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.

Oxidative stress involvement in the molecular pathogenesis and progression of multiple sclerosis: a literature review.

Multiple sclerosis (MS) is an autoimmune debilitating disease of the central nervous system caused by a mosaic of interactions between genetic predisposition and environmental factors. The pathological hallmarks of MS are chronic inflammation, demyelination, and neurodegeneration. Oxidative stress, a state of imbalance between the production of reactive species and antioxidant defense mechanisms, is considered one of the key contributors in the pathophysiology of MS. This review is a comprehensive overview of the cellular and molecular mechanisms by which oxidant species contribute to the initiation and progression of MS including mitochondrial dysfunction, disruption of various signaling pathways, and autoimmune response activation. The detrimental effects of oxidative stress on neurons, oligodendrocytes, and astrocytes, as well as the role of oxidants in promoting and perpetuating inflammation, demyelination, and axonal damage, are discussed. Finally, this review also points out the therapeutic potential of various synthetic antioxidants that must be evaluated in clinical trials in patients with MS.

Overexpression of alpha synuclein disrupts APP and Endolysosomal axonal trafficking in a mouse model of synucleinopathy.

Mutations or triplication of the alpha synuclein (ASYN) gene contribute to synucleinopathies including Parkinson's disease (PD), Dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). Recent evidence suggests that ASYN also plays an important role in amyloid-induced neurotoxicity, although the mechanism(s) remains unknown. One hypothesis is that accumulation of ASYN alters endolysosomal pathways to impact axonal trafficking and processing of the amyloid precursor protein (APP). To define an axonal function for ASYN, we used a transgenic mouse model of synucleinopathy that expresses a GFP-human ASYN (GFP-hASYN) transgene and an ASYN knockout (ASYN-/-) mouse model. Our results demonstrate that expression of GFP-hASYN in primary neurons derived from a transgenic mouse impaired axonal trafficking and processing of APP. In addition, axonal transport of BACE1, Rab5, Rab7, lysosomes and mitochondria were also reduced in these neurons. Interestingly, axonal transport of these organelles was also affected in ASYN-/- neurons, suggesting that ASYN plays an important role in maintaining normal axonal transport function. Therefore, selective impairment of trafficking and processing of APP by ASYN may act as a potential mechanism to induce pathological features of Alzheimer's disease (AD) in PD patients.

Impact of Ketamine on Quality of Recovery after Laparoscopic Surgery: A Single-Centre Single-Blinded Trial Using the QoR-15 Questionnaire.

Background: The quality of recovery is a cluster of patient-related outcomes that emphasise not only pain but different physical and emotional dimensions. Traditionally, ketamine is used to improve postoperative analgesia and avoid opioid consumption and opioid-related side effects. Objective: The present study sought to evaluate if intraoperative ketamine administration (as a part of multimodal analgesia) influences the quality of recovery after laparoscopic surgery. Design: A prospective two-armed, single-blinded trial. Settings. Tertiary single-centre trial between July 2021 and January 2022. Patients. From the 146 patients initially admitted to the study, 127 patients were enrolled, 60 in the ketamine group (group K) and 67 in the control group (group NK). Intervention. Both groups received a rigid intraoperative anaesthesia protocol; furthermore, in group K, 0.5 mg/kg of the ideal body weight of ketamine was administered. Main Outcome Measures. The primary outcome was to evaluate the effect of ketamine administration on the postoperative quality of recovery using the Portuguese version of the Quality of Recovery-15 (QoR-15) Questionnaire 24 h after surgery. The total score and minimal clinically significant difference (MCID) of the QoR-15 were compared. Other variables were also assessed such as the presence of emergence delirium (ED), the Numeric Rating Scale (NRS) for pain, and the presence of postoperative nausea and vomiting (PONV). Results: A total of 127 patients were allocated to the study groups, 60 in group K and 67 in group NK. Regarding the primary outcome, no differences were found in individual categories (15 items) and in the total score of QoR-15 (p=0.214). Concerning improvement (MCID ≥ 8) or worsening (MCID ≤ 8) in quality of recovery, no difference was found between the groups (24 vs. 32 and 6 vs. 6; p=0.776). Finally, no difference was found in secondary postoperative outcomes including ED (p=0.55), NRS (p=0.401), and PONV (p=0.55). Conclusion: In this study, the administration of ketamine in laparoscopic surgery had no impact on the quality of recovery 24 h after surgery. This trial is registered with NCT03724019.

Difference in mortality rates in hospitalized COVID-19 patients identified by cytokine profile clustering using a machine learning approach: An outcome prediction alternative.

