Combination therapy of Epidermal Growth Factor and Growth Hormone-Releasing Hexapeptide in acute ischemic stroke: a phase I/II non-blinded, randomized clinical trial.

Objective: This study tested the hypothesis that a neuroprotective combined therapy based on epidermal growth factor (EGF) and growth hormone-releasing hexapeptide (GHRP6) could be safe for acute ischemic stroke patients, admitting up to 30% of serious adverse events (SAE) with proven causality. Methods: A multi-centric, randomized, open-label, controlled, phase I-II clinical trial with parallel groups was conducted (July 2017 to January 2018). Patients aged 18-80 years with a computed tomography-confirmed ischemic stroke and less than 12 h from the onset of symptoms were randomly assigned to the study groups I (75 µg rEGF + 3.5 mg GHRP6 i.v., n=10), II (75 µg rEGF + 5 mg GHRP6 i.v., n=10), or III (standard care control, n=16). Combined therapy was given BID for 7 days. The primary endpoint was safety over 6 months. Secondary endpoints included neurological (NIHSS) and functional [Barthel index and modified Rankin scale (mRS)] outcomes. Results: The study population had a mean age of 66 ± 11 years, with 21 men (58.3%), a baseline median NIHSS score of 9 (95% CI: 8-11), and a mean time to treatment of 7.3 ± 2.8 h. Analyses were conducted on an intention-to-treat basis. SAEs were reported in 9 of 16 (56.2%) patients in the control group, 3 of 10 (30%) patients in Group I (odds ratio (OR): 0.33; 95% CI: 0.06-1.78), and 2 of 10 (20%) patients in Group II (OR: 0.19; 95% CI: 0.03-1.22); only two events in one patient in Group I were attributed to the intervention treatment. Compliance with the study hypothesis was greater than 0.90 in each group. Patients treated with EGF + GHRP6 had a favorable neurological and functional evolution at both 90 and 180 days, as evidenced by the inferential analysis of NIHSS, Barthel, and mRS and by their moderate to strong effect size. At 6 months, proportion analysis evidenced a higher survival rate for patients treated with the combined therapy. Ancillary analysis including merged treated groups and utility-weighted mRS also showed a benefit of this combined therapy. Conclusion: EGF + GHRP6 therapy was safe. The functional benefits of treatment in this study supported a Phase III study. Clinical Trial Registration: RPCEC00000214 of the Cuban Public Registry of Clinical Trials, Unique identifier: IG/CIGB-845I/IC/1601.

Janus kinase inhibitors modify the fatty acid profile of extracellular vesicles and modulate the immune response.

Background: Janus kinase inhibitors (jakinibs) are immunomodulators used for treating malignancies, autoimmune diseases, and immunodeficiencies. However, they induce adverse effects such as thrombosis, lymphocytosis, and neutropenia that could be mediated by extracellular vesicles (EVs). These particles are cell membrane-derived structures that transport cellular and environmental molecules and participate in intercellular communication. Jakinibs can modify the content of EVs and enable them to modulate the activity of different components of the immune response. Objective: to evaluate the interactions between immune system components of healthy individuals and EVs derived from monocytic and lymphoid lineage cells generated in the presence of baricitinib (BARI) and itacitinib (ITA) and their possible effects. Methods: EVs were isolated from monocytes (M) and lymphocytes (L) of healthy individuals, as well as from U937 (U) and Jurkat (J) cells exposed to non-cytotoxic concentrations of BARI, ITA, and dimethyl sulfoxide (DMSO; vehicle control). The binding to and engulfment of EVs by peripheral blood leukocytes of healthy individuals were analyzed by flow cytometry using CFSE-stained EVs and anti-CD45-PeCy7 mAb-labeled whole blood. The effect of EVs on respiratory burst, T-cell activation and proliferation, cytokine synthesis, and platelet aggregation was evaluated. Respiratory burst was assessed in PMA-stimulated neutrophils by the dihydrorhodamine (DHR) test and flow cytometry. T-cell activation and proliferation and cytokine production were assessed in CFSE-stained PBMC cultures stimulated with PHA; expression of the T-cell activation markers CD25 and CD69 and T-cell proliferation were analyzed by flow cytometry, and the cytokine levels were quantified in culture supernatants by Luminex assays. Platelet aggregation was analyzed in platelet-rich plasma (PRP) samples by light transmission aggregometry. The EVs' fatty acid (FA) profile was analyzed using methyl ester derivatization followed by gas chromatography. Results: ITA exposure during the generation of EVs modified the size of the EVs released; however, treatment with DMSO and BARI did not alter the size of EVs generated from U937 and Jurkat cells. Circulating neutrophils, lymphocytes, and monocytes showed a 2-fold greater tendency to internalize ITA-U-EVs than their respective DMSO control. The neutrophil respiratory burst was attenuated in greater extent by M-EVs than by L-EVs. Autologous ITA-M-EVs reduced T-cell proliferation by decreasing IL-2 levels and CD25 expression independently of CD69. A higher accumulation of pro-inflammatory cytokines was observed in PHA-stimulated PBMC cultures exposed to M-EVs than to L-EVs; this difference may be related to the higher myristate content of M-EVs. Platelet aggregation increased in the presence of ITA-L/M-EVs by a mechanism presumably dependent on the high arachidonic acid content of the vesicles. Conclusions: Cellular origin and jakinib exposure modify the FA profile of EVs, enabling them, in turn, to modulate neutrophil respiratory burst, T-cell proliferation, and platelet aggregation. The increased T-cell proliferation induced by BARI-L/M-EVs could explain the lymphocytosis observed in patients treated with BARI. The higher proportion of arachidonic acid in the FA content of ITA-L/M-EVs could be related to the thrombosis described in patients treated with ITA. EVs also induced a decrease in the respiratory burst of neutrophils.

