Activity of PD-1 blockade with nivolumab among patients with recurrent atypical/anaplastic meningioma: phase II trial results

BackgroundProgrammed death ligand 1 (PD-L1) contributes to tumor immunosuppression and is upregulated in aggressive meningiomas. We performed a phase II study of nivolumab, a programmed death 1 (PD-1) blocking antibody among patients with grade ≥2 meningioma that recurred after surgery and radiation therapy.MethodsTwenty-five patients received nivolumab (240 mg biweekly) until progression, voluntary withdrawal, unacceptable toxicity, or death. Tumor mutational burden (TMB) and quantification of tumor-infiltrating lymphocytes (TIL) were evaluated as potential immunocorrelative biomarkers. Change in neurologic function was prospectively assessed using the Neurologic Assessment in Neuro-Oncology (NANO) scale.ResultsEnrolled patients had multiple recurrences including ≥3 prior surgeries and ≥2 prior courses of radiation in 60% and 72%, respectively. Nivolumab was well tolerated with no unexpected adverse events. Six-month progression-free survival (PFS-6) rate was 42.4% (95% CI: 22.8, 60.7) and the median OS was 30.9 months (95% CI: 17.6, NA). One patient achieved radiographic response (ongoing at 4.5 years). TMB was >10/Mb in 2 of 15 profiled tumors (13.3%). Baseline TIL density was low but increased posttreatment in 3 patients including both patients with elevated TMB. Most patients who achieved PFS-6 maintained neurologic function prior to progression as assessed by NANO.ConclusionNivolumab was well tolerated but failed to improve PFS-6, although a subset of patients appeared to derive benefit. Low levels of TMB and TIL density were typically observed. NANO assessment of neurologic function contributed to outcome assessment. Future studies may consider rationally designed combinatorial regimens.     

Functional Analysis of Spike from SARS-CoV-2 Variants Reveals the Role of Distinct Mutations in Neutralization Potential and Viral Infectivity

Enhanced viral transmission and escape from vaccine–elicited neutralizing antibodies drive worldwide spread of SARS-CoV-2 variants and promote disease progression. However, the impact of specific spike mutations that are carried by different viral variants on viral infectivity and neutralization sensitivity has not been completely defined. Here, we use pseudoviruses to assess the contribution of spike mutations within the Receptor Binding Domain (RBD) and the Furin Cleavage Site (FCS), and appear in circulating viral variants, on viral infectivity and neutralization potential against sera that was drawn from fully vaccinated individuals. Our functional analysis demonstrates that single, P681H, P681R or A701V–FCS mutations do not play a role in viral infectivity and neutralization potential. However, when in conjunction with the RBD–N501Y mutation, viral infectivity is enhanced. Similarly, combining the E484K–RBD mutation to the spike that carries FCS mutations reduces neutralization sensitivity with no effects on viral infectivity. Employing a similar approach onto the spike from Delta or Lota SARS-CoV-2 variants further reveals that specific RBD mutations affect neutralization sensitivity or viral infectivity differently. Our results validate the efficacy of the Pfizer third dose vaccine against Delta and Lota SARS-CoV-2 variants, and outline the significance of distinct RBD mutations in promoting viral infectivity and neutralization sensitivity to post–vaccination sera.     

Pulmonary coccidioidomycosis acquired during travel-a diagnostic and therapeutic challenge

Reports of coccidioidomycosis are rare outside the Western hemisphere. We report the case of a 57 year-old Israeli who had returned from California with pneumonia. As his condition had deteriorated despite macrolides and beta-lactams, coccidioidomycosis was suspected. Both sputum culture and serology confirmed the diagnosis. Conventional doses of fluconazole were marginally beneficial, and a complete resolution was achieved only with very high doses. Travel to the South-Western United States may expose travelers to this uncommon disease.     

Clinical presentation of wandering spleen

Background: Wandering spleen (WS) is an uncommon condition with a variety of clinical presentations. Methods: The medical files of 5 children who underwent operation for WS in the authors' department during the period 1996 through 2000 were retrospectively reviewed. Results: Splenic salvage procedures (retroperitoneal splenopexy) were performed in 4 patients. One patient underwent splenectomy because of splenic necrosis. Conclusions: Early diagnosis and surgical treatment is mandatory to prevent complications. Every effort should be made to preserve the spleen, especially among the pediatric population, and splenopexy is the procedure of choice even in the asymptomatic patient. J Pediatr Surg 37:E30.     

Post-traumatic symptoms,emotional distress and quality of life in long-term survivors of breast cancer: a preliminary research

The present study is a preliminary study assessing long-term psychological effects in survivors of breast cancer. Thirty-nine long-term female survivors of breast cancer were compared with 39 matched women who had not been exposed to any chronic disease regarding post-traumatic stress disorder (PTSD), quality of life (QoL), emotional distress and coping styles. Survivors revealed significantly higher rates of full and partial PTSD, scored significantly higher on emotional distress, scored significantly lower on physical and psychological QoL and exhibited coping styles significantly different from those of the control group. PTSD was associated with the coping style of suppression. Multiple regression analysis showed that receiving chemotherapy and disease stage, as well as the interaction between chemotherapy and disease stage, were significant predictors of hyperarousal. The findings show that post-traumatic symptoms are a common sequel after recovery from cancer. Furthermore, finding suggest a conceptual distinction between PTSD symptoms and QoL in the study of long-term effects of cancer.     

Spatial clustering of hemorrhages in probable cerebral amyloid angiopathy

Cerebral amyloid angiopathy (CAA) is a common cause of symptomatic intracerebral hemorrhage (ICH), as well as small asymptomatic hemorrhage in the elderly. We used gradient-echo MRI to analyze spatial distribution of 321 hemorrhages in 59 patients with probable CAA-related ICH. Hemorrhagic lesions were found preferentially in the temporal (ratio of actual to expected hemorrhages = 1.37) and occipital lobes (ratio = 1.45, p < 0.0001). Within individuals, hemorrhages tended to cluster, regardless of lobe (p < 0.0001). Among subjects followed prospectively for recurrence, clustering of new symptomatic and asymptomatic hemorrhages was observed. These data suggest that regional differences within the brain play a role in the development of CAA-related hemorrhage.