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Hydatidiform moles, including both complete and partial moles, constitute a subset of gestational trophoblastic diseases characterized by abnormal fertilization resulting in villous hydrops and trophoblastic hyperplasia with or without embryonic development. This involves chromosomal abnormalities, where one or two sperms fertilize an empty oocyte (complete hydatidiform mole (CHM); mostly 46,XX) or two sperms fertilize one oocyte (partial hydatidiform mole (PHM); mostly 69,XXY). Notably, recurrent occurrences are associated with abnormal genomic imprinting of maternal effect genes such as NLRP7 (chromosome 19q13.4) and KHDC3L (chromosome 6q1). Ongoing efforts to enhance identification methods have led to the identification of growth-specific markers, including p57 (cyclin-dependent kinase inhibitor 1C; CDKN1C), which shows intact nuclear expression in the villous cytotrophoblast and villous stromal cells in PHMs and loss of expression in CHMs. Treatment of hydatidiform moles includes dilation and curettage for uterine evacuation of the molar pregnancy followed by surveillance of human chorionic gonadotropin (HCG) levels to confirm disease resolution and rule out the development of any gestational trophoblastic neoplasia. In this review, we provide a synopsis of the existing literature on hydatidiform moles, their diagnosis, histopathologic features, and management. [ABSTRACT FROM AUTHOR]

Simple Summary: In this review paper, we outline the role of GLP-1-RAs in potentially influencing PCa development and progression. While GLP-1-RAs show promise in inhibiting cancer cell proliferation, particularly when combined with metformin or radiotherapy, clinical data on their impact on PCa outcomes are limited. Future research should focus on dedicated trials to evaluate GLP-1-RA's role in PCa management, including its potential as a prophylactic treatment and adjunct therapy in various PCa stages. Glucagon-like peptide-1 (GLP-1), an incretin hormone renowned for its role in post-meal blood sugar regulation and glucose-dependent insulin secretion, has gained attention as a novel treatment for diabetes through GLP-1 receptor agonists (GLP-1-RA). Despite their efficacy, concerns have been raised regarding the potential associations between GLP-1-RA and certain malignancies, including medullary thyroid cancer. However, evidence of its association with prostate cancer (PCa) remains inconclusive. This review delves into the intricate relationship between GLP-1-RA and PCa, exploring the mechanisms through which GLP-1-Rs may impact PCa cells. We discuss the potential pathways involving cAMP, ERK, AMPK, mTOR, and P27. Furthermore, we underscore the imperative for additional research to elucidate the impact of GLP-1-RA treatment on PCa progression, patient outcomes, and potential interactions with existing therapies. Translational studies and clinical trials are crucial for a comprehensive understanding of the role of GLP-1-RA in PCa management. [ABSTRACT FROM AUTHOR]

Tumor prognosis hinges on accurate cancer staging, a pivotal process influenced by the identification of lymphovascular invasion (LVI), i.e., blood vessel and lymphatic vessel invasion. Protocols by the College of American Pathologists (CAP) and the World Health Organization (WHO) have been established to assess LVI in various tumor types, including, but not limited to, breast cancer, colorectal cancer (CRC), pancreatic exocrine tumors, and thyroid carcinomas. The CAP refers to blood vessel invasion as "angioinvasion" (vascular invasion) to differentiate it from lymphatic vessel invasion (lymphatic invasion). For clarity, the latter terms will be used throughout this review. The presence of lymphatic and/or vascular invasion has emerged as a pivotal prognostic factor; therefore, its accurate identification is crucial not only for staging but also for providing the patient with an honest understanding of his/her prognosis. Given the prognostic importance of the correct identification of LVI, specific staining techniques are employed to distinguish lymphatic vessel invasion from angioinvasion and to differentiate true LVI from artifact. These encompass hematoxylin and eosin (H&E) staining, elastic staining, Factor VIII staining, Ulex europaeus I agglutinin staining, CD31, CD34, D2-40, ERG, and D2-40 (podoplanin) immunohistochemical (IHC) stains among others. Based on a review of numerous publications regarding the efficacy of various methods for LVI detection, elastin staining demonstrated superior accuracy and prognostic value, allowing for more targeted treatment strategies. The clinical significance of accurately detecting LVI cannot be overstated, as it is strongly linked to higher cancer-related mortality and an increased risk of tumor recurrence. This review aims to examine the existing literature on the use of elastin stains in the detection of vascular invasion among different types of tumors and its prognostic value. [ABSTRACT FROM AUTHOR]