COVID-19 is a disease caused by the novel Coronavirus SARS-CoV-2 causing an acute respiratory disease that can eventually lead to severe acute respiratory syndrome (SARS). An exacerbated inflammatory response is characteristic of SARS-CoV-2 infection, which leads to a cytokine release syndrome also known as cytokine storm associated with the severity of the disease. Considering the importance of this event in the immunopathology of COVID-19, this study analyses cytokine levels of hospitalized patients to identify cytokine profiles associated with severity and mortality. Using a machine learning approach, 3 clusters of COVID-19 hospitalized patients were created based on their cytokine profile. Significant differences in the mortality rate were found among the clusters, associated to different CXCL10/IL-38 ratio. The balance of a CXCL10 induced inflammation with an appropriate immune regulation mediated by the anti-inflammatory cytokine IL-38 appears to generate the adequate immune context to overrule SARS-CoV-2 infection without creating a harmful inflammatory reaction. This study supports the concept that analyzing a single cytokine is insufficient to determine the outcome of a complex disease such as COVID-19, and different strategies incorporating bioinformatic analyses considering a broader immune profile represent a more robust alternative to predict the outcome of hospitalized patients with SARS-CoV-2 infection.

Lipopolysaccharide from Porphyromonas gingivalis, but Not from Porphyromonas endodontalis, Induces Macrophage M1 Profile.

Apical Lesions of Endodontic Origin (ALEO) are initiated by polymicrobial endodontic canal infection. Porphyromonas gingivalis (Pg) and Porphyromonas endodontalis (Pe) lipopolysaccharides (LPS) can induce a pro-inflammatory macrophage response through their recognition by TLR2 and TLR4. However, polarization responses induced by Pg and/or Pe LPS in macrophages are not fully understood. We aimed to characterize the polarization profiles of macrophages differentiated from THP-1 cells following Pg and/or Pe LPS stimulation from reference strain and clinical isolates. A modified LPS purification protocol was implemented and the electrophoretic LPS profiles were characterized. THP-1 human monocytes differentiated to macrophages were stimulated with Pg and Pe LPS. Polarization profiles were characterized through cell surface markers and secreted cytokines levels after 24 h of stimulation. TLR2 and TLR4 cell surfaces and transcriptional levels were determined after 24 or 2 h of LPS stimulation, respectively. LPS from Pg induced a predominant M1 profile in macrophages evidenced by changes in the expression of the surface marker CD64 and pro-inflammatory cytokine profiles, TNF-α, IL-1ß, IL-6, and IL-12. Pe LPS was unable to induce a significant response. TLR2 and TLR4 expressions were neither modified by Pg or Pe LPS. Pg LPS, but not Pe LPS, induced a macrophage M1 Profile.

Capsaicin 8% for Peripheral Neuropathic Pain Treatment: A Retrospective Cohort Study.

BACKGROUND: Chronic neuropathic pain is a disabling condition that affects quality of life. Despite recommendations and guidelines, treatment remains suboptimal as it often does not result in significant symptom relief. Capsaicin 8% patch has been used for the treatment of several peripheral neuropathic pain etiologies with encouraging results. OBJECTIVES: To assess the results of capsaicin 8% patch on neuropathic pain by evaluating pain intensity and the painful treatment area. STUDY DESIGN: Observational retrospective cohort study. SETTING: All patients submitted to capsaicin treatment at the Chronic Pain Unit of the Hospital Centre of Tondela Viseu, from 2011 through 2019. METHODS: Records of capsaicin treatments were reviewed, and the data collected. The primary outcome was pain intensity and painful treatment area reduction between the first and last treatment. Also, the number of treatments performed, neuropathic pain duration, anatomic location, pain etiology, and concomitant oral pain medication at baseline and upon treatment conclusion was also listed. RESULTS: Postsurgical neuropathic pain was the most common etiology (49%), followed by postherpetic (28%). The median (interquartile range [IQR]) baseline pain intensity assessed by the Numeric Rating Scale (NRS-11) was 6 (5-8) and the median (IQR) final NRS-11 was 3 (1-5), with a median (IQR) relative difference of -0.5 (-0.85-0.17) with statistically significant differences (P < 0.001) between baseline and last pain intensity, regarding all groups. Also, there was a reduction in the painful treatment area between baseline and the last evaluation, with a median (IQR) relative difference of -0.4 (-0.625-0.167). LIMITATIONS: A relatively small sample and occasional different timing for pain intensity and pain treatment area assessment due to logistical difficulties. CONCLUSIONS: Capsaicin 8% patch is a valuable option for the treatment of peripheral neuropathic pain, providing a significant reduction in pain intensity and painful area. It is well tolerated and has a high treatment compliance.Ethics Committee Reference Number: 16/16//04/2021.

Discovery and Characterization of a Novel Aryl Hydrocarbon Receptor Inhibitor, IK-175, and Its Inhibitory Activity on Tumor Immune Suppression.

