Summary Background Erlotinib is approved for the treatment of all patients with advanced non-small cell lung cancer (NSCLC), but is most active in the treatment of EGFR mutant NSCLC. Cabozantinib, a small molecule tyrosine kinase inhibitor, targets MET, VEGFR, RET, ROS1, and AXL, which are implicated in lung cancer tumorigenesis. We tested the efficacy of cabozantinib and the combination of erlotinib plus cabozantinib, as compared with erlotinib, in patients with EGFR wild-type NSCLC. Methods In this three arm, randomised phase 2 study, the primary endpoint was to compare progression-free survival (PFS) of patients treated with cabozantinib versus erlotinib alone, and the combination of erlotinib plus cabozantinib versus erlotinib alone. Patients were eligible if they had received 1–2 previous treatments for advanced non-squamous EGFR wild-type NSCLC. Patients were stratified by performance status and line of therapy, then randomised using permuted blocks within strata to receive open label oral daily dosing of erlotinib (150 mg), cabozantinib (60 mg), or erlotinib (150 mg) and cabozantinib (40 mg). Imaging was performed every 8 weeks. At the time of radiographic progression, there was optional crossover for patients in either single agent arm to receive combination therapy. The comparison between erlotinib and each of the arms was powered (91%) to detect a PFS hazard ratio (HR) of 0.5 (1-sided p-value 0.10-level). Secondary objectives were overall survival (OS), radiographic response by RECIST version 1.1 and description of adverse events by CTCAE version 4.0. This trial is registered with ClinicalTrials.gov, number NCT01708954. Findings At complete enrollment, we randomised 125 patients (42 assigned to erlotinib, 40 assigned to cabozantinib, 43 assigned to the combination), of which 111 (89%) were eligible and received treatment per protocol were included in the primary analysis (38, 38, and 35 patients on erlotinib, cabozantinib, and combination, respectively). Compared to erlotinib alone (median 1.8 months), PFS was significantly improved in the cabozantinib arm (4.3 months, HR 0.39, 1-sided p=0.0003, 80% CI 0.27–0.55) and also in the erlotinib plus cabozantinib arm (4.7 months, HR 0.37, 1-sided p=0.0003, 80% CI 0.25–0.53). The safety analysis population included all patients who received study therapy regardless of eligibility. The most common grade 3 or 4 adverse events were diarrhea (3 [8%] in the erlotinib group vs 3 [8%] in the cabozantinib group vs 11 [28%] in the erlotinib and cabozantinib group), hypertension (none vs 10 [25%] vs 1 [3%]), fatigue (5 [13%] vs 6 [15%] vs 6 [15%]), oral mucositis (none vs 4 [10%] vs 1 [3%]), and thromboembolic event (none vs 3 [8%] vs 2 [5%]). Adverse events that were grade 3 or worse occurred in 13 (33%) patients in the erlotinib group, in 28 (70%) patients in the cabozantinib group, and in 28 (72%) patients in the erlotinib and cabozantinib group. One death of respiratory failure occurred in the cabozantinib group, deemed possibly related to either drug or diseas...

IntroductionBrain metastases (BM) are associated with dismal prognosis, and there is a dearth of effective systemic therapy. In this study, patients with BM from multiple solid tumors were identified from TriNetX databases, their clinicopathological features were evaluated, and the effects of immune checkpoint inhibitor (ICI) therapy were assessed.MethodsVariables, including median overall survival (OS), Eastern Cooperative Oncology Group (ECOG) performance status, primary diagnosis, and date of diagnosis, were retrieved from TriNetX, a real-world database. Kaplan-Meier plots and log-rank tests were applied to assess significance of differences in survival. Hazard ratio (HR) and 95% confidence interval (CI) values were calculated. All patient data were deidentified.ResultsA total of 227,255 patients with BM were identified in the TriNetX database; median OS was 12.3 months from initial cancer diagnosis and 7.1 months from development of BM. OS of BM from nonsmall-cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), melanoma, and renal cell carcinoma (RCC) were 8.7, 14.7, 17.8, and 15.6 months, respectively. After matching patient baseline characteristics, OS of cohorts with or without exposure to ICIs was evaluated. For all types of cancer, median OS durations for the ICI and no-ICI cohorts were 14.0 and 7.9 months, respectively (HR: 0.88; 95% CI: 0.85–0.91). More specifically, OS was remarkably prolonged in patients with NSCLC (14.4 vs. 8.2 months; HR: 0.86; 95% CI: 0.82–0.90), TNBC (23.9 vs. 11.6 months; HR: 0.87; 95% CI: 0.82–0.92), and melanoma (27.6 vs. 16.8 months; HR: 0.80; 95% CI: 0.73–0.88) if patients had exposure to ICIs. In contrast, there was no significant difference in OS of patients with RCC treated with and without ICIs (16.7 vs. 14.0 months; HR: 0.96; 95% CI: 0.86–1.10).ConclusionsOverall, BM indicates poor patient outcome. Treatment with ICIs improves survival of patients with NSCLC, TNBC, and melanoma and BM; however, no significant improvement was observed in RCC. Investigations to identify prognostic features, oncogenomic profiles, and predictive biomarkers are warranted.

