Multimodal Analgesia Approach in Acute Low Back Pain Management: A Phase III Study of a Novel Analgesic Combination of Etoricoxib/Tramadol.

INTRODUCTION: Pain and disability management are crucial for a speedy recovery. Combining analgesics with different mechanisms of action provides greater pain relief with lower doses, promoting efficient multimodal analgesia. This study evaluated the efficacy and safety between two fixed-dose combinations (FDC): etoricoxib/tramadol compared to paracetamol/tramadol for the management of acute low back pain (LBP) in a 7-day treatment. METHODS: We conducted a phase IIIb, prospective, randomized, and multicenter study in patients with acute LBP treated with etoricoxib 90 mg/tramadol 50 mg (one packet of granules diluted in 100 ml of water, once a day [QD], for 7 days) or paracetamol 975 mg/tramadol 112.5 mg (one tablet of 325 mg/37.5 mg, three times a day [TID], for 7 days) to assess the efficacy (in terms of pain and disability improvement) and safety. RESULTS: One hundred and twenty-four patients were randomized to receive either etoricoxib/tramadol QD (n = 61) or paracetamol/tramadol TID (n = 63). From the magnitude of change in pain evaluations, differences were observed between the treatment groups at 3 [p = 0.054, CI 95% - 0.648 (- 0.010 to 1.306)] and 5 days (p = 0.041). The proportion of patients with a 30% reduction in Visual Analogue Scale (VAS) score was statistically significant when comparing the treatment groups on the third day of follow-up [p = 0.008, CI 95% 0.241 (0.061-0.421)]. An improvement in LBP's disability to perform activities of daily routine (Oswestry and Roland-Morris questionnaires) was observed in both treatment groups. A total of 79 adverse events (AEs) (38 [48.1%] with etoricoxib/tramadol and 41 [51.9%] with paracetamol/tramadol) were reported. The most frequent AEs were nausea (17.7%) and dizziness (16.4%). CONCLUSIONS: The results show the clinical benefits of etoricoxib/tramadol FDC, such as the sparing effect of tramadol dose per day, early therapeutic response rate compared with paracetamol/tramadol; which translates into faster pain relief, better adherence, less tramadol drug dependency, and a reduction of related AEs incidence. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04968158.

Microplastics in coral from three Mascarene Islands, Western Indian Ocean.

Little is known about microplastics (MPs) in corals from the Indian Ocean. We compared MP concentrations, morphotypes, size, colours, and polymer compositions in six coral genera from three remote Mascarene islands (Rodrigues, St. Brandon's Atoll, and Agalega) of the Republic of Mauritius, on a 1200 km transect located in the South Equatorial Current (SEC). The mean MP concentration was 0.78 n/g (53 % fibres) with no significant differences between islands. Polymers were polypropylene (78 %) and polyethylene (18 %). We conclude that the SEC's MP concentrations and compositions have homogenized over thousands of kilometres across the Indian Ocean. We discuss the lack of hazardous polyurethane MPs in coral samples given obvious sources on St Brandon. To the best of our knowledge, this study is the first to report on MPs in coral from the Western Indian Ocean and the Mascarene Islands providing a baseline for further research, monitoring, mitigation, and policy development.

Antioxidant Functions of Vitamin D and CYP11A1-Derived Vitamin D, Tachysterol, and Lumisterol Metabolites: Mechanisms, Clinical Implications, and Future Directions.

Evidence is increasing that vitamin D and CYP11A1-derived vitamin D, tachysterol, and lumisterol metabolites play a significant antioxidant role beyond its classical functions in bone health and calcium metabolism. Several recent studies have linked these elements to reduced oxidative stress as well as improved immune, cardiovascular, and neurological functions as a result of chronic kidney disease and cancer. Additionally, supplementation with this vitamin has been shown to be one of the most cost-effective micronutrient interventions worldwide, highlighting its potential as a therapeutic approach. The underlying mechanisms and implications of this antioxidant function of vitamin D or CYP11A1-derived vitamin D, tachysterol, and lumisterol metabolites are not well understood. This comprehensive and narrative review is aimed at summarizing the current evidence regarding the molecular mechanisms implicated in this antioxidant function of vitamin D, as well as to provide a general overview and to identify key research areas for the future, offering an extensive perspective that can guide both researchers and clinicians in the management of diseases associated with oxidative stress and/or insufficient vitamin D status.