Aryl hydrocarbon receptor (AHR) is a transcription factor that regulates the activity of multiple innate and adaptive immune cells subsequent to binding to numerous endogenous and exogenous ligands. For example, AHR is activated by the metabolite kynurenine, which is secreted into the tumor microenvironment by cancer cells leading to broad immunosuppression. Therefore, AHR inhibition provides a novel and ideal approach to stimulate immune-mediated recognition and subsequent eradication of tumor cells. We report here the discovery and characterization of IK-175, a novel, potent and selective AHR antagonist with favorable ADME and pharmacokinetic profiles in preclinical species. IK-175 inhibits AHR activity in experimental systems derived from multiple species including mouse, rat, monkey, and humans. In human primary immune cells, IK-175 decreased AHR target gene expression and anti-inflammatory cytokine release and increased proinflammatory cytokine release. Moreover, IK-175 led to a decrease in suppressive IL17A-, IL-22+ expressing T cells in a Th17 differentiation assay. IK-175 dose dependently blocks ligand-stimulated AHR activation of Cyp1a1 transcription in mouse liver and spleen, demonstrating on-target in vivo activity. IK-175 increases proinflammatory phenotype of the tumor microenvironment in mouse syngeneic tumors and in adjacent tumor-draining lymph nodes. As a monotherapy and combined with an anti-PD-1 antibody, IK-175 demonstrates antitumor activity in syngeneic mouse models of colorectal cancer and melanoma. IK-175 also demonstrates antitumor activity combined with liposomal doxorubicin in syngeneic mouse tumors. These studies provide rationale for targeting AHR in patients with cancer. IK-175 is being evaluated in a phase I clinical trial in patients with advanced solid tumors.

Neuromyelitis Optica Spectrum Disorder in Central America and the Caribbean: A Multinational Clinical Characterization Study.

Here, a study of NMOSD in Central America and the Caribbean with a multinational collaborative, multicentric and descriptive approach involving 25 institutions from 9 countries is presented. Demographics, clinical manifestations, expanded disability scale status (EDSS), brain and spinal cord MRI, serological anti-AQP4-IgG and anti-MOG-IgG antibodies, and cerebrospinal fluid (CSF) oligoclonal bands were included. A central serological repository utilized the cell-based assay. The specimens outside of this network employed diverse methodologies. Data were collected at the Gorgas Commemorative Institute of Health Studies (ICGES), Panama, and included 186 subjects, of which 84% were females (sex ratio of 5.6:1). Mestizos constituted 72% of the study group. The median age was 42.5 years (IQR: 32.0-52.0). Associated autoimmune diseases (8.1%) were myasthenia gravis, Sjögren's syndrome and systemic lupus erythematosus. The most common manifestation was optic neuritis-transverse myelitis (42.5%). A relapsing course was described in 72.3% of cases. EDSS scores of 0-3.5 were reported in 57.2% of cases and higher than 7.0 in 14.5%. Positive anti-AQP4-IgG antibody occurred in 59.8% and anti-MOG-IgG antibody in 11.5% of individuals. Antibody testing was lacking for 13.4% of patients. The estimated crude prevalence of NMOSD from Panama and the Dominican Republic was 1.62/100,000 (incidence of 0.08-0.41) and 0.73/100,000 (incidence 0.02-0.14), respectively. This multinational study contributes additional insights and data on the understanding of NMOSD in this Latin American region.

Utilización de láser diodo en tejidos blandos: reporte de 3 casos / Use of diode laser in soft tissue: report of 3 cases

Existen diversas condiciones anatómicas o alteraciones mucogingivales que pueden afectar tanto el normal funcionamiento como la estética gingival de piezas dentarias e implantes dentales. Si bien los tratamientos de estas condiciones se han realizado tradicionalmente con bisturí, el desarrollo tecnológico ha permitido que actualmente se pueden realizar con láser. Existen diferentes tipos de láser, siendo el diodo uno de los más utilizados debido a su menor tamaño, portabilidad, fácil configuración y menor costo. El láser ha adquirido mayor popularidad en cirugías de tejido blando dado sus múltiples beneficios: menor tiempo operatorio, control del sangrado y de la hemostasia, reducción de la cantidad de anestesia, posibilidad de no requerir suturas y minimización del dolor e inflamación postquirúrgica. El propósito de este trabajo es presentar la resolución de tres casos clínicos a los cuales se les realizaron los procedimientos de frenectomía labial, remoción de melanosis gingival y resección de fibroma irritativo mediante el uso de láser diodo. Para desarrollar todos los procedimientos se utilizó un equipo de láser diodo de 940 nm (Biolase®, USA) con una potencia que varió entre 2 y 2.5 W en modo continuo utilizando una pieza quirúrgica con una punta de 300 µm (E 3-4), la que fue activada antes de empezar. Posterior a la cirugía se bioestimuló para disminuir el dolor y edema postoperatorio utilizando la punta de dolor a 4 W por 30 segundos a una distancia de 1 cm directo en la zona intervenida a todos los casos. La conclusión arroja que en todos los casos, el láser de diodo permitió un resultado exitoso. El procedimiento fue seguro, la técnica fue sencilla y de tiempo clínico reducido. El postoperatorio ocurrió con ausencia de dolor o molestias, generando una mayor satisfacción del paciente. Cabe señalar que la técnica depende de la habilidad del profesional que la realiza.

