Diagnostic potential of exosomal extracellular vesicles in oncology.

Liquid biopsy can detect circulating cancer cells or tumor cell-derived DNA at various stages of cancer. The fluid from these biopsies contains extracellular vesicles (EVs), such as apoptotic bodies, microvesicles, exomeres, and exosomes. Exosomes contain proteins and nucleic acids (DNA/RNA) that can modify the microenvironment and promote cancer progression, playing significant roles in cancer pathology. Clinically, the proteins and nucleic acids within the exosomes from liquid biopsies can be biomarkers for the detection and prognosis of cancer. We review EVs protein and miRNA biomarkers identified for select cancers, specifically melanoma, glioma, breast, pancreatic, hepatic, cervical, prostate colon, and some hematological malignancies. Overall, this review demonstrates that EV biomolecules have great potential to expand the diagnostic and prognostic biomarkers used in Oncology; ultimately, EVs could lead to earlier detection and novel therapeutic targets. Clinical implicationsEVs represent a new paradigm in cancer diagnostics and therapeutics. The potential use of exosomal contents as biomarkers for diagnostic and prognostic indicators may facilitate cancer management. Non-invasive liquid biopsy is helpful, especially when the tumor is difficult to reach, such as in pancreatic adenocarcinoma. Moreover, another advantage of using minimally invasive liquid biopsy is that monitoring becomes more manageable. Identifying tumor-derived exosomal proteins and microRNAs would allow a more personalized approach to detecting cancer and improving treatment.

[Involvement of medical students in research. Facilitators and constraints]. / Investigación en pregrado de las escuelas de Medicina de Chile: percepción sobre facilitadores y limitantes entre los asistentes al III Congreso Chileno de Estudiantes de Medicina (CoCEM).

BACKGROUND: Scientific research is fundamental to the education of medical students. However, their involvement in research is limited. AIM: To describe the perceptions of medical students about facilitators and constraints to perform undergraduate research. MATERIAL AND METHODS: Medical students attending the Chilean Congress of Medical Students in the Metropolitan Region in 2018, were surveyed. The responses obtained were subjected to a qualitative content analysis and were grouped according to perceptions of facilitators and constraints. RESULTS: The main facilitators reported were linkage with research teachers, personal motivation towards research, and research-oriented curriculum. The main constraints were lack of time for research, lack of access to formal information channels to engage in research, and sub-optimal conditions for research. CONCLUSIONS: The main factor promoting research at the undergraduate level was the link with the teacher, mainly through informal channels. The lack of official information provided through formal instances and lack of time hampers the access to research.

[Participation of Chilean undergraduate medical students in scientific research]. / Investigación en pregrado de las escuelas de medicina de Chile: Motivación y participación de estudiantes de medicina asistentes al Congreso Chileno de Estudiantes de Medicina (COCEM).

BACKGROUND: The participation of medical students in research generates professional, scientific, and personal benefits for the student. AIM: To evaluate the interest and opportunities for medical students in Chile to participate in scientific research and their perceptions about factors influencing research. MATERIAL AND METHODS: All students attending the 2018 Chilean Congress for Medical Students were invited to answer a 44 questions survey about interest and opportunities to participate in research. RESULTS: The survey was answered by 489 of the 538 students attending the congress. Eighty five percent referred interest in conducting scientific research, but only 47% had the opportunity to actively participate in a research project. The main research area providing opportunities was epidemiology and the main form to access a research project was through direct contact with a medical professor or researcher. Seventy seven percent of respondents had courses of scientific investigation in their medical curriculum and 92% had a scientific society for medical students in their university. CONCLUSIONS: Respondents showed a great deal of interest in participating in scientific research. However, there is a gap between this interest and the available opportunities. Medical professors should promote and facilitate the participation of their students in research.

Risk Factors for HIV Acquisition in Urban Latinos and Implications for Prevention.

The risk of HIV in the Latino population in the United States is increasing. This population has a disproportionate number of new HIV cases, with the largest burden in the seventeen southern states. The purpose of this study is to assess risk factors for HIV among HIV-positive Latinos in care in New Orleans, Louisiana, through a retrospective chart review. The Chi square test of proportions, Student's t-test, and Wilcox rank sum test were used to test differences by sex and immigration status. Men were more likely to be incarcerated, use drugs, and drink alcohol. Undocumented Latinos were younger and had increased language barriers. Legally documented participants were more likely to use drugs, have a psychiatric diagnosis, and syphilis. Understanding the complex risk factors that surround HIV in the Latino population is useful for the development of effective and comprehensive prevention programs.