Síndrome de la costilla deslizante en la edad pediátrica. Serie de casos / Slipping rib syndrome in childhood. A case series

Entre las causas de dolor torácico, la costilla deslizante presenta baja prevalencia, antecedentes traumáticos y manejo controvertido. Este síndrome merece ser incluido en el diagnóstico diferencial de causas de dolor torácico en niños. Al no asociarse a traumatismos previos y la deformidad de cartílagos, nos induce a pensar en una alteración en el desarrollo costal, al margen de la etiología traumática típica en adultos. Se presenta una serie de pacientes pediátricos intervenidos por costilla deslizante en un centro de referencia entre 2001 y 2022. Se incluyeron nueve pacientes, con un rango de edades de 11 a 16 años. Solo dos casos describen traumatismo previo. Todos presentan un inicio súbito de dolor toracoabdominal intenso. Los pacientes fueron intervenidos mediante resección abierta de cartílagos costales afectos, con resolución del dolor.

Among the causes of chest pain, slipping rib has a low prevalence, usually with a history of trauma, and its management is controversial. Slipping rib syndrome should be included in the differential diagnosis of causes of chest pain in children. When not associated with previous trauma and cartilage deformity, it is necessary to consider an alteration in rib development, regardless of the typical traumatic etiology in adults. Here we describe a series of pediatric patients with slipping rib seen at a referral hospital between 2001 and 2022. Nine patients aged 11 to 16 years were included. Only 2 had a history of trauma. All patients described a sudden onset of severe thoracic abdominal pain. The patients underwent open resection of the affected costal cartilages, with resolution of pain.

Fallopian Tube-Derived High-Grade Serous Cancers Influence Ovarian Production of Norepinephrine and Generate Specific Metabolomic Signatures.

High-grade serous ovarian cancer is the most common and lethal gynecologic malignancy, which is often attributed to the lack of available screenings, allowing the disease to progress unnoticed until it is diagnosed at more aggressive stages. As such, identifying signals in the tumor microenvironment involved in the primary metastasis of tumorigenic fallopian tube epithelial (FTE) cells to the ovary could provide new avenues for prevention, diagnostics, or therapeutic intervention. Since our previous work identified that the interaction of tumorigenic FTE and the ovary causes the release of norepinephrine (NE) from the ovary, we intended to determine the effects of ovarian NE on signaling and invasion of tumorigenic FTE models and high-grade serous ovarian cancer cell lines. We demonstrate that NE does not universally enhance migration, invasion, or adhesion by using multiple cell types but does alter specific oncogenic protein expression in certain models. In vivo, we found that blocking NE signaling via slow-release propranolol pellets significantly increased survival time in mice injected intraperitoneally with murine FTE cells engineered to stably express shRNA for PTEN and an activated KRAS expression construct. Finally, we identified that the metabolome released from the ovary is variable depending upon which cell type it is cocultured with, suggesting that distinct driver mutations in fallopian tube epithelial tumor models and early lesions can alter specific metabolomes within the surrounding ovarian microenvironment. These metabolomes provide the next frontier for evaluating local signals of the tumor microenvironment that facilitate ovarian spread of FTE lesions.

Comparative Bioavailability of a Novel Fixed-dose Combination Etoricoxib and Tramadol.

