Photoangiolytic Lasers for Treatment of Benign Laryngeal Lesions: A Systematic Review and Meta-Analysis.

OBJECTIVES: To compare the efficacy of the 445-nm blue laser to the 585-nm pulsed dye laser (PDL) and 532-nm potassium-titanyl-phosphate (KTP) laser in the treatment of benign laryngeal lesions. DATA SOURCES: Cochrane Library, PubMed, Scopus, and CINAHL. REVIEW METHODS: Following PRISMA guidelines, databases were searched from inception through January 29, 2024, for studies reporting the use of photoangiolytic lasers for treatment of benign laryngeal lesions, including the 585-nm PDL, 532-nm KTP laser, and 445-nm blue laser. Outcome measures included lesion resolution (%), mean differences (Δ) in Voice Handicap Index (VHI-10), and summed dysphonia grade, roughness, and breathiness (GRB) scale. RESULTS: A total of 45 studies were included for meta-analysis, consisting of 348 patients treated with PDL, 550 patients with KTP laser, and 338 patients with blue laser. Treatment with blue laser resulted in the greatest lesion resolution (94.0%; 95% confidence interval [CI]: 90.2%-96.7%), followed by KTP laser (90.4%; 95% CI: 84.1%-95.2%), and PDL (86.9%; 95% CI: 62.9%-99.2%). VHI-10 improved significantly in patients following treatment with blue laser (Δ13.3; 95% CI: 10.7-16.0; p < 0.0001), KTP laser (Δ10.3; 95% CI: 7.4-13.3; p < 0.0001), and PDL (Δ7.4; 95% CI: 4.8-10.1; p < 0.0001). GRB improved significantly in patients following treatment with blue laser (Δ4.1; 95% CI: 2.9-5.2; p < 0.0001), KTP laser (Δ3.0; 95% CI: 2.0-4.0; p < 0.0001), and PDL (Δ2.5; 95% CI: 0.8-4.2; p = 0.005). CONCLUSIONS: Photoangiolytic lasers are effective in treating benign laryngeal lesions. Blue lasers are promising for laryngeal laser surgery. Laryngoscope, 2024.

Sex and human papillomavirus in oropharyngeal cancer: A systematic review and meta-analysis.

INTRODUCTION: While the presence of human papillomavirus (HPV) is known to affect the outcomes of oropharyngeal squamous cell carcinoma (OPSCC), there is a significant gap in research regarding the potential sex-based differences. This systematic review-metanalysis (SR-MA) aims to evaluate if sex is a prognostic factor in HPV-associated OPSCC. METHODS: A systematic review and meta-analysis was performed. COCHRANE Library, CINAHL, PubMed, and Scopus were searched for English-language articles from 1966 to October 2023. Studies with multivariable analysis of overall survival (OS) based on sex were included. Adjusted hazard ratios (aHRs) with a 95 % confidence interval (CI) were presented for the reported outcome. A meta-analysis of single means, proportions, and aHRs with a 95 % CI was conducted. RESULTS: This SR-MA included 24 studies (n = 101,574). The proportion of female patients was 16.6 % [15.4 %-17.8 %]. A meta-analysis of all included studies with OS showed no significant difference in survival between male and female patients. In US-based studies, no significant difference in OS is observed between male and female patients. International studies reported a better OS for female patients (aHR = 0.68, 95 % CI, 0.48-0.95). CONCLUSION: This meta-analysis suggests that sex does not represent a significant prognostic factor for patients affected by HPV associated OPSCC. When stratified by geographic location, findings suggests that female patients from the US with HPV OPSCC have similar OS than male patients but in international studies it suggests male patients have worse OS.

Audiovestibular outcomes in adult patients with cogan syndrome: a systematic review.

