Vaccination with a shared oncogenic tumor-self antigen elicits a population of CD8+ T cells with a regulatory phenotype.

Cancer immunotherapy is a powerful tool for inducing antigen-specific antitumor cytotoxic T lymphocytes (CTLs). Next-generation strategies may include vaccination against overexpressed oncogenic tumor-self antigens. Previously, we reported vaccination against the oncogenic tumor-self antigen D52 (D52) was effective in preventing tumor growth. We recently reported that D52-vaccinated IL-10-deficient mice generated a significant memory response against tumor recurrence compared to wild-type mice and that vaccine-induced CD8+ IL-10+ T cells may possess regulatory function. Herein, we extended these studies by testing the hypothesis that D52-vaccine-elicited CD8+ IL-10+ T cells represent a distinct T cell population with a regulatory phenotype. C57Black/6J mice deficient in IL-10 or IFN-γ were vaccinated with the murine orthologue of D52; vaccination of wild-type (wt) mice served as a control for comparison. T cells were isolated from all three groups of vaccinated mice, and RNA was extracted from purified CD8+ T cells for deep sequencing and expression analysis. Chemokine receptor 8 (CCR8) and inducible co-stimulator (ICOS) were overexpressed in CD8+ T cells that produced IL-10 but not IFN-γ. These surface markers are associated with IL-10 producing CD4+ T regulatory cells thus supporting the possibility that CD8+ IL-10+ T cells elicited by D52 vaccination represent a unique regulatory T cell subset. The current phenotypic analyses of D52 vaccine elicited CD8+ T cells strengthen our premise that CD8+ IL-10+ T cells elicited by D52 tumor-self protein vaccination likely contribute to the suppression of memory CTL responses and inhibition of durable tumor immunity.

Immediate changes in intra-abdominal pressure and lung indicators in patients undergoing complex ventral hernia repair with the transversus abdominis muscle release, with and without preoperative botulinum toxin.

PURPOSE: The current treatment of complex ventral hernias involves muscle closure with components separation techniques and mesh placement. The purpose of this study is to evaluate the immediate postoperative changes in the intra-abdominal pressure (IAP), and lung indicators after treatment of complex ventral hernias with the transversus abdominis reléase (TAR) technique. METHODS: All patients with complex ventral hernias treated between November 28th, 2016 and October 6th, 2021 were initially included. We excluded patients with lung and/or heart comorbidities. A total of 43 patients were studied, measuring IAP, lung compliance, pulmonary plateau pressure (PPP), and end-tidal CO2 before and after surgical treatment. RESULTS: Median IAP increased from 5 to 9 mmHg (p < 0.0001), and PPP from 11 to 12 mmHg (p = 0.004). Increased body mass index (BMI) was associated to a PPP increase above normal values. Postoperative changes were not different in patients receiving preoperative preparation with botulinum toxin. CONCLUSION: After complex ventral hernia closure, there is an immediate impact on IAP and PPP, the latter more frequent in patients with the highest BMI, and this may not be prevented by the preoperative administration of botulinum toxin.

Survival and functionality in the elderly over 85 years of age with hip fracture. / Supervivencia y funcionalidad en ancianos mayores de 85 años con fractura de cadera.

BACKGROUND: There is a tendency for the aging population to fracture their hips. Our aim was to compare survival and functionality at one year, among elderly and very elderly patients with hip fracture. MATERIAL AND METHODS: A prospective cohort of patients included in the Institutional Registry of Elderly Patients with Hip Fracture between 2014 and 2017. We classified patients as elderly patients (EP) <65 and <85 years and very elderly patients (VEP) ≥85 years. RESULTS: We included 952 patients, 43% were EP and 57% were VEP. The proportion of women was 84% and 86% (P=.33) and with 2 or more points in the Charlson comorbidities index (28 and 31%, P= .36), respectively. The VEP were more dependent according to the Barthel score (34% and 62%, P<.01) and frailer according to the Edmonton score (30% and 61%, P<.01). One-year survival was 91% (95% CI 86-93) in the EP and 76% (95% CI 70-89) in the VEP. In-hospital complications were more frequent in the VEP 12% (7% in the EP, P<.01). Age is an independent risk factor for one-year survival (HR 2.11; 95% CI 1.36-3.29, P<.001). CONCLUSIONS: Age is a risk factor for the VEP group survival despite fragility and comorbidities. Because of their vulnerability, an appropriate care plan should be considered for VEP.