Assessment of Central Auditory Processing in Children Using a Novel Tablet-Based Platform: Application for Low- and Middle-Income Countries.

OBJECTIVE: Evaluate whether a portable, tablet-based central auditory processing (CAP) test system using native language training videos and administered by minimally trained community health workers can produce CAP results comparable to previously published norms. Our secondary aim was to determine subject parameters that influence test results. STUDY DESIGN: Cross-sectional study. SETTING: Community-based settings in Chontales, Nicaragua, New Hampshire, and Florida. PATIENTS: English- and/or Spanish-speaking children and adolescents (n = 245; average age, 12.20 yr; range, 6-18 yr). MAIN OUTCOME MEASURES: Completion of the following tests with responses comparable to published norms: Pure-tone average (PTA), gap detection threshold (GDT), fixed-level frequency threshold, masking level difference (MLD), Hearing in Noise Test (HINT), Dichotic Digits Test (DDT), and Frequency Pattern Recognition (FPR) test. RESULTS: GDT, HINT, and DDT had comparable results to previously published normative values. MLD and FPR results differed compared with previously published normative values. Most CAP tests (MLD, GDT, HINT) results were independent of age and PTA (p = 0.1-0.9). However, DDT was associated with age and PTA (p < 0.0001). CONCLUSIONS: Pediatric CAP testing can be successfully completed in remote low- and middle- income country environments using a tablet-based platform without the presence of an audiologist. Performance on DDT improved with age but deteriorated with hearing loss. Further investigation is warranted to assess the variability of FPR.

B cell-targeted polylactic acid nanoparticles as platform for encapsulating jakinibs: potential therapeutic strategy for systemic lupus erythematosus.

Background: B cells are pivotal in systemic lupus erythematosus and autoimmune disease pathogenesis. Materials & methods: To address this, Nile Red-labeled polylactic acid nanoparticles (NR-PLA NPs) loaded with the JAK inhibitor baricitinib (BARI), specifically targeting JAK1 and JAK2 in B cells, were developed. Results: Physicochemical characterization confirmed NP stability over 30 days. NR-PLA NPs were selectively bound and internalized by CD19+ B cells, sparing other leukocytes. In contrast to NR-PLA NPs, BARI-NR-PLA NPs significantly dampened B-cell activation, proliferation and plasma cell differentiation in healthy controls. They also inhibited key cytokine production. These effects often surpassed those of equimolar-free BARI. Conclusion: This study underscores the potential of PLA NPs to regulate autoreactive B cells, offering a novel therapeutic avenue for autoimmune diseases.

In this study, a new approach to treating autoimmune diseases, particularly systemic lupus erythematosus, was investigated by focusing on a type of immune cell called B cells. Special nanoparticles (NPs) labeled with Nile Red (NR) and made from polylactic acid (PLA) were created. These NPs were loaded with a drug called baricitinib (BARI), which targets specific proteins (JAK1 and JAK2) in B cells. This was done to determine if these NPs could help control the behavior of B cells, which are important in autoimmune diseases. First, these NPs remained stable for a long time (30 days). The NR-labeled PLA NPs (NR-PLA NPs) were also good at attaching to and entering a specific type of B cell called CD19⁺ B cells while leaving other types of immune cells alone. The use of NR-PLA NPs loaded with BARI produced exciting results. These NPs were better at reducing the activity, growth and transformation of B cells into plasma cells compared with the drug BARI by itself. They also stopped the production of certain immune system signals called cytokines, which are usually overactive in autoimmune diseases. This work suggests that PLA NPs could be a promising way to control overactive B cells that contribute to autoimmune diseases like systemic lupus erythematosus. This could open a new and exciting path for developing treatments for these conditions.

Nanoparticles targeting monocytes and macrophages as diagnostic and therapeutic tools for autoimmune diseases.

