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Glioblastoma multiforme represent > 50% of primary gliomas and have five year survival rates of ~ 5%. Maximal safe surgical resection followed by radiotherapy with concurrent and adjuvant temozolomide remains the standard treatment since published by Stupp et al. (in N Engl J Med 352:987-996, 2005), with additional benefit for patients with MGMT-methylated tumors. We review the current treatment landscape and ongoing efforts to improve these outcomes. An extensive literature search of Pubmed and Google Scholar involving the search terms "glioblastoma," "glioblastoma multiforme," or "GBM" for papers published to July 2021 was conducted and papers evaluated for relevance. As well as current data that informs clinical practice, we review ongoing clinical research in both newly diagnosed and recurrent settings that provides hope for a breakthrough. The Stupp protocol remains standard of care in 2021. Addition of tumor treating fields improved mOS modestly, with benefit seen in MGMT-methylated and unmethylated cohorts and also improved time to cognitive decline but has not been widely adopted. The addition of lomustine to temozolomide, in MGMT-methylated patients, also showed a mOS benefit but further investigation is required. Other promising therapeutic strategies including anti-angiogenic therapy, targeted therapy, and immunotherapy have yet to show a survival advantage. Improvements in the multidisciplinary management, surgical techniques and equipment, early palliative care, carrier support, and psychological support may be responsible for improving survival over time. Despite promising preclinical rationale, immunotherapy and targeted therapy are struggling to impact survival. A number of ongoing clinical trials provide hope for a breakthrough. [ABSTRACT FROM AUTHOR]

Myelomeningocele (MMC) affects one in 1000 newborns annually worldwide and each surviving child faces tremendous lifetime medical and caregiving burdens. Both genetic and environmental factors contribute to disease risk but the mechanism is unclear. This study examined 506 MMC subjects for ultra-rare deleterious variants (URDVs, absent in gnomAD v2.1.1 controls that have Combined Annotation Dependent Depletion score ≥ 20) in candidate genes either known to cause abnormal neural tube closure in animals or previously associated with human MMC in the current study cohort. Approximately 70% of the study subjects carried one to nine URDVs among 302 candidate genes. Half of the study subjects carried heterozygous URDVs in multiple genes involved in the structure and/or function of cilium, cytoskeleton, extracellular matrix, WNT signaling, and/or cell migration. Another 20% of the study subjects carried heterozygous URDVs in candidate genes associated with gene transcription regulation, folate metabolism, or glucose metabolism. Presence of URDVs in the candidate genes involving these biological function groups may elevate the risk of developing myelomeningocele in the study cohort. [ABSTRACT FROM AUTHOR]

Purpose: Loneliness is a challenge for individuals with psychosis; however, interventions rarely target loneliness in this group.Method: We developed a pilot positive psychology group intervention designed to reduce loneliness in psychosis and examined its feasibility and acceptability.Results: Sixteen participants attended 5.38 (SD = 0.70) out of six sessions, with a dropout rate of 10%. Participants were significantly less lonely at post-treatment (p < 0.001, d = 1.51), and maintained their improvements from post-treatment to follow-up (p = 0.81, d = 0.07).Conclusions: Loneliness may be a feasible and acceptable treatment target within psychosocial treatments. [ABSTRACT FROM AUTHOR]

Treatment guidelines for first episode psychosis (FEP) recommend at least 1 year of antipsychotic treatment following remission; however, in light of some recent research and the preference of some individuals to discontinue their medication sooner, this recommendation can be questioned. The aim of this article is to appraise the current discontinuation studies given our views on how this field should progress. We conducted a review of randomized controlled trials investigating dose-reduction/medication discontinuation compared with treatment maintenance in clinically remitted FEP patients. Seven trials were identified, and these reported a higher rate of relapse in the dose reduction or discontinuation groups. Relapse rates were higher when a lower threshold for relapse was utilized. However, only three studies specified that concurrent psychosocial interventions were also provided, despite an evidence base for these interventions in reducing symptom severity and relapse. Length of follow-up may also be important, as the study with the longest follow-up (7 years), albeit with some methodological shortcomings, found greater functional recovery in the dose-reduction group and that relapse rates between the two groups (dose-reduction vs. maintenance) were equal after 3 years. Finally, in addition to discontinuation or dose reduction, a diagnosis of schizophrenia, a longer duration of illness, and poor premorbid functioning were associated with a greater risk of relapse. Further trials are needed in this area to establish the long-term risk-benefit ratio of antipsychotic medication in FEP. Meanwhile, young people with FEP who do not fulfil criteria for a diagnosis of a schizophrenia disorder, achieve clinical remission for at least 3 months, attain early functional recovery, and have good social support may be possible candidates for discontinuation of antipsychotic medication bolstered by effective psychosocial interventions provided in the context of a specialized FEP service. [ABSTRACT FROM AUTHOR]