PURPOSE: To determine factors associated with steroid responsiveness and efficacy of biologic disease-modifying anti-rheumatic (DMARD) use in patients with Cogan Syndrome (CS). METHODS: A systematic search of Cochrane Library, PubMed, CINAHL, and Scopus was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Any study describing audiometric or vestibular data and pharmacologic treatment in patients with CS was included. Due to limited literature, only case reports/case series were included. RESULTS: Seventy case reports or case series studies comprising 79 individual cases of CS were included. A difference in vestibular symptoms with a higher prevalence in the steroid-resistant group than the steroid-responsive group was found (79.5% vs 57.9%, p = 0.04). Eighteen (60.0%) patients treated only with oral steroids had no audiological improvement, while twelve (n = 12; 85.7%) patients treated with biologic DMARD showed audiological improvement. The steroid-responsive group had an overall better response to DMARDs than the steroid-resistant group (62.1% vs 45.0%; 100.0% vs 77.8%). CONCLUSIONS: Our study synthesized the available literature to better characterize steroid resistance in patients with Cogan syndrome and treatment outcomes. Vestibular symptoms were noted to be more prevalent in patients who were eventually labeled as steroid resistant. There were higher rates of audiological improvement in patients given biologic DMARDs rather than conventional DMARDs or steroids only. Further studies are needed to characterize each individual vestibular symptom and investigate the utility and timing of biologic DMARDs in managing patients with Cogan syndrome.

Beyond cancer treatment: dermo-aesthetic and other wellness recommendations for breast cancer patients.

Breast cancer, a prevalent malignancy among women, has various physical and psychological impacts. This comprehensive review offers an in-depth look at multidisciplinary dermo-aesthetic intervention approaches, emphasizing the balance between oncological therapies and the management of these effects. The information presented spans specialties such as aesthetic medicine, plastic surgery, dermatology, physiotherapy, nutrition, odontology, and gynecology. This review, which serves as a clinical guide, aims to establish a safe protocol for non-medical interventions involving oncologists, physicians, and specialists from various areas in patients with breast cancer focused on improving their quality of life. This work offers personalized and integrative care strategies for the eradication of cancer. However, it is still necessary for patients to consult with their oncologist before undergoing any dermo aesthetic treatment. However, it is still necessary for patients to consult with their oncologist before undergoing any dermo aesthetic treatment.

CSF1R Inhibition in Patients With Advanced Solid Tumors or Tenosynovial Giant Cell Tumor: A Phase 1 Study of Vimseltinib.

PURPOSE: Tenosynovial giant cell tumor (TGCT) is a locally aggressive neoplasm caused by dysregulation of the colony-stimulating factor 1 (CSF1) gene and overexpression of the CSF1 ligand. Surgery is the standard of care for most patients, but there are limited treatment options for patients with TGCT not amenable to surgery. This study evaluates vimseltinib, an investigational, oral, switch-control tyrosine kinase inhibitor designed to selectively and potently inhibit the CSF1 receptor. PATIENTS AND METHODS: This first-in-human, multicenter, open-label, phase 1/2 study of vimseltinib in patients with malignant solid tumors (N = 37) or TGCT not amenable to surgery (N = 32) followed a pharmacologically guided 3 + 3 study design (NCT03069469). The primary objectives were to assess safety and tolerability, determine the recommended phase 2 dose (RP2D), and characterize the pharmacokinetics (PK); exploratory objectives included pharmacodynamics and efficacy. RESULTS: Vimseltinib was well tolerated; the majority of non-laboratory treatment-emergent adverse events were grade 1/2. There was no evidence of cholestatic hepatotoxicity or drug-induced liver injury. The RP2D was determined to be 30 mg twice weekly (no loading dose), and vimseltinib plasma exposure increased with the dose. In patients with TGCT, the median treatment duration was 25.1 months (range, 0.7 to 46.9), and the objective response rate as assessed by independent radiological review using Response Evaluation Criteria in Solid Tumors version 1.1 was 72%. CONCLUSIONS: Vimseltinib demonstrated long-term tolerability, manageable safety, dose-dependent exposure, and robust antitumor activity in patients with TGCT whose disease is not amenable to surgery.

Tirofiban versus aspirin to prevent in-stent thrombosis after emergent carotid artery stenting in acute ischemic stroke.

