Follow-up of the aortic valve replacement surgery in a national reference hospital in Lima, Peru, period 2016-2019

Objetivo : Describir el seguimiento de los resultados de la cirugía de reemplazo valvular aórtico en un hospital de referencia nacional en Lima Perú, periodo 2016- 2019. Materiales y métodos : Se realizó un estudio retrospectivo de pacientes intervenidos quirúrgicamente de reemplazo valvular aórtico entre 2016 y 2019. Se determinaron las características pre, intra y postoperatorias, así como el seguimiento clínico y ecocardiográfico. Resultados : Se incluyeron 110 pacientes (59,1% varones), la edad media fue de 65,2 ± 11,3 años, la mayoría con hipertensión arterial (47,3%). La etiología más frecuente fue la degenerativa (47,3%). Se implantó prótesis mecánica en el 59,1%. En el postoperatorio se observó una mediana de tiempo de ventilación mecánica de 8 horas, con una estancia media en UCI de 5,8 ± 6,7 días. Las complicaciones más frecuentes fueron atelectasias (21,8%), fibrilación auricular (19,1%), síndrome de bajo gasto, neumonía y daño renal agudo (7,3% cada una). La mortalidad hospitalaria fue del 5,5% (shock cardiogénico como causa frecuente). Durante el seguimiento a un año el 41,2% de pacientes estaban asintomáticos y el 57,7% fueron clasificados como NYHA II, se encontró disfunción de la prótesis en el 13,3% (la mayoría por fuga paravalvular). Conclusiones : La cirugía de reemplazo valvular aórtico en nuestro medio implica una mejora en la calidad de vida con buenos resultados funcionales, tasa de complicaciones y morbimortalidad comparable con la literatura mundial.

Objective : To describe the follow-up of the results of aortic valve replacement surgery in a national reference hospital in Lima, Peru, period 2016-2019. Materials and methods : A retrospective study of patients who underwent aortic valve replacement surgery between 2016 and 2019 was carried out. Pre, intra, and postoperative characteristics were determined, as well as clinical and echocardiographic follow-up. Results :110 patients were included (59.1% male), the mean age was 65.2 ± 11.3 years, the majority with arterial hypertension (47.3%). The most frequent etiology was degenerative (47.3%). A mechanical prosthesis was implanted in 59.1%. In the postoperative period, a median mechanical ventilation time of 8 hours was observed, with an average stay in the ICU of 5.8 ± 6.7 days. The most frequent complications were atelectasis (21.8%), atrial fibrillation (19.1%), low output syndrome, pneumonia, and acute kidney injury (7.3% each). Hospital mortality was 5.5% (cardiogenic shock as the frequent cause). During follow-up at one year, 41.2% of the patients were asymptomatic and 57.7% were classified as NYHA II, prosthesis dysfunction was found in 13.3% (the majority due to paravalvular leak). Conclusions : Aortic valve replacement surgery in our setting implies an improvement in quality of life with good functional results, complication rate, and morbidity and mortality comparable with the world literature.

Clinical grade adjuvants to mature CD141+ DCs for immunotherapy.

Stimulation of dendritic cells (DC) is considered critical in cancer immunotherapy. BATF-3-dependent subsets, that express in humans CD141 (BDCA-3), promote CD8 T-cell cross-priming against tumor antigens. Here, we evaluate two clinical-grade stimuli for peripheral blood CD141+ myeloid dendritic cells (mDCs), a rare DC subset that is currently being explored for use in immunotherapy. In contrast to routine evaluation methods, which focus on predefined maturation markers on the surface or factors released from the activated cells, we applied an unbiased transcriptome-based method using both RNA-sequencing (RNA-seq) and microarrays. Specifically, we analyzed the mRNA of CD141+ mDCs from five human donors upon activation with two clinical-grade adjuvants, Hiltonol (poly-ICLC, a TLR3 ligand) and protamine RNA (pRNA, a TLR7/8 ligand), and compared these samples to unstimulated counterparts. Both methods, RNA-seq, and microarray showed that Hiltonol and pRNA lead to almost identical changes in the transcriptome of CD141+ mDCs. A gene ontology (GO) term analysis suggested that these changes were mainly related to activation and maturation pathways, including induction of type I IFN and IL-12 transcription, while pathways related to adverse effects or cell damage were not strongly affected. The combination of both reagents in the DC cultures gave a very similar result as compared to either stimulus alone, suggesting no synergistic effect. Furthermore, our analysis demonstrates that microarray and RNA-seq analysis gave similar conclusions about the activation status of these cells. Importantly, microarray analyses instead of the advantages of RNA sequencing may still be suitable for studying the activation of rare cell types that are minimally represented or in very low frequency in the organism. Together, our results indicate that both stimuli are potent clinical grade adjuvants with comparable effects to mature CD141+ mDCs in short-term cultures to be used in immunotherapy.