There are various anatomical conditions or mucogingival alterations that can affect the normal functioning and the gingival aesthetics of teeth and dental implants. Although the treatments of these conditions have been traditionally performed with a scalpel, technological development has allowed that they can be now performed with lasers. There are different types of lasers, being the diode one of the most used due to its smaller size, portability, easy configuration, and lower cost. The laser has become more popular in soft tissue surgeries due to its multiple benefits: shorter operating time, control of bleeding and hemostasis, reduction in the amount of anesthesia, possibility of not requiring sutures, and minimization of post-surgical pain and inflammation. The purpose of this work is to present the resolution of three clinical cases which underwent labial frenectomy procedures, removal of gingival melanosis and resection of irritative fibroma using diode laser. To develop all the procedures, a 940 nm diode laser equipment (Biolase®, USA) was used with a power that varied between 2 and 2.5 W in continuous mode, using a 300 µm tip (E 3-4), which was activated before starting. After surgery, biostimulation was carried out to reduce postoperative pain and edema using the pain tip at 4 W for 30 seconds at a distance of 1 cm directly in the operated area in all cases. In all cases, the diode laser allowed a successful result. The procedure was safe, the technique was simple, and the clinical time was short. The postoperative period occurred with the absence of pain or discomfort, generating greater patient satisfaction. It should be noted that the technique depends on the skill of the professional who performs it.

Utilización de láser diodo en el tratamiento de la peri-implantitis: reporte de 3 casos / Use of diode laser in peri-implantitis treatment: report of 3 cases

Los implantes dentales son ampliamente usados para el reemplazo de piezas dentarias y se han convertido en el "gold standard" de las terapias protésicas en odontología. Dado el mayor uso de éstos, las investigaciones epidemiológicas recientes han demostrado elevadas tasas de prevalencia de enfermedad periimplantaria. En el presente estudio se presentan tres casos clínicos diagnosticados con periimplantitis. Todos los casos presentaron aumento de la profundidad al sondaje periimplantario en relación a controles anteriores, supuración, sangramiento al sondaje y pérdida ósea confirmada a través de tomografía computada cone beam. El tratamiento indicado para todos los casos fue una terapia conjunta entre un tratamiento mecánico mediante ultrasonido con la utilización de puntas plásticas (P.I EMS®, Suiza) y la terapia con láser. Para la laserterapia se utilizó un equipo de láser diodo de 940 nm (Biolase®, USA) con una potencia de 2 W en modo CW, utilizando una punta de 300 µm. El láser de diodo no daña la superficie de titanio y es capaz de descontaminar las superficies rugosas de los implantes. En este reporte, el uso de una terapia combinada mecánica y láser fue efectiva en todos los casos. En los controles clínicos, la mucosa periimplantaria no presentó signos de supuración ni sangramiento, y la profundidad al sondaje también se vió disminuída. El nivel óseo se controló a través de una tomografía computada cone beam y no se evidenciaron cambios significativos. En la actualidad, la evidencia clínica para el tratamiento periimplantario mediante la fototerapia todavía es limitada. Sin embargo, el láser ofrece un enfoque técnico novedoso que es completamente diferente de los instrumentos mecánicos y tiene varios efectos beneficiosos, por lo que puede desempeñar un papel importante, en la resolución de la peri-implantitis.

Dental implants are widely used for the replacement of teeth and have become the "gold standard" of prosthetic therapies in dentistry. Given the increased use of these, recent epidemiological investigations have shown high prevalence rates of peri-implant disease. In the present study, three clinical cases diagnosed with peri-implantitis are presented. All cases presented increased depth to peri-implant probing in relation to previous controls, suppuration, bleeding and bone loss confirmed by cone beam computed tomography. The treatment indicated for all cases was a joint therapy between a mechanical ultrasound treatment with the use of plastic tips (P.I EMS®, Switzerland) and laser therapy. For laser therapy, a 940 nm diode laser equipment was used (Biolase®, USA) with a power of 2W in continuous laser beam mode, using a 300 µm tip. The diode laser does not damage the titanium surface and is capable of decontaminating the rough surfaces of the implants. In this report, the use of a combined mechanical and laser therapy was effective in all cases. In clinical controls, the peri-implant mucosa did not show signs of suppuration or bleeding, and the depth on probing was decreased. The bone level was controlled through a cone beam computed tomography and no significant changes were evidenced. At present, the clinical evidence for peri-implant treatment using phototherapy is still limited. However, the laser offers a novel technical approach that is completely different from mechanical instruments and has several beneficial effects, so it can play an important role in the resolution of peri-implantitis.

Intravenous tocilizumab in the management of rheumatoid arthritis: Clinical practice findings from a 6-month international, multicentre, observational study in Central America and the Caribbean / El tocilizumab intravenoso en el tratamiento de la artritis reumatoide: resultados de la práctica clínica de un estudio internacional, multicéntrico y observacional de 6 meses de duración en América Central y el Caribe