Background: A 66 years old presented with abnormal postmenopausal vaginal bleeding and was diagnosed with an endometrial lymphoma (diffuse large B cell type, DLBCL). A left breast lesion was found on PET CT which was subsequently biopsy-proven as a separate stage IE DLBCL, but she had no lymph node, bone marrow or spleen involvement. Aims: This study aimed to review the available literature and discuss the management and staging of synchronous extra-nodal DLBCL's. Results: Our patient was staged as having synchronous stage IE DLBCL's of the endometrium and breast. Subsequent molecular analysis (IgH gene rearrangement analysis) on both lesions, confirmed the two lesions to be clonally unrelated. Conclusions: Staging of synchronous extra-nodal lymphomas, particularly when they arise in rare sites such as the endometrium and breast, is difficult and previously unreported. We present our rationale for defining our patient's disease as synchronous stage IE DLBCL's. [ABSTRACT FROM AUTHOR]

GISTs are the most common mesenchymal neoplasms of the gastrointestinal tract. The last 20 years have been revolutionary in the understanding of these tumours and began with the discovery of c-KIT, a proto oncogene that when mutated forms the molecular basis for the growth and development of these malignancies. Surgery was previously considered to be the only treatment modality in both local and advanced disease, however, the introduction of immunotherapy agents such as tyrosine kinase inhibitors has had profound effects on how we now approach and manage these tumours. These novel agents have significantly reduced the frequency of disease recurrence and dramatically improved survival, and serve as a model for the study of targeted therapies in other solid tumors. We present a review of gastrointestinal stromal tumours and consider the current evidence based detection and management of these unique tumors. [ABSTRACT FROM AUTHOR]

Aim: The aim of the study is to assess the feasibility of whole-body low-dose computed tomography (WBLDCT) in the diagnosis and staging of multiple myeloma and compare to skeletal survey (SS), using bone marrow biopsy and whole-body magnetic resonance imaging (WBMRI; where available) as gold standard.Materials and Methods: Patients referred over an 18-month period for investigation of suspected multiple myeloma or restaging of myeloma were randomized to undergo one of two WBLDCT protocols using high kVp, low mAs technique (140 kVp, 14 mAs; or 140 kVp, 25 mAs). Recent WBMRI scans were reviewed in 23 cases. Each imaging modality was assessed by two radiologists in consensus and scored from 0-3 (0 = normal, 1 = 1-4 lesions, 2 = 5-20 lesions, 3 >or= 20 lesions/diffuse disease) in ten anatomical areas. Overall stage of disease, image quality score, and the degree of confidence of diagnosis were recorded. Diagnostic accuracy of skeletal survey and WBLDCT were determined using a gold standard of bone marrow biopsy and distribution of disease was compared to WBMRI.Results: Thirty-nine patients were evaluated. WBLDCT identified more osteolytic lesions than skeletal survey with a greater degree of diagnostic confidence and led to restaging in 18 instances (16 upstaged, two downstaged). In those with recent WBMRI, distribution of disease on WBLDCT showed superior correlation with WBMRI when compared with SS. Overall reader impression of stage on WBLDCT showed significant correlation with WBMRI (kappa = 0.454, p < 0.05). WBLDCT provided complementary information to WBMRI in nine patients with normal marrow signal following treatment response, but which were shown to have diffuse residual cortical abnormalities on CT.Conclusion: WBLDCT at effective doses lower than previously reported, is superior to SS at detecting osteolytic lesions and at determining overall stage of multiple myeloma, and provides complementary information to WBMRI. [ABSTRACT FROM AUTHOR]

In 27 cases of acute severe asthma, a loading dose of 5 mg/kg of aminophylline (omitted if already receiving oral theophylline) followed by a continuous infusion of 1 mg/kg per hour gave satisfactory theophylline levels at 4 h and 24 h. Theophylline clearance rates varied widely, vomiting was common, but unrelated to blood theophylline levels. [ABSTRACT FROM AUTHOR]