Use of Equine Sperm Cryopreservation Techniques as a Conservation Method of Donkey Germplasm.

The aim of this study was to test equine semen cryopreservation techniques for the conservation of donkey germplasm. Ejaculates of three male donkeys were used (n = 18; six ejaculates per donkey; six repetitions), collected by the artificial vagina method. To remove the seminal plasma, the ejaculates were split and submitted to filtration or centrifugation methods. To assess the freezing method, each fraction was submitted to the automated system or the conventional system, and groups were formed: automated centrifuge, automated filtrate, conventional centrifuge and conventional filtrate. After thawing (37°C/30 seconds), were analyzed the sperm kinetic parameters, integrity and functionality of the plasma membrane and mitochondrial membrane potential. Highest sperm concentration (P < .05) was observed in the filtrate groups; the conventional filtrate group presented lower (P < .05) progressive motility and curvilinear velocity compared to the other groups; no difference was observed (P > .05) among the groups for the membrane integrity and functionality, and mitochondrial membrane potential. Thus, centrifugation is the most indicated technique to remove donkey seminal plasma and the automated and conventional freezing methods can be used in donkey semen conservation.

Cancer Immunology: From Molecular Mechanisms to Therapeutic Opportunities.

The gradual and more profound dissection of the molecular basis of cancer progression, carcinogenesis, and metastatic spread of cancer cells has led to more focused, effective, and targeted therapeutic approaches in the disparate types of solid and hematological tumors, particularly those with high ability to metastasize distant organs [...].

Implication of Interleukin Family in Cancer Pathogenesis and Treatment.

Cytokines are small proteins that are crucial for controlling the growth and activity of blood cells and other cells of the immune system [...].

CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity.

Neutrophils are expanded and abundant in cancer-bearing hosts. Under the influence of CXCR1 and CXCR2 chemokine receptor agonists and other chemotactic factors produced by tumors, neutrophils, and granulocytic myeloid-derived suppressor cells (MDSCs) from cancer patients extrude their neutrophil extracellular traps (NETs). In our hands, CXCR1 and CXCR2 agonists proved to be the major mediators of cancer-promoted NETosis. NETs wrap and coat tumor cells and shield them from cytotoxicity, as mediated by CD8+ T cells and natural killer (NK) cells, by obstructing contact between immune cells and the surrounding target cells. Tumor cells protected from cytotoxicity by NETs underlie successful cancer metastases in mice and the immunotherapeutic synergy of protein arginine deiminase 4 (PAD4) inhibitors, which curtail NETosis with immune checkpoint inhibitors. Intravital microscopy provides evidence of neutrophil NETs interfering cytolytic cytotoxic T lymphocytes (CTLs) and NK cell contacts with tumor cells.

Significance of the IL-8 pathway for immunotherapy.

IL-8 (CXCL-8) is a chemoattractant factor for myeloid leukocytes, that is produced in large quantities by many solid tumors. Levels of IL-8, which can act upon a variety of immune and nonimmune cells, can tell us a lot about tumors, including their size (positive association) and how likely they are to respond to immunotherapy (negative association). This is because the IL-8 produced by tumors can promote angiogenesis, recruit immunosuppressive cells like neutrophils and myeloid-derived suppressor cells (MDSCs), and stimulate epithelial-to-mesenchymal transition, which is a precursor to metastasis. In a pooled analysis of several clinical trials in kidney cancer, melanoma, and lung cancer, it was found that patients with higher baseline concentrations of IL-8 in the blood experienced worse outcomes and lower overall survival after being treated with immunotherapy. Currently, the field that relates IL-8 to immunotherapy is leading to numerous and promising clinical trials that combine the inhibition of IL-8 with existing immunotherapeutic therapies. For this reason, multiple constructs based on IL-8 agonists are being developed clinically by the pharmaceutical and biotech industries.