Analysis of the CD8+ IL-10+ T cell response elicited by vaccination with the oncogenic tumor-self protein D52.

Development of cancer vaccines targeting tumor self-antigens is complex and challenging due to the difficulty of overcoming immune tolerance to self-proteins. Vaccination against tumor self-protein D52 (D52) has been successful, although complete protection appears impaired by immune regulation. Our previous studies suggest that vaccine elicited CD8 + T cells producing interleukin 10 (IL-10) may have a negative impact on tumor protection. Understanding the role CD8+ IL-10 + T cells play in the immune response following vaccination with D52 could result in a more potent vaccine. To address this, we vaccinated IL-10 deficient mice with the murine orthologue of D52; vaccination of wild type (wt) C57BL/6J served as a control for comparison. In separate experiments, D52 vaccinated wt mice were administered IL-10R-specific mAb to neutralize IL-10 function. Interestingly, we observed similar protection against primary tumor challenge in the experimental groups compared to the controls. However, individual IL-10 deficient mice that rejected the primary tumor challenge were re-challenged 140 days post-primary challenge to access vaccine durability and immunologic memory against tumor recurrence. Mice deficient in IL-10 demonstrated a memory response in which 100% of the mice were protected from secondary tumor challenge, while wt mice had diminished recall response (25%) against tumor recurrence. These results with analysis of vaccine-elicited CD8 + T cells for tumor-specific killing and regulatory cell marker expression, add further support to our premise that CD8+ IL-10 + T cells elicited by D52 tumor-self protein vaccine contribute to the suppression of a memory CTL responses and durable tumor immunity.

Factores asociados a recidiva de hernia de disco lumbar luego de una microdiscectomía / Factors associated with lumbar disc hernia recurrence after microdiscectomy

Introducción. Las hernias de disco lumbares son una causa frecuente de cirugía lumbar. La recurrencia herniaria es una complicación prevalente. Objetivo. Analizar los factores de riesgo asociados a recurrencia herniaria en pacientes intervenidos por hernia discal lumbar en nuestra institución. Materiales y métodos. Se analizaron en forma retrospectiva una serie de 177 microdiscectomías lumbares entre 2010 y 2014; se excluyeron pacientes con cirugías previas, hernias foraminales y extraforaminales. Los pacientes con recurrencia herniaria constituyeron el grupo de casos y los que no presentaron recurrencia fueron el grupo control; se analizó: sexo, edad, índice de masa corporal, nivel, degeneración facetaria, altura discal y protrusión discal. Resultados. Hubo 177 pacientes con microdiscectomía lumbar, de los cuales 30 (16%) presentaron recurrencia herniaria; de ellos, 27 fueron reoperados. Entre los factores de riesgo asociados a recurrencia observamos mayor índice de altura discal, mayor porcentaje de canal ocupado por la hernia y mayor presencia de cambios degenerativos facetarios; no observamos diferencias en cuanto al sexo, índice de masa corporal y edad. Discusión. Estudios previos muestran el aumento de altura discal y pacientes jóvenes como posibles factores asociados a recidiva. Conclusión. En nuestra serie encontramos que el mayor índice de altura discal, el porcentaje de canal ocupado por la hernia y los cambios degenerativos facetarios se asociaron a recurrencia herniaria (AU)