Multimodal analgesia is defined as using several drugs or techniques simultaneously to target different pain pathways or receptors to avoid pain propagation. This study evaluated the pharmacokinetic profile and comparative bioavailability of etoricoxib 90 mg and tramadol 50 mg dosing alone (reference drugs) or in a novel fixed-dose combination (test drug) under fasting conditions in Mexican healthy volunteers. This was a randomized, open-label, 3-way, crossover, single-dose, prospective, and longitudinal study with a 14-day washout period. Eligible subjects were healthy Mexican adult volunteers. The drugs were dosing orally, according to the randomization sequence, after 10 hours of fasting and 4 hours before breakfast with 250 mL of water at room temperature. Serial blood samples were collected before and after dosing, both drugs were quantified using high-performance liquid chromatography coupled with tandem mass spectrometry. Forty-two subjects were enrolled and 38 completed the study (28 men and 14 women, mean age 25.2 years, mean weight 66.6 kg). Test products were considered to have comparative bioavailability if confidence intervals of natural log-transformed for (maximum plasma drug concentration (Cmax), (area under the plasma drug concentration-time curve form 0 up to last sampling time (AUC0-t), and (area under the plasma drug concentration-time curve from 0 up to infinity (AUC0-∞) data were within the range of 80%-125%. Non-serious adverse events were observed. The results demonstrate that the pharmacokinetic profile and bioavailability of the etoricoxib/tramadol fixed-dose combination are comparable to those of the reference products.

Comparing Survival of Perihilar Cholangiocarcinoma After R1 Resection Versus Palliative Chemotherapy for Unresected Localized Disease.

BACKGROUND: Resection of perihilar cholangiocarcinoma (pCCA) is a complex procedure with a high risk of postoperative mortality and early disease recurrence. The objective of this study was to compare patient characteristics and overall survival (OS) between pCCA patients who underwent an R1 resection and patients with localized pCCA who received palliative systemic chemotherapy. METHODS: Patients with a diagnosis of pCCA between 1997-2021 were identified from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) registry. pCCA patients who underwent an R1 resection were compared with patients with localized pCCA (i.e., nonmetastatic) who were ineligible for surgical resection and received palliative systemic chemotherapy. The primary outcome was OS. RESULTS: Overall, 146 patients in the R1 resection group and 92 patients in the palliative chemotherapy group were included. The palliative chemotherapy group more often underwent biliary drainage (95% vs. 66%, p < 0.001) and had more vascular encasement on imaging (70% vs. 49%, p = 0.012) and CA 19.9 was more frequently >200 IU/L (64 vs. 45%, p = 0.046). Median OS was comparable between both groups (17.1 vs. 16 months, p = 0.06). Overall survival at 5 years after diagnosis was 20.0% with R1 resection and 2.2% with chemotherapy. Type of treatment (i.e., R1 resection or palliative chemotherapy) was not an independent predictor of OS (hazard ratio 0.76, 95% confidence interval 0.55-1.07). CONCLUSIONS: Palliative systemic chemotherapy should be considered instead of resection in patients with a high risk of both R1 resection and postoperative mortality.

Presurgical invasive mediastinal staging in lung cancer, unexpected N2 and long-term survival: a registry-based study with data from the Spanish group for video-assisted thoracic surgery.

Background: Mediastinal lymph node staging is a key element in the diagnosis of lung cancer. The combination of computed tomography (CT) and positron emission tomography (PET) has improved staging but some circumstances are known to influence their negative predictive value. The objective of this study was to assess the impact on survival of avoiding invasive mediastinal staging in surgical lung cancer patients with negative mediastinum in CT and PET and intermediate risk of unexpected pN2. Methods: Data were collected from the prospective cohort of the Spanish Group for Video-Assisted Thoracic Surgery (GEVATS), from December 2016 to March 2018. For this study, patients were selected if they had negative mediastinum in CT and PET findings but tumours >3 cm or located centrally, or with cN1 disease. Patients who did and did not undergo invasive staging [invasive group (IG) and non-invasive group (NIG)] were compared, analysing unexpected pN2 and survival with Kaplan-Meier curves and Cox regression. Results: A total of 2,826 patients underwent surgery for primary lung cancer. We selected 1,247 patients who had tumours >3 cm, central tumours or cN1. Invasive staging was performed in 275 (22.1%) cases. The unexpected pN2 rate was 9.6% in the NIG and 13.8% in the IG, but half of them were discovered prior to surgery in the IG. Five-year overall survival (OS) was poorer in the IG (52.4% vs. 64%; P<0.001). In the Cox regression model, male sex, older age, diabetes, synchronous tumour, lower diffusing capacity for carbon monoxide, larger tumour size, higher pathological N-stage, and IG status were significant independent risk factors. Conclusions: Invasive staging recommended by guidelines could be reduced with an appropriate selection in mediastinal CT- and PET-negative patients with risk factors for unexpected pN2, because rates of pN2 and survival did not worsen without invasive staging.

