Tackling the Unyielding Challenge of Necrotic Unresectable Hepatocellular Carcinoma: A Liver Necrosectomy Approach for Intratumoral Hemorrhage and Abscess Resolution.

Hepatocellular carcinoma (HCC) is one of the most common causes of gastrointestinal and hepatobiliary cancer worldwide. Chronic liver disease and cirrhosis persist as the most common risk factors, typically linked to instances of alcohol abuse or viral infections, notably hepatitis B and hepatitis C infection. Diagnosis can be made using patient history and image studies as there is no need for pathological confirmation. The only curative treatment is surgical resection, and in cases where the tumor is unresectable, as the one presented in this case, and when there are no contraindications, the only option is an orthotopic liver transplantation. This malignancy is not only associated with high mortality but also high morbidity associated with severe complications, such as hemorrhage, necrosis, and infection of the tumor. The significant relevance of this case lies in its capacity to illustrate that despite remaining in non-surgical management for months when an acute complication presented, it was timely identified and surgically treated. The emergence of complications, such as necrosis accompanied by abscess formation and intratumoral hemorrhage, represents an indication for prompt surgical management.

Exploring Gastric Perforation as an Uncommon yet Critical Complication of Gastrointestinal Stromal Tumors.

Hollow viscus perforation poses a significant diagnostic and therapeutic dilemma for the majority of clinicians. It is vitally important that in cases of gastrointestinal perforation, the tissue that was perforated is always evaluated, since a malignant tumor can cause this complication as a presentation form. Here, we present the case of a patient whose first manifestation of a malignant gastric tumor was its perforation and the presence of septic shock secondary to this. This case exemplifies the importance of innovative thinking in facilitating a comprehensive diagnostic and therapeutic strategy, leading to the timely identification and management of a malignant tumor by the oncology team; such interventions not only enhance patient outcomes but also mitigate morbidity and mortality rates.

Disruption of polyunsaturated fatty acid biosynthesis drives STING-dependent acute myeloid leukemia cell maturation and death.

The role of polyunsaturated fatty acid (PUFA) biosynthesis in acute myeloid leukemia (AML) remains largely undefined. A comparative expression analysis of 35 genes encoding fatty acid biosynthesis enzymes showed that fatty acid desaturase 1 (FADS1) was highly expressed across multiple AML subtypes relative to healthy controls and that elevated FADS1 expression correlates with worse overall AML patient survival. Functionally, shRNA-mediated inhibition of FADS1 reduced AML cell growth in vitro and significantly delayed leukemia onset in an AML mouse model. AML cell lines depleted of FADS1 arrested in the G1/S-phase of the cell cycle, acquired characteristics of myeloid maturation and subsequently died. To understand the molecular consequences of FADS1 inhibition, a combination of mass spectrometry-based analysis of complex lipids and gene expression analysis (RNA-seq) was performed. FADS1 inhibition caused AML cells to exhibit significant lipidomic remodeling, including depletion of PUFAs from the phospholipids, phosphatidylserine, and phosphatidylethanolamine. These lipidomic alterations were accompanied by an increase induction of inflammatory and stimulator of interferon genes (STING)-mediated type-1 interferon signaling. Remarkably, genetic deletion of STING largely prevented the AML cell maturation and death phenotypes mediated by FADS1 inhibition. Highlighting the therapeutic implications of these findings, pharmacological blockade of PUFA biosynthesis reduced patient-derived AML cell numbers ex vivo but not that of healthy donor cells. Similarly, STING agonism attenuated patient-derived-AML survival; however, STING activation also reduced healthy granulocyte numbers. Collectively, these data unveil a previously unrecognized importance of PUFA biosynthesis in leukemogenesis and that imbalances in PUFA metabolism can drive STING-mediated AML maturation and death.

Anaplastic Carcinoma Arising From a Mural Nodule in Benign Mucinous Cystadenoma.

Giant abdominopelvic tumors continue to present a diagnostic and therapeutic challenge for all surgeons despite all the advances in the world of imaging. Particularly, one of the most important challenges is to determine its probable origin for adequate surgical planning. Even though mostly all of these tumors are benign ovarian tumors, extraordinarily, malignant mural nodules may develop from the wall of these benign tumors, carrying an invariable unfavorable prognosis for the patient. This case highlights the importance of a correct diagnostic approach using ultrasound and abdominal computed tomography scans and confirming the diagnosis through a histopathologic examination. The treatment for these cases is surgical resection and posterior oncological treatment if needed. This case shows how timely treatment is one of the principal determinators of morbidity and mortality.