BACKGROUND: Several antithrombotic treatments during emergent carotid artery stenting (eCAS) have been proposed, but an appropriate protocol to balance risk-benefit is not well known. OBJECTIVE: To investigate the efficacy and safety of tirofiban compared with aspirin in patients with acute ischemic stroke undergoing eCAS. METHODS: We conducted a retrospective single-center study of the prospective ARTISTA Registry, including patients with atherosclerotic internal carotid artery occlusion treated with eCAS. Two groups, according to antiplatelet drug, were studied: aspirin (250-500 mg single-dose) versus tirofiban (500 µg bolus+200 µg/h). Primary outcomes were the rate of in-stent thrombosis and symptomatic intracranial hemorrhage (sICH) within the first 24 hours. RESULTS: During the period 2019-2023, 181 patients were included, 103 received aspirin, 78 tirofiban; 149 (82.3%) had tandem lesions. The primary efficacy outcome occurred in 9 (9.4%) in the aspirin group, as compared with 1 (1.3%) in the tirofiban group (adjusted odds ratio (aOR)=0.11, 95% CI 0.01 to 0.98; P=0.048). The primary safety outcome was detected in 12 (11.7%) in the aspirin group, as compared with 2 (2.6%) in the tirofiban group (aOR=0.16, 95% CI 0.03 to 0.87; P=0.034). The tirofiban group presented a lower risk of parenchymal hemorrhage (18 (17.4%) vs 4 (5.2%), aOR=0.27, 95% CI 0.09 to 0.88; P=0.029) and an increased rate of excellent recanalization (expanded Treatment in Cerebral Infarction (eTICI) 2c-3) (50 (48.5%) vs 54 (69.2%); aOR=2.15, 95% CI 1.12 to 4.13; P=0.02). There were no differences in functional outcomes or mortality at 3 months. CONCLUSIONS: Periprocedural antithrombotic therapy with tirofiban was associated with a lower risk of in-stent thrombosis and sICH at 24 hours from eCAS compared with aspirin. Prospective randomized clinical trials are needed to confirm our results.

Neoadjuvant Treatment of Locally Advanced Thyroid Cancer: A Preliminary Latin American Experience.

Background: Surgical resection is not always achievable in thyroid cancer patients. Neoadjuvant therapy is rarely used, but recent trends favor multikinase inhibitors or selective tyrosine kinase inhibitors. These aim to reduce tumor volume, enabling previously unfeasible surgeries. Patients and Methods: Consecutive patients with locally advanced malignant thyroid tumors who received systemic therapies with a neoadjuvant intention were included in this retrospective multicenter case series conducted in five Latin American referral centers. Primary outcomes were pre- versus postneoadjuvant response evaluations using the Response Evaluation Criteria in Solid Tumors, feasibility of surgery, and completeness of resection. Secondary outcomes were mortality and status at the last visit. Results: Twenty-seven patients were included in this analysis. Patients with unresectable differentiated thyroid cancer (DTC) or poorly differentiated thyroid cancer (PDTC) received sorafenib (n = 6) or lenvatinib (n = 12), those with medullary thyroid cancer (MTC) were treated with vandetanib (n = 5) or selpercatinib (n = 1), and those with anaplastic thyroid cancer (ATC) harboring a BRAFV600E mutation (n = 3) received dabrafenib and trametinib. The median patient age was 66 years (range 12-82), and 52% of the patients were female. In patients with PTC and PDTC, the median reduction in the diameter of the primary tumor was 25% (range 0-100%) after a median of 6 months of treatment. Surgical intervention was performed in 10 (55%) of the patients. Among these, six patients (60%) achieved R0/R1 resection status. Six patients with MTC had a median reduction in tumor diameter of 24.5% (range 1-49) after a median treatment time of 9.5 months. Only one patient receiving selpercatinib, with a tumoral reduction of 25% could undergo surgery, resulting in an R2 resection due to extensive mediastinal extension. Three patients with ATC showed a median tumor diameter reduction of 42% (range 6.7-50) after a median treatment time of 2 months. Two patients underwent surgical intervention and achieved R1 and R2 resection, respectively. Conclusions: While neoadjuvant therapy achieved tumoral responses, surgical resection was feasible in 55% of DTC, 33% of ATC, and 16% of MTC patients, with R0/R1 resection in 26% of the cohort, underscoring the need for patient selection and further research in this area.

Development of a Risk Prediction Nomogram for Carotid Re-Stenosis in the One Year RECAST Registry.

