Development and validation of a predictive model for choledocholithiasis.

BACKGROUND: Gallstone-related conditions affect a significant portion of the population, with varying prevalence among different ethnic groups. Complications such as pancreatitis and cholangitis are associated with the presence of common bile duct (CBD) stones. Existing guidelines for diagnosing choledocholithiasis lack precision, leading to excessive use of invasive procedures like endoscopic retrograde cholangiopancreatography (ERCP). METHODS: A prospective study was conducted at Hospital Central "Dr. Ignacio Morones Prieto," involving 374 patients in the development cohort and 154 patients in the validation cohort. Patients meeting inclusion criteria underwent biochemical testing and ultrasonography. A predictive scoring system was developed using logistic regression and validated in an independent cohort. Clinical and laboratory variables were collected, and model performance was assessed using receiver-operator characteristic (ROC) curves. RESULTS: The predictive model incorporated variables such as age, pancreatitis, cholangitis, bilirubin levels, and CBD stone presence on ultrasound. The model demonstrated an area under the ROC curve (AUC) of 93.81% in the validation dataset. By adjusting the threshold defining high-risk probability to 40%, the model improved specificity and sensitivity compared to existing guidelines. Notably, the model reclassified patients, leading to a more accurate risk assessment. CONCLUSIONS: The developed algorithm accurately predicts choledocholithiasis non-invasively in patients with symptomatic gallstones. This tool has the potential to reduce reliance on costly or invasive procedures like magnetic resonance cholangiopancreatography and ERCP, offering a more efficient and cost-effective approach to patient management. The user-friendly calculator developed in this study could streamline diagnostic procedures, particularly in resource-limited healthcare settings, ultimately improving patient care.

ATTRv-V30M Type A amyloid fibrils from heart and nerves exhibit structural homogeneity.

ATTR amyloidosis is a systemic disease characterized by the deposition of amyloid fibrils made of transthyretin, a protein integral to transporting retinol and thyroid hormones. Transthyretin is primarily produced by the liver and circulates in blood as a tetramer. The retinal epithelium also secretes transthyretin, which is secreted to the vitreous humor of the eye. Because of mutations or aging, transthyretin can dissociate into amyloidogenic monomers triggering amyloid fibril formation. The deposition of transthyretin amyloid fibrils in the myocardium and peripheral nerves causes cardiomyopathies and neuropathies, respectively. Using cryo-electron microscopy, here we determined the structures of amyloid fibrils extracted from cardiac and nerve tissues of an ATTRv-V30M patient. We found that fibrils from both tissues share a consistent structural conformation, similar to the previously described structure of cardiac fibrils from an individual with the same genotype, but different from the fibril structure obtained from the vitreous humor. Our study hints to a uniform fibrillar architecture across different tissues within the same individual, only when the source of transthyretin is the liver. Moreover, this study provides the first description of ATTR fibrils from the nerves of a patient and enhances our understanding of the role of deposition site and protein production site in shaping the fibril structure in ATTRv-V30M amyloidosis.

Surgical treatment of pituitary neuroendocrine tumors with coexisting intracranial lesions: A case series and review of the literature.

Background: Pituitary neuroendocrine tumors (PitNETs) are a diverse group of benign neoplasms that account for a significant proportion of intracranial tumors (13%). The coexistence of PitNET with other intracranial lesions, such as meningiomas and intracranial aneurysms, has been constantly reported in the literature; yet, the pathophysiological mechanisms remain unknown, and the appropriate management is controversial. This study aims to describe the clinical characteristics, surgical treatment, and outcomes of patients with PitNET with coexisting intracranial lesions in a single healthcare center. Methods: A retrospective analysis was conducted on 12 patients who underwent surgical treatment for PitNET and another intracranial lesion at our single tertiary referral center over 15 years from January 2008 to May 2023. Results: Among these coexisting lesions, aneurysms were the most commonly found (41.67%), followed by meningiomas (33.33%). Surgical intervention for both lesions was performed in a single-stage procedure for most cases (75%), employing transcranial, endoscopic endonasal, and combined approaches. We found low preoperative Karnofsky Performance Scale scores in three patients, with significant differences in functional outcomes. Conclusion: These findings contribute to the limited knowledge about PitNET coexisting with other intracranial lesions and emphasize the importance of patient-tailored, multidisciplinary management in these unusual scenarios.