ABSTRACT Tocilizumab (TCZ), an 1interieukin-6 receptor-α Inhibitor, is Indicated in patients with moderate to severe rheumatoid arthritis with inadequate response to disease modifying drugs. ACT UP is a multinational project co11ecting information from severa1 post-marketing TCZ studies. Aim: To determine the proportion of patients in the routine clinical care setting receiving intravenous TCZ after 6 months treatment. Identification of TCZ treatment patterns, efficacy, and safety were also recorded. Method: This prospective non-interventional 6-month study, collected real-world information from 169 Central American and Caribbean patients. No interventional procedures or additional visits outside routine clinical care practice were performed. Statistical analysis was essentially descriptive. Results: Adherence rate was 74.0%, with 97% of patients receiving TCZ as first biological therapy line and there were no deviations from the local label. Almost 85% of patients started with combination therapy, and the majority remained under this scheme throughout the study. A significant decrease in disease activity assessments and acute phase reactants values were detected during TCZ treatment. The percentage of patients that achieved improvement according to the different levels of the American College of Rheumatology (ACR) increased during the study, and relevant enhancements in quality of life were also accomplished. Adverse events (AEs) occurred in 35 patients, with metabolic and nutritional disorders being the most common. Serious AEs were reported in 3% of patients, and special interest AEs occurred in 6 patients. Conclusion: Treatment adherence was mainly determined by follow-up and compliance with the administration schedule. Efficacy analysis showed better results than those reported in international literature. The incidence of AEs was also lower than in previously published data.

RESUMEN El tocilizumab (TCZ) está indicado en la artritis reumatoide moderada a severa, principalmente en respuestas inadecuadas a fármacos convencionales. ACT UP es un proyecto multinacional que recopila información relacionada con varios estudios de poscomercialización. Objetivo: Determinar la proporción de pacientes en la atención clínica de rutina que continúan en tratamiento con TCZ intravenoso después de 6 meses. Se llevó a cabo la identificación de patrones de administración, eficacia y seguridad. Método: Este estudio observacional prospectivo recopiló información de la vida real de 169 pacientes de América Central y el Caribe. No se hicieron intervenciones ni visitas adicionales fuera de la práctica clínica habitual. El análisis estadístico fue esencialmente descriptivo. Resultados: La tasa de adherencia al tratamiento fue del 74,0%, el 97% de los pacientes reci bieron TCZ como primera línea biológica y no existieron desviaciones en las indicaciones de administración según el inserto local. Aproximadamente el 85% de los pacientes inició TCZ como terapia combinada, y la mayoría permaneció bajo este esquema. Se evidenció una dis minución en la actividad de la enfermedad y un aumento en el porcentaje de pacientes que lograron respuesta según los diferentes grados del Colegio Americano de Reumatología. En 35 pacientes se presentaron eventos adversos (EA), siendo los relacionados con metabolismo y nutrición los más comunes. Se informaron EA graves en el 3% de los pacientes y de interés especial en 6 casos. Conclusión: El seguimiento de los pacientes y el cumplimiento del programa fueron los prin cipales determinantes en la adherencia. El análisis de eficacia mostró mejores resultados que los reportados previamente y la incidencia de EA fue menor que en otros estudios.

Blockade of the AHR restricts a Treg-macrophage suppressive axis induced by L-Kynurenine.

Tryptophan catabolism by the enzymes indoleamine 2,3-dioxygenase 1 and tryptophan 2,3-dioxygenase 2 (IDO/TDO) promotes immunosuppression across different cancer types. The tryptophan metabolite L-Kynurenine (Kyn) interacts with the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) to drive the generation of Tregs and tolerogenic myeloid cells and PD-1 up-regulation in CD8+ T cells. Here, we show that the AHR pathway is selectively active in IDO/TDO-overexpressing tumors and is associated with resistance to immune checkpoint inhibitors. We demonstrate that IDO-Kyn-AHR-mediated immunosuppression depends on an interplay between Tregs and tumor-associated macrophages, which can be reversed by AHR inhibition. Selective AHR blockade delays progression in IDO/TDO-overexpressing tumors, and its efficacy is improved in combination with PD-1 blockade. Our findings suggest that blocking the AHR pathway in IDO/TDO expressing tumors would overcome the limitation of single IDO or TDO targeting agents and constitutes a personalized approach to immunotherapy, particularly in combination with immune checkpoint inhibitors.

Contact dermatitis: Clinical practice findings from a single tertiary referral hospital, a 4-Year retrospective study.

BACKGROUND: It is estimated that 20% of the general population is sensitized to some kind of contact allergen. Contact dermatitis is one of the major occupational diseases worldwide. This disease has a higher prevalence in the female gender and is more frequently observed in the third or fourth decade of life. The main objective of this study was to describe the main sociodemographic and clinical characteristics of patients with contact dermatitis treated in the Allergy Unit of the San Juan De Dios Hospital - Caja Costarricense de Seguro Social. METHODS: Clinical records of contact dermatitis outpatients from a single hospital were analyzed, in a 4-year retrospective observational study. RESULTS: At the time of the patch testing, patients showed a mean age of 42.2 years. Disease frequency was higher in the female population (female/male ratio of 4.2:1) and in patients mostly dedicated to household workchores. Most patients presented several years of disease history, and the hands were the highest affected body part. Patch testing revealed that nickel sulfate, Cl+Me-Isothiazolinone (Kathon CG), and thimerosal were allergens regularly associated with contact dermatitis in the analyzed population. CONCLUSIONS: To a great extent, sociodemographic and clinical characteristics identified in these patients resemble what is reported in other regions, including the Americas and worldwide. It is worth highlighting a high female proportion rate probably related to cultural aspects, a smaller percentage of irritant contact dermatitis that may be associated to institutional patient management, and a slight difference in the most common allergens when compared to other published studies.

