PURPOSE:Immunotherapy targeting PD-L1 improves outcomes in patients with unresectable stage III non-small cell lung cancer (NSCLC) and no progression after definitive, concurrent chemoradiotherapy (cCRT). Earlier administration of immunotherapy, simultaneously with cCRT, may improve outcomes further. METHODS:Eligible patients were randomly assigned (2:1) to receive either durvalumab or placebo administered from the start of cCRT. Patients without progression after completing cCRT received consolidation durvalumab or placebo (per initial random assignment) until progression. The primary end point was progression-free survival (PFS) by blinded independent central review. Key secondary end points included objective response rate (ORR), overall survival (OS), the proportion of patients alive at 24 months (OS24), and safety. RESULTS:In total, 328 patients were randomly assigned to receive durvalumab (n = 219) or placebo (n = 109). There was no statistically significant difference with durvalumab versus placebo in PFS (hazard ratio [HR], 0.85 [95% CI, 0.65 to 1.12]; P = .247) or OS (HR, 1.03 [95% CI, 0.78 to 1.39]; P = .823); OS24 was 58.4% versus 59.5%, respectively. Confirmed ORR was 60.7% with durvalumab versus 60.6% with placebo (difference, 0.2% [95% CI, -15.2 to 16.3%]; P = .976). With durvalumab versus placebo, respectively, maximum grade 3 or 4 adverse events (AEs) occurred in 53.4% versus 59.3% of patients, pneumonitis or radiation pneumonitis (group term) in 28.8% (grade ≥3: 4.6%) versus 28.7% (grade ≥3: 5.6%), AEs leading to discontinuation of durvalumab or placebo in 25.6% versus 12.0%, and fatal AEs in 13.7% versus 10.2%. CONCLUSION:Among patients with unresectable stage III NSCLC, durvalumab administered from the start of cCRT failed to demonstrate additional benefit compared with cCRT plus placebo. Consolidation durvalumab following definitive cCRT remains the standard of care in this setting.
Cavernous sinus thrombosis is a rare, potentially fatal condition. When septic, it occurs due to bacterial embolization to the region, most commonly by Staphylococcus aureus, affecting venous drainage, with local inflammation and compression of adjacent structures. A 46-year-old man with no comorbidities, smoker, and intranasal cocaine user presented with frontal headache and mucopurulent nasal discharge for two weeks. He was initially treated at a primary care clinic for sinusitis with amoxicillin-clavulanate, without clinical improvement. Three days later, he developed purulent discharge from the left eye with edema, hyperemia, proptosis, left eyelid ptosis, and was hospitalized with suspected periorbital cellulitis. Cranial and sinus CT scans revealed acute inflammatory sphenoidal and left maxillary sinusitis associated with signs of cavernous sinus venous thrombosis, thrombosis of the left superior ophthalmic vein and left sigmoid sinus. MRI of the orbits with gadolinium confirmed bilateral cavernous sinus thrombosis. HIV serology and blood cultures were negative. At the time of diagnosis of septic cavernous sinus thrombosis, antibiotic therapy with oxacillin and ceftriaxone was changed to meropenem plus vancomycin for better coverage and CNS penetration. Ophthalmologic evaluation showed preserved fundus and visual acuity. The patient underwent sinusotomy performed by otorhinolaryngology, and, per neurology assessment, anticoagulation with rivaroxaban was initiated due to ophthalmic vein thrombosis, with a plan to maintain therapy for at least 6 months according to neurology's recommendations. He completed three weeks of intravenous antibiotics with full clinical response. Given that bilateral septic cavernous sinus thrombosis is a rare complication in the antibiotic era, high clinical suspicion is required, taking into account symptom duration, prior nasal cavity disease, and previous treatments. A multidisciplinary approach is essential due to potential need for interventions and management of associated complications.
Introduction Central nervous system tumors are not among the most common neoplasms. However, when present, they are associated with significant mortality and morbidity, which underscores the need for accurate diagnosis to determine the most appropriate oncological treatment. The present study aimed to analyze the clinical profile, the performance of the surgical technique, and the concordance rate between histopathological and neuroimaging diagnoses in patients undergoing stereotactic biopsy between 2010 and 2023 at a tertiary hospital in the city of Porto Alegre, Brazil. Materials and Methods We conducted a retrospective cohort study using secondary data and a quantitative approach, analyzing 109 procedures. Results The study revealed a predominance of male patients (57.8%) and a mean age of 55.49 +/- 15.74 years. The most frequent histopathological diagnosis was high-grade glioma (42.2%), and the region most commonly affected was the corpus callosum (23.9%). No clinical correlation was found between hematoma diameter and neurological alteration. The prevalence- bias-adjusted Kappa (PABAK) index indicated moderate agreement for gliomas and a high level of agreement with the Magnetic Resonance Imaging (MRI) scans for metastases (0.87). Conclusion The procedures performed at the institution demonstrated a high diagnostic success rate, with the analyzed sample being similar to what was expected, despite minor differences from the literature. The replacement of invasive techniques with non-invasive methods is not yet a reality due to the necessity of tissue analysis to define oncological strategies and guide chemotherapy and/or radiotherapy. It is important to point out that the routine use of advanced technologies, such as spectroscopy, in the differential diagnosis of brain tumors, remains crucial.
Objectives:To evaluate 30-day mortality in Enterobacter cloacae complex (Ecc) bloodstream infections (BSIs) according to third-generation cephalosporin and carbapenem resistance profiles, and to investigate factors contributing to the association between antimicrobial resistance and this outcome. Methods:Multicentre retrospective cohort including adults with healthcare-associated Ecc BSI from four Brazilian tertiary hospitals. Isolates were categorized as: third-generation cephalosporin-susceptible (3GCS), third-generation cephalosporin-resistant (3GCR), or carbapenem-resistant (CR). A hierarchical Cox model assessed the effect of resistance profiles on 30-day mortality, adjusting sequentially for: (i) baseline status, (ii) BSI-related variables and (iii) antimicrobial therapy. Results:Of 429 patients, 300 (69.9%) had 3GCS, 103 (24.0%) 3GCR and 26 (6.1%) CR Ecc BSIs. Thirty-day mortality was 22.6% (20.6%, 25.2% and 34.6%, respectively; P = 0.20). In unadjusted analysis, 3GCR (HR 1.10; 95% CI 0.70-1.73) and CR (HR 1.42; 95% CI 0.70-2.86) were not significantly associated with mortality. Hierarchical adjustment revealed that the association between CR and mortality was attenuated after adjustment for baseline severity, while adjustment for appropriate therapy attenuated the associations observed for both resistance profiles. Higher Charlson and Pitt scores, lower baseline glomerular filtration rate and polymicrobial BSI were independently associated with higher mortality; adequate therapy at any time was strongly protective. Conclusions:Non-statistically significant mortality rates were observed in patients with 3GCR and CR Ecc BSIs. Baseline severity and, most importantly, less frequent appropriate antimicrobial therapy attenuated the effect of resistance profiles on the outcome. Improving antimicrobial therapy against resistant Ecc isolates has great potential to reduce mortality.