Clinical and pathological differences between early- and late-onset colorectal cancer and determinants of one-year all-cause mortality among advanced-stage patients: a retrospective cohort study in Medellín, Colombia.

OBJECTIVE: To identify the differences between early- (EOCRC) and late-onset colorectal cancer (LOCRC), and to evaluate the determinants of one-year all-cause mortality among advanced-stage patients. METHODS: A retrospective cohort study was carried out. CRC patients ≥ 18 years old were included. Chi-Square test was applied to compare both groups. Uni- and multivariate regressions were performed to evaluate the determinants of one-year all-cause mortality in all advanced-stage patients regardless of age of onset. RESULTS: A total of 416 patients were enrolled; 53.1 % were female. Ninety cases (21.6 %) had EOCRC and 326 (78.4 %) had LOCRC. EOCRC cases were predominantly sporadic (88.9 %). Histology of carcinoma other than adenocarcinoma (p= 0.044) and rectum tumors (p= 0.039) were more prevalent in EOCRC. LOCRC patients were more likely to have smoking history (p < 0.001) and right colon tumors (p = 0.039). Alcohol consumption history (odds ratio [OR]: 3.375, 95 %CI: 1.022-11.150) and stage IV (OR: 12.632, 95 %CI: 3.506-45.513) were associated with higher one-year all-cause mortality among advanced-stage patients, the opposite was noted with left colon tumors (OR: 0.045, 95 %CI: 0.003-0.588). CONCLUSION: EOCRC was predominantly sporadic and had more cases of uncommon histological subtypes and rectal tumors. LOCRC was characterized by a higher prevalence of smoking history. Multivariate regression revealed an association between higher one-year all-cause mortality and alcohol consumption history and stage IV in advanced-stage patients. CRC exhibited differences based on age of onset. The evaluated factors associated with CRC mortality provide valuable insights for healthcare professionals, emphasizing the importance of adequate clinical assessment and early CRC diagnosis.

Intussusception of Gastrojejunostomy After Pancreatoduodenectomy With Billroth II Reconstruction.

Gastrojejunal anastomosis or gastrojejunostomy (GJ) is a surgical procedure used for allowing gastric emptying, especially in cases where complex reconstructions are needed. One of the less common complications but one of the most relevant in morbidity is the intussusception of the GJ. It requires a high index of suspicion, preoperative optimization of the patient, diagnostic corroboration, and identification of associated complications with the use of contrasted imaging. It was described for the first time by Bozzi in 1914; currently, multiple cases have been described in the literature, being more frequent in bariatric surgeries and reconstructions after distal gastrectomy. In hepatopancreaticobiliary surgery, it is an even uncommon complication. We present the case of a 60-year-old man with intussusception of the efferent loop of the GJ after a pylorus-preserving pancreatoduodenectomy with a Billroth II reconstruction in the setting of malignancy of the extrahepatic bile duct along with our emergency surgical treatment.

Dosimetry in cranial photobiomodulation therapy: effect of cranial thickness and bone density.

This research aims to examine the influence of human skull bone thickness and density on light penetration in PBM therapy across different wavelengths, focusing on how these bone characteristics affect the absorption of therapeutic light. Analyses explored the effect of skull bone density and thickness on light penetration in PBM, specifically using Low-Level Laser Therapy (LLLT) for efficacy prediction. Measurements of bone thickness and density were taken using precise tools. This approach emphasizes LLLT's significance in enhancing PBM outcomes by assessing how bone characteristics influence light penetration. The study revealed no significant correlation between skull bone density and thickness and light penetration capability in photobiomodulation (PBM) therapy, challenging initial expectations. Wavelengths of 405 nm and 665 nm showed stronger correlations with bone density, suggesting a significant yet weak impact. Conversely, wavelengths of 532 nm, 785 nm, 810 nm, 830 nm, 980 nm, and 1064 nm showed low correlations, indicating minimal impact from bone density variations. However, data variability (R2 < 0.4) suggests that neither density nor thickness robustly predicts light power traversing the bone, indicating penetration capability might be more influenced by bone thickness at certain wavelengths. The study finds that the effectiveness of photobiomodulation (PBM) therapy with bone isn't just based on bone density and thickness but involves a complex interplay of factors. These include the bone's chemical and mineral composition, light's wavelength and energy dose, treatment duration and frequency, and the precise location where light is applied on the skull.