Perineural invasion (PNI) is defined as the dissemination of neoplastic cells within the perineural space. PNI can be a strong indicator of malignancy and is linked to poor prognosis and adverse outcomes in various malignant neoplasms; nevertheless, it can also be seen in benign pathologic conditions. In this review article, we discuss various signaling pathways and neurotrophic factors implicated in the development and progression of PNI. We also describe the methodology, benefits, and limitations of different in vitro, ex vivo, and in vivo models of PNI. The spectrum of presentation for PNI can range from diffuse spread within large nerves ("named" nerves) all the way through localized spread into unnamed microscopic nerves. Therefore, the clinical significance of PNI is related to its extent rather than its mere presence or absence. In this article, we discuss the guidelines for the identification and quantification of PNI in different malignant neoplasms based on the College of American Pathologists (CAP) and World Health Organization (WHO) recommendations. We also describe benign pathologic conditions and neoplasms demonstrating PNI and potential mimics of PNI. Finally, we explore avenues for the future development of targeted therapy options via modulation of signaling pathways involved in PNI. [ABSTRACT FROM AUTHOR]

Objectives To improve documentation of blood product administration by assessing the completion status of blood transfusions. In this way, we can ensure compliance with the Association for the Advancement of Blood & Biotherapies standards and facilitate investigation of potential blood transfusion reactions. Methods This before-and-after study includes the implementation of an electronic health record (EHR)–based, standardized protocol for documenting the completion of blood product administration. Twenty-four months of retrospective data (January-December 2021) and prospective data (January-December 2022) were collected. Meetings were held before the intervention. Ongoing daily, weekly, and monthly reports were prepared, and targeted education to deficient areas as well as spot in-person audits by the blood bank residents were conducted. Results During 2022, 8,342 blood products were transfused, of which 6,358 blood product administrations were documented. The overall percentage of completed transfusion order documentation improved from 35.54% (units/units) in 2021 to 76.22% (units/units) in 2022. Conclusions Interdisciplinary collaborative efforts helped produce quality audits to improve the documentation of blood product transfusion through a standardized and customized EHR-based blood product administration module. [ABSTRACT FROM AUTHOR]

Fluid overload-associated large B-cell lymphoma (FO-LBCL) is a new entity described in the fifth edition of the World Health Organization (WHO) Classification of Hematolymphoid Tumors (WHO-HAEM5). It refers to malignant lymphoma present with symptoms of serous effusions in body cavities (pleural, peritoneal, and/or pericardial) in the absence of an identifiable tumor mass. We present a case of an 82-year-old man with a history of atrial fibrillation and atrial flutter, status post-ablation, essential hypertension (HTN), hyperlipidemia (HLD), and diabetes mellitus (DM) type 2 who was referred to our hospital for shortness of breath due to recurrent pleural effusion. Right video-assisted thoracoscopy with right pleural biopsy was performed. Histopathological examination of the pleural biopsy revealed dense fibrous tissue, chronic inflammation, lymphoid aggregates, and granulation tissue, with no evidence of lymphoma. Cytology of the right pleural fluid revealed large lymphoid cells, which were positive for CD45, CD20, PAX-5, MUM-1, BCL2, BCL6, and MYC protein. They were negative for CD3, CD10, CD138, and HHV-8 by immunohistochemistry (IHC). Epstein–Barr virus (EBV) was negative by in situ hybridization (ISH). Due to the absence of any evidence of lymphoma elsewhere, a diagnosis of fluid overload-associated large B-cell lymphoma (FO-LBCL) was made. We provide a synopsis of the main clinicopathological features of FO-LBCL and the two main differential diagnoses, primary effusion lymphoma (PEL) and diffuse large B-cell lymphoma (DLBCL). [ABSTRACT FROM AUTHOR]