Galectin-3 depletion tames pro-tumoural microglia and restrains cancer cells growth.

Galectin-3 (Gal-3) is a multifunctional protein that plays a pivotal role in the initiation and progression of various central nervous system diseases, including cancer. Although the involvement of Gal-3 in tumour progression, resistance to treatment and immunosuppression has long been studied in different cancer types, mainly outside the central nervous system, its elevated expression in myeloid and glial cells underscores its profound impact on the brain's immune response. In this context, microglia and infiltrating macrophages, the predominant non-cancerous cells within the tumour microenvironment, play critical roles in establishing an immunosuppressive milieu in diverse brain tumours. Through the utilisation of primary cell cultures and immortalised microglial cell lines, we have elucidated the central role of Gal-3 in promoting cancer cell migration, invasion, and an immunosuppressive microglial phenotypic activation. Furthermore, employing two distinct in vivo models encompassing primary (glioblastoma) and secondary brain tumours (breast cancer brain metastasis), our histological and transcriptomic analysis show that Gal-3 depletion triggers a robust pro-inflammatory response within the tumour microenvironment, notably based on interferon-related pathways. Interestingly, this response is prominently observed in tumour-associated microglia and macrophages (TAMs), resulting in the suppression of cancer cells growth.

Critical Examination of Modeling Approaches Used in Economic Evaluations of First-Line Treatments for Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations: A Systematic Literature Review.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with up to 32% of patients with NSCLC harboring an epidermal growth factor receptor (EGFR) mutation. NSCLC harboring an EGFR mutation has a dedicated treatment pathway, with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy often being the therapy of choice. OBJECTIVE: The aim of this study was to systemically review and summarize economic models of first-line treatments used for locally advanced or metastatic NSCLC harboring EGFR mutations, as well as to identify areas for improvement for future models. METHODS: Literature searches were conducted via Ovid in PubMed, MEDLINE, MEDLINE In-Process, Embase, Evidence-Based Medicine Reviews: Health Technology Assessment, Evidence-Based Medicine Reviews: National Health Service Economic Evaluation Database, and EconLit. An initial search was conducted on 19 December 2022 and updated on 11 April 2023. Studies were selected according to predefined criteria using the Population, Intervention, Comparator, Outcome and Study design (PICOS) framework. RESULTS: Sixty-seven articles were included in the review, representing 59 unique studies. The majority of included models were cost-utility analyses (n = 52), with the remaining studies being cost-effectiveness analyses (n = 4) and a cost-minimization analysis (n = 1). Two studies incorporated both a cost-utility and cost-minimization analysis. Although the model structure across studies was consistently reported, justification for this choice was often lacking. CONCLUSIONS: Although the reporting of economic models in NSCLC harboring EGFR mutations is generally good, many of these studies lacked sufficient reporting of justification for structural choices, performing extensive sensitivity analyses and validation in economic evaluations. In resolving such gaps, the validity of future models can be increased to guide healthcare decision making in rare indications.

Visual outcomes in tuberculum sellae meningiomas comparing transcranial and endoscopic endonasal approaches.