Retroperitoneal Peripancreatic Ganglioneuroma Encasing the Celiac Trunk and Superior Mesenteric Artery.

A retroperitoneal ganglioneuroma is an exceptionally rare surgical entity, even more so in pancreaticoduodenal tumors. These well-differentiated neuroepithelial tumors originate in the neural crest, emerge in the sympathetic nervous system, and consist of ganglion cells and stromal Schwann cells. Generally, these tumors, despite being mostly benign, may be associated with venous or arterial vascular involvement. The symptomatology presented will depend on the mass effect due to tumor growth, and surgical excision is the only therapeutic option offered today to these patients. However, encapsulation of the main vessels represents a great surgical complexity. Various surgical approaches have been employed throughout history; however, the current preferred method is an open midline laparotomy, involving an extensive Kocher maneuver and an artery-first approach, aiming for an R0 resection of the tumor with total vascular preservation to the greatest extent possible. We present a case of an R2 resection involving a 95 mm x 85 mm retroperitoneal peripancreatic ganglioneuroma with double vascular involvement (celiac trunk and superior mesenteric artery). The procedure utilized an artery-first approach with total vascular preservation in a 17-year-old woman who had long-standing gastrointestinal symptoms due to the mass effect.

Ageism: the -ism affecting the lives of older people living with HIV.

WHO defines ageism as stereotypes, prejudice, and discrimination based on age. Ageism is a multidimensional concept that encompasses multiple components related to the individual, the social group, and the institution in different cultural and environmental settings. In people ageing with HIV these elements include self-stigma, discrimination in society, and experiences in care, many of which are unique to older people. In this Position Paper, we use experience of people with HIV and clinicians taking care of them to explore these issues in high-income countries. The intersectionality of multiple -isms, which affect the lives of older people living with HIV, and ageism enhance several HIV-related issues, including self-inflicted stigma, and loneliness. Research is needed to explore how ageism contributes to worse physical, mental, and social wellbeing outcomes for people with HIV. The model of care for older people living with HIV needs to go beyond virological success by adopting a geriatric mindset, which is attentive to the challenge of ageism and is proactive in promoting a comprehensive approach for the ageing population. All stakeholders and the community should work together to co-create institutional strategies and educational programmes and enable respectful intergenerational dialogue to foster a stigma-free future for older people living with HIV.

Percepciones de profesores y estudiantes acerca de la utilización del portafolios en la asignatura Prevención en Salud

Fundamento: en el ámbito de la pedagogía universitaria, el modelo docente adopta una nueva visión, el aprendizaje desarrollador y la evaluación educativa; en este contexto ha surgido, en los últimos años, el portafolios. Objetivo valorar la percepción de profesores y estudiantes sobre la utilización del portafolio como herramienta de aprendizaje en la asignatura Prevención en Salud. Métodos: investigación educacional, realizada en la Universidad de Ciencias Médicas de Cienfuegos en el primer período del curso 2022, sobre un universo constituido por el total de estudiantes de segundo año que cursaron la asignatura y los profesores que fungieron como tutores. La muestra fue seleccionada al azar, 64 estudiantes y 36 profesores, que aceptaron participar en la investigación respetando los principios éticos. Se empleó la técnica de la entrevista, se diseñó un cuestionario semiestructurado para explorar la opinión de estudiantes y profesores. Resultados: los docentes consideraron de utilidad el portafolio para el aprendizaje, al permitir objetivar y documentar las competencias, logrando dinamismo y estímulo para la reflexión; alegaron inconformidad en la evaluación refiriendo que requiere de mucho tiempo. Los estudiantes recibieron orientaciones sobre el portafolio, que les permitieron prepararse para su profesión, organizarse y autoevaluarse. Como debilidad destacaron la laboriosidad al considerarlo estresante, refiriéndose a la responsabilidad y al tiempo disponible e insuficiente motivación que brindan los tutores. Conclusiones: el portafolio es un instrumento centrado en el aprendizaje de competencias, con participación del estudiante y un tipo de evaluación que estimula la responsabilidad aplicando los conocimientos de la vida real en la práctica médica.