Influence of Interleukin-8 and Neutrophil Extracellular Trap (NET) Formation in the Tumor Microenvironment: Is There a Pathogenic Role?

In this review, we will highlight several studies that revolve around interleukin-8 (IL-8) and show the multiple facets that could take in the tumor microenvironment. Chemokines that attract neutrophils (to a large extent, IL-8) can have a bimodal behavior inducing the migration of them in the first place and later favoring the formation of NETs in the place of emission focus of the chemokine. Also, this mechanism occurs when neutrophils migrate to tumor cells and where the extrusion of NETs in the tumor is observed. A possible participation of NETs in cancer progression was considered; however, until now, it is difficult to decide if NETosis plays a pro- or antitumor role, although it is necessary to emphasize that there is more experimentation focused on the protumorigenic aspect of the NETs. The formation of NETs has a relevant role in the inhibition of the immune response against the tumor generated by neutrophils and in turn favoring the processes involved in the development of tumor metastasis. It is striking that we do not have more complete information about the effects of circulating chemokines on neutrophils in cancer patients and hence the suitability of this review. No one has observed to date the impact that it could have on other cell populations to inhibit the arrival of neutrophils and the formation/elimination of NETs. However, the extent to which NETs affect the function of other cells of the immune system in the tumor context has not been directly demonstrated. It is necessary to identify possible combinations of immunotherapy that involve the modulation of neutrophil activity with other strategies (immunomodulatory antibodies or adoptive cell therapy). Therefore, knowing the mechanisms by which tumors take advantage of this ability of neutrophils to form NETs is very important in the search for antitumor therapies and thus be able to take advantage of the possible immunotherapeutic combinations that we currently have in clinical practice.

Microbiological, molecular, and histopathological findings in goats experimentally infected with Actinobacillus seminis.

The objective of this study was to experimentally evaluate the pathogenicity of an Actinobacillus seminis isolate named SAAS01 in goats. Animals were challenged with 2 mL of a suspension containing 1,5 × 108 CFU/mL of A. seminis (SAAS01 isolate) through the intrapreputial, epididymis tail, and conjunctival routes. Epididymis and testicular fragments were submitted to histopathological exam, and semen samples underwent microbiological and molecular diagnoses. Clinically, a unilateral increase in firm consistency was observed in the epididymis and testicles of two animals inoculated in epididymis tail and in one animal inoculated through conjunctival sac; this firmness continued until the day of euthanasia. Two goats inoculated through epididymis tail and conjunctival sac routes presented histopathological findings with macroscopically and microscopically significant changes. A. seminis was isolated from semen samples collected from goats inoculated through the epididymis tail and conjunctival sac routes. A. seminis DNA was amplified from six semen samples of three goats inoculated through the epididymis tail, two in conjunctival sac and one through intrapreputial route. The experimental infection model using goats confirmed the pathogenicity of the A. seminis isolate, demonstrating the predilection of the agent for the epididymis, with clinical signs, histopathological lesions, bacterial isolation, and a positive molecular diagnosis.

From Cystostomy to Active Decompression: The Surgeons' Battle Against Odontogenic Cysts.

Odontogenic cysts represent a challenge for oral and maxillofacial surgeons. Treatment options include resective surgery and conservative approaches. The purpose of this paper is to review the history of marsupialization/decompression and other techniques based on similar principles.

A randomized phase II clinical trial of dendritic cell vaccination following complete resection of colon cancer liver metastasis.