Background: Tuberculum sellae meningiomas (TSM) account for 3-10% of intracranial meningiomas. Visual loss is the presenting symptom in up to 80% of cases. Surgical management poses a great challenge due to tumor proximity to neurovascular structures such as the optic nerve and the internal carotid artery (ICA); hence, there is controversy regarding the optimal approach. The aim of this study is to determine differences in visual outcomes between transcranial (TCA) and endoscopic endonasal (EEA) approaches. Methods: A retrospective study including 29 patients with TSM surgically treated by TCA or EEA between 2011 and 2023 in a single referral center was conducted. Pre-and post-operative neuro-ophthalmologic evaluations, focusing on visual acuity and campimetry, were evaluated. Results: Sixteen (55.16%) patients were intervened through a TCA and the remaining 13 (44.84%) via an EEA. The lesions in each group were similar in terms of pre- operative volume (15.12 vs 12.9 cm3, p = 0.497) and neurovascular invasion (optic canal invasion 48.26 vs 41.37%, p = 0.664; ICA 44.81 vs 31.03%, p = 0.797). There were no significant differences in visual outcomes between both approaches; TCA presented an improvement of 5.18 points in visual fields (p = 0.140), whereas EEA had an improvement of 17.39 points in visual acuity (p = 0.114). Conclusion: EEA seems to offer greater improvement in visual acuity than TCA. However, the ideal approach should be individualized; taking into account the tumor's volume and invasiveness, as well as the patient's visual complaints.

Transfection of the BDNF Gene in the Surviving Dopamine Neurons in Conjunction with Continuous Administration of Pramipexole Restores Normal Motor Behavior in a Bilateral Rat Model of Parkinson's Disease.

In Parkinson's disease (PD), progressive degeneration of nigrostriatal innervation leads to atrophy and loss of dendritic spines of striatal medium spiny neurons (MSNs). The loss disrupts corticostriatal transmission, impairs motor behavior, and produces nonmotor symptoms. Nigral neurons express brain-derived neurotropic factor (BDNF) and dopamine D3 receptors, both protecting the dopamine neurons and the spines of MSNs. To restore motor and nonmotor symptoms to normality, we assessed a combined therapy in a bilateral rat Parkinson's model, with only 30% of surviving neurons. The preferential D3 agonist pramipexole (PPX) was infused for four ½ months via mini-osmotic pumps and one month after PPX initiation; the BDNF-gene was transfected into the surviving nigral cells using the nonviral transfection NTS-polyplex vector. Overexpression of the BDNF-gene associated with continuous PPX infusion restored motor coordination, balance, normal gait, and working memory. Recovery was also related to the restoration of the average number of dendritic spines of the striatal projection neurons and the number of TH-positive neurons of the substantia nigra and ventral tegmental area. These positive results could pave the way for further clinical research into this promising therapy.

Compounds Consisting of Quinazoline, Ibuprofen, and Amino Acids with Cytotoxic and Anti-Inflammatory Effects.

In this research work, a series of 16 quinazoline derivatives bearing ibuprofen and an amino acid were designed as inhibitors of epidermal growth factor receptor tyrosine kinase domain (EGFR-TKD) and cyclooxygenase-2 (COX-2) with the intention of presenting dual action in their biological behavior. The designed compounds were synthesized and assessed for cytotoxicity on epithelial cancer cells lines (AGS, A-431, MCF-7, MDA-MB-231) and epithelial non-tumorigenic cell line (HaCaT). From this evaluation, derivative 6 was observed to exhibit higher cytotoxic potency (IC50) than gefitinib (reference drug) on three cancer cell lines (0.034 µM in A-431, 2.67 µM in MCF-7, and 3.64 µM in AGS) without showing activity on the non-tumorigenic cell line (>100 µM). Furthermore, assessment of EGFR-TKD inhibition by 6 showed a discreet difference compared to gefitinib. Additionally, 6 was used to conduct an in vivo anti-inflammatory assay using the 12-O-tetradecanoylphorbol-3-acetate (TPA) method, and it was shown to be 5 times more potent than ibuprofen. Molecular dynamics studies of EGFR-TKD revealed interactions between compound 6 and M793. On the other hand, one significant interaction was observed for COX-2, involving S531. The RMSD graph indicated that the ligand remained stable in 50 ns.

Technetium-99m-ubiquicidin 29-41 SPECT-CT to detect postsurgical spinal infection: A case report.