Foundation: in the university pedagogy field, the teaching model adopts a new vision: developer learning and educational evaluation; in this context, the portfolio has emerged in recent years. Objective: to assess the perception of teachers and students about the use of the portfolio as a learning tool in the Health Prevention subject. Methods: educational research, at the Cienfuegos Medical Sciences University in the first period of the 2022 academic year, a universe made up of the total number of second-year students who took the subject and the professors who served as tutors. The sample was randomly selected, 64 students and 36 teachers, who agreed to participate in the research respecting ethical principles. The interview technique was used, a semi-structured questionnaire was designed, exploring the opinion of students and teachers. Results: the teachers considered the portfolio useful for learning, as it allowed objectifying and documenting the competencies, achieving dynamism and stimulating reflection, they claimed disagreement in the evaluation, stating that it requires a lot of time. The students received guidance on the portfolio, which allowed them to prepare for their profession, organize and self-evaluate. As a weakness, they highlighted industriousness, considering it stressful, referring to the responsibility and the time available and insufficient motivation provided by the tutors. Conclusions: the portfolio is an instrument focused on learning competencies, with student participation and a type of evaluation that stimulates responsibility by applying real-life knowledge in medical practice.

Major revision version 12.0 of the European AIDS Clinical Society guidelines 2023.

BACKGROUND: The European AIDS Clinical Society (EACS) guidelines were revised in 2023 for the 19th time, and all aspects of HIV care were updated. KEY POINTS OF THE GUIDELINES UPDATE: Version 12.0 of the guidelines recommend the same six first-line treatment options for antiretroviral treatment (ART)-naïve adults as versions 11.0 and 11.1: tenofovir-based backbone plus an unboosted integrase inhibitor or doravirine; abacavir/lamivudine plus dolutegravir; or dual therapy with lamivudine or emtricitabine plus dolutegravir. The long-acting section has been expanded in the ART and drug-drug interaction (DDI) panels. Tables for preferred and alternative ART in children and adolescents have been updated, as has the section on prevention of vertical transmission, particularly with new guidance for breastfeeding. A new DDI table has been included for the ART and anti-infective drugs used for opportunistic infections, sexually transmitted infections, and other infectious conditions; lenacapavir has been included in all DDI tables. New sections on alcohol use and patient-reported outcome measures (PROMs) have been included in the comorbidity panel, in addition to updates on many relevant topics, such as new resource guidance for deprescribing in people with HIV. Other sections, including travel, cognitive impairment, cancer screening, sexual health, and diabetes have also been revised extensively. The algorithm for the management of acute hepatitis C virus infection has been removed, as current guidelines recommend immediate treatment of all people with recently acquired hepatitis C virus. Updates on vaccination for hepatitis B virus and recommendations for simplification to tenofovir-free two-drug regimens in people with isolated anti-hepatitis B core antibodies are provided. In the opportunistic infections and COVID-19 panel, guidance on the management of COVID-19 in people with HIV has been updated according to the most up-to-date evidence, and a new section on monkeypox has been added. CONCLUSIONS: In 2023, the EACS guidelines were updated extensively and now include several new sections. The recommendations are available as a free app, in interactive web format, and as a pdf online.

Unreported ent-rosane diterpenes from Croton niveus Jacq. (Euphorbiaceae). Cytotoxic activity and docking studies.

From the bioactive extract of the euphorbiaceous Croton niveus Jacq., three previously unreported ent-rosane diterpenes have been isolated and characterized by conventional methods, in addition to the known compounds lupeol, cajucarinolide and some phytosterols. Two of the ent-rosane diterpenes displayed activity against HCT-15 and PC-3 cancer cell lines, and the results of docking calculations of these compounds with NF-κB and STAT3 receptors agreed with the proposed mode of action of diterpenes against PC-3 cells.

VE-Cadherin modulates ß-catenin/TCF-4 to enhance Vasculogenic Mimicry.