Pancreatic hemolymphangioma.

CONTEXT: Hemolymphangioma of pancreas is a tumor has its origins on vascular and lymphatic vessels malformation. At this time, only eight cases have been reported (PubMed). CASE REPORT: A 52-year-old woman with history of abdominal pain and early satiety was admitted to our external consultation. Laboratory data were normal. CT initially showed a high vascularized solid tumor, apparently arising from the right hepatic lobe, and it was considered to be a hemangioma. Two sessions of CT guided embolizations were performed. Control CT scan revealed a reduction in tumor´s size and location confined to pancreatic head. With this diagnosis studies and suspicion of neoplastic tumor, it was performed a pylorus preserving pancreatoduodenectomy. Pathology report was to be a pancreatic head hemolymphangioma. CONCLUSION: Diagnosis and management of cystic pancreatic tumors can be challenging. Cystectomy or even surgical procedures as pancreatoduodenectomy should be performed when is possible. We report a case of pancreatic hemolymphangioma, a benign cystic tumor with a rare incidence.

Evaluating the Integration of Patient Safety in Medical Training in Spain.

Objectives: The aim of this study was to determine the degree of integration of patient safety in the training of medical faculties at universities in Spain. Methods: A descriptive, cross-sectional study was conducted. An assessment was made of the curse syllabi of Spanish medical schools, summarizing the proportion of faculties that present each of the topics recommended in the WHO's curriculum guide. Results: Of the 49 faculties, access to the curse syllabus of the subjects for the academic year 2023-2024 was obtained from 38 (78%). Although 82% of the faculties integrated some patient safety topic, only 56% included between 1 and 3 of the 11 topics recommended by WHO. The maximum number of integrated topics was 7, and this was only achieved by 1 faculty. Conclusion: There is progress in the incorporation of fundamental concepts in patient safety, but the comprehensive implementation of all topics recommended by the WHO in Spanish medical schools is insufficient.

Cystocerebral Syndrome in a Patient with Altered Mental Status.

BACKGROUND Cystocerebral syndrome is delirium occurring in the elderly that results from urinary retention and acute bladder distension. Urinary retention can cause cerebral issues, such as altered mental status, without having an infection present. The pathophysiology is possibly due to increased catecholamine secretion while attempting to micturate. Due to its presenting symptoms, most physicians begin cerebrovascular workup, performing unnecessary and, often, invasive imaging studies. Although easily overlooked as a differential diagnosis, cystocerebral syndrome is an easily treatable cause of delirium and should be considered during treatment of elderly patients with delirium. CASE REPORT The patient was an 89-year-old man with a medical history of chronic obstructive airway disease, dementia, hypertensive disorder, and gastroesophageal reflux disease who presented with altered mental status secondary to urinary incontinence. The computed tomography scan without contrast showed a large volume of impacted stool in the cecum, with a distended urinary bladder. This case report describes his presentation, medical treatment, and outcome and discusses areas of gap improvement. CONCLUSIONS To date, there are only a handful of published articles on cystocerebral syndrome. This case report aims to add the awareness of bladder distention as an etiology of cystocerebral syndrome to the body of knowledge in the scientific community in the hope that patients will be identified and treated earlier, more safely, and at a reduced cost. Cystocerebral syndrome needs to be extensively addressed in research, and physicians should consider it one of the important differential diagnoses of delirium among elderly men.

An analysis of chronic kidney disease risk factors in a Louisiana nursing home population: a cross-sectional study.