The Peptidoglycan Recognition Protein 1 confers immune evasive properties on pancreatic cancer stem cells.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options, particularly with immune checkpoint inhibitors. Highly chemoresistant 'stem-like' cells, known as cancer stem cells (CSCs), are implicated in PDAC aggressiveness. Thus, comprehending how this subset of cells evades the immune system is crucial for advancing novel therapies. DESIGN: We used the KPC mouse model (LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre) and primary tumour cell lines to investigate putative CSC populations. Transcriptomic analyses were conducted to pinpoint new genes involved in immune evasion. Overexpressing and knockout cell lines were established with lentiviral vectors. Subsequent in vitro coculture assays, in vivo mouse and zebrafish tumorigenesis studies, and in silico database approaches were performed. RESULTS: Using the KPC mouse model, we functionally confirmed a population of cells marked by EpCAM, Sca-1 and CD133 as authentic CSCs and investigated their transcriptional profile. Immune evasion signatures/genes, notably the gene peptidoglycan recognition protein 1 (PGLYRP1), were significantly overexpressed in these CSCs. Modulating PGLYRP1 impacted CSC immune evasion, affecting their resistance to macrophage-mediated and T-cell-mediated killing and their tumourigenesis in immunocompetent mice. Mechanistically, tumour necrosis factor alpha (TNFα)-regulated PGLYRP1 expression interferes with the immune tumour microenvironment (TME) landscape, promoting myeloid cell-derived immunosuppression and activated T-cell death. Importantly, these findings were not only replicated in human models, but clinically, secreted PGLYRP1 levels were significantly elevated in patients with PDAC. CONCLUSIONS: This study establishes PGLYRP1 as a novel CSC-associated marker crucial for immune evasion, particularly against macrophage phagocytosis and T-cell killing, presenting it as a promising target for PDAC immunotherapy.

Exercise interventions following bariatric surgery are poorly reported: A systematic review and a call for action.

OBJECTIVES: This study assessed the transparency and replicability of exercise-based interventions following bariatric surgery by evaluating the content reporting of exercise-based clinical trials. DESIGN: The study design of the present article is a systematic review. DATA SOURCES: PubMed, Scopus, Web of Sciences, PsycINFO, and Cochrane were searched from their inception to May 2023. ELIGIBILITY CRITERIA: Eligible studies were clinical trials including exercise interventions in participants following bariatric surgery. There were 28 unique exercise interventions. Two independent reviewers applied the exercise prescription components of Frequency, Intensity, Time, and Type (FITT; four items) and the Consensus on Exercise Reporting Template (CERT; 19 items). Exercise interventions were organized into four major exercise components: aerobic training, resistance training, concurrent training, and "others." RESULTS: The FITT assessment revealed that 53% of the trials did not report the training intensity, whereas 25% did not indicate the duration of the major exercise component within the training session. The mean CERT score was 5 out of a possible score of 19. No studies reached CERT score >10, while 13 out of the total 19 CERT items were not adequately reported by ≥75% of the studies. CONCLUSION: This study highlights that the exercise interventions following bariatric surgery are poorly reported, non-transparent, and generally not replicable. This precludes understanding the dose-response association of exercise and health-related effects and requires action to improve this scientific field.

Hypotension prediction index guided goal-directed therapy to reduce postoperative acute kidney injury during major abdominal surgery: study protocol for a multicenter randomized controlled clinical trial.