Vasculogenic Mimicry (VM) refers to the capacity to form a blood network from aggressive cancer cells in an independent way of endothelial cells, to provide nutrients and oxygen leading to enhanced microenvironment complexity and treatment failure. In a previous study, we demonstrated that VE-Cadherin and its phosphorylation at Y658 modulated kaiso-dependent gene expression (CCND1 and Wnt 11) through a pathway involving Focal Adhesion kinase (FAK). In the present research, using a proteomic approach, we have found that ß-catenin/TCF-4 is associated with nuclear VE-cadherin and enhances the capacity of malignant melanoma cells to undergo VM in cooperation with VE-Cadherin; in addition, preventing the phosphorylation of Y658 of VE-cadherin upon FAK disabling resulted in VE-Cadherin/ß-catenin complex dissociation, increased ß-catenin degradation while reducing TCF-4-dependent genes transcription (C-Myc and Twist-1). Uveal melanoma cells knockout for VE-Cadherin loses ß-catenin expression while the rescue of VE-Cadherin (but not of the phosphorylation defective VE-Cadherin Y658F mutant) permits stabilization of ß-catenin and tumor growth reduction in vivo experiments. In vivo, the concomitant treatment with the FAK inhibitor PF-271 and the anti-angiogenic agent bevacizumab leads to a strong reduction in tumor growth concerning the single treatment. In conclusion, the anomalous expression of VE-Cadherin in metastatic melanoma cells (from both uveal and cutaneous origins), together with its permanent phosphorylation at Y658, favors the induction of the aggressive VM phenotype through the cooperation of ß-catenin with VE-Cadherin and by enhancing TCF-4 genes-dependent transcription.

Gaining Wings to FLY: Using Drosophila Oogenesis as an Entry Point for Citizen Scientists in Laboratory Research.

Citizen science is a productive approach to include non-scientists in research efforts that impact particular issues or communities. In most cases, scientists at advanced career stages design high-quality, exciting projects that enable citizen contribution, a crowdsourcing process that drives discovery forward and engages communities. The challenges of having citizens design their own research with no or limited training and providing access to laboratory tools, reagents, and supplies have limited citizen science efforts. This leaves the incredible life experiences and immersion of citizens in communities that experience health disparities out of the research equation, thus hampering efforts to address community health needs with a full picture of the challenges that must be addressed. Here, we present a robust and reproducible approach that engages participants from Grade 5 through adult in research focused on defining how diet impacts disease signaling. We leverage the powerful genetics, cell biology, and biochemistry of Drosophila oogenesis to define how nutrients impact phenotypes associated with genetic mutants that are implicated in cancer and diabetes. Participants lead the project design and execution, flipping the top-down hierarchy of the prevailing scientific culture to co-create research projects and infuse the research with cultural and community relevance.

Investigation of the causal etiology in a patient with T-B+NK+ immunodeficiency.

Newborn screening for severe combined immunodeficiency (SCID) has not only accelerated diagnosis and improved treatment for affected infants, but also led to identification of novel genes required for human T cell development. A male proband had SCID newborn screening showing very low T cell receptor excision circles (TRECs), a biomarker for thymic output of nascent T cells. He had persistent profound T lymphopenia, but normal numbers of B and natural killer (NK) cells. Despite an allogeneic hematopoietic stem cell transplant from his brother, he failed to develop normal T cells. Targeted resequencing excluded known SCID genes; however, whole exome sequencing (WES) of the proband and parents revealed a maternally inherited X-linked missense mutation in MED14 (MED14V763A), a component of the mediator complex. Morpholino (MO)-mediated loss of MED14 function attenuated T cell development in zebrafish. Moreover, this arrest was rescued by ectopic expression of cDNA encoding the wild type human MED14 ortholog, but not by MED14V763A , suggesting that the variant impaired MED14 function. Modeling of the equivalent mutation in mouse (Med14V769A) did not disrupt T cell development at baseline. However, repopulation of peripheral T cells upon competitive bone marrow transplantation was compromised, consistent with the incomplete T cell reconstitution experienced by the proband upon transplantation with bone marrow from his healthy male sibling, who was found to have the same MED14V763A variant. Suspecting that the variable phenotypic expression between the siblings was influenced by further mutation(s), we sought to identify genetic variants present only in the affected proband. Indeed, WES revealed a mutation in the L1 cell adhesion molecule (L1CAMQ498H); however, introducing that mutation in vivo in mice did not disrupt T cell development. Consequently, immunodeficiency in the proband may depend upon additional, unidentified gene variants.

Cardio-renal benefits of sacubitril/valsartan in patients with advanced chronic kidney disease: experience in daily clinical practice.