Background: Postsurgical spinal infections are a severe complication and a challenge to the neurosurgeon due to their complex management. Revision surgeries and the removal of hardware are usually necessary. Recently, advances in nuclear medicine have made it possible to employ radiotracers to identify infections. The radiolabeled antimicrobial peptide technetium-99m-ubiquicidin (99mTc-UBI) (29-41) has been demonstrated to detect bacterial infections. UBI 29-41 is a peptide sequence with selective binding to the anionic cell membrane of bacteria, which has recently been used to differentiate between infection and inflammation. Here, we describe the clinical utility of 99mTc-UBI 29-41 single-photon emission computed tomography-computed tomography (SPECT-CT) in a patient suspected of a postoperative infection. Case description: A 54-year-old male who presented with conus medullaris syndrome secondary to T12 spondylodiscitis and multiple abscess collections was initially managed with debridement, corpectomy, and minimally invasive lateral instrumentation. The patient developed postsurgical empyema near the surgical site. The image study avoided the need for a second surgery and hardware removal. Conclusion: The use of 99mTc-UBI 29-41 SPECT-CT served as a tool to avoid a second invasive procedure; instead, conservative management with antibiotics was performed with an effective outcome after two weeks. This radiotracer has utility in cases in which infection is suspected, but the location is not entirely clear, and information is needed to guide the therapeutic approach.

Structural polymorphism of amyloid fibrils in ATTR amyloidosis revealed by cryo-electron microscopy.

ATTR amyloidosis is caused by the deposition of transthyretin in the form of amyloid fibrils in virtually every organ of the body, including the heart. This systemic deposition leads to a phenotypic variability that has not been molecularly explained yet. In brain amyloid conditions, previous studies suggest an association between clinical phenotype and the molecular structures of their amyloid fibrils. Here we investigate whether there is such an association in ATTRv amyloidosis patients carrying the mutation I84S. Using cryo-electron microscopy, we determined the structures of cardiac fibrils extracted from three ATTR amyloidosis patients carrying the ATTRv-I84S mutation, associated with a consistent clinical phenotype. We found that in each ATTRv-I84S patient, the cardiac fibrils exhibited different local conformations, and these variations can co-exist within the same fibril. Our finding suggests that one amyloid disease may associate with multiple fibril structures in systemic amyloidoses, calling for further studies.

Justifying the source of external comparators in single-arm oncology health technology submissions: a review of NICE and PBAC assessments.

Background: The drive to expedite patient access for diseases with high unmet treatment needs has come with an increasing use of single-arm trials (SATs), especially in oncology. However, the lack of control arms in such trials creates challenges to assess and demonstrate comparative efficacy. External control (EC) arms can be used to bridge this gap, with various types of sources available to obtain relevant data. Objective: To examine the source of ECs in single-arm oncology health technology assessment (HTA) submissions to the National Institute for Health and Care Excellence (NICE) and the Pharmaceutical Benefits Advisory Committee (PBAC) and how this selection was justified by manufacturers and assessed by the respective HTA body. Methods: Single-arm oncology HTA submission reports published by NICE (England) and PBAC (Australia) from January 2011 to August 2021 were reviewed, with data qualitatively synthesized to identify themes. Results: Forty-eight oncology submissions using EC arms between 2011 and 2021 were identified, with most submissions encompassing blood and bone marrow cancers (52%). In HTA submissions to NICE and PBAC, the EC arm was typically constructed from a combination of data sources, with the company's justification in data source selection infrequently provided (PBAC [2 out of 19]; NICE [6 out of 29]), although this lack of justification was not heavily criticized by either HTA body. Conclusion: Although HTA bodies such as NICE and PBAC encourage that EC source justification should be provided in submissions, this review found that this is not typically implemented in practice. Guidance is needed to establish best practices as to how EC selection should be documented in HTA submissions.

Navigating the unknown: how to best 'reflect' standard of care in indications without a dedicated treatment pathway in health technology assessment submissions.