BACKGROUND: Acute kidney injury (AKI) is a significant postoperative complication associated with increased mortality and hospital costs. Hemodynamic strategies, such as goal-directed therapy, might reduce AKI risk. Predicting and proactively managing intraoperative hypotension may be helpful. This trial aims to investigate if a preemptive hemodynamic strategy guided by the hypotension prediction index (HPI) can decrease the incidence of moderate-to-severe AKI within 30 days following major elective abdominal surgery. METHODS: This is an open-label, controlled, multicenter, randomized clinical trial that involves daily patient follow-up until hospital discharge. Inclusion criteria are patients aged over 65 and/or categorized as ASA III or IV physical status, undergoing major elective abdominal surgery (general, urological, or gynecological procedures) via laparoscopic or open approach under general or combined anesthesia. INTERVENTION: In the intervention group, hemodynamic management will be based on the HPI and the advanced functional hemodynamic variables provided by the Hemosphere platform and the AcumenIQ® sensor (Edwards Lifesciences). The primary outcome is the incidence of moderate-to-severe AKI within 7 days post-surgery. Secondary outcomes include postoperative complications and 30-day mortality. DISCUSSION: This study explores the potential of HPI-guided hemodynamic management in reducing AKI after major elective abdominal surgery, with implications for postoperative outcomes and patient care. TRIAL REGISTRATION: ClinicalTrials.gov NCT05569265. Registered on October 6, 2022.

Diagnósticos retrasados y administración de ondansetron en el tratamiento de los vómitos en urgencias pediátricas

Introducción : El ondasentrón es un agente farmacológico de uso frecuente para el tratamiento sintomático de los vómitos originados por gastroenteritis. Sin embargo, podría enmascarar patologías más graves que ameriten reconsultas y hospitalización. Objetivo: Indagar si la administración del ondansetrón como tratamiento sintomático de los vómitos en el departamento de emergencias pediátricas (DEP) retrasó el diagnóstico de patologías graves. Materiales y métodos: Estudio observacional, descriptivo de corte transverso retrospectivo. Fueron elegibles pacientes que consultaron en el DEP, recibieron tratamiento con ondansetron, y reconsultaron dentro de las 24 horas. Los datos fueron recolectados de la base de datos de consultas del DEP, el comando reconsultas y entrevista telefónica a los padres. Las variables fueron edad, sexo, procedencia, motivo de la segunda consulta, diagnósticos finales en la segunda consulta. Los datos fueron analizados en SPSS utilizando estadística descriptiva. Resultados En el periodo de estudio consultaron por vómitos y recibieron ondasentrón 2018 pacientes. Reconsultaron dentro de las 24 horas 212, cumpliendo con los criterios de inclusión 205 pacientes. Se constató un 24,8% nuevos diagnósticos durante la reconsulta, de los cuales 35% requirieron hospitalización. Los diagnósticos fueron fiebre sin foco 2,9%, neumonía 2,4%, infección de vías urinarias 1%, sospecha de chikunguya 1,5%, adenitis mesentérica 0,5%, abdomen agudo quirúrgico 0,5%. Conclusión: Se identificó diagnósticos diferentes a la primera consulta en pacientes que recibieron ondansetrón como tratamiento sintomático de los vómitos en urgencias pediátricas, requiriendo hospitalización el 35% de los mismos.

Introduction: Ondansetron is a pharmacological agent frequently used for the symptomatic treatment of vomiting caused by gastroenteritis. However, it could mask more serious pathologies that require repeat consultations and hospitalization. Objective: To investigate whether the administration of ondansetron as a symptomatic treatment of vomiting in the pediatric emergency department (PED) delayed the diagnosis of serious pathologies. Materials and methods: This was an observational, descriptive, retrospective and cross-sectional study. Patients who consulted at the PED, received treatment with ondansetron, and returned for consultation within 24 hours were eligible. Data were collected from the PED consultation database, the follow-up consultation request, and a telephone interview with parents. The variables were age, sex, origin, reason for the second consultation, and final diagnoses in the second consultation. The data were analyzed in SPSS using descriptive statistics. Results: During the study period, 2018 patients consulted for vomiting and received ondansetron. 212 were consulted again within 24 hours, with 205 patients meeting the inclusion criteria. There were 24.8% new diagnoses during the follow-up consultation, of which 35% required hospitalization. The diagnoses were fever without source 2.9%, pneumonia 2.4%, urinary tract infection 1%, suspected chikunguya 1.5%, mesenteric adenitis 0.5%, and surgical acute abdomen 0.5%. Conclusion: Diagnoses different from the first consultation were identified in patients who received ondansetron for symptomatic treatment of vomiting in pediatric emergencies, with 35% requiring hospitalization.