High thoracic kyphosis: impact on total thoracic kyphosis and cervical alignment in patients with adolescent idiopathic scoliosis.

PURPOSE: To evaluate the impact of proximal thoracic segment (T1-T5) on global thoracic kyphosis, as well as its influence on cervical alignment (lordotic, kyphotic or straight) in patients with adolescent idiopathic scoliosis (AIS). METHODS: We conducted a retrospective study of 80 patients with AIS. The inclusion criteria were patients between 10 and 18 years of age with a posteroanterior (PA) and lateral full-length radiographs, excluding those subjected to surgery, orthotic treatment, with other spinal disease or with poor X-ray quality. The parameters evaluated were age, sex, pelvic incidence (PI), sacral slop (SS), pelvic tilt (PT), global sagittal balance (GSB), scoliotic curvatures (differentiated according to primary curve, lumbar modifier and sagittal modifier), cervical spine alignment, thoracic sagittal Cobb angle between T1 and T5, T5 and T12 and between T1 and T12. RESULTS: In patients with AIS, the proximal sagittal thoracic Cobb segment, contrary to the distal, demonstrated a significant positive correlation with cervical spine alignment (p < 0.05). As there is an increase in proximal thoracic angle, there is an increase in cervical lordosis. We also demonstrated that the correlation between an increase in scoliotic curvature and a decrease in kyphosis only occurred in the distal thoracic segment (T5-T12). Relative to the spinopelvic parameters, the PI was not related with the dorsal kyphosis or shape of the cervical spine. CONCLUSIONS: In AIS, proximal (T1-T5) and distal (T5-T12) thoracic kyphosis have different contributions on the global thoracic sagittal curvature and in the phenomenon of hypokyphosis. On the other hand, only the proximal segment is significantly related to the shape of the cervical spine. LEVEL OF EVIDENCE: IV.

Biological models in multiple sclerosis.

Considering the etiology of multiple sclerosis (MS) is still unknown, experimental models resembling specific aspects of this immune-mediated demyelinating human disease have been developed to increase the understanding of processes related to pathogenesis, disease evolution, evaluation of therapeutic interventions, and demyelination and remyelination mechanisms. Based on the nature of the investigation, biological models may include in vitro, in vivo, and ex vivo assessments. Even though these approaches have disclosed valuable information, every disease animal model has limitations and can only replicate specific features of MS. In vitro and ex vivo models generally do not reflect what occurs in the organism, and in vivo animal models are more likely used; nevertheless, they are able to reproduce only certain stages of the disease. In vivo MS disease animal models in mammals include: experimental autoimmune encephalomyelitis, viral encephalomyelitis, and induced demyelination. This review examines and describes the most common biological disease animal models for the study of MS, their specific characteristics and limitations.

Leg length discrepancy in adolescent idiopathic scoliosis / Dismetria dos membros inferiores na escoliose idiopática do adolescente / Discrepancia de la longitud de las piernas en la escoliosis idiopática del adolescente

ABSTRACT Objective The objective of this study is to evaluate leg length discrepancy in adolescent idiopathic scoliosis. Methods A retrospective study of 80 subjects with adolescent idiopathic scoliosis (AIS) was conducted. The inclusion criteria were patients aged 10 to 18 years old with posteroanterior (PA) and lateral full-length radiographs. The exclusion criteria were patients subjected to surgery or orthotic treatment, those with other spinal disease, and those with poor quality x-rays. The parameters evaluated were: age, sex, Risser stage (RS), triradiate cartilage (TC), scoliotic curvatures, differentiated according to Lenke classification, sagittal (SB) and coronal balance (CB), and leg length discrepancy, which was assessed through the difference between the femoral heads (LLD) and through the assessment of pelvic obliquity (PO). Results The majority of patients with AIS demonstrated a mild LLD (<1 cm). The mean LLD was significantly different (p<0.01) between the scoliotic population with a main thoracolumbar curvature and those with a main lumbar curvature. When there was an LLD, it was the left limb that was shortened in most cases. The side of the longer lower limb had a direct influence on the CB (p=0.052). Conclusions This study demonstrates that in an AIS population with small LLD values, the extent of the shortening has a stronger impact on coronal balance and location than on the dimension of the main scoliotic curvature. These results demonstrate the importance of a more in-depth study on the effects of LLD <1 cm in the development of AIS and coronal imbalance. Level of evidence IV; Case Series.

