariate analysis were the chronic smoking (P < 0.001), the existence of COPD (P = 0.001) and of a previous thoracic surgery (P = 0.01). Operational data like a right- side pulmonary resection (P < 0.001), the type of bronchial stup carried out (P = 0.03) as and an extended pneumonectomy to the auricule (P = 0.03) were significant risk factors. With the logistic regression the significant risk factors were the chronic smoking (P = 0.002), the existence of COPD (P = 0.003), a previous pulmonary surgery (P = 0.03) and the right - side of the pneumonectomy (P < 0.001). The indication of the pneumonectomy was retained neither by the univariate analysis, nor by the logistic regression significant risk factors. CONCLUSION: The predictive factors of a bronchial fistula after a pneumonectomy are dominated by respiratory co-morbidities. To prevent this complication, we insist on the stop of the tobacco, a better respiratory preparation and the acquisition of a protocol adapted of the bronchial stub after a pneumonectomy particularly on the right side.