Caracterización de pacientes con infección de sitio quirúrgico en post-operados de cirugía abdominal de urgencias hospitalizados

Introducción: Las infecciones de sitio quirúrgico están asociadas con infecciones relacionadas a la asistencia sanitaria (IRAS), causadas por bacterias que ingresan a través de las incisiones efectuadas durante un procedimiento quirúrgico. Objetivo: Describir la frecuencia y características de las infecciones de sitio quirúrgico en las cirugías de urgencias en pacientes pediátricos hospitalizados en el Hospital General Pediátrico. Materiales y Métodos: Estudio observacional descriptivo, retrospectivo, de corte transversal. Población: Pacientes de 0 a 18 años sometidos a intervención quirúrgica abdominal de urgencia. Variables estudiadas: Edad, Sexo, Procedencia, Comorbilidad, reingreso hospitalario, tiempo trascurrido entre la intervención quirúrgica y la aparición de la infección en sitio quirúrgico. Datos obtenidos del análisis de fichas clínicas y la base de datos del HIS en el paquete estadístico SPSv23 (IBM SPSS, DEMO) utilizando estadística descriptiva. Resultados: Fueron incluidas 440 fichas de pacientes, la mediana de edad fue de 10 años, el 60,5% fueron del sexo masculino y el 71,4% procedían del Departamento Central. Se observó que el diagnóstico más frecuente fue peritonitis de origen apendicular 53,2%. El estado nutricional de la población en estudio fue normal en 93,2%, y fueron reingresos el 3% de los pacientes intervenidos. Presentaron infección de sitio quirúrgico el 4,8%, de los cuales 11/21 fueron absceso de pared. En cuanto al tiempo trascurrido entre la cirugía y la aparición de la infección la mediana fue de 14 días. Conclusión: La frecuencia de infección del sitio quirúrgico encontrada en este estudio fue del 4,8%. La patología quirúrgica con mayor porcentaje fue la peritonitis y el tipo de infección absceso de pared. La mayoría de los pacientes eran escolares con buen estado nutricional.

Introduction: Surgical-site infections are associated with healthcare-associated infections (HAIs), caused by bacteria that enter through the incisions made during a surgical procedure. Objective: To describe the frequency and characteristics of surgical site infections in emergency surgeries in pediatric patients hospitalized at a Pediatric General Hospital. Materials and Methods: This was a descriptive, retrospective and cross-sectional observational study. Population: Patients aged 0 to 18 years undergoing emergency abdominal surgery. Variables studied: Age, Sex, Origin, Comorbidity, hospital readmission, time elapsed between the surgical intervention and the appearance of the surgical site infection. Data obtained from the analysis of clinical records and the electronic health record database in the SPSv23 statistical package (IBM SPSS, DEMO) using descriptive statistics. Results: 440 patient records were included, the median age was 10 years, 60.5% were male and 71.4% came from the Central Department. It was observed that the most frequent diagnosis was peritonitis of appendiceal origin 53.2%. The nutritional status of the study population was normal in 93.2%, and 3% of the operated patients were readmitted. 4.8% had surgical site infection, of which 11/21 were wall abscesses. Regarding the time elapsed between surgery and the appearance of the infection, the median was 14 days. Conclusion: The frequency of surgical-site infection found in this study was 4.8%. The surgical pathology with the highest percentage was peritonitis and the wall abscess type of infection. Most of the patients were schoolchildren with good nutritional status.