OBJECTIVE: The long term benefit of carotid angioplasty and stenting (CAS) can be reduced by recurrent stroke related to in stent re-stenosis (ISR). An individualised predictive tool is needed to identify ISR events. A nomogram for individual risk assessment of ISR ≥ 70% after CAS is proposed. METHODS: A national observational, prospective, multicentre registry was conducted between January 2015 and December 2020. Cohorts of patients with symptomatic or asymptomatic severe carotid stenosis who underwent CAS with a follow up of at least one year after CAS were included. Duplex ultrasound was used to assess in stent re-stenosis. Pre-operative factors were compared between the non-ISR and ISR groups. Kaplan-Meier and Cox regression were used for variable selection. The nomogram was formulated and validated by concordance indices and calibration curves. An in stent re-stenosis risk table was generated for risk stratification. RESULTS: A total of 354 patients were included in the analysis. The ISR rate of ≥ 70% was 7.6% (n = 27). Peripheral arterial disease (hazard ratio [HR] 3.18, 95% confidence interval [CI] 1.23 - 8.24, p = .017), anterior communicating artery absence (HR 3.38, 95% CI 1.27 - 8.94, p = .016), diabetes mellitus (HR 3.34, 95% CI 1.21 - 9.26, p = .020), female sex (HR 2.99, 95% CI 1.04 - 8.60, p = .041), and pre-procedure pathological ultrasound vasoreactivity (HR 3.87, 95% CI 1.43 -10.50, p = .008), as independent risk factors for ISR of ≥ 70%, were included in the nomogram. The concordance index at 12 and 24 months was 0.83. In low risk groups, ISR of ≥ 70% occurred in 4.8% of patients during follow up compared with 56.2% of patients in the high risk groups (p < .001). CONCLUSION: The nomogram and risk evaluation score have good predictive ability for ISR. They can be used as practical clinical tools for individualised risk assessment.

Medical Management of Headache and Facial Pain in CRS: A Systematic Review and Meta-Analysis.

OBJECTIVES: This study aims to characterize the effect of medical therapy on headache and facial pain/pressure among patients with chronic rhinosinusitis (CRS). DATA SOURCES: CINAHL, PubMed, and Scopus. METHODS: CINAHL, PubMed, and Scopus were searched from inception through April 10th, 2024, for English language articles reporting headache or facial pain/pressure outcomes in CRS patients. Inclusion was restricted to studies reporting results of the medical treatment of CRS in nonsurgical cohorts. Primary outcome measures included the sino-nasal outcome test (SNOT) and the visual analogue scale (VAS). Meta-analyses of continuous measures (mean), mean difference (Δ), and proportions (%) were conducted. RESULTS: The initial search yielded 2429 unique articles. After a full-text review of 272 articles, 17 studies reporting outcomes for 2269 patients were included in the meta-analysis. The mean patient age was 48.6 years (range 18.0-86.0; 95% CI: 46.5 to 50.6), among which 55.4% (95% CI: 51.5 to 59.4) were male and 82.9% (95% CI: 68.8 to 93.4) had nasal polyposis. SNOT facial pain/pressure scores improved by 1.1 points (95% CI: -1.7 to -0.5; relative reduction 40.4%) with non-biologic therapies and 1.0 point (95% CI: -1.4 to -0.6; relative reduction 54.6%) with biologic therapies. On an 11-point scale, VAS headaches scores improved by 1.8 units (95% CI: -3.3 to -0.3; 42.1% relative reduction) in CRSwNP patients and 1.0 unit (95% CI: -1.7 to -0.3; 54.0% relative reduction) in CRSsNP patients. CONCLUSIONS: Our findings suggest medical therapy significantly reduces facial pain and pressure in the CRS population. Laryngoscope, 2024.

Surgical management of headache and facial pain/pressure in chronic rhinosinusitis: A systematic review and meta-analysis.