Introduction. Lumbar disc hernias are a common cause of spinal surgery. Hernia recurrence is a prevalent complication. Objective. To analyse the risk factors associated with hernia recurrence in patients undergoing surgery in our institution. Materials and methods. Lumbar microdiscectomies between 2010 and 2014 were analysed, patients with previous surgeries, extraforaminales and foraminal hernias were excluded. Patients with recurrent hernia were the case group and those who showed no recurrence were the control group. Results. 177 patients with lumbar microdiscectomy, of whom 30 experienced recurrence (16%), and of these 27 were reoperated. Among the risk factors associated with recurrence, we observed a higher rate of disc height, higher percentage of spinal canal occupied by the hernia and presence of degenerative facet joint changes; we observed no differences in sex, body mass index or age. Discussion. Previous studies show increased disc height and young patients as possible factors associated with recurrence. Conclusion. In our series we found that the higher rate of disc height, the percentage of spinal canal occupied by the hernia and degenerative facet joint changes were associated with hernia recurrence (AU)

Factors associated with lumbar disc hernia recurrence after microdiscectomy. / Factores asociados a recidiva de hernia de disco lumbar luego de una microdiscectomía.

INTRODUCTION: Lumbar disc hernias are a common cause of spinal surgery. Hernia recurrence is a prevalent complication. OBJECTIVE: To analyse the risk factors associated with hernia recurrence in patients undergoing surgery in our institution. MATERIALS AND METHODS: Lumbar microdiscectomies between 2010 and 2014 were analysed, patients with previous surgeries, extraforaminales and foraminal hernias were excluded. Patients with recurrent hernia were the case group and those who showed no recurrence were the control group. RESULTS: 177 patients with lumbar microdiscectomy, of whom 30 experienced recurrence (16%), and of these 27 were reoperated. Among the risk factors associated with recurrence, we observed a higher rate of disc height, higher percentage of spinal canal occupied by the hernia and presence of degenerative facet joint changes; we observed no differences in sex, body mass index or age. DISCUSSION: Previous studies show increased disc height and young patients as possible factors associated with recurrence. CONCLUSION: In our series we found that the higher rate of disc height, the percentage of spinal canal occupied by the hernia and degenerative facet joint changes were associated with hernia recurrence.

Central nervous system manganese induced lesions and clinical consequences in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: Around 47-74% of patients with hereditary hemorrhagic telangiectasia (HHT) have hepatic vascular malformations (HVMs); magnetic resonance images (MRI) of the central nervous system (CNS) might show in T1 sequences a hyper-intensity signal in different areas, mainly in the basal ganglia (BG) as consequence of manganese (Mn) deposits as observed in cirrhotic patients. These patients might suffer from different neuropsychiatric disorders (hepatic encephalopathy). In HHT patients, even in the presence of hepatic shunts, hepatocellular function is usually preserved. Additionally, Mn shares iron absorption mechanisms, transferrin and CNS transferrin receptors. In iron deficiency conditions, the Mn may harbor transferrin and access BG. The objectives were to describe frequency of BG Mn deposit-induced lesions (BGMnIL) in HHT patients, its relationship with iron deficiency anemia (IDA) and HVMs. Finally, explore the association between neuropsychological and motor consequences. We performed a cross-sectional study. We determined HHT patients with or without BG-MnIL by the MRI screening of the CNS. We included all patients with lesions and a random sample of those without lesions. All patients underwent standardized and validated neuropsychological assessment to evaluate BG actions. Results were analyzed with multiple logistic regression, adjusting for potential confounders. RESULTS: Among 307 participants from a cohort included in the Institutional HHT Registry, 179 patients had MRI performed and Curaçao Criteria ≥3. The prevalence of BG-MnIL was 34.6% (95%CI 27.69-42.09). While neuropsychological symptoms were present in all patients, BG-MnIL patients performed poorly in three of the neuropsychological tests (serial dotting, line tracing time, number connection test A). HVMs frequency in BG-MnIL was 95.1%, versus 71.4% in those without lesions (p < 0.001). IDA frequency was 90.3% versus 54% (p < 0.001). When IDA is present, estimated risk for BG-MnIL is remarkably high (OR 7.73, 95%CI 2.23-26.73). After adjustment for possible confounders (gender, age, presence of HVMs), IDA was still associated with increased risk of BG-MnIL (adjusted OR 6.32, 95% CI 2.32-17.20; p < 0.001). CONCLUSIONS: Physicians should assess BG-MnIL in HHT patients in CNS-MRI. IDA and HVMs present increased risk of lesions. Patients with BG-MnIL have neuropsychological impairment, and they might benefit from sparing IDA, or undergoing future therapeutic options. TRIAL REGISTRATION: NCT01761981 . Registered January 3rd 2013.

