Tumor Treating Fields dually activate STING and AIM2 inflammasomes to induce adjuvant immunity in glioblastoma

Tumor Treating Fields (TTFields), an approved therapy for glioblastoma (GBM) and malignant mesothelioma, employ noninvasive application of low-intensity, intermediate-frequency, alternating electric fields to disrupt the mitotic spindle, leading to chromosome missegregation and apoptosis. Emerging evidence suggests that TTFields may also induce inflammation. However, the mechanism underlying this property and whether it can be harnessed therapeutically are unclear. Here, we report that TTFields induced focal disruption of the nuclear envelope, leading to cytosolic release of large micronuclei clusters that intensely recruited and activated 2 major DNA sensors — cyclic GMP-AMP synthase (cGAS) and absent in melanoma 2 (AIM2) — and their cognate cGAS/stimulator of interferon genes (STING) and AIM2/caspase 1 inflammasomes to produce proinflammatory cytokines, type 1 interferons (T1IFNs), and T1IFN-responsive genes. In syngeneic murine GBM models, TTFields-treated GBM cells induced antitumor memory immunity and a cure rate of 42% to 66% in a STING- and AIM2-dependent manner. Using single-cell and bulk RNA sequencing of peripheral blood mononuclear cells, we detected robust post-TTFields activation of adaptive immunity in patients with GBM via a T1IFN-based trajectory and identified a gene panel signature of TTFields effects on T cell activation and clonal expansion. Collectively, these studies defined a therapeutic strategy using TTFields as cancer immunotherapy in GBM and potentially other solid tumors.     

Orthopedic Implant Retrieval—Imperatives and Possibilities

Premature orthopedic implant failure occurs for a variety of reasons. In such scenarios implant retrieval is an issue that has a potential for further investigation leading to redesign of components and to improve implant longevity. While strict standards must be adhered to in order to gain FDA approval to use an implant, capturing, and recording the contributing factors leading to explantation and that of retrieved implant is neither strictly adhered to nor enforced. This article presents data illustrating implant standards both pre-market approval as well as in the retrieval scenarios. This paper provides a compilation of specific specifications on implant retrieval handling and storage, compelling imperatives and possibilities at national or global scale. The need for a user-definable, searchable interface is proposed in this paper to facilitate such an important task.     

Eales disease--an update

Eales disease, first described by Henry Eales in 1880, remains an enigma. The disease, observed more commonly in the Indian subcontinent than in the rest of the world, occurs in young healthy adult males, initially presenting as retinal periphlebitis and later as retinal ischemia that may lead to vascular alterations and neovascularization. Recurrent vitreous hemorrhage with or without retinal detachment is the common sequelae. In recent years, immunological, molecular biological, and biochemical studies have indicated the role of human leukocyte antigen, retinal autoimmunity, mycobacterium tuberculosis genome, and free radical mediated damage in the etiopathogenesis of this disease. However, its etiology appears to be multifactorial. The management depends on the stage of the disease and consists of medical treatment with oral corticosteroids in the active inflammatory stage and laser photocoagulation in the advanced retinal ischemia and neovascularization stages. The results of vitreoretinal surgery have been found to be satisfactory in case of vitreous hemorrhage with or without retinal detachment.     

Balloon dilation for achalasia of the cardia: experience in 76 patients

PURPOSE: To report our experience with balloon dilation for achalasia of the cardia. MATERIALS AND METHODS: Seventy-six patients (mean age, 51 years) underwent balloon dilation with radiologic guidance. A total of 110 procedures were performed from April 1994 to April 2000. Diagnosis of achalasia was established with clinical, radiologic, and manometric data. Dysphagia was a presenting symptom in most patients (90%), regurgitation was present in 39%, retrosternal pain in 22%, and weight loss in 12%. The dilations were performed in a progressive manner starting with a 15-mm-diameter balloon and progressing to 20-, 30-, and 40-mm balloons, as required. Follow-up data were collected retrospectively from patient notes and telephone interviews with the patients and/or their local doctors (mean follow-up, 26 months). RESULTS: There were no cases of esophageal perforation; 89% (98 of 110) of dilations were considered to be successful, with the patients having restoration of normal or near-normal swallowing (excellent or good initial responses). Fifty-two patients required a single dilation; 22 patients, between two and four dilations; and two patients, five dilations. CONCLUSION: Balloon dilation with fluoroscopic guidance is a safe and successful treatment for achalasia of the cardia.     

Early experience with laparoscopic inguinal hernia repair in a district general National Health Services hospital

The introduction of laparoscopic hernia repair into the National Health Services (NHS) gave us an opportunity to study the feasibility and practicality of carrying out this modern hernia repair technique in a district general NHS hospital. The laparoscopic tension-free transabdominal preperitoneal (TAPP) method of hernia repair, as we do it, is cost-effective and efficacious. Most patients can be treated as day cases. We discovered incidental hernias in 18.8% of patients, which were treated simultaneously. A low recurrence rate (0.17%) with low morbidity makes it an attractive method for routine treatment of groin hernias in the NHS.     

The clinical spectrum and treatment outcome of retinoblastoma in Indian children

PURPOSE: To study the clinical spectrum and treatment outcome of retinoblastoma in Indian children. PATIENTS AND METHODS: This retrospective study analyzed 488 eyes of 355 retinoblastoma patients treated at a tertiary care ophthalmic hospital in southern India during a 14-year period. RESULTS: Retinoblastoma involved one eye in 177 (50%) and both eyes in 178 (50%) patients. Mean age at presentation was 23.98 +/- 23.37.