RESUMO Objetivo O objetivo deste estudo é avaliar a discrepância no comprimento dos membros inferiores numa população com escoliose idiopática do adolescente. Métodos Foi realizado um estudo retrospetivo de 80 indivíduos com escoliose idiopática do adolescente (AIS). Os critérios de inclusão foram pacientes de 10 a 18 anos com radiografias coronais e sagitais extralongas, excluindo-se aqueles submetidos à cirurgia ou tratamento com coletes Milwaukee ou Boston, com outras doenças da coluna vertebral ou com exames que não cumpriam a qualidade radiográfica protocolada pelo Centro Hospitalar. Os parâmetros avaliados foram: idade, sexo, estadio de Risser (RS), cartilagem trirradiada (TC), curvaturas escolióticas diferenciadas segundo a classificação de Lenke, balanço sagital (SB), coronal (CB) e discrepância no comprimento dos membros inferiores, avaliado pelo desnível entre as cabeças femorais (LLD) e através da avaliação da obliquidade pélvica (PO). Resultados A maioria dos pacientes com AIS demonstrou LLD ligeira (<1 cm). A média de discrepância no comprimento dos membros inferiores foi significativamente diferente (p<0,01) entre a população escoliótica com uma curvatura toracolombar principal em relação àquela com uma curvatura lombar principal. Quando existe LLD, o membro esquerdo encontra-se encurtado na maioria dos casos e a discrepância dos membros inferiores influencia diretamente no balanço coronal (p=0,052). Conclusão A partir deste estudo, verificamos que, na população com AIS com pequenos valores de LLD, a magnitude do encurtamento tem um impacto de maior relevo no equilíbrio coronal e na localização do que na dimensão da curvatura escoliótica principal. Estes resultados levantam a importância de um estudo mais aprofundado sobre a importância da LLD <1 cm no desenvolvimento de AIS e no desequilíbrio coronal. Nível de evidência IV; Série de Casos.

RESUMEN Objetivos El objetivo de este estudio es evaluar la diferencia de la longitud de los miembros inferiores en la escoliosis idiopática del adolescente. Métodos Se realizó un estudio retrospectivo de 80 pacientes con escoliosis idiopática de adolescente (EIA). Los criterios de inclusión fueron los pacientes de 10 a 18 años con radiografías posteroanteriores (PA) y laterales de longitud completa. Los criterios de exclusión fueron los pacientes sometidos a cirugía o tratamiento ortopédico, aquellos con otra enfermedad de la columna y aquellos con radiografías de mala calidad. Los parámetros evaluados fueron: edad, sexo, estadio Risser (RS), cartílago trirradiado (CT), curvaturas escolióticas, diferenciadas según la clasificación de Lenke, balance sagital (BS) y coronal (BC) y discrepancia en la longitud de la pierna (DLP), que se evaluó a través de la diferencia entre las cabezas femorales y mediante la evaluación de la oblicuidad pélvica (OP). Resultados La mayoría de los pacientes con EIA demostró DLP leve (< 1 cm). La media de la DLP fue significativamente distinta (p < 0,01) entre la población escoliótica con una curvatura toracolumbar principal y los pacientes con curvatura lumbar principal. Cuando había DLP, la extremidad izquierda se acortaba en la mayoría de los casos. El lado de la extremidad más larga tuvo influencia directa en el BC (p = 0,052). Conclusiones Este estudio demuestra que en una población con EIA y bajos valores de DLP, la extensión del acortamiento tiene impacto mayor en el balance y la ubicación coronal que en la dimensión de la curvatura escoliótica principal. Estos resultados muestran la importancia de un estudio más profundo sobre los efectos de DLP < 1 cm en el desarrollo de EIA y el desequilibrio coronal. Nivel de evidencia - IV; Serie de Casos.

Embarazo ectópico cervical: diagnóstico preciso y enfoque de manejo médico. Reporte de caso / Ectopic Cervical Pregnancy ­ Precise Diagnosis and Medical Management Approach. Case Report

El embarazo ectópico cervical es una condición exótica. Su diagnóstico y manejo plantean un desafío importante, dada su asociación con desenlaces maternos graves. La sospecha clínica y la juiciosa aplicación de los criterios diagnósticos permiten establecer modalidades de terapia conservativa. Este artículo reporta un caso de embarazo ectópico cervical con diagnóstico de imágenes de ultrasonido y resonancia nuclear magnética en el que se administró tratamiento con metotrexato. El seguimiento clínico, de los exámenes paraclínicos y de ultrasonido mostraron la resolución completa de la condición. Se revisan aspectos relacionados con el diagnóstico y tratamiento.

Cervical ectopic pregnancy is an exotic condition. Its diagnosis and management pose a major challenge given its association with serious maternal outcomes. The clinical suspicion and the judicious application of the diagnostic criteria allow for conservative therapy modalities. In this article, a case of cervical ectopic pregnancy is reported to diagnostic ultrasound imaging and nuclear magnetic resonance in which treatment with Methotrexate was administered. Clinical follow-up of the laboratory test and ultrasound showed complete resolution of the condition. Aspects related to the diagnosis and treatment are reviewed.

Molecular Pathogenesis of Alzheimer's Disease: An Update.

Dementia is a chronic or progressive syndrome, characterized by impaired cognitive capacity beyond what could be considered a consequence of normal aging. It affects the memory, thinking process, orientation, comprehension, calculation, learning ability, language, and judgment; although awareness is usually unaffected. Alzheimer's disease (AD) is the most common form of dementia; symptoms include memory loss, difficulty solving problems, disorientation in time and space, among others. The disease was first described in 1906 at a conference in Tubingen, Germany by Alois Alzheimer. One hundred and ten years since its first documentation, many aspects of the pathophysiology of AD have been discovered and understood, however gaps of knowledge continue to exist. This literature review summarizes the main underlying neurobiological mechanisms in AD, including the theory with emphasis on amyloid peptide, cholinergic hypothesis, glutamatergic neurotransmission, the role of tau protein, and the involvement of oxidative stress and calcium.