EPIDEMIOLOGÍA DE ANAFILAXIA EN UN SISTEMA DE SALUD PREPAGO DE LA CIUDAD DE BUENOS AIRES, ARGENTINA / Epidemiology of anaphylaxis in a medical care program in Buenos Aires, Argentina

Fundamentos. Anafilaxia es una reacción alérgica seria y que puede causar la muerte. Existen pocos datos sobre la incidencia y las características de anafilaxia en Argentina. Objetivos. Estimar la incidencia de anafilaxia en un sistema de salud prepago de la Ciudad de Buenos Aires. Describir el conocimiento de los pacientes con diagnóstico de anafilaxia sobre medidas de prevención y tratamiento. Marco de referencia. Hospital Italiano de la Ciudad de Buenos Aires, Argentina. Diseño. Cohorte retrospectiva Población. Padrón del Hospital Italiano de Buenos Aires con diagnóstico de anafilaxia desde enero de 2006 a abril de 2014. Método. Se revisaron las historias clínicas electrónicas de 211 pacientes. La evaluación comprendió tanto el ámbito ambulatorio como internación y central de emergencias. Se realizó una encuesta telefónica para conocer el comportamiento y conocimiento de los pacientes que presentaron un episodio de anafilaxia. Se utilizó el software estadístico SPSS 19.0. Resultados. La densidad de incidencia calculada por cada 100.000 personasaño fue de 9,03 (IC95%: 7,53-10,84) para todas las causas de anafilaxia. Las causas más comunes reportadas fueron medicamentos 49,5% y alimentos 19,79%. El 63,4% no recibió prescripción de adrenalina autoinyectable, sólo el 30,9% tienen un plan de acción ante un nuevo evento. Conclusión. La anafilaxia es un problema de salud importante y común. Este estudio demuestra posibles deficiencias en la atención de los episodios de anafilaxia, no sólo en el tratamiento de episodios pasados, sino también por la falta de preparación adecuada para futuros episodios. (AU)

Background. Anaphylaxis is a serious allergic reaction that can cause death. There are few data of the incidence and characteristics of anaphylaxis in the population of Argentina. Objectives. estimate the incidence of anaphylaxis in medical care program of Buenos Aires city. Describe the knowledge of patients with diagnosis of anaphylaxis about prevention and treatment. Setting. Italian Hospital of Buenos Aires, Argentina. Design. Retrospective cohort. Population. Census of the Italian Hospital of Buenos Aires with a diagnosis of anaphylaxis in electronic health records from January 2006 to April 2014. Method. Electronic medical records of 211 patients were reviewed, the evaluation included both inpatient and outpatient setting and emergency center. A telephone survey was conducted to understand the behavior and knowledge of the patients who had an episode of anaphylaxis. SPSS 19.0 statistical software was used. Results. The density of incidence calculated per 100,000 person-years was 9.03 (95% CI: 7.53-10.84) for all causes of anaphylaxis. The most commonly reported causes were drugs 49.5% and food 19.79%. The 63.4% of patients had never received the prescription of self-injectable epinephrine; only 30.9% have a plan of action before a new event. Conclusion. Anaphylaxis is an important and common health problem. This study demonstrates the potential gaps in care episodes of anaphylaxis, not only in the treatment of past episodes, also by the lack of adequate preparation for future episodes(AU)

Vigilancia y control de la infección asociada a endoscopios / Surveillance and control of infection associated with endoscopes

Las técnicas endoscópicas han experimentado un desarrollo muy importante tanto en el campo de la cirugía como en el de la medicina, por lo que la posibilidad de desarrollar una infección nosocomial tras la realización de éstas técnicas debe tomarse en consideración. Sobre la base de la epidemiología de estos procesos se detallan las actuaciones a realizar para la prevención, diagnóstico y control de la infección nosocomial asociada a la realización de técnicas endoscópicas, tanto generales ( profilaxis antibiótica, desinfección de alto nivel, etc.) como específicas en razón de las distintas localizaciones y/o técnicas utilizadas (AU)

A case of amiodarone and neuromyopathy.