Autoimmune diseases are chronic conditions that result from an inadequate immune response to self-antigens and affect many people worldwide. Their signs, symptoms, and clinical severity change throughout the course of the disease, therefore the diagnosis and treatment of autoimmune diseases are major challenges. Current diagnostic tools are often invasive and tend to identify the issue at advanced stages. Moreover, the available treatments for autoimmune diseases do not typically lead to complete remission and are associated with numerous side effects upon long-term usage. A promising strategy is the use of nanoparticles that can be used as contrast agents in diagnostic imaging techniques to detect specific cells present at the inflammatory infiltrates in tissues that are not easily accessible by biopsy. In addition, NPs can be designed to deliver drugs to a cell population or tissue. Considering the significant role played by monocytes in the development of chronic inflammatory conditions and their emergence as a target for extracorporeal monitoring and precise interventions, this review focuses on recent advancements in nanoparticle-based strategies for diagnosing and treating autoimmune diseases, with a particular emphasis on targeting monocyte populations.

Study on the insecticidal activity of entomopathogenic fungi for the control of the fruit fly (Anastrepha obliqua), the main pest in mango crop in Colombia.

The aim of this study was to evaluate and select entomopathogenic fungi that produces insecticidal compounds for the control of adults of Anastrepha obliqua Macquart (Diptera: tephritidae) that are the main pest of mango (Mangifera indica L. Bark) in Colombia. Nine entomopathogenic fungi isolates were evaluated, five belonging to the genus Metarhizium and four belonging to the genus Beauveria. One strain of the species Metarhizium robertsii with insecticidal activity was selected. By column fractionation, an active fraction was obtained, which caused mortalities higher than 90% after 48 h of exposure. Through HPLC it was determined that the active fraction is composed of more than 22 metabolites. Identification of the metabolites by UHPLC MS/MS revealed the presence of destruxin in E, D, A and B groups (destruxin E-diol, destruxin D, destruxin D1, destruxin D2, destruxin A2, destruxin A, destruxin A3, dihydrodestruxin A, desmB, destruxin B2, destruxin B and destruxin B1). The evaluation of the insecticidal capacity of the organic fractions obtained by HPLC indicated that the extract obtained from the isolate M. robertsii had a compound with high activity on adults of A. obliqua (destruxin A) causing massive mortality of up to 100%, after 48 h of the treatment administration. Furthermore, two other compounds with medium activity were found (destruxin A2 and destruxin B), showing mortalities between 60.0 and 81.3%, respectively. The extract of the isolate MT008 of M. robertsii showed higher insecticidal activity and a potential source for the control of A. obliqua.

Test-Retest repeatability of automated threshold audiometry in Nicaraguan schoolchildren.

OBJECTIVE: Automated threshold audiometry (ATA) could increase access to paediatric hearing assessment in low- and middle-income countries, but few studies have evaluated test-retest repeatability of ATA in children. This study aims to analyse test-retest repeatability of ATA and to identify factors that affect the reliability of this method. DESIGN: ATA was performed twice in a cohort of Nicaraguan schoolchildren. During testing, the proportion of responses occurring in the absence of a stimulus was measured by calculating a stimulus response false positive rate (SRFP). Absolute test-retest repeatability was determined between the two trials, as well as the impact of age, gender, ambient noise, head circumference, and SRFP on these results. STUDY SAMPLE: 807 children were randomly selected from 35 schools in northern Nicaragua. RESULTS: Across all frequencies, the absolute value of the difference between measurements was 5.5 ± 7.8 dB. 89.6% of test-retest differences were within 10 dB. Intra-class correlation coefficients between the two measurements showed that lower SRFP was associated with improved repeatability. No effect of age, gender, or ambient noise was found. CONCLUSIONS: ATA produced moderate test-retest repeatability in Nicaraguan schoolchildren. Participant testing behaviours, such as delayed or otherwise inappropriate response patterns, significantly impacts the repeatability of these measurements.

Epicardial adipose tissue thickness is related to early subclinical myocardial dysfunction, particularly in patients with type 2 diabetes mellitus: a case control study.

BACKGROUND: Cardiac myofibrillary dysfunction, which can be measure by echocardiographical strain value, represents an early subclinical manifestation of heart failure. Epicardial Adipose tissue (EAT) is related to low degree inflammation and oxidative damage in the adjacent tissue. AIM: To explore whether EAT affects early myocardial dysfunction, as assessed strain values. METHODS: Case-Control design. Patients lacking clinical significant heart failure, thyroid or renal disease or malignant abnormalities were included. Clinical-demographic and biochemical data were collected. EAT and myofibril deformation were measured by echocardiography. RESULTS: A total of 71 patients were analyzed, and further subdivided according to type 2 Diabetes Mellitus (t2DM). Higher strain value (higher than -22.4%cut-off value) was associated with male sex and higher anthropometric and metabolic risk measures; particularly those with t2DM. Higher EAT was also associated higher strain value (AUC = 0.92 ± 0.06, p = 0.004), and further correlation was evidenced (rho = 0.488, p < 0.001), with significant influence of t2DM. CONCLUSION: EAT was related to strain value, suggesting the influence of cardiac adipose tissue on the deformability of cardiac myofibril, with a more significant effect in the population with t2DM.

