TERT Immunohistochemistry as a Surrogate Marker for TERT Promoter Mutations in Infiltrating Gliomas.

Genomic alterations are critical for the diagnosis, prognostication, and treatment of patients with infiltrating gliomas. Telomerase reverse transcriptase promoter ( TERT p) mutations are among such crucial alterations. Although DNA sequencing is the preferred method for identifying TERT p mutations, it has limitations related to cost and accessibility. We tested telomerase reverse transcriptase (TERT) immunohistochemistry (IHC) as a surrogate for TERT p mutations in infiltrating gliomas. Thirty-one infiltrating gliomas were assessed by IHC using an anti-TERT Y182 antibody. IHC results were analyzed by a board-certified neuropathologist. Tumors were analyzed by targeted next-generation sequencing. A literature review of the use of TERT antibodies as a surrogate for TERT p mutations was performed. Eighteen gliomas harbored TERT p mutations. Overall, TERT IHC demonstrated a sensitivity of 61.1% and a specificity of 69.2% for identifying TERT p mutations. Among the 19 IDH1/IDH2 -wild-type gliomas, 16 (84%) harbored TERT p mutations, and TERT IHC had a sensitivity of 62.5% and a specificity of 33.3%. Among the 12 IDH1/IDH2 -mutant gliomas, 2 (17%) harbored TERT p mutations, and TERT IHC had a sensitivity of 50% and a specificity of 80%. TERT IHC had low positive and negative likelihood values in the identification of TERT p mutations. The literature review included 5 studies with 645 patients and 4 different TERT antibodies. The results consistently showed poor sensitivity and specificity of TERT IHC for identifying TERT p mutations. TERT IHC is a suboptimal surrogate marker for TERT p mutations in infiltrating gliomas. The need remains for cost-effective, efficient, and accessible alternatives to next-generation sequencing for the evaluation of TERT p mutations in gliomas.

Malignant Phyllodes Tumor with Heterologous Osteosarcomatous and Rhabdomyosarcomatous Elements: A Case Report and Literature Review.

Phyllodes tumor (PT) is an uncommon fibroepithelial lesion of the breast. PT can be classified as benign, borderline, and malignant based on semi-quantitative assessment of stromal hypercellularity and overgrowth, cytologic atypia, mitotic activity, tumor border, and presence of malignant heterologous elements. PT is considered malignant by default, if malignant heterologous elements are encountered. The heterologous elements include liposarcoma, angiosarcoma, osteosarcoma, chondrosarcoma, and rhabdomyosarcoma. Malignant PT (MPT) with rhabdomyosarcomatous component is extremely rare, and only a few cases are reported. Here, we present a case of MPT with mixed osteosarcomatous and rhabdomyosarcomatous elements in a 51-year-old female, with review of the literatures and discussion of the differential diagnosis.

Two Cases of Biphasic Synovial Sarcoma With Expression of PAX8 and ER: A Diagnostic Pitfall.

Synovial sarcoma (SS) is a high-grade malignant neoplasm frequently arising in the deep soft tissue of the lower and upper extremities of young adults. Primary SS in the pelvis is extremely rare with scattered case reports. It often causes a diagnostic challenge in small biopsy and/or with aberrant expression of immunohistochemical markers. Here, we report 2 unusual cases of SS in the pelvis. Microscopically both cases present with biphasic morphology including spindle and epithelioid cells. In addition, the tumor cells in both cases expressed PAX8 and estrogen receptor. PAX8 is a transcription factor usually expressed in tumors of thyroid gland, kidney, and Müllerian system origin. The expression of PAX8 especially with co-expression of estrogen receptor can be misleading and result in a diagnosis of Müllerian tumors in female patients with pelvic masses. The diagnosis of SS for both cases was confirmed either with the fluorescence in situ hybridization or reverse transcription polymerase chain reaction showing a SS18 (SYT) (18q11) gene rearrangement. It is imperative to include SS in the differential diagnosis for malignant neoplasms exhibiting monotonous spindle cells (monophasic SS) and biphasic mixed monotonous spindle and epithelioid tumor cells in female patients with a pelvic mass. Molecular study for SS18 translocation is essential for the diagnosis in such cases.

Novel Coronavirus (SARS-CoV-2) in Water and Environment-A Scoping Review.

A pneumonia outbreak was primarily reported in the fall of 2019 in Wuhan, Hubei province, China, with the identity SARS-CoV-2, a novel coronavirus. It quickly grew from a local epidemic to a global pandemic and was declared a public health emergency by the WHO. A total of three prominent waves were identified across the globe, with a slight temporal variability as per the geographical locations, and has impacted several sectors which connect the world. By March 2022, the coronavirus had infected 444.12 million people and claimed 6.01 million human lives worldwide, and these numbers have not yet stabilized. Our paper enlightens readers on the seven strains of human coronaviruses, with special emphasis on the three severe deadliest outbreaks (SARS-2002, MERS-2012, and COVID-19). This work attempts a comprehensive understanding of the coronavirus and its impact on the possible sectors that link the world through the economic chain, climate conditions, SDGs, recycling of the event, and mitigations. There are many points that are raised by the authors in the possible sectors, which are emerging or are as yet unnoticed and thus have not been taken into consideration. This comprehension will leave sets of new challenges and opportunities for the researchers in various streams, especially in earth sciences. Science-integrated research may help to prevent upcoming disasters as a by-product of (existing) epidemics in the form of coronavirus.