Is histological confirmation necessary to avoid futile resections? Comparative of 4 university hospitals.

OBJECTIVES: There is no consensus in the literature on preoperative histological analysis for lung cancer. The objective of this study was to assess 4 diagnostic models used in different hospitals with differing practices regarding preoperative histological diagnosis and the consequences in terms of unnecessary surgery and futile major resection. METHODS: We carried out a retrospective observational study collected from 4 university hospitals in Spain over 3 years (January 2019 to December 2021). We included all patients with a confirmed diagnosis of primary lung cancer and any patients with suspected primary lung cancer who had undergone surgery. All patients underwent computed tomography and positron emission tomography/computed tomography scans. Each multidisciplinary committee was free to choose whether to perform flexible bronchoscopic or transthoracic lung biopsy. Decisions concerning whether to perform intraoperative sample analysis, the surgical approach and the type of resection were left to the surgical team. RESULTS: We included a total of 1642 patients. The use of flexible endoscopy and its diagnostic performance varied substantially between hospitals (range: 23.8-79.3% and 25-60.7%, respectively); and the same was observed for transthoracic biopsy and its performance (range: 16.9-82.3% and 64.6-97%, respectively). Regarding major resection surgery (lobectomy or more extensive resection), the lowest rate was observed in hospital C (1%) and the highest in hospital B (2.8%), with between-hospital differences not reaching significance (P = 0.173). CONCLUSIONS: The rate of histological sampling before lung cancer surgery still varies between hospitals. In spite of very diverse multidisciplinary management, the rate of futile lobectomy is not significantly higher in hospitals with lower rates of preoperative histological analysis.

Antinociceptive effects of Raphanus sativus sprouts involve the opioid and 5-HT1A serotonin receptors, cAMP/cGMP pathways, and the central activity of sulforaphane.

Raphanus sativus L. cv. Sango, commonly known as red radish, is widely consumed around the world as a vegetable, but its benefit in pain relief is not sufficiently investigated. This study aimed to evaluate the antinociceptive effects of R. sativus and a possible mechanism of action. An aqueous extract of R. sativus sprouts (AERSS) was investigated by parenteral (10, 30, and 100 mg kg-1, i.p.) and enteral (500 mg kg-1, p.o.) administration in the neurogenic and inflammatory phases of the formalin test, where gastric damage was also evaluated as a possible adverse effect. Ketorolac (5 mg kg-1, i.p.) was used as the reference drug. Endogenous opioid and 5-HT1A serotonin receptors, as well as the cAMP/NO-cGMP pathways, were explored in the study of a possible mechanism of action by using their corresponding antagonists: naloxone, 1 mg kg-1, i.p., WAY100635, 1 mg kg-1, i.p., and enzymatic activators or inhibitors, respectively. Sulforaphane (SFN), a known bioactive metabolite, was analyzed using electroencephalography (EEG) to evidence its central involvement. A significant and dose-dependent antinociceptive activity was observed with the AERSS resembling the antinociceptive effect of the reference drug, with an equivalent significant response with a dose of 500 mg kg-1, p.o. without causing gastric damage. The participation of the endogenous opioid and 5-HT1A serotonin receptors at central and peripheral levels was also observed, with a differential participation of cAMP/NO-cGMP. SFN as one metabolite produced significant changes in the EEG analysis, reinforcing its effects on the CNS. Our preclinical evidence supports the benefits of consuming Raphanus sativus cv. Sango sprouts for pain relief.

Radiation therapy for optic nerve sheath meningiomas: Local control and treatment related visual changes.