Comparative study on the treatment of disc herniations / Estudio comparativo del tratamiento de las hernias discales / Estudo comparativo de tratamento de hérnias de disco

ABSTRACT Objective: To compare the results of treatment of patients with low back pain and radiculalgia resulting from disc herniation associated with disc degeneration through instrumentation with pedicle screws and dynamic rod, with root release and without diskectomy compared with other non-instrumented techniques (microdiskectomy with or without foraminotomy). Methods: This is a retrospective descriptive study of interventions for patients with herniated discs in the Traumatology and Neurosurgery that used the following variables: age, sex, type of technique, surgical time, time of evolution, degree of satisfaction, and complications. Two groups were formed: instrumentation with dynamic rods and non-instrumented techniques, comparing the results of each group. The software used was the SPSS v20.0. Results: We presented 142 interventions carried out between 2009 and 2012, 86 with dynamic instrumentation and 56 by other decompression techniques without instrumentation. No statistically significant differences were observed between age and sex groups and time elapsed until intervention. We found statistically significant differences (p=0.001) in surgical time, which was lower in the instrumented technique. No significant differences were found in complications between the techniques in both re-operations and in infections. Conclusions: In this study, we found no significant differences between the use of instrumentation with dynamic rods with respect to other non-instrumented surgical techniques in the treatment of herniated discs over 6 months of evolution or the complications and the degree of the patients' satisfaction.

RESUMEN Objetivo: Comparar los resultados del tratamiento de pacientes con lumbalgia y radiculalgia secundaria a hernia discal asociada a degeneración del disco, mediante la instrumentación con tornillos pediculares y barra dinámica, liberando la raíz sin discectomía frente a otras técnicas no instrumentadas (microdiscectomía con o sin foraminotomía). Métodos: Se ha realizado un estudio descriptivo retrospectivo de las intervenciones realizadas en pacientes con hernias discales por los servicios de Traumatología y Neurocirugía, recogiendo las siguientes variables: edad, sexo, tipo de técnica, tiempo de intervención, tiempo de evolución, grado de satisfacción y complicaciones. Se constituyeron dos grupos: instrumentación con barras dinámicas y técnicas no instrumentadas, comparando los resultados de cada grupo. Se utilizó el software SPSS v20.0. Resultados: Presentamos 142 intervenciones realizadas entre 2009 y 2012, 86 mediante instrumentación dinámica y 56 por técnicas de descompresión sin instrumentación. No se observaron diferencias estadísticamente significativas entre los grupos respecto a edad, sexo, ni tiempo de evolución hasta la intervención. Se observaron diferencias estadísticamente significativas (p = 0,001) en el tiempo de intervención, siendo menor en la técnica instrumentada. Respecto a las complicaciones de las técnicas no se hallaron diferencias significativas ni en las reintervenciones ni en las infecciones. Conclusiones: No encontramos diferencias significativas entre la utilización de instrumentación con barras dinámicas frente a otras técnicas quirúrgicas no instrumentadas en el tratamiento de las hernias discales de más de 6 meses de evolución, ni respecto a las complicaciones y ni al grado de satisfacción de los pacientes.

RESUMO Objetivo: Comparar os resultados do tratamento de pacientes com dor lombar e radiculalgia decorrente de hérnia de disco associada à degeneração do disco, por meio de instrumentação com parafusos pediculares e barra dinâmica com liberação da raiz sem discotomia em comparação com outras técnicas não instrumentadas (microdiscotomia com ou sem foraminotomia). Métodos: Foi realizado um estudo retrospectivo e descritivo de intervenções realizadas em pacientes com hérnia de disco nos serviços de Traumatologia e Neurocirurgia, empregando-se as seguintes variáveis: idade, sexo, tipo de técnica, tempo de cirurgia, tempo de evolução, grau de satisfação e complicações. Foram formados dois grupos: instrumentação com barras dinâmicas e técnicas não instrumentadas, comparando os resultados de cada grupo. O software utilizado foi o SPSS v20.0. Resultados: Apresentamos 142 intervenções realizadas entre 2009 e 2012, 86 por instrumentação dinâmica e 56 por técnicas de descompressão sem instrumentação. Não foram observadas diferenças estatisticamente significativas entre os grupos de idade, sexo e tempo de evolução até a intervenção. Constataram-se diferenças estatisticamente significativas quanto ao tempo cirúrgico (p = 0,001), sendo menor na técnica instrumentada. Com relação às complicações das técnicas, não houve diferença significativa nas re-operações nem nas infecções. Conclusões: Não foram encontradas diferenças significativas entre o uso de instrumentação com barras dinâmicas com respeito a outras técnicas cirúrgicas não instrumentadas no tratamento da hérnia de disco com mais de 6 meses de evolução nem a complicações e ao grau de satisfação dos pacientes.