Surgically resectable synchronic and metachronic liver metastases of colon cancer have high risk of relapse in spite of standard-of-care neoadjuvant and adjuvant chemotherapy regimens. Dendritic cell vaccines loaded with autologous tumor lysates were tested for their potential to avoid or delay disease relapses (NCT01348256). Patients with surgically amenable liver metastasis of colon adenocarcinoma (n = 19) were included and underwent neoadjuvant chemotherapy, surgery and adjuvant chemotherapy. Fifteen patients with disease-free resection margins were randomized 1:1 to receive two courses of four daily doses of dendritic cell intradermal vaccinations versus observation. The trial had been originally designed to include 56 patients but was curtailed due to budgetary restrictions. Follow-up of the patients indicates a clear tendency to fewer and later relapses in the vaccine arm (median disease free survival -DFS-) 25.26 months, 95% CI 8.74-n.r) versus observation arm (median DFS 9.53 months, 95% CI 5.32-18.88).

Ovary and vaginal epithelium dynamics during the estrous cycle in Dasyprocta prymnolopha Wagler, 1831: ultrasound and cytological examinations.

The objective of the present study was to monitor and characterize morphological alterations in ovaries of agouti (Dasyprocta prymnolopha), reared in captivity, by using abdominal ultrasonography. All animals underwent daily vaginal cytological examination to identify the current cycle phase. For each phase of the estrous cycle, ultrasound examinations were carried out to identify and describe the morphology of both ovaries. Topographic parameters in an ultrasound window were established to locate the ovaries. The agouti estrous cycle lasted an average of 29.94 ± 6.77 days. During vaginal cytology examinations, all cell types were identified, and each phase of the estrous cycle was established by cell counts. No significant alterations were observed in the assessed ovarian morphometry measurements. In 75% of the animals examined, ovarian follicle presence was observed in the proestrus phase.

Interleukin-8 in cancer pathogenesis, treatment and follow-up.

Interleukin-8 (CXCL8) was originally described asa chemokine whose main function is the attraction of a polymorphonuclear inflammatory leukocyte infiltrate acting on CXCR1/2. Recently, it has been found that tumors very frequently coopt the production of this chemokine, which in this malignant context exerts different pro-tumoral functions. Reportedly, these include angiogenesis, survival signaling for cancer stem cells and attraction of myeloid cells endowed with the ability to immunosuppress and locally provide growth factors. Given the fact that in cancer patients IL-8 is mainly produced by tumor cells themselves, its serum concentration has been shown to correlate with tumor burden. Thus, IL-8 serum concentrations have been shown to be useful asa pharmacodynamic biomarker to early detect response to immunotherapy. Finally, because of the roles that IL-8 plays in favoring tumor progression, several therapeutic strategies are being developed to interfere with its functions. Such interventions hold promise, especially for therapeutic combinations in the field of cancer immunotherapy.

Prevalencia de asimetrías mandibulares en radiografías panorámicas de población de Bogotá-Colombia / Mandibular asymmetries prevalence in panoramic radiographies in a Bogotá­ Colombia population

La simetría mandibular es esencial para determinar los patrones no solo de belleza facial sino de función masticatoria; las alteraciones de crecimiento y desarrollo, patologías genéticas, traumáticas o neoplásicas o por características propias de cada población, que afectan a la mandíbula, generan consecuencias que llevan a tratamientos inclusive quirúrgicos para su corrección. El análisis de Thilander en radiografías panorámicas, permite la valoración de la magnitud de las asimetrías mandibulares, como parte de los exámenes complementarios en el proceso diagnóstico. Determinar la frecuencia de asimetrías condilares, de cuerpo y rama mandibular en radiografías panorámicas digitales. Estudio descriptivo de corte transversal en 500 radiografías panorámicas digitales, de adecuado contraste y densidad, obtenidas de pacientes mayores de 18 años de edad, con dentición completa; se registró sexo, edad y mediante el programa CliniView 9.1 se tomaron las medidas mandibulares propuestas por Thilander calculando las diferencias con la fórmula de Bezzur. La prevalencia de asimetrías condilares patológicas en la población mayor de 18 años es del 6 %. Se encontró una diferencia significativa en las medidas verticales entre los dos lados sin que en ellas tenga influencia el género o la edad. Las diferencias en la altura de la rama mandibular se encuentran en la mayoría de los casos a expensas del cóndilo y las discrepancias entre los lados derecho e izquierdo, deben considerarse como elemento diagnóstico en posibles patologías articulares.