BACKGROUND: Chronic Kidney Disease (CKD) and its progression are associated with multiple risk factors. CKD is prevalent in nursing homes residents, but factors related to CKD in this setting have not been defined. METHODS: A cross-sectional study was conducted (n=103). Data was abstracted using standardized forms and analyzed (SAS 9.2). Chi square and t-test statistics were used to compare proportions and means; correlation coefficients were used to describe associations. Logistic models were fit to the data to determine multivariate associations. Modification of Diet in Renal Disease (MDRD) formula was used to estimate GFR. CKD was defined according to established standards. A cutoff point of 60 was chosen for further analysis. RESULTS: Twenty-three percent of subjects had CKD. Mean age for eGFR <60 was 70.8 +/- 13 and for eGFR >60 was 61.7 +/-14. Frequent co-morbidities were hypertension (75%), GERD (40%), obesity (39%), dyslipidemia (35%), depression (34%), anemia (32%), and diabetes (32%). CONCLUSIONS: Our population is unique in terms of its age and reasons for nursing home admission. Factors associated with CKD in our study include age >65 years old, being male, having a positive history of cardiovascular disease (including congestive heart failure and coronary artery disease,) anemia, polypharmacy, and being obese (BMI >30). Further analysis showed that age and anemia are the strongest factors associated with CKD in our population. Management targeted at CKD risk factor reduction may play a vital role in controlling the magnitude of this disease. Prospective studies to investigate the relationship between gender, a BMI greater than 30, cardiovascular disease, and CKD and its complications are warranted.

Excerno: Using Mutational Signatures in Sequencing Data to Filter False Variants Caused by Clinical Archival.

The accurate detection of point mutations from pathology slides using sequencing data is of great importance in cancer genomics and precision oncology. Formalin-fixation paraffin-embedding (FFPE) is a widely used technique to preserve pathology tissues. The FFPE process introduces artificial C > T mutations in next-generation sequencing, so we set out to develop excerno, a method to score and filter such spurious variants. FFPE mutational artifacts follow a mutational signature. By using the FFPE signature and Bayes' formula, we can calculate the probability of a mutation resulting from the FFPE process and use this probability to filter FFPE variants. We implement this method as the excerno R package. We tested excerno by simulating mutations across all 60-baseline mutational signatures from the Catalog of Somatic Mutations in Cancer (COSMIC) and combining them with mutations following the FFPE mutational signature. The sensitivity and specificity of excerno are adversely affected by the cosine similarity between the baseline and FFPE signatures (cosFFPE). Higher percentages of FFPE mutations (pctFFPE) result in increased sensitivity and reduced specificity. The specificity and sensitivity of excerno can be predicted as linear model with an interaction term using cosFFPE and pctFFPE, with an R2of0.84 and 0.79, respectively. Finally, we tested excerno using six RNA sequencing cancer samples and observed concordant trends of specificity and sensitivity with respect to our simulated data. The excerno R package can be used to annotate and filter FFPE-induced mutations in cancer genomics. Our method is adversely affected by cosFFPE and pctFFPE.

Comparison of Inpatient Outcomes Between HIV Positive and Negative Hospitalizations for Autologous Stem Cell Transplant Treatment among Lymphoid Malignancies.

BACKGROUND: Comorbidity burden is higher among people living with HIV (PLWH). In addition, they experience adverse effects associated with antiretrovirals. In this study we looked for differences in adverse hospital outcomes between those with and without HIV among hospitalizations for autologous stem cell transplantations (ASCTs) for lymphoid malignancies. MATERIALS AND METHODS: The current study was a retrospective analysis using the National Inpatient Sample (NIS) database, for the years 2005 to 2014. Adult hospitalizations ≥18 years of age, for ASCTs were included for the analysis, and were stratified into those with and without HIV. The primary outcome variables were in-hospital mortality, prolonged length of stay, and adverse dispositions. RESULTS: We included a total of 117,686 ASCT hospitalizations, of which, 468 (0.4%) were HIV positive. Among HIV-positive hospitalizations, there were 251 (53.4%), non-Hodgkin lymphoma, 128 (27.4%), Hodgkin lymphoma, and 89 (19.2%) multiple myeloma cases. Only half of the PLWH among Black population received ASCT, compared to Whites (26.8% vs. 54.8%). Regression analyses showed that the odds of in-hospital mortality (OR, 0.77; 95% CI, 0.13-4.44), prolonged length of stay (OR, 1.18; 95% CI, 0.67-2.11), and dispositions other than home (OR, 1.26; 95% CI, 0.61-2.59) did not differ significantly between 2 groups. DISCUSSION: We found that adverse hospital outcomes did not differ between those with and without HIV among hospitalized autologous stem cell transplant recipients. However, the rates of ASCT were substantially lower among Black PLWH. New interventions and approaches should be developed to improve ASCT rates among HIV positive racial minorities.

Development of purpura fulminans by Candida glabrata and Mucormycosis infection post-surgery.