School Hearing Screening With a Portable, Tablet-Based, Noise-Attenuating Audiometric Headset in Rural Nicaragua.

OBJECTIVE: To investigate the utility and effectiveness of a noise-attenuating, tablet-based mobile health system combined with asynchronous telehealth evaluations for screening rural Nicaraguan schoolchildren for hearing loss. STUDY DESIGN: Prospective population-based survey. SETTING: Rural Nicaraguan communities. PATIENTS: There were 3,398 school children 7 to 9 years of age. INTERVENTIONS: Diagnostic automated and manual audiometry, detailed asynchronous telehealth evaluations. MAIN OUTCOME MEASURES: Referral rates, ambient noise levels, and audiometric results as well as hearing loss prevalence, types, and risk factors. RESULTS: Despite high ambient noise levels during screening (46.7 dBA), no effect of noise on referral rates on automated audiometry or confirmatory manual audiometry in those who failed automated testing was seen. The overall audiometric referral rate was 2.6%. Idiopathic sensorineural hearing loss (SNHL) and cerumen impaction were the most common types of hearing loss in this population with an estimated prevalence of hearing loss (all types) of 18.3 per 1,000 children. SNHL was associated with both drug exposure during pregnancy (p = 0.04) and pesticide exposure in the home (p = 0.03). CONCLUSION: Hearing screening using a tablet-based, noise-attenuating wireless headset audiometer is feasible and effective in rural low-resource environments with moderately elevated ambient noise levels. The referral rate with noise-attenuating headsets was much lower than that previous reports on this population. In addition, manual audiometry resulted in much lower referral rates than automated audiometry. The confirmed hearing loss rate in this study is comparable to reports from other low-income countries that use some form of noise attenuation during screening. Pesticide exposure and drug exposure during pregnancy are potential causes of SNHL in this population.

Community health workers and mHealth systems for hearing screening in rural Nicaraguan schoolchildren.

Background: We aimed to investigate the effectiveness of using minimally trained community health workers (CHW) to screen schoolchildren in rural Nicaragua for hearing loss using a tablet-based audiometric system integrated with asynchronous telehealth evaluations and mobile health (mHealth) appointment reminders. Methods: A population-based survey was conducted using community health workers (CHWs) to perform tablet-based audiometry, asynchronous telehealth evaluations, and mHealth reminders to screen 3398 school children (7-9 years of age) in 92 rural Nicaraguan communities. The accuracy of screening, test duration, testing efficiency, telehealth data validity, and compliance with recommended clinic visits were analyzed. Results: Minimally trained CHWs successfully screened children within remote rural schools with automated audiometry (test duration = 5.8 minutes) followed by manual audiometry if needed (test duration = 4.3 minutes) with an estimated manual audiometry validity of 98.5% based on a review of convergence patterns. For children who were referred based on audiometry, the otoscopy and tympanometry obtained during telehealth evaluations were high quality (as reviewed by 3 experts) in 44.6% and 80.1% of ears, respectively. A combination of automated short message service (SMS) text messages and voice reminders resulted in a follow-up compliance of 75.2%. No families responded to SMS messages alone. Conclusions: Tablet-based hearing screening administered by minimally trained CHWs is feasible and effective in low- and middle-income countries. Manual audiometry was as efficient as automated audiometry in this setting. The physical exam tasks of otoscopy and tympanometry require additional training. Mobile phone messages improve compliance for confirmatory audiometry, but the utility of SMS messaging alone is unclear in this population.

HIV Antiretroviral Medication Neuropenetrance and Neurocognitive Outcomes in HIV+ Adults: A Review of the Literature Examining the Central Nervous System Penetration Effectiveness Score.

This literature review summarizes the existing research examining the CNS penetration effectiveness (CPE) score and neurocognitive outcomes (i.e., neuropsychological assessment and neurocognitive screening) in HIV+ individuals. Despite the effectiveness of Combined Antiretroviral Therapy (CART) in reducing mortality and morbidity in HIV and controlling viral replication, HIV often persists in the Central Nervous System (CNS), and rates of neurocognitive impairment remain higher than predicted in the post-CART era. The CPE score was developed to rank antiretroviral regimens on their ability to penetrate the CNS and potency in inhibiting the virus, and it has been examined in relation to neurocognitive functioning for over a decade. Based on the results of 23 studies, we conclude that CPE is not as strongly associated with neurocognitive outcomes as initially hypothesized, although higher CPE ARV regimens may be associated with modest, improved outcomes in global neurocognitive functioning, and to a lesser extent attention/working memory and learning/memory. Conclusions, however, are limited by the heterogeneity in study design and methods, and the lack of a more recent CPE metric update. It is recommended that future research in this area employ comprehensive, standardized neuropsychological test batteries and examine domain-level performance, and use the newer 2010 CPE metric, although an updated CPE ranking is urgently needed.