BACKGROUND: The association between cardiac complications, such as heart failure (HF), and chronic kidney disease (CKD) is well known. In this study, we examined the effectiveness and safety of treatment with neprilysin inhibition in patients with advanced chronic kidney disease (stage 3b-4). METHODS: This single-centre, longitudinal, retrospective study of 31 months duration involved consecutive patients with CKD and HF with a reduced ejection fraction (HFrEF) who started treatment with sacubitril/valsartan. Glomerular filtration rate (GFR), cardiovascular risk factors, proteinuria, potassium, echocardiographic parameters and admissions for heart failure were analysed. RESULTS: The study comprised 25 patients with a median age of 73.2 ± 5.9 years. The most frequent aetiology of heart failure was ischemic heart disease. The median GFR was 29.4 ± 8.3 ml/min/1.73 m2 and the left ventricular ejection fraction (LVEF) 36.4 ± 8.9%. The GFR improved after initiating the treatment (F = 3.396, p = 0.019), as did the LVEF at one year of follow-up (p = 0.018). The number of visits to the emergency department for heart failure was also reduced. No patients needed to start renal replacement therapy. CONCLUSIONS: This study shows that sacubitril/valsartan may play a beneficial role in patients who have advanced CKD and HFrEF, with a satisfactory safety profile.

Implications of Hyperoxia over the Tumor Microenvironment: An Overview Highlighting the Importance of the Immune System.

Hyperoxia is used in order to counteract hypoxia effects in the TME (tumor microenvironment), which are described to boost the malignant tumor phenotype and poor prognosis. The reduction of tumor hypoxic state through the formation of a non-aberrant vasculature or an increase in the toxicity of the therapeutic agent improves the efficacy of therapies such as chemotherapy. Radiotherapy efficacy has also improved, where apoptotic mechanisms seem to be implicated. Moreover, hyperoxia increases the antitumor immunity through diverse pathways, leading to an immunopermissive TME. Although hyperoxia is an approved treatment for preventing and treating hypoxemia, it has harmful side-effects. Prolonged exposure to high oxygen levels may cause acute lung injury, characterized by an exacerbated immune response, and the destruction of the alveolar-capillary barrier. Furthermore, under this situation, the high concentration of ROS may cause toxicity that will lead not only to cell death but also to an increase in chemoattractant and proinflammatory cytokine secretion. This would end in a lung leukocyte recruitment and, therefore, lung damage. Moreover, unregulated inflammation causes different consequences promoting tumor development and metastasis. This process is known as protumor inflammation, where different cell types and molecules are implicated; for instance, IL-1ß has been described as a key cytokine. Although current results show benefits over cancer therapies using hyperoxia, further studies need to be conducted, not only to improve tumor regression, but also to prevent its collateral damage.

The ERK2-DBP domain opposes pathogenesis of a mouse JAK2V617F-driven myeloproliferative neoplasm.

Although Ras/mitogen-activated protein kinase (MAPK) signaling is activated in most human cancers, attempts to target this pathway using kinase-active site inhibitors have not typically led to durable clinical benefit. To address this shortcoming, we sought to test the feasibility of an alternative targeting strategy, focused on the ERK2 substrate binding domains, D and DEF binding pocket (DBP). Disabling the ERK2-DBP domain in mice caused baseline erythrocytosis. Consequently, we investigated the role of the ERK2-D and -DBP domains in disease, using a JAK2-dependent model of polycythemia vera (PV). Of note, inactivation of the ERK2-DBP domain promoted the progression of disease from PV to myelofibrosis, suggesting that the ERK2-DBP domain normally opposes progression. ERK2-DBP inactivation also prevented oncogenic JAK2 kinase (JAK2V617F) from promoting oncogene-induced senescence in vitro. The ERK2-DBP mutation attenuated JAK2-mediated oncogene-induced senescence by preventing the physical interaction of ERK2 with the transcription factor Egr1. Because inactivation of the ERK2-DBP created a functional ERK2 kinase limited to binding substrates through its D domain, these data suggested that the D domain substrates were responsible for promoting oncogene-induced progenitor growth and tumor progression and that pharmacologic targeting of the ERK2-D domain may attenuate cancer cell growth. Indeed, pharmacologic agents targeting the ERK2-D domain were effective in attenuating the growth of JAK2-dependent myeloproliferative neoplasm cell lines. Taken together, these data indicate that the ERK-D and -DBP domains can play distinct roles in the progression of neoplasms and that the D domain has the potential to be a potent therapeutic target in Ras/MAPK-dependent cancers.