BACKGROUND: Headache and facial pain are common symptoms of chronic rhinosinusitis (CRS). However, given the numerous etiologies that can cause these symptoms, the impact of sinus surgery is not well characterized. METHODS: A systematic review was performed by searching the literature from inception through June 6, 2023. English-language articles reporting outcomes for facial pain/pressure or headache following endoscopic sinus surgery were selected for inclusion. Meta-analyses were performed using random and fixed effect models on continuous measures (mean), mean difference (Δ), and proportions (%). RESULTS: A total of 26 articles reporting on 2839 patients were selected for inclusion. The mean patient age was 44.0 ± 3.9 (range 16.0-84.0), with an average symptom duration of 5.3 ± 2.8 years. Among these patients, 56.5% (95% confidence interval [CI]: 52.3-60.6) were male and 77.0% (95% CI: 56.6-92.3) had nasal polyposis (NP). Patients with and without NP reported substantial reductions in both 22-item sino-nasal outcome test facial pain/pressure (with NP: -1.4 [95% CI: -1.6 to -1.2; relative reduction 59.1%]; without NP: -1.5 [95% CI: -1.9 to -1.1; relative reduction 60.9%]) and visual analogue scale (VAS) headache (with NP: -2.5 [95% CI: -2.8 to -2.1; relative reduction 67.2%]; without NP: -2.8 [95% CI: -4.7 to -1.0; relative reduction 42.7%]). Symptom reductions were greater in the without NP versus with NP group; VAS facial pain/pressure: Δ0.4 (95% CI: 0.2-0.6; p = 0.0006) and VAS headache: Δ0.4 (95% CI: 0.1-0.7; p = 0.02). CONCLUSIONS: Our findings suggest that CRS patients, regardless of polyp status, benefit from significant reductions in facial pain/pressure and headache following surgical therapy.

Spanish translation and validation of the Music-Related Quality of Life Questionnaire (MuRQoL) in postlingually deaf cochlear implant users.

PURPOSE: The aim of this study was to translate and validate the "Music-Related Quality of Life Questionnaire" into Spanish (sMuRQoL) and assess its convergent validity and discriminative capacity by comparing its scores with the outcomes of the musical perception test Meludia. METHODS: The sMuRQoL was completed by 129 patients: 55 cochlear implant (CI) users and 74 normal hearing (NH) individuals. Conducted in this study were an exploratory factor analysis, an evaluation of internal consistency, an assessment of score stability through test-retest reliability, a comparison of sMuRQoL scores between CI users and NH individuals and an examination of potential evidence of convergent validity and discriminative capacity of sMuRQoL in relation to other tools. This involved the comparison of the questionnaire scores with the Meludia outcomes. RESULTS: The sMuRQoL demonstrated a two-dimensional structure. All the dimensions displayed high internal consistency (α = 0.879-0.945) and score stability (ICC = 0.890-0.942). There were significant differences in the Frequency test between NH and CI users (d = 1.19-1.45). There's evidence of convergent validity between the scores of the Frequency test and the results of Meludia (r = 0.242-0.645). Additionally, the Frequency test demonstrate a good discriminative capacity to identify patients with poorer musical perception. CONCLUSIONS: The sMuRQoL is a reliable questionnaire, with adequate evidence of validity based on internal structure. This study provides an accessible, cost-effective, and quick-to-administer instrument in Spanish, optimizing available healthcare resources and bringing us closer to the patient needs.

Hysteroscopic subchorionic injection of methotrexate followed by laparoscopic excision of the gestational sac for the management of cesarean scar ectopic pregnancy: an innovative dual approach of a challenging pathology.