Background: PRAME (PReferentially expressed Antigen in MElanoma) is a tumor‐associated antigen that has been studied in various cutaneous melanocytic lesions. p16, on the other hand, has been proposed to aid in distinguishing between benign and malignant melanocytic neoplasms. Studies on the diagnostic utility of PRAME and p16 in combination in differentiating nevi from melanoma are limited. We aimed to assess the diagnostic utility of PRAME and p16 in melanocytic tumors and their role in distinguishing between malignant melanomas and melanocytic nevi. Methods: This is a single‐center retrospective cohort analysis over a 4‐year period (2017–2020). We used the pathological database of malignant melanomas (77 cases) and melanocytic nevi (51 cases) specimens from patients who underwent shave/punch biopsies or surgical excisions and evaluated immunohistochemical staining percentage positivity and intensity for PRAME and p16. Results: Most malignant melanomas showed positive/diffuse PRAME expression (89.6%); on the other hand, 96.1% of nevi did not express PRAME diffusely. p16 was expressed consistently in nevi (98.0%). However, p16 expression in malignant melanoma was infrequent in our study. PRAME had a sensitivity and specificity of 89.6% and 96.1%, respectively, for melanomas versus nevi; on the other hand, p16 had a sensitivity and specificity of 98.0% and 28.6%, respectively, for nevi versus melanoma. Also, a PRAME+/p16− melanocytic lesion is unlikely to be a nevus where most nevi were PRAME−/p16+. Conclusion: In conclusion, we confirm the potential utility of PRAME and p16 for distinguishing melanocytic nevi from malignant melanomas. [ABSTRACT FROM AUTHOR]

Amyloidosis is a term describing the extracellular deposit of fibrils composed of subunits of several different normal serum proteins in various tissues. Amyloid light chain (AL) amyloidosis contains fibrils that are composed of fragments of monoclonal light chains. Many different disorders and conditions can lead to spontaneous splenic rupture, including AL amyloidosis. We present a case of a 64-year-old woman with spontaneous splenic rupture and hemorrhage. A final diagnosis of systemic amyloidosis secondary to plasma cell myeloma was made with infiltrative cardiomyopathy and possible diastolic congestive heart failure exacerbation. We also provide a narrative review of all documented cases of splenic rupture associated with amyloidosis from the year 2000 until January 2023, along with the main clinical findings and management strategies. [ABSTRACT FROM AUTHOR]

Ganglioneuromas (GNs) are rare, benign tumors composed of ganglion cells, nerve fibers, and glial cells. Three types of colonic GN lesions exist: polypoid GNs, ganglioneuromatous polyposis, and diffuse ganglioneuromatosis. Less than 100 cases of GN are documented in the literature. A 10-year retrospective search of the pathology database at our institution identified eight cases of colonic GNs. All cases were incidental. Seven of the eight cases presented with colonoscopy findings of small sessile polyps (ranging between 0.1 and 0.7 cm) treated with polypectomy, whereas one case showed a 4 cm partially circumferential and partially obstructing mass in the ascending colon, treated with right hemicolectomy. Almost two-thirds of the cases (5/8) demonstrated associated diverticulosis. All cases were positive for S100 protein and Synaptophysin via immunohistochemistry (IHC). No syndromic association was identified in any of the cases. We also conducted a comprehensive review using PubMed to identify cases of colonic GN reported in the literature. In total, 173 studies were retrieved, among which 36 articles met our inclusion criteria (35 patients and 3 cases on animals). We conclude that while most GNs are incidental and solitary small sessile lesions, many can be diffuse and associated with syndromes. In these cases, the tumor can result in bowel obstruction simulating adenocarcinoma. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate cancer (PCa) is the second most frequent type of cancer in men worldwide. Treatment options for early-stage PCa include external beam radiation therapy, brachytherapy, radical prostatectomy, active surveillance, or a combination of these. In most patients, however, PCa eventually progresses to castration-resistant prostate cancer (CRPC). Transition of PCa from an androgen-dependent to androgen-independent state is not yet fully understood, but epithelial-to-non-epithelial ("mesenchymal") transition (EMT) plays a crucial role in this process. In this review, we provide a synopsis of the transcriptional factors and signaling pathways involved in EMT, besides the diagnostic and prognostic biomarkers that have been identified in this process. Prostate cancer (PCa) is the second most frequent type of cancer in men worldwide, with 288,300 new cases and 34,700 deaths estimated in the United States in 2023. Treatment options for early-stage disease include external beam radiation therapy, brachytherapy, radical prostatectomy, active surveillance, or a combination of these. In advanced cases, androgen-deprivation therapy (ADT) is considered the first-line therapy; however, PCa in most patients eventually progresses to castration-resistant prostate cancer (CRPC) despite ADT. Nonetheless, the transition from androgen-dependent to androgen-independent tumors is not yet fully understood. The physiological processes of epithelial-to-non-epithelial ("mesenchymal") transition (EMT) and mesenchymal-to-epithelial transition (MET) are essential for normal embryonic development; however, they have also been linked to higher tumor grade, metastatic progression, and treatment resistance. Due to this association, EMT and MET have been identified as important targets for novel cancer therapies, including CRPC. Here, we discuss the transcriptional factors and signaling pathways involved in EMT, in addition to the diagnostic and prognostic biomarkers that have been identified in these processes. We also tackle the various studies that have been conducted from bench to bedside and the current landscape of EMT-targeted therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: The standard of care therapy for early prostate cancer (PCa) includes external beam radiation therapy (EBRT), brachytherapy, radical prostatectomy, active surveillance, or a combination approach. For advanced disease, androgen deprivation therapy (ADT) and other neoadjuvant therapies are considered. Nevertheless, castration-resistant prostate cancer (CRPC) develops in many patients. This instigated the development of novel therapeutic approaches using targeted therapies, including prostate cancer stem cell (PCSC)-targeted therapies. Here, we summarize the mechanisms of action of PCSC-targeted therapies and discuss avenues of future development. Prostate cancer (PCa) is the second-most commonly diagnosed cancer in men around the world. It is treated using a risk stratification approach in accordance with the National Comprehensive Cancer Network (NCCN) in the United States. The main treatment options for early PCa include external beam radiation therapy (EBRT), brachytherapy, radical prostatectomy, active surveillance, or a combination approach. In those with advanced disease, androgen deprivation therapy (ADT) is considered as a first-line therapy. However, the majority of cases eventually progress while receiving ADT, leading to castration-resistant prostate cancer (CRPC). The near inevitable progression to CRPC has spurred the recent development of many novel medical treatments using targeted therapies. In this review, we outline the current landscape of stem-cell-targeted therapies for PCa, summarize their mechanisms of action, and discuss avenues of future development. [ABSTRACT FROM AUTHOR]