Necesidad de cuidados paliativos en pacientes VIH/sida en un hospital de tercer nivel en La Habana. Utilidad del cuestionario NECPAL / Need for palliative care in HIV/aids patients in a tertiary hospital in Havana. Usefulness of the NECPAL questionnaire

Introducción: La atención a la infección por el VIH/sida en Cuba como enfermedad crónica demanda soluciones integradoras, para las cuales la perspectiva de la atención paliativa podría ser una importante contribución.Objetivo: Explorar la necesidad de cuidados paliativos en pacientes VIH/sida, hospitalizados por parte de los proveedores de salud.Método: Se realizó un estudio observacional, de corte transversal, en el Instituto de Medicina Tropical “Pedro Kourí” entre los meses de marzo y abril del 2016, con pacientes infectados por el virus de la inmunodeficiencia humana en etapa sida. Se previeron como criterios de exclusión la voluntad del paciente de no formar parte del estudio y aquellos casos que fallecieran 48 horas después del ingreso. Se aplicó a los médicos de asistencia el cuestionario NECPAL para la identificación de los pacientes con necesidades de atención paliativa.Resultados: De los 123 pacientes estudiados, el 87,8 % fueron hombres, menores de 45 años (66,7 %), con más de 10 años de diagnóstico de VIH (33,3 %). El 65,0 % contaba con CD4+< 200 cél./ml y el 87,0 % con CV detectables. El instrumento NECPAL mostró en 75 pacientes (61,0 %) una identificación positiva. El síndrome de desgaste (p > 0,006, OR 3,9 [IC 95 % 1,4-10,4]) y la presencia de anemia (p > 0,001, OR 4,7 [IC 95 %1,9-11,8]) fueron las variables que se relacionaron con la identificación positiva del NECPAL.Conclusión: El instrumento NECPAL fue útil en la detección de necesidades paliativas por el personal médico de asistencia que atiende a los pacientes VIH/sida, y que no tiene formación en cuidados paliativos. (AU)

Introduction: Management of HIV/AIDS infection in Cuba as a chronic disease demands integrative solutions, to which the perspective of palliative care could be an important contribution.Objective: To explore the need for palliative care in hospitalized HIV/AIDS patients by health providers.Method: An observational, cross-sectional study was carried out at the “Pedro Kourí” Institute of Tropical Medicine between March and April 2016, with patients infected by the human immunodeficiency virus in the AIDS stage. The exclusion criteria were the willingness of the patient not to be part of the study and those cases who died 48 hours after admission. The NECPAL questionnaire was given to attending physicians in order to identify patients with palliative care needs.Results: Of the 123 patients studied, 87.8 % were men, under 45 years of age (66.7 %), with more than 10 years of HIV diagnosis (33.3 %); 65.0 % had CD4+ < 200 cells/mL and 87.0 % had detectable CV. The NECPAL instrument yielded 75 patients (61.0 %) with a positive identification. The wasting syndrome (p > 0.006, OR 3.9 [95 % CI, 1.4-10.4]) and the presence of anemia (p > 0.001, OR 4.7 [95 % CI, 1.9 -11.8]) were the variables that were related to a positive identification by NECPAL.Conclusions: The NECPAL instrument was useful in detecting palliative needs by medical personnel who care for HIV/AIDS patients, and who do not have training in palliative care. (AU)

Úlcera rectal solitaria como simulador de cáncer colorrectal y enfermedad de Crohn: reporte de caso / Solitary rectal ulcer simulating colorectal cancer and Crohn's disease: Case report

Resumen La úlcera rectal solitaria es una patología poco frecuente de naturaleza benigna que debe diferenciarse de otras entidades en su presentación inicial, con mecanismos fisiopatológicos definidos y con sintomatología variada. Se presenta el caso de una paciente de 31 años sin antecedentes de importancia, que consultó a nuestra institución por un cuadro de 3 años de sangrado rectal asociado con episodios de diarrea, manejada con múltiples diagnósticos.

Abstract Solitary rectal ulcer is a rare condition of benign nature that must be differentiated from other disorders with defined pathophysiological mechanisms and varied symptoms. The following is the case of a 31-year-old female patient with no relevant history, who consulted our institution due to symptoms of rectal bleeding associated with episodes of diarrhea for three years, who received multiple diagnoses.