There is an urgent need for expedited approval and access for new health technologies targeting rare and very rare diseases, some of which are associated with high unmet treatment needs. Once a new technology achieves regulatory approval, the technology needs to be assessed by health technology assessment (HTA) bodies to inform coverage and reimbursement decisions. This assessment quantitatively examines the clinical effectiveness, safety and/or economic impact of the new technology relative to standard of care (SoC) in a specific market. However, in rare and very rare diseases, the patient populations are small and there is often no established treatment pathway available to define 'SoC'. In these situations, several challenges arise to assess the added benefit of a new technology - both clinically and economically - due to lack of established SoC to guide an appropriate comparator selection. These challenges include: How should 'SoC' be defined and characterized in HTA submissions for new technologies aiming to establish new treatment standards? What is usual care without an established clinical pathway? How should the evidence for the comparator 'SoC' (i.e., usual care) arm be collected in situations with low patient representation and, sometimes, limited disease-specific clinical knowledge in certain geographies? This commentary outlines the evidence generation challenges in designing clinical comparative effectiveness for a new technology when there is a lack of established SoC. The commentary also proposes considerations to facilitate the reliable integration of real-world evidence into HTA and decision-making based on the collective experience of the authors.

Circulating Tumor Cells: From Basic to Translational Research.

BACKGROUND: Metastasis is the leading cause of cancer-related deaths. Most studies have focused on the primary tumor or on overt metastatic lesions, leaving a significant knowledge gap concerning blood-borne cancer cell dissemination, a major step in the metastatic cascade. Circulating tumor cells (CTCs) in the blood of patients with solid cancer can now be enumerated and investigated at the molecular level, giving unexpected information on the biology of the metastatic cascade. CONTENT: Here, we reviewed recent advances in basic and translational/clinical research on CTCs as key elements in the metastatic cascade. SUMMARY: Findings from translational studies on CTCs have elucidated the complexity of the metastatic process. Fully understanding this process will open new potential avenues for cancer therapeutic and diagnostic strategies to propose precision medicine to all cancer patients.

Circulating tumour cells and PD-L1-positive small extracellular vesicles: the liquid biopsy combination for prognostic information in patients with metastatic non-small cell lung cancer.

BACKGROUND: Circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), and extracellular vesicles (EVs) are minimally invasive liquid biopsy biomarkers. This study investigated whether they predict prognosis, alone or in combination, in heterogenous unbiased non-small cell lung cancer (NSCLC) patients. METHODS: Plasma samples of 54 advanced NSCLC patients from a prospective clinical trial. CtDNA mutations were identified using the UltraSEEK™ Lung Panel (MassARRAY® technology). PD-L1 expression was assessed in small EVs (sEVs) using an enzyme-linked immunosorbent assay. RESULTS: At least one ctDNA mutation was detected in 37% of patients. Mutations were not correlated with overall survival (OS) (HR = 1.1, 95% CI = 0.55; 1.83, P = 0.980) and progression-free survival (PFS) (HR = 1.00, 95% CI = 0.57-1.76, P = 0.991). High PD-L1+ sEV concentration was correlated with OS (HR = 1.14, 95% CI = 1.03-1.26, P = 0.016), but not with PFS (HR = 1.08, 95% CI = 0.99-1.18, P = 0.095). The interaction analysis suggested that PD-L1+ sEV correlation with PFS changed in function of CTC presence/absence (P interaction = 0.036). The combination analysis highlighted worse prognosis for patients with CTCs and high PD-L1+ sEV concentration (HR = 7.65, 95% CI = 3.11-18.83, P < 0.001). The mutational statuses of ctDNA and tumour tissue were significantly correlated (P = 0.0001). CONCLUSION: CTCs and high PD-L1+ sEV concentration correlated with PFS and OS, but not ctDNA mutations. Their combined analysis may help to identify patients with worse OS. TRIAL REGISTRATION: NCT02866149, Registered 01 June 2015, https://clinicaltrials.gov/ct2/show/study/NCT02866149 .

Applicability of the Barcelona scale to assess the quality of cleanliness of mucosa at esophagogastroduodenoscopy.