Narrative review of clinical practice guidelines for treating people with moderate or severe traumatic brain injury.

BACKGROUND: Practice guidelines (CPGs) provide informed treatment recommendations from systematic reviews and assessment of the benefits and harms that are intended to optimize patient care. Review of CPGs addressing rehabilitation for people with moderate/severe traumatic brain injury (TBI), has not been fully investigated. OBJECTIVE: Identify published, vetted, clinical practice guidelines that address rehabilitation for people with moderate/severe TBI. METHODS: Six data bases were accessed using key word search terms: "Traumatic Brain Injury" and "Clinical Practice Guidelines" and "Rehabilitation". Further inclusions included "adult" and "moderate or severe". Exclusions included: "mild" and "concussive injury". Three reviewers read abstracts and manuscripts for final inclusion. The AGREE II template was applied for additional appraisal. RESULTS: There were 767 articles retrieved using the search terms, 520 were eliminated because of content irrelevance; and 157 did not specify rehabilitation treatment or did not follow a process for CPGs. A total of 17 CPGs met all criteria and only 4 of these met all AGREE II criteria. CONCLUSION: There are few CPGs addressing rehabilitation for people with moderate/severe TBI. More interventional trials are needed to determine treatment effectiveness. Timely and methodologically sound vetting of studies are needed to ensure CPG reliability and facilitate access to quality, effective treatment for people with moderate/severe TBI.

Major Histocompatibility Complex Class I-Related Chain A Alleles and Histology of Nonalcoholic Fatty Liver Disease.

Major histocompatibility complex class I-related chain A (MICA) is a highly polymorphic gene that modulates immune surveillance by binding to its receptor on natural killer cells, and its genetic polymorphisms have been associated with chronic immune-mediated diseases. The progressive form of nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), is characterized by accumulation of fat and inflammatory cells in the hepatic parenchyma, potentially leading to liver cell injury and fibrosis. To date, there are no data describing the potential role of MICA in the pathogenesis of NAFLD. Therefore, our aim was to assess the association between MICA polymorphism and NASH and its histologic features. A total of 134 subjects were included. DNA from patients with biopsy-proven NAFLD were genotyped using polymerase chain reaction-sequence-specific oligonucleotide for MICA alleles. Liver biopsies were assessed for histologic diagnosis of NASH and specific pathologic features, including stage of fibrosis and grade of inflammation. Multivariate analysis was performed to draw associations between MICA alleles and the different variables; P ≤ 0.05 was considered significant. Univariate analysis showed that MICA*011 (odds ratio [OR], 7.14; 95% confidence interval [CI], 1.24-41.0; P = 0.04) was associated with a higher risk for histologic NASH. Multivariate analysis showed that MICA*002 was independently associated with a lower risk for focal hepatocyte necrosis (OR, 0.24; 95% CI, 0.08-0.74; P = 0.013) and advanced fibrosis (OR, 0.11; 95% CI, 0.02-0.70; P = 0.019). MICA*017 was independently associated with a higher risk for lymphocyte-mediated inflammation (OR, 5.12; 95% CI, 1.12-23.5; P = 0.035). Conclusion: MICA alleles may be associated with NASH and its histologic features of inflammation and fibrosis. Additional research is required to investigate the potential role of MICA in increased risk or protection against NAFLD.

Analysis of human leukocyte antigen allele polymorphism in patients with non alcoholic fatty liver disease.

The human leukocyte antigen (HLA) genes may play a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH). The aim of this study was to assess the association of HLA class I and II alleles with NASH and its histological features.Deoxyribonucleic acid (DNA) was extracted from 140 subjects (85 biopsy-proven NAFLD and 55 controls) and genotyped for HLA (-A, -B, -C, -DR1, -DR3, -DQ, and -DP). Liver biopsies were assessed for presence of NASH, degree of fibrosis and inflammation. Multivariate analysis was performed to assess associations between HLA genes and different histologic features of NAFLD.Our data for HLA class I showed that HLA-C*4 was associated with lower risk for histologic NASH and HLA-C*6 was protective against portal fibrosis. Conversely, HLA-B*27 was associated with high-grade hepatic steatosis, while HLA-A*31 was associated with increased risk for advanced fibrosis. Among HLA class II alleles, HLA-DQA1*01 was associated with lower risk for NASH while HLA-DRB1*03 was associated with increased risk for NASH.Our findings indicate that HLA class I and II gene polymorphism may be associated with susceptibility to NASH, fibrosis and other pathologic features and may be involved in the pathogenesis of NAFLD.