Paraneoplastic pemphigus as an atypical presentation of Castleman disease / Pénfigo paraneoplásico como presentación atípica de la enfermedad de Castleman

Abstract Castleman disease is a non-clonal lymphoproliferative disorder with a broad range of clinical manifestations. We present the case of a male patient with a clinical picture of asthenia, adynamia, hyporexia, weight loss, oral and genital ulcers, and red, itchy eyes. The physical exam showed conjunctival redness and oral and genital ulcers. Computed axial tomography with contrast of the chest and abdomen revealed multiple enlarged mediastinal and retroperitoneal lymph nodes, and a solid 94x51 mm retroperitoneal mass. A biopsy of the mass was taken, which reported the hyaline vascular variant of Castleman disease. A scrotal lesion biopsy was also ordered, with a histopathological analysis compatible with pemphigus. In addition, direct immunofluorescence was positive in the epidermal intercelullar spaces, as well as immunoprecipitation with anti-desmoglein, anti-desmoplakin, anti-envoplakin and pemphigoid ampule antigen. Thus, the presence of multicentric Castleman disease associated with paraneoplastic pemphigus was established. (Acta Med Colomb 2021; 46. DOI: https://doi.org/10.36104/amc.2021.1964)

Resumen La enfermedad de Castleman es un trastorno linfoproliferativo no clonal con amplia gama de manifestaciones clínicas. Se presenta el caso de paciente masculino con cuadro clínico consistente en astenia, adinamia, hiporexia, pérdida ponderal, úlceras orales y genitales, prurito ocular e hi peremia conjuntival. El examen físico evidenció hiperemia conjuntival, úlceras orales y genitales. La tomografía axial computarizada contrastada de tórax y abdomen reveló múltiples adenopatías mediastinales, retroperitoneales y masa sólida de 94 x 51 milímetros de localización retroperitoneal. Se realizó biopsia de la masa previamente descrita, que reportó enfermedad de Castleman variante hialino vascular. También se indicó biopsia de lesión escrotal cuyo análisis histopatológico fue compatible con pénfigo, además la fluorescencia inmunológica directa fue positiva en los espacios intercelulares de la epidermis al igual que inmunoprecipitación con anticuerpos anti-desmogleina, anti-desmoplaquina, anti-envoplaquina y antígeno del penfigoide ampollar. Por lo anteriormente descrito se definió la existencia de enfermedad de Castleman multicéntrica asociada a pénfigo paraneoplásico. (Acta Med Colomb 2021; 46. DOI: https://doi.org/10.36104/amc.2021.1964)

Melanoma amelanótico diseminado / Disseminated amelanotic melanoma

El melanoma amelanótico es una de las neoplasias con mayor índice de mortalidad por su alta agresividad y baja probabilidad diagnóstica. Afecta a la población de todo el orbe, más frecuente en caucásicos, con predisposición genética y factores de riesgo como la exposición al sol. Presenta tasas de supervivencia menor a 10 por ciento a 5 años y de recurrencia elevadas; con evidencia de procesos metastásicos a distancia en órganos como cerebro, tejido celular subcutáneo, pulmón, peritoneo, hueso, lo que ensombrece el pronóstico. Se presenta el caso de una paciente de 21 años de edad que acude al hospital por presentar lesiones equimóticas, nódulos subcutáneos y cefalea hemicránea izquierda de dos meses de evolución. Se le realizó tomografías de tórax abdomen y resonancia magnética de cráneo y evidenciaron diseminación metastásica. Se realizó estudio histopatológico con inmunohistoquímica que informó melanoma amelanótico(AU)

Amelanotic melanoma is one of the neoplasms with the highest mortality rate because it is highly aggressive and the diagnostic probability is low. It affects the population of the entire globe, more frequent in Caucasians, with genetic predisposition and risk factors such as sun exposure. It presents survival rates of less than 10 percent at 5 years and high recurrence rates; with evidence of distant metastatic processes in organs such as brain, subcutaneous cellular tissue, lung, peritoneum, bone, which casts a shadow on the prognosis. We report the case of a 21-year-old patient who came to the hospital due to ecchymotic lesions, subcutaneous nodules and a two-month evolution of left hemicrania headache. She underwent chest and abdomen tomography and MRI of the skull. They showed metastatic spread. Histopathological study was performed with immunohistochemistry that reported amelanotic melanoma(AU)

Anti-EGF antibodies as surrogate biomarkers of clinical efficacy in stage IIIB/IV non-small-cell lung cancer patients treated with an optimized CIMAvax-EGF vaccination schedule.