BACKGROUND AND OBJECTIVES: There are few scales with prospective validation for the assessment of the upper gastrointestinal mucosal cleanliness during an esophagogastroduodenoscopy (EGD). The aim of this study was to develop a valid and reproducible cleanliness scale for use during an EGD. METHODS: We developed a cleanliness scale (Barcelona scale) with a score (0-2 points) of five segments of the upper gastrointestinal tract with thorough cleaning techniques (esophagus, fundus, body, antrum, and duodenum). First, 125 photos (25 of each area) were assessed, and a score was assigned to each image by consensus among 7 experts endoscopists. Subsequently, 100 of the 125 images were selected and the inter- and intra-observer variability of 15 previously trained endoscopists was evaluated using the same images at two different times. RESULTS: In total, 1500 assessments were performed. In 1336/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.83 (0.45-0.96). In the second evaluation, in 1330/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.82 (0.45-0.93). The intra-observer variability was 0.89 (0.76-0.99). CONCLUSIONS: The Barcelona cleanliness scale is a valid measure and reproducible with minimal training. Its application in clinical practice is a significant step to standardize the quality of the EGD.

Efficacy of Mobocertinib and Amivantamab in Patients With Advanced Non-Small Cell Lung Cancer With EGFR Exon 20 Insertions Previously Treated With Platinum-Based Chemotherapy: An Indirect Treatment Comparison.

INTRODUCTION: Exon 20 insertions (ex20ins) mutations of the EGFR gene account for 1% to 2% of all non-small-cell lung cancers (NSCLCs). Targeted therapies have been developed to treat this cancer type but have not been studied in head-to-head trials. Our objective was to use a matching-adjusted indirect comparison (MAIC) to assess the efficacy of mobocertinib and amivantamab in patients with NSCLC EGFR ex20ins mutations who were previously treated with platinum-based chemotherapy. MATERIALS AND METHODS: An unanchored MAIC was conducted to estimate the treatment effects of mobocertinib and amivantamab using individual-level data from the mobocertinib phase I/II single-arm trial (NCT02716116) and published data from the amivantamab single-arm CHRYSALIS trial (NCT02609776). Confirmed overall response rate (cORR), progression-free survival (PFS), overall survival (OS), and duration of response (DoR) were assessed. RESULTS: Both trials were comparable in terms of study population, study design, and outcome definitions and included 114 patients who received mobocertinib and 114 patients who received amivantamab. After MAIC weighting, all reported baseline characteristics were balanced between mobocertinib and amivantamab. The weighted odds ratio (OR) [95% confidence interval (CI)] comparing mobocertinib to amivantamab was 0.56 (0.30-1.04) for independent review committee (IRC)-assessed cORR and 0.98 (0.53-1.82) for investigator (INV)-assessed cORR. The weighted hazard ratio (HR) comparing mobocertinib to amivantamab was 0.74 (0.51-1.07) for IRC-assessed PFS, 0.92 (0.57-1.48) for OS, and 0.59 (0.30-1.18) for INV-assessed DoR. CONCLUSION: MAIC analysis showed that mobocertinib and amivantamab had similar efficacy in patients with NSCLC harboring EGFR ex20ins mutations whose disease progressed during or after platinum-based chemotherapy. These findings may benefit patients by supporting future treatment options.

Beyond direct exposure to violence: effects of living in disordered and violent communities on psychological distress in young Mexican people / Más allá de la exposición directa a la violencia: efectos de residir en comunidades desordenadas y violentas sobre el distrés psicológico entre jóvenes mexicanos / Além da exposição direta à violência: efeitos de viver em comunidades desordenadas e violentas sobre o estresse psicológico entre jovens mexicanos

Abstract: The association between community violence and mental health has been studied by reports of individual experiences, particularly in adolescents and youths, but little is known about the effect of living in disordered and violent communities. This study aims to determine the possible relation between living in disordered and violent community environments and psychological distress in Mexican adolescents and youths regardless of their individual experience of victimization and to assess the potential modifying effect of sex and age on this association. Data come from a cross-sectional survey with a representative sample of adolescents and youths living in Mexican municipalities, including 39,639 participants aged from 12 to 29 years. Disordered and violent community environments were assessed using reports from a secondary sample of adults who lived in the same communities as participants. Using exploratory factor analysis, three contextual variables related to disordered and violent community environment were created: social disorder, vandalism, and criminality. Multilevel linear regression models with random intercept were estimated. Adolescents and youths who lived in environments with higher social disorder had more psychological distress. Men in environments with greater vandalism had a higher level of psychological distress. Unexpectedly, women from communities with higher levels of crime had fewer symptoms. It is necessary to address the violence that exists in these communities, creating strategies that reduce not only crime, but also the social disorder and vandalism that could contribute to developing negative effects on mental health.