OBJECTIVE: To describe an effective two-step surgical approach for the management of cesarean scar ectopic pregnancies (CSEPs). CSEPs occur at an estimated frequency of 1 in 1,800 pregnancies, constituting approximately 6% of ectopic pregnancies in women with a history of prior cesarean delivery [1, 2]. Despite numerous recommended therapeutic approaches, the most effective treatment strategy remains uncertain [3]. DESIGN: We present an innovative double-step technique for the management of a patient with a CSEP involving hysteroscopic subchorionic injection of methotrexate (MTX), followed by laparoscopic resection of the residual gestational sac and simultaneous repair of the uterine defect. SETTING: Academic tertiary hospital. PATIENT: A 34-year-old G2P1001 with a history of prior cesarean section presented at 10 weeks of gestation. Ultrasound revealed a gestational sac within the niche of the previous cesarean scar, confirming the diagnosis of a CSEP. The patient included in this video gave consent for publication of the video and posting of the video online, including on social media, the journal website, scientific literature websites (such as PubMed, ScienceDirect, and Scopus, among others), and other applicable sites. INTERVENTION: The initial treatment involved hysteroscopic administration of MTX within the placental intervillous spaces, ensuring precise medication delivery. The administered dose of MTX was 1 mg/kg. Following the normalization of beta-human chorionic gonadotrophin (ß-hCG) levels, laparoscopic resection of the remaining gestational sac and reconstruction of the uterine wall defect were performed. MAIN OUTCOME MEASURES: We have implemented a management strategy focusing on ectopic pregnancy removal and addressing defect revision. The hysteroscopic approach allows for a clear assessment of the ectopic pregnancy and facilitates precise MTX administration, enhancing its effectiveness by increasing drug concentration within the placental intervillous space. Delaying surgical repair until after the ß-hCG levels have decreased reduces the risk of excessive bleeding during the procedure, as lower ß-hCG levels are associated with reduced vascularity at the ectopic site. Subsequent laparoscopic resection allows for complete removal of the remaining products of conception and repair of the defect, preserving the uterus and restoring normal anatomy. Compared to other surgical approaches, our two-step approach enables a more precise evaluation of placental implantation, making it a highly effective surgical method. RESULTS: We successfully managed a CSEP using a double-step technique. This involved hysteroscopic injection of subchorionic MTX, followed by laparoscopic resection of the residual gestational sac. Concurrently, we repaired the uterine defect. Both procedures were performed in an outpatient setting without complications detected during or after treatment. At the follow-up visit, the patient reported good health, and subsequent ultrasound confirmed an empty isthmocele. CONCLUSION: This sequential hysteroscopic and laparoscopic approach represents a definitive and effective minimally invasive surgical option for the treatment of CSEP.

Derazantinib alone and with atezolizumab in metastatic urothelial carcinoma with activating FGFR aberrations.

BACKGROUND: This Phase 1b/2 study assessed the efficacy in terms of objective response rate (ORR) of the FGFR1/2/3 kinase inhibitor derazantinib as monotherapy or in combination with atezolizumab in patients with metastatic urothelial cancer (mUC) and FGFR1-3 genetic aberrations (FGFR1-3GA). METHODS: This multicenter, open-label study comprised 5 substudies. In Substudies 1 and 5, patients with mUC with FGFR1-3GA received derazantinib monotherapy (300 mg QD in Substudy 1, 200 mg BID in Substudy 5). In Substudy 2, patients with any solid tumor received atezolizumab 1200 mg every 3 weeks plus derazantinib 200 or 300 mg QD. In Substudy 3, patients with mUC harboring FGFR1-3GA received derazantinib 200 mg BID plus atezolizumab 1200 mg every 3 weeks. In Substudy 4, patients with FGFR inhibitor-resistant mUC harboring FGFR1-3GA received derazantinib 300 mg QD monotherapy or derazantinib 300 mg QD plus atezolizumab 1200 mg every 3 weeks. RESULTS: The ORR for Substudies 1 and 5 combined was 4/49 (8.2%, 95% confidence interval = 2.3% to 19.6%), which was based on 4 partial responses. The ORR in Substudy 4 was 1/7 (14.3%, 95% confidence interval = 0.4% to 57.9%; 1 partial response for derazantinib 300 mg monotherapy, zero for derazantinib 300 mg plus atezolizumab 1200 mg). In Substudy 2, derazantinib 300 mg plus atezolizumab 1200 mg was identified as a recommended dose for Phase 2. Only 2 patients entered Substudy 3. CONCLUSIONS: Derazantinib as monotherapy or in combination with atezolizumab was well-tolerated but did not show sufficient efficacy to warrant further development in mUC. Clinicaltrials.gov NCT04045613, EudraCT 2019-000359-15.

Management of embolic splenic abscess secondary to aortic valve endocarditis - case report and review of literature.

BACKGROUND: Splenic abscess is a serious complication associated with infective endocarditis. There is still contradicting evidence regarding the optimal treatment pathway including timing of valve intervention and the approach for managing splenic foci. CASE PRESENTATION: We present a case of a hybrid staged approach in which we successfully performed a laparoscopic splenectomy following percutaneous abscess drainage and a delayed aortic valve replacement. CONCLUSIONS: A multidisciplinary teamwork is fundamental in providing optimal care for patients with distant complications associated with infective endocarditis. Our hybrid approach seems safe and feasible.