Guía de práctica clínica para el diagnóstico y tratamiento de la distrofia muscular de Duchenne. Sociedad Peruana de Neurología. Versión Corta / Clinical Practice Guidelines for diagnosis and treatment of Duchenne muscular dystrophy. Peruvian Neurology Society. Short Version

RESUMEN Objetivo : Elaborar una guía de práctica clínica peruana para el diagnóstico y tratamiento de la Distrofia Muscular de Duchenne y Becker (DMD). Materiales y métodos : Se conformó un grupo elaborador de la guía (GEG) que incluyó médicos especialistas en neurología, neuropediatría, genética y metodología. El GEG formuló ocho preguntas para desarrollar las recomendaciones de la Guía de Práctica Clínica (GPC). Se realizó una búsqueda sistemática en Medline, Scopus y CCRT durante el periodo enero-abril 2021 para responder a las preguntas PICO. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Resultados : Las preguntas PICO, se orientaron para explorar el tamizaje, diagnóstico y tratamiento de la DMD. Se formularon 15 recomendaciones (10 fuertes, 5 condicionales) y 11 puntos de buena práctica clínica Conclusión : Se presenta la guía para el diagnóstico y tratamiento de la DMD, elaborada bajo una metodología basada en las evidencias actuales.

ABSTRACT Objective : to provide evidence-based clinical recommendations for the diagnosis and treatment of Duchenne Muscular Dystrophy. Methods : a guideline development group (GEG) was formed that included specialized physicians in the fields of neurology, neuropediatrics, genetics, and methodology. The GEG asked eight clinical questions to be answered by recommendations in this clinical practice guidelines (CPG). We conducted a systematic search and - when deemed relevant - primary studies in Medline, Scopus, and the Cochrane Controlled Register of Trials during 2021 were reviewed. Evidence was selected to answer each of the clinical questions posed. Certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. In periodic work meetings, the GEG used the GRADE methodology to review the evidence and formulate recommendations, points of good clinical practice, and a diagnosis and treatment flowchart. Results : this CPG addressed eight clinical questions, divided into three topics: screening, diagnosis, and treatment. Based on these questions, fifteen recommendations were formulated (10 strong, 5 conditional) and 11 points for good clinical practice. Conclusion : this paper summarizes the methodology and evidence- based conclusions of the CPG for the diagnosis and treatment of Duchenne muscular dystrophy.

Perception of HIV physicians in Spain towards diagnosis and management of neuropsychiatric comorbidities in people with HIV.

OBJECTIVES: Despite the importance of neuropsychiatric comorbidities (NPCs) in people with HIV, the degree of physician compliance with recommendations for diagnosis and management is unknown. This study assessed the perceptions, knowledge, skills, and attitudes of physicians regarding the diagnosis and management of NPCs in people with HIV in hospital settings in Spain. METHODS: This was a cross-sectional study including non-psychiatrist HIV specialist physicians responsible for antiretroviral therapy (ART) prescription and clinical care of ≥50 people with HIV/month, who completed an online survey of 34 questions. RESULTS: The 115 physicians who completed the survey (totally) agreed that assessing mental health was relevant (97.4%) and that NPCs were underdiagnosed (76.6%) and were very/fairly sensitized (67.8%). However, they reported receiving little/no training on the detection of NPCs (64.3%). Physicians considered that patients underreported NPCs (53.9%) and that alcohol (94.8%), recreational substances (97.4%), and tobacco consumption (95.6%) were (very) relevant. Physicians agreed that NPCs were difficult to identify (52.2%) and that few tools were available (53.0%) and failed to use questionnaires (79.1%) and follow guidelines (77.4%) for the detection of NPCs. The main reasons precluding appropriate diagnosis and evaluation were lack of proactive attitudes and specific training and limited visit time. Upon detection of NPCs, physicians referred patients to the in-house psychiatry/psychology centre (61.7%), adjusted ART to minimize interactions (96.5%), and managed NPCs in conjunction with mental health professionals (71.3%). CONCLUSIONS: Physicians in hospital settings in Spain were aware of the relevance of NPC diagnosis and their underdiagnosis. However, they still failed to routinely evaluate NPCs, follow guideline recommendations, and use questionnaires, highlighting opportunities for improved NPC detection and management in people with HIV.