The mandibular symmetry is essential to determine the patterns, not only of facial beauty, but also in the masticatory function. The growth and development alterations, genetic pathologies, traumatic, neoplasic or the characteristics of each population, that affect the jaw, generate consequences that may lead to even surgical treatments for correction. Thilander analysis on panoramic x-rays, allows the assessment of the magnitude of mandibular asymmetries, as part of the complementary exams in the diagnostic process. The objective of the study was to determine the frequency of condylar asymmetries in mandibular body and ramus in digital panoramics x-rays. A cross-sectional study was carried out in 500 digital panoramic x-rays with adequate contrast and density, obtained from patients over 18 years of age, with full dentition. Sex and age were registered by 9.1 CliniView program. Proposed mandibular measurements were recorded by Thilander, calculating the differences with the Bazzur's formula. The prevalence of pathological condylar asymmetries in the population over 18 years is 6 %. A significant difference was found in the vertical measurements between the two sides, though there was no influence by either sex or age. The differences in the height of the mandibular ramus are, in most cases, at the expense of the condyle. The discrepancies between the left and right sides must be considered as diagnostic element in possible articular pathologies.

Behavior Knowledge Space-Based Fusion for Copy-Move Forgery Detection.

The detection of copy-move image tampering is of paramount importance nowadays, mainly due to its potential use for misleading the opinion forming process of the general public. In this paper, we go beyond traditional forgery detectors and aim at combining different properties of copy-move detection approaches by modeling the problem on a multiscale behavior knowledge space, which encodes the output combinations of different techniques as a priori probabilities considering multiple scales of the training data. Afterward, the conditional probabilities missing entries are properly estimated through generative models applied on the existing training data. Finally, we propose different techniques that exploit the multi-directionality of the data to generate the final outcome detection map in a machine learning decision-making fashion. Experimental results on complex data sets, comparing the proposed techniques with a gamut of copy-move detection approaches and other fusion methodologies in the literature, show the effectiveness of the proposed method and its suitability for real-world applications.

Tumor-Produced Interleukin-8 Attracts Human Myeloid-Derived Suppressor Cells and Elicits Extrusion of Neutrophil Extracellular Traps (NETs).

PURPOSE: Myeloid-derived suppressor cells (MDSC) are considered an important T-cell immunosuppressive component in cancer-bearing hosts. The factors that attract these cells to the tumor microenvironment are poorly understood. IL8 (CXCL8) is a potent chemotactic factor for neutrophils and monocytes. EXPERIMENTAL DESIGN: MDSC were characterized and sorted by multicolor flow cytometry on ficoll-gradient isolated blood leucokytes from healthy volunteers (n = 10) and advanced cancer patients (n = 28). In chemotaxis assays, sorted granulocytic and monocytic MDSC were tested in response to recombinant IL8, IL8 derived from cancer cell lines, and patient sera. Neutrophil extracellular traps (NETs) formation was assessed by confocal microscopy, fluorimetry, and time-lapse fluorescence confocal microscopy on short-term MDSC cultures. RESULTS: IL8 chemoattracts both granulocytic (GrMDSC) and monocytic (MoMDSC) human MDSC. Monocytic but not granulocytic MDSC exerted a suppressor activity on the proliferation of autologous T cells isolated from the circulation of cancer patients. IL8 did not modify the T-cell suppressor activity of human MDSC. However, IL8 induced the formation of NETs in the GrMDSC subset. CONCLUSIONS: IL8 derived from tumors contributes to the chemotactic recruitment of MDSC and to their functional control. Clin Cancer Res; 22(15); 3924-36. ©2016 AACR.