We previously reported that CIMAvax-EGF vaccine is safe, immunogenic and efficacious to treat advanced non-small-cell lung cancer (NSCLC) patients. A phase III trial was designed using an optimized immunization schedule. It included higher antigen dose and injections at multiple sites. Immune response and circulating biomarkers were studied in a subset of patients. EGF-specific antibody titers, IgG subclasses, peptide immunodominance and circulating biomarkers were assessed by ELISA. In vitro EGF-neutralization capacity of immune sera and EGF-IgG binding kinetics was evaluated by Western Blot and Surface Plasmon Resonance (SPR) technology, respectively. We show that CIMAvax-EGF elicited mainly IgG3/IgG4 antibodies at titers exceeding 1:4000 in 80% of vaccinated patients after 3 months of treatment. The EGF-specific humoral response was directed against the central region of the EGF molecule. For the first time, the kinetic constants of EGF-specific antibodies were measured evidencing affinity maturation of antibody repertoire up to month 12 of vaccination. Notably, the capacity of post-immune sera to inhibit EGFR phosphorylation significantly increased during the course of the immunization scheme and was related to clinical outcome (P = .013, log-rank test). Basal concentrations of EGF and TGFα in the serum were affected by EGF-based immunization. In conclusion, the CIMAvax-EGF vaccine induces an EGF-specific protective humoral response in a high percent of NSCLC vaccinated patients, the quantity and quality of which were associated with clinical benefit (clinical trial registration number: RPCEC00000161, http://registroclinico.sld.cu/). Abbreviations: EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; Ab: antibody; AR: amphiregulin; NSCLC: non-small-cell lung cancer; rhEGF: recombinant human epidermal growth factor; BSC: best supportive care; TGFα: tumor growth factor alpha; IL-8: interleukin 8; MAb: monoclonal antibody; SPR: surface plasmon resonance.

Disparities in Electronically Monitored Antiretroviral Adherence and Differential Adherence Predictors in Latinx and Non-Latinx White Persons Living with HIV.

Antiretroviral therapy (ART) adherence is vital for optimal HIV treatment. However, there is limited ART adherence research on the US Latinx population, who are at increased risk for HIV infection and worse HIV health outcomes. This study examined electronically measured ART adherence (Medication Event Monitoring System) and its association with demographic, clinical, neurocognitive, and sociocultural variables in Latinx and non-Latinx white (NLW) persons living with HIV [PLWH (N = 128)]. Latinx participants demonstrated worse adherence than NLW participants (p = 0.04). Linear regressions revealed different predictors of adherence. Among Latinx participants, recent cocaine use, stress, and, unexpectedly, higher US acculturation predicted worse adherence (ps < 0.05). Among NLW participants, recent cocaine use predicted worse adherence (p < 0.05). Intergroup comparisons within the Latinx group were not conducted due to subsample size. Thus, ethnicity, sociocultural variables, and cocaine use are important considerations for ART adherence, and poor ART adherence may be one pathway explaining worse outcomes in Latinx PLWH. Culturally tailored adherence interventions incorporating substance use treatment, acculturation, and stress management are warranted to improve health outcomes.

La COVID-19: un reto para la salud mundial / COVID-19: a challenge for global health

Introducción: La enfermedad producida por el Coronavirus 2019 ha impactado al mundo más allá de los límites de la salud pública a tres meses del diagnóstico del primer caso en China. En la actualidad afecta a 182 países, por lo que fue declarada pandemia por la Organización Mundial de la Salud. Objetivo: Revisar los aspectos clínico-epidemiológicos más importantes reportados sobre esta enfermedad. Desarrollo: La enfermedad se trasmite por las microgotas de saliva entre personas y por contacto con superficies contaminadas o heces. El periodo de incubación es hasta 14 días, en los cuales puede ocurrir trasmisión viral. Se caracteriza por un espectro sintomático variable, los pacientes pueden permanecer asintomáticos o presentar síntomas como fiebre, dolor de garganta, tos, anosmia y disnea. Aproximadamente 14 por ciento de los casos presenta formas graves y 5 por ciento evoluciona a estado crítico, asociado a complicaciones como el síndrome de distress respiratorio o shock séptico. El diagnóstico confirmatorio es a través de los estudios de reacción en cadena de polimerasa en tiempo real, en muestras respiratorias. No existe un tratamiento efectivo, aunque se emplean medicamentos, la mayoría de ellos como parte de ensayos clínicos. Conclusiones: Es un fenómeno sin precedentes en el último siglo en relación al número de personas y países que ha afectado y al impacto en las dinámicas sociales y económicas del mundo actual(AU)