Objective: Our primary objective is to evaluate the local control of optic nerve sheath meningiomas (ONSMs) treated with ionizing radiation and related visual changes after treatment. Our secondary objective is to describe the clinical characteristics and perform an analysis of the treatment impact on the functional status of this group of patients. Methods: We present our series of 19 patients treated with ionizing radiation therapy at our radio-neurosurgery unit between 2016 and 2022. The setting, ophthalmological follow-up, morbidity, and survival are analyzed and discussed. Results: Patients were followed up, and the impact of treatment on local disease control, visual alterations of the affected eye, and functional status of the patient were analyzed. The progression-free survival (PFS) median was 60 months (95% CI 50.3-69.6 months). The estimated PFS rates at 48 and 66 months were 100% and 66%, respectively. At diagnosis, nine (47.3%) eyes were in amaurosis and ten (52.6%) with vision. Of the ten patients without amaurosis at the time of diagnosis, three (30%) maintained unchanged visual acuity, and seven (70%) had decreased visual acuity; three of them developed amaurosis during the first year after treatment (p = 0.018). Conclusions: Using ionizing radiation therapy is a successful treatment for the local control of ONSMs. This therapeutic modality can compromise the visual acuity of the affected eye and improve dyschromatopsia and campimetry defects. The life prognosis is good for these patients, with a zero mortality rate, but their vision prognosis is poor.

Slipping rib syndrome in childhood. A case series. / Síndrome de la costilla deslizante en la edad pediátrica. Serie de casos.

Among the causes of chest pain, slipping rib has a low prevalence, usually with a history of trauma, and its management is controversial. Slipping rib syndrome should be included in the differential diagnosis of causes of chest pain in children. When not associated with previous trauma and cartilage deformity, it is necessary to consider an alteration in rib development, regardless of the typical traumatic etiology in adults. Here we describe a series of pediatric patients with slipping rib seen at a referral hospital between 2001 and 2022. Nine patients aged 11 to 16 years were included. Only 2 had a history of trauma. All patients described a sudden onset of severe thoracic abdominal pain. The patients underwent open resection of the affected costal cartilages, with resolution of pain.

Entre las causas de dolor torácico, la costilla deslizante presenta baja prevalencia, antecedentes traumáticos y manejo controvertido. Este síndrome merece ser incluido en el diagnóstico diferencial de causas de dolor torácico en niños. Al no asociarse a traumatismos previos y la deformidad de cartílagos, nos induce a pensar en una alteración en el desarrollo costal, al margen de la etiología traumática típica en adultos. Se presenta una serie de pacientes pediátricos intervenidos por costilla deslizante en un centro de referencia entre 2001 y 2022. Se incluyeron nueve pacientes, con un rango de edades de 11 a 16 años. Solo dos casos describen traumatismo previo. Todos presentan un inicio súbito de dolor toracoabdominal intenso. Los pacientes fueron intervenidos mediante resección abierta de cartílagos costales afectos, con resolución del dolor.

MANNosylation of Mesoporous Silica Nanoparticles Modifies TLR4 Localization and NF-κB Translocation in T24 Bladder Cancer Cells.

D-mannose is widely used as non-antibiotic treatment for bacterial urinary tract infections. This application is based on a well-studied mechanism of binding to the type 1 bacterial pili and, therefore, blocking bacteria adhesion to the uroepithelial cells. To implement D-mannose into carrier systems, the mechanism of action of the sugar in the bladder environment is also relevant and requires investigation. Herein, two different MANNosylation strategies using mesoporous silica nanoparticles (MSNs) are described. The impact of different chemical linkers on bacterial adhesion and bladder cell response is studied via confocal microscopy imaging of the MSN interactions with the respective organisms. Cytotoxicity is assessed and the expression of Toll-like receptor 4 (TLR4) and caveolin-1 (CAV-1), in the presence or absence of simulated infection with bacterial lipopolysaccharide (LPS), is evaluated using the human urinary bladder cancer cell line T24. Further, localisation of the transcription factor NF-κB due to the MANNosylated materials is examined over time. The results show that MANNosylation modifies bacterial adhesion to the nanomaterials and significantly affects TLR4, caveolin-1, and NF-κB in bladder cells. These elements are essential components of the inflammatory cascade/pathogens response during urinary tract infections. These findings demonstrate that MANNosylation is a versatile tool to design hybrid nanocarriers for targeted biomedical applications.