Amiodarone is a drug broadly used on cardiac arrhythmias despite its multiple side-effects. We present the case of an adult male with symptomatic ventricular tachycardia, receiving longterm amiodarone, who showed increased CK serum levels, sensorimotor neuropathy and secondary myopathy. Quadriceps biopsy showed atrophic changes and sural nerve intralysosomal deposits with intense axonal degeneration. The case illustrates the need to investigate and monitor peripheral neuropathy and muscular atrophy in chronic amiodarone use.

Utilidad de la tinción de la hemosiderina y la determinación de ferremia en el diagnóstico de las anemias / Utility of hemosiderin tinction and blood iron determination in Anaemia diagnosis

En este trabajo realizado con el material de 100 casos, se evalúa la relación entre la determinación de hierro sérico, la hemosiderina tisular y el conteo de sideroblastos. Los resultados permiten demostrar que cuando la CFFeS está elevada, el 91%de los casos tiene sideroblastos ausentes o bajos. El hierro en el eritroblasto se halla normalmente entre un 28 - 81%. Se puede así, conjungándolos, definir diagnósticos de deficiencia de hierro, anemia de enfermedad crónica, disponibilidad inadecuada del hierro para la eritropoyesis, bloqueo del paso de hierro tisular al glóbulo rojo y sobrecargas de hierro, encontrándose entre ellos dependencia estadística. Se proponen distintos patrones que pueden derivarse del análisis de estas determinaciones, cuando se realizan simultáneamente

Estudio sobre la leucemia mieloide crónica Hospital San Juan de Dios / Study on the chronic myeloid leukemia. Hospital San Juan de Dios

Se presentan 35 casos de leucemia mielocítica crónica (LMCC), estudiados en el Servicio de Hematología del Hospital San Juan de Dios, en un período de 5 años. El análisis del material permite señalar que en el grupo estudiado la mediana de sobrevida de LMC fue de 1,8 años, condición que precisa mejorar con otras condiciones terapéuticas como son la utilización de interferón y el transplante medular. No hay pacientes que hayan sobrevivido más de 8 años. Una vez desarrollada la fase blástica la sobrevida no fue mayor a los 4,13 meses. Se indica la importancia de la detección precoz de esta complicación por medio del análisis citogenético. (Rev. Cost. Cienc. Méd. 1988; 9(4): 19-23)

Impact of preceptor counseling on medical resident prescription writing.

A collaborative study was conducted by pharmacists and the clinical preceptor of the otolaryngology outpatient clinic of the University of Texas Medical Branch (UTMB). This study focused on decreasing the percent of legal or procedural errors made by resident physicians. During the study period all prescriptions written by house staff were reviewed by a pharmacist for compliance to previously established criteria. Noncompliant prescriptions were photocopied by the pharmacist and recorded for review by the resident's clinical preceptor. After an 8-week period of baseline data collection, residents were counseled privately by the clinical preceptor and critique on their ability to write a legally and procedurally correct prescription. The residents were made aware of their major deficiencies to enable them to correct the problems. During an unannounced 4-week period, beginning 5 months after preceptor consultation, resident prescription writing was again audited. The result, an overall decrease of 78.5% in noncompliant prescriptions, illustrates that establishing lines of communication between pharmacists and physicians can demonstrably improve health care services. If this change in the quality of prescription writing could be achieved in all of the institution's ambulatory care clinics, an annual conservation of at least $57,000 in pharmacist salaries would be realized.