Resumen: La asociación entre la violencia comunitaria y la salud mental se ha evaluado mediante informes de experiencias individuales, especialmente de adolescentes y jóvenes, pero poco se sabe sobre el efecto de residir en comunidades desordenadas y violentas. El objetivo de este estudio fue comprobar si existe una relación entre residir en entornos comunitarios desordenados y violentos y el distrés psicológico en adolescentes y jóvenes mexicanos, independientemente de su experiencia individual de victimización, así como evaluar el posible efecto modificador del sexo y la edad en esta asociación. Los datos provienen de una encuesta transversal que tomó como muestra representativa a 39.639 adolescentes y jóvenes de entre 12 y 29 años, residentes en ciudades mexicanas. Los entornos comunitarios desordenados y violentos se evaluaron mediante informes de una muestra secundaria de adultos que residían en las mismas comunidades donde vivían los participantes. El análisis exploratorio de datos posibilitó crear tres variables contextuales relacionadas con el entorno comunitario desordenado y violento: desorden social, vandalismo y delincuencia. Se estimaron modelos de regresión lineal multinivel con intercepto aleatorio. Los adolescentes y jóvenes que residían en ambientes con mayor desorden social presentaron mayor distrés psicológico. Los varones en entornos con más vandalismo tenían un mayor nivel de distrés psicológico. Inesperadamente, las mujeres que viven en comunidades con mayores niveles de delincuencia tuvieron menos síntomas. Es necesario enfrentar la violencia existente en las comunidades para generar estrategias que reduzcan no solo la delincuencia, sino también el desorden social y el vandalismo que pueden contribuir al desarrollo de efectos negativos en la salud mental.

Resumo: A associação entre violência comunitária e saúde mental tem sido estudada por meio de relatos de experiências individuais, particularmente em adolescentes e jovens, mas pouco se sabe sobre o efeito de viver em comunidades desordenadas e violentas. O objetivo deste estudo é determinar se há relação entre viver em ambientes comunitários desordenados e violentos e estresse psicológico em adolescentes e jovens mexicanos, independentemente de sua experiência individual de vitimização, e avaliar o potencial efeito modificador do sexo e da idade sobre essa associação. Os dados são de uma pesquisa transversal com uma amostra representativa de adolescentes e jovens residentes em cidades mexicanas, incluindo 39.639 participantes com idades de 12 a 29 anos. Ambientes comunitários desordenados e violentos foram avaliados por meio de relatos de uma amostra secundária de adultos que viviam nas mesmas comunidades onde os participantes viviam. Por meio da análise exploratória de dados, foram criadas três variáveis contextuais relacionadas ao ambiente comunitário desordenado e violento: desordem social, vandalismo e criminalidade. Foram estimados modelos de regressão linear multinível com interceptação aleatória. Adolescentes e jovens que viviam em ambientes com maior desordem social apresentaram maior estresse psicológico. Homens em ambientes com mais vandalismo apresentaram maior nível de estresse psicológico. Inesperadamente, as mulheres de comunidades com níveis mais altos de criminalidade tiveram menos sintomas. É preciso enfrentar a violência existente nas comunidades, gerando estratégias que reduzam não só a criminalidade, mas também a desordem social e o vandalismo que possam contribuir para o desenvolvimento de efeitos negativos na saúde mental.