Terapia de laser de baja potencia en mucositis oral / Low-power laser therapy in oral mucositis

La mucositis oral es una complicación frecuente del tratamiento antineoplásico, producto de efectos citotóxicos por la quimioterapia y radioterapia de cabeza y cuello, dependiendo de su severidad puede dificultar el habla, la deglución y predispone al paciente a deficiencias nutricionales, infecciones secundarias, sepsis grave, provocando alta morbilidad del paciente. La mayoría de investigadores concluyen que la terapia Laser de baja potencia es una alternativa de primera elección para la prevención y tratamiento de mucositis oral, comprobado en diversos estudios que estimula la producción de colágeno, elastina , proteoglicanos, la revascularización, entre otras propiedades que aceleran el proceso de cicatrización, además del efecto antiinflamatorio por inhibición de la COX- 2 así como no presentar efectos colaterales significativos, técnica atraumática y de costo bajo...

Oral mucositis is a common complication of cancer treatment, due to cytotoxic effects of chemotherapy and radiotherapy for head and neck, depending on its severity may hinder speech, swallowing and predisposes the patient to nutritional deficiencies, secondary infections, severe sepsis, causing high morbidity of the patient. Most researchers conclude that low-power laser therapy is an alternative of choice for the prevention and treatment of oral mucositis, proven in several studies that stimulates production of collagen, elastin, proteoglycans, revascularization, among other properties that accelerate the healing process, besides the anti-inflammatory effect by inhibiting COX-2 and not present significant side effects, atraumatic and inexpensive...

Functional expression of CD137 (4-1BB) on T helper follicular cells.

CD137 (4-1BB) is a surface protein initially discovered to mark activated T lymphocytes. However, its broader expression pattern also encompasses activated NK cells, B cells and myeloid cells, including mature dendritic cells. In this study, we have immunostained for CD137 on paraffin-embedded lymphoid tissues including tonsils, lymph nodes, ectopic tertiary lymphoid tissue in Hashimoto thyroiditis and cancer. Surprisingly, immunostaining mainly decorated intrafollicular lymphocytes in the tissues analyzed, with only scattered staining in interfollicular areas. Moreover, pathologic lymphoid follicles in follicular lymphoma and tertiary lymphoid tissue associated with non-small cell lung cancer showed a similar pattern of immunostaining. Multispectral fluorescence cytometry demonstrated that CD137 expression was restricted to CD4+ CXCR5+ follicular T helper lymphocytes (TFH cells) in tonsils and lymph nodes. Short-term culture of lymph node cell suspensions in the presence of either an agonistic anti-CD137 monoclonal antibody (mAb) or CD137-ligand stimulated the functional upregulation of TFH cells in 3 out of 6 cases, as indicated by CD40L surface expression and cytokine production. As a consequence, immunostimulatory monoclonal antibodies targeting CD137 (such as urelumab and PF-05082566) should be expected to primarily act on this lymphocyte subset, thus modifying ongoing humoral immune responses in patients with autoimmune disease and cancer.

Nivolumab and Urelumab Enhance Antitumor Activity of Human T Lymphocytes Engrafted in Rag2-/-IL2Rγnull Immunodeficient Mice.

A current pressing need in cancer immunology is the development of preclinical model systems that are immunocompetent for the study of human tumors. Here, we report the development of a humanized murine model that can be used to analyze the pharmacodynamics and antitumor properties of immunostimulatory monoclonal antibodies (mAb) in settings where the receptors targeted by the mAbs are expressed. Human lymphocytes transferred into immunodeficient mice underwent activation and redistribution to murine organs, where they exhibited cell-surface expression of hCD137 and hPD-1. Systemic lymphocyte infiltrations resulted in a lethal CD4(+) T cell-mediated disease (xenograft-versus-host disease), which was aggravated when murine subjects were administered clinical-grade anti-hCD137 (urelumab) and anti-hPD-1 (nivolumab). In mice engrafted with human colorectal HT-29 carcinoma cells and allogeneic human peripheral blood mononuclear cells (PBMC), or with a patient-derived gastric carcinoma and PBMCs from the same patient, we found that coadministration of urelumab and nivolumab was sufficient to significantly slow tumor growth. Correlated with this result were increased numbers of activated human T lymphocytes producing IFNγ and decreased numbers of human regulatory T lymphocytes in the tumor xenografts, possibly explaining the efficacy of the therapeutic regimen. Our results offer a proof of concept for the use of humanized mouse models for surrogate efficacy and histology investigations of immune checkpoint drugs and their combinations.