Background: The role of intubation is practiced in most respectful universities for many medical students, especially the paramedic and anesthesia students through controlled anesthesia simulation labs. Aim: The study aims to evaluate the learning outcomes of various types of intubation for paramedic and anesthesia students before and after studying two courses of airway management in the department of clinical technology. Methods: A model for measuring, comparing, and analyzing the fields of knowledge about skills and experiences obtained by the students is prepared. Students are enrolled from the emergency medical service and the anesthesia department of clinical sciences at the Faculty of Applied Medical Sciences at Umm Al-Qura University in Makkah Al-Mukarramah. Results: Psychomotor skills were the most important domain among students in EMS department, followed by airway compromise knowledge, intention or attitude, and effective communication.

We report the first case of a nodal marginal zone large B-cell lymphoma and the first with MYC rearrangement. This high proliferation rate lymphoma (40% of cells) occurred in the bilateral cervical, axillary, and para-aortic lymph nodes of an 82 year old woman. It involved extensively her bone marrow, and was lethal. Malignant B-cells were CD10 negative, harbored Burkitt translocation, and multiple chromosomal changes including trisomies of chromosomes 3 and 18, and three copies of 8q with an intact q24 cytoband (in addition to MYC rearrangement), associated with overexpression of BCL6, BCL2, and MYC respectively. We suggest that in aggressive nodular marginal zone lymphomas (clinical picture or high proliferation rate of lymphoma cells), fluorescence in situ hybridization analysis for MYC rearrangement, with break-apart probe, and for MYC/IGH translocation, in addition to chromosome analysis, should be performed. MYC rearrangement associated with a more rapid progression of the neoplasia, might warrant a more aggressive treatment. 〔J Clin Exp Hematop 55(3) : 175-180, 2015〕

Background: The presence of two hollow viscus perforations in a single patient is a rare entity and no case report is available in the literature which shows the finding of duodenal ulcer perforation and enteric perforation in the same patient. Case presentation: A 55-year-old male presented in the emergency department of East Surgical Ward of Mayo Hospital, Lahore, Pakistan, in January 2020 with complaint of abdominal pain and vomiting for the past 3 days and fever for the past 5 days. He was a chronic smoker with a history of 10 pack-years. On examination, he had tachycardia with a pulse rate of 114 beats/minutes and respiratory rate was 30/minutes and his whole abdomen was guarding with absent bowel sounds. X-ray of the chest showed free gas under the right hemidiaphragm. The patient was resuscitated and plan of exploration was made with diagnosis of perforated duodenal ulcer. We found a 0.5 × 0.5 cm perforation on the anterior surface of the first part of the duodenum along with a 1 × 1 cm perforation on antimesenteric surface of ileum that is 1 feet proximal to ileocolic junction. Graham’s patch repair was carried out for duodenal perforation, while loop ileostomy was made for ileal perforation. The patient was discharged on the 5th postoperative day. The reversal of loop ileostomy was carried out after 2 months. Conclusion: In cases of peritonitis, general inspection of the whole gastrointestinal tract plays a very important role as more than one hollow viscus perforation can be found in a single patient which can be missed and can lead to peritonitis again.