Introduction: The disease caused by Coronavirus 2019 has impacted the world beyond the limits of public health three months after the first case was diagnosed in China. It currently affects 182 countries; hence it is was declared a pandemic by the World Health Organization. Objective: To review the most important clinical-epidemiological aspects reported on this disease. Findings: The disease is transmitted by droplets of saliva between people and by contact with contaminated surfaces or faeces. The incubation period is up to 14 days, in which viral transmission can occur. It is characterized by a variable symptom spectrum, patients can remain asymptomatic or present symptoms such as fever, sore throat, cough, anosmia and dyspnea. Approximately 14 percent of cases present severe forms and 5 percent progresses to a critical state, associated with complications such as respiratory distress syndrome or septic shock. The confirmatory diagnosis is through real-time polymerase chain reaction studies in respiratory samples. There is no effective treatment, although medications are used, most of them as part of clinical trials. Conclusions: It is, in the last century, an unprecedented phenomenon regarding the number of people and countries it has affected and concerning the impact on the social and economic dynamics currently in the world(AU)

Induction of NF-κB inflammatory pathway in monocytes by microparticles from patients with systemic lupus erythematosus.

BACKGROUND: Elevated levels of circulating microparticles (MPs) and molecules of the complement system have been reported in patients with systemic lupus erythematosus (SLE). Moreover, microparticles isolated from patients with SLE (SLE-MPs) contain higher levels of damage-associated molecular patterns (DAMPs) than MPs from healthy controls (CMPs). We hypothesize that the uptake of MPs by monocytes could contribute to the chronic inflammatory processes observed in patients with SLE. Therefore, the aim of this study was to evaluate the expression of activation markers, production of proinflammatory mediators, and activation of the NF-κB signaling pathway in monocytes treated with CMPs and SLE-MPs. METHODOLOGY: Monocytes isolated from healthy individuals were pretreated or not with pyrrolidine dithiocarbamate (PDTC) and cultured with CMPs and SLE-MPs. The cell surface expression of CD69 and HLA-DR were evaluated by flow cytometry; cytokine and eicosanoid levels were quantified in culture supernatants by Cytokine Bead Array and ELISA, respectively; and the NF-κB activation was evaluated by Western blot and epifluorescence microscopy. RESULTS: The cell surface expression of HLA-DR and CD69, and the supernatant levels of IL-6, IL-1ß, PGE2, and LTB4 were higher in cultures of monocytes treated with SLE-MPs than CMPs. These responses were blocked in the presence of PDTC, a pharmacological inhibitor of the NF-κB pathway, with concomitant reduction of IκBα and cytoplasmic p65, and increased nuclear translocation of p65. CONCLUSIONS: The present findings indicate that significant uptake of SLE-MPs by monocytes results in activation, production of inflammatory mediators, and triggering of the NF-κB signaling pathway.

Caracterización de pacientes con fiebre de origen desconocido recurrente / Characterizing patients with recurrent fever of unknown origin

Introducción: La fiebre de origen desconocido es un síndrome que genera un gran desafío para el pensamiento clínico; el patrón recurrente es el subtipo más retador y de difícil diagnóstico etiológico. Objetivo: Caracterizar los pacientes con fiebre de origen desconocido con patrón recurrente. Método: Se realizó un estudio descriptivo de corte transversal en el periodo de enero de 2008 a diciembre de 2015. La muestra quedó constituida por 48 pacientes, los cuales fueron hospitalizados y se les realizó una evaluación clínica en el Hospital Clínico Quirúrgico Hermanos Amejeiras. Para el análisis de los datos se utilizaron medidas de resumen para las variables cualitativas y para las cuantitativas, media y desviación estándar. Resultados: La edad media fue 41,3 años, predominaron los hombres (62,5 por ciento), la duración media de la fiebre fue de 497 días y las pistas clínicas más importantes fueron los hallazgos de adenopatías (43,8 por ciento) y hepatomegalia (22,9 por ciento). Los casos sin diagnóstico fueron 45,8 por ciento. Conclusiones: La fiebre de origen desconocido con patrón recurrente es de difícil diagnóstico. A pesar de una evaluación clínica minuciosa, la mayoría de los pacientes quedan sin diagnóstico(AU)

Introduction: Fever of unknown origin is a syndrome that generates great challenge for clinical thought; the recurrent pattern is the most challenging subtype and with difficult etiological diagnosis. Objective: To describe patients with fever of unknown origin with recurring pattern. Method: A descriptive cross-sectional study was carried out from January 2008 to December 2015. Forty-eight patients formed the sample. They were hospitalized and underwent clinical evaluation at Hermanos Amejeiras Surgical Clinical Hospital. For data analysis, summary measures were used for qualitative variables and mean and standard deviation variables were used for quantitative. Results: The mean age was 41.3 years, men predominated (62.5 percent), the mean duration of fever was 497 days, and the most important clinical signs were the findings of lymphadenopathy (43.8 percent) and hepatomegaly. (22.9 percent). Undiagnosed cases were 45.8 percent. Conclusions: Fever of unknown origin with recurring pattern is difficult to diagnose. Despite careful clinical evaluation, most patients remain undiagnosed(AU)