Efectividad del uso de la entrevista motivacional en la consulta de nutrición sobre el riesgo cardiometabólico de pacientes con trastorno bipolar / Effectiveness of the motivational interviewing on cardiometabolic indicators of patients with bipolar disorder

Resumen El propósito de este trabajo fue evaluar la efectividad de la entrevista motivacional en la consulta de nutrición sobre indicadores de riesgo cardiometabólico en pacientes con trastorno bipolar. Se realizó un estudio experimental en que el grupo control recibió orientación nutricional basada en planes de alimentación y el grupo de intervención recibió consulta nutricional incorporando los principios y habilidades de la entrevista motivacional. Los participantes fueron seguidos por tres meses y se realizaron evaluaciones de hábitos alimenticios, actividad física, riesgo cardiometabólico, composición corporal y calidad de vida. El grupo de entrevista motivacional redujo el consumo de carnes (B=-0.45, p=0.032) y embutidos (B=-0.60, p=0.002). Asimismo, la presión arterial diastólica (B=-6.97, p=0.029) y glucemia (B=-9.27, p=0.097) de estos pacientes tendieron a disminuir. La entrevista motivacional promueve cambios que pueden hacer una diferencia clínica; aun en reducidos periodos de tiempo. Los nutriólogos capacitados para su implementación disponen de una herramienta adicional para el manejo de comorbilidad cardiometabólica en población vulnerable.

Abstract The purpose of this work was to assess the effectiveness of the motivational interviewing in the nutrition consultation on indicators of cardiometabolic risk in patients with bipolar disorder. An experimental study was conducted in which the control group receives nutritional guidance based on feeding plans and the intervention group received nutritional consultation incorporating the principles and skills of the motivational interviewing. Participants were followed by three months and evaluations of eating habits, physical activity, cardiometabolic risk, body composition and quality of life were carried out. The motivational interviewing group reduced the consumption of meats (B=-0.45, p=0.032) and sausages (B=-0.60, p=0.002). Likewise, the diastolic blood pressure (B=-6.97, p=0.029) and glycemia (B=-9.27, p=0.097) of these patients tended to decrease. Motivational interviewing promotes changes that can make a clinical difference, even in short periods of time. Nutritionists trained for its implementation have an additional tool for the management of cardiometabolic comorbidity in a vulnerable population.

Unilateral caudate infarct following pituitary adenoma resection.

Cerebral ischemic complications after pituitary surgery are not frequently reported. Multiple mechanisms have been proposed, including vasospasm, and delayed cerebral ischemia resulting from postoperative subarachnoid bleeding. Given the unknown etiology of vasospasm following these situations, little is known about its prevention. Through a case report and bibliographic review, the authors warn about the importance of recognizing key signs postoperatively that could indicate increased risk for cerebral vasospasm and must be recognized in a timely manner, with appropriate treatment strategies implemented once these symptoms present.

Overcoming chemotherapy resistance in low-grade gliomas: A computational approach.

Low-grade gliomas are primary brain tumors that arise from glial cells and are usually treated with temozolomide (TMZ) as a chemotherapeutic option. They are often incurable, but patients have a prolonged survival. One of the shortcomings of the treatment is that patients eventually develop drug resistance. Recent findings show that persisters, cells that enter a dormancy state to resist treatment, play an important role in the development of resistance to TMZ. In this study we constructed a mathematical model of low-grade glioma response to TMZ incorporating a persister population. The model was able to describe the volumetric longitudinal dynamics, observed in routine FLAIR 3D sequences, of low-grade glioma patients acquiring TMZ resistance. We used the model to explore different TMZ administration protocols, first on virtual clones of real patients and afterwards on virtual patients preserving the relationships between parameters of real patients. In silico clinical trials showed that resistance development was deferred by protocols in which individual doses are administered after rest periods, rather than the 28-days cycle standard protocol. This led to median survival gains in virtual patients of more than 15 months when using resting periods between two and three weeks and agreed with recent experimental observations in animal models. Additionally, we tested adaptive variations of these new protocols, what showed a potential reduction in toxicity, but no survival gain. Our computational results highlight the need of further clinical trials that could obtain better results from treatment with TMZ in low grade gliomas.