Real-world experience with pertuzumab and trastuzumab combined with chemotherapy in neoadjuvant treatment for patients with early-stage HER2-positive breast cancer: the NEOPERSUR study.

PURPOSE: HER2-targeted therapies have dramatically improved outcomes of patients with HER2-positive breast cancer (BC), as demonstrated in neoadjuvant trials. This study aims to provide real-world evidence on the use and effectiveness of combined pertuzumab, trastuzumab and chemotherapy (CT) in early-stage HER2-positive BC. METHODS: A retrospective, multicentre study was conducted on patients diagnosed with HER2-positive early BC treated with neoadjuvant pertuzumab and trastuzumab plus CT at 13 Spanish sites. The primary endpoint was pathological complete response (pCR). RESULTS: A total of 310 patients were included. Pertuzumab and trastuzumab were combined with anthracyclines and taxanes, carboplatin and docetaxel, and taxane-based CT in 77.1%, 16.5%, and 6.5% of patients, respectively. Overall, the pCR rate was 62.2%. The pCR was higher amongst patients with hormone receptor-negative tumours and with tumours expressing higher levels of Ki-67 (> 20%). After postoperative adjuvant treatment, 13.9% of patients relapsed. Those patients who did not achieve pCR, with tumours at advanced stages (III), and with node-positive disease were more likely to experience distant relapse. Median overall survival (OS) and distant disease-free survival (D-DFS) were not reached at the study end. The estimated mean OS and D-DFS times were 7.5 (95% CI 7.3-7.7) and 7.3 (95% CI 7.1-7.5) years, respectively (both were significantly longer amongst patients who achieved pCR). Grade 3-4 anti-HER2 related toxicities were reported in six (1.9%) patients. CONCLUSION: Neoadjuvant pertuzumab and trastuzumab plus CT achieve high pCR rates in real-life patients with HER2-positive early BC, showing an acceptable safety profile. Innovative adjuvant strategies are essential in patients at high risk of distant disease recurrence.

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.

Unraveling lipid and inflammation interplay in cancer, aging and infection for novel theranostic approaches.

The synergistic relationships between Cancer, Aging, and Infection, here referred to as the CAIn Triangle, are significant determinants in numerous health maladies and mortality rates. The CAIn-related pathologies exhibit close correlations with each other and share two common underlying factors: persistent inflammation and anomalous lipid concentration profiles in the membranes of affected cells. This study provides a comprehensive evaluation of the most pertinent interconnections within the CAIn Triangle, in addition to examining the relationship between chronic inflammation and specific lipidic compositions in cellular membranes. To tackle the CAIn-associated diseases, a suite of complementary strategies aimed at diagnosis, prevention, and treatment is proffered. Our holistic approach is expected to augment the understanding of the fundamental mechanisms underlying these diseases and highlight the potential of shared features to facilitate the development of novel theranostic strategies.

Moderate-High Blood Eosinophilia Is Associated with Increased Hospitalization and Other Asthma Comorbidities.

(1) Background: Eosinophilia has traditionally been linked to eosinophilic asthma, for which it is the gold-standard prognostic biomarker. However, the association between eosinophilia and the presence of other diseases and comorbidities is yet unclear. (2) Methods: For this retrospective study, we reviewed the electronic medical records of 49,909 subjects with blood eosinophilia to gather data on the presence of asthma, COPD, sleep apnea, tuberculosis, dyslipidemia, hypertension, and other cardiovascular diseases and severe CRSwNP among these subjects. Demographic features including age, sex, and smoking habits were collected, as well as the number of hospitalizations and emergency department visits. T-tests, ANOVA, Fisher test, and logistic regression models were used. (3) Results: For all age groups studied, eosinophilia was significantly more prevalent among asthmatic subjects than nonasthmatics, especially in patients also presenting CRSwNP, hypertension, and dyslipidemia. The likelihood of developing asthma, COPD, and CRSwNP, and hospitalization, was increased when BEC was above 600 eosinophils/µL. The association between asthma, CRSwNP, and BEC was corroborated by multiple logistic regressions models. (4) Conclusions: We demonstrated the association of having over 600 blood eosinophils/µL with a higher number of hospitalizations and comorbidities (CRSwNP and COPD), which proves that BEC is a highly useful parameter to consider in subjects who present blood eosinophilia.