Purpura fulminans (PF) is a disorder with multifactorial causes that lead to acute localize skin microvasculature thrombosis. PF can be classified as one of the manifestations of disseminated vascular coagulation (DIC). Although, there are three types of PF including hereditary (autosomal dominant) due to mutations in single nucleotide polymorphisms (PROC and PROS1) and serpin family C member 1 (SERPINC1) genes. Idiopathic or acquired type of PF is complex and the pathophysiology is ambiguous, however, low levels of protein C and S were observed. The acute infectious form of PF occurs post-bacterial infection (e.g., Neisseria). The clinical presentation is limited to skin findings or systematic manifestation (shock, disseminated intravascular coagulation, or death). We are presenting two cases of PF sharing similar clinical manifestations developed within 12 h post-operatively with distinct micro-organisms infection. The first patient's wound culture grew fluffy mold, and the sequencing confirmed a Mucormycosis, Absidia corymbifera species, while the second patient was infected by cutaneous Candida glabrata which led to the development of PF. Our findings suggest that surgery can trigger local immunological responses in susceptible individuals such as concealed protein C and S deficiency or microorganism toxins that initiated the rapidly developing of PF in those patients.

Conceptual Design and Numerical Validation of a Carbon-Based Ink Injector.

This paper shows the design of an injector, using carbon nanotubes as inkjet material, implemented in a 3D printer. According to the available literature, few injectors are capable of depositing material. Due to the lack of information, the central part of this research is to develop a suitable device for ink injection that is capable of applying the Fused Deposition Modeling (FDM) method to print nanomaterial ink. The injector was designed using a CAD program based on an open-source desktop 3D printer, which allows it to be modified according to the needs of the injector. This prototype was manufactured in aluminum alloy 7075T6. Computational fluid dynamics (CFD) were carried out to analyze the behavior of the fluid when it passes through the injector, obtaining parameters such as pressure, velocity, and vorticity. An experimental matrix of the injector operation was carried out to achieve an adequate printing speed. The results show that the optimum speed was 250 ms, considering that a temperature of 100 °C is needed in the heated bed to dry the ink so that it does not undergo expansion.

Characterization of HIV-associated Hodgkin's lymphoma in HIV-infected patients: a single-center experience.

INTRODUCTION: Although the incidence and prevalence of AIDS-defining malignancies has decreased in the era of highly active antiretroviral therapy (HAART), the incidence and prevalence of Hodgkin's lymphoma (HL) in the HIV-infected population continues to rise. Compared with the general population, HIV-infected patients exhibit a 5-10-fold increased risk for developing HL. METHODS: A retrospective review of charts and electronic records from 2000-2010 at the HIV outpatient clinic (HOP)-Louisiana State University in New Orleans was conducted, and pathologically confirmed cases of HIV-HL were identified within this cohort. RESULTS: We found a prevalence of 6.3 cases per 1,000 patients per year of HIV-HL over a period of 10 years in our HIV outpatient clinic. The mean absolute CD4 count before treatment was 284 cells/mm(3) and after treatment was 194 cells/mm(3). The average time from the diagnosis of HIV infection to the diagnosis of HIV-HL was 7.6 years. The most common histopathologic type was mixed cellularity followed by lymphocytic predominance. The majority of patients had 6 cycles delivered. In terms of HL staging 87% presented with advanced stages (III B or IV). To the best of our knowledge 5 out of the 14 patients remain alive. CONCLUSIONS: Patients in our cohort were older than most patients identified in other cohorts. All of our patients had coexisting chronic illnesses associated with inflammation, as well as detectable HIV viral loads and CD4 count >200, suggesting a role for both HIV- and non-HIV-associated inflammation in HIV-HL pathogenesis in this population. The role of HIV virus and other oncogenic viruses (EBV, HPV, and others) in the pathogenesis of Hodgkin's lymphoma in this group of patients needs to be elucidated.

Sex and race effects on risk for selected outcomes among elderly HIV-infected patients.

The HIV-infected population in the United States is aging. A retrospective study of 132 patients (26 women, 106 men) ≥59 years of age was undertaken to evaluate the effect of race and sex on selected outcomes. With the exception of women being more likely to have diagnosis of depression compared with men, sex had little influence on risk for other conditions among elderly patients with HIV. In contrast, African American race was significantly associated with the risk for several selected disorders and outcomes. These results can assist in future prevention efforts among senior individuals with HIV infection.