Brenner tumors (BTs) are surface-epithelial stromal cell tumors that are categorized by the World Health Organization as benign, borderline, and malignant. Due to the rarity of BTs, the published literature on these tumors is comprised primarily of case reports and small retrospective studies. We performed a pathology database review spanning the last ten years at our institution revealing nine reported benign BTs. We collected the clinical and pathological data of patients associated with those BTs, describing the clinical presentation and imaging results, and assessing the possible risk factors associated with them. The average age at diagnosis was 58 years. BTs were discovered incidentally in 7/9 cases. The tumor was multifocal and bilateral in 1/9 cases and ranged in size from 0.2 cm to 7.5 cm. Associated Walthard rests were found in 6/9 cases and transitional metaplasia of surface ovarian and/or tubal epithelium was found in 4/9 cases. One patient had an associated mucinous cystadenoma in the ipsilateral ovary. Another patient had an associated mucinous cystadenoma in the contralateral ovary. In conclusion, we found that Walthard rests and transitional metaplasia are common findings in association with BTs. Additionally, pathologists and surgeons need to be aware of the association between mucinous cystadenomas and BTs. [ABSTRACT FROM AUTHOR]

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. We evaluated the immunohistochemical (IHC) expression of p63 and p53 in DLBCL and their significance on overall survival (OS) and progression-free survival (PFS). We conducted a retrospective cohort study of 177 patients with DLBCL who presented to Mount Sinai Medical Center of Florida (Miami Beach, Florida) between 2010 and 2020. IHC staining for p63 and p53 protein expression was performed. A significant correlation was found between p63 positivity and p53 expression, p53/p63 co-positivity, Ki-67 proliferation index, MYC expression, and MYC/BCL2 double expression. Regardless of the germinal center B-cell like (GCB) subgrouping, there was a trend among p53+ patients to have MYC/BCL2 double expression, positive MYC expression, and lower OS and PFS. A tendency of poor OS was seen in p53+ patients in the non-GCB, GCB, and double expressors subgroups and poor PFS in p53+ patients regardless of the subgrouping. In conclusion, our results suggest that p63 and p53 may represent potential additional prognostic biomarkers in DLBCL and may be included in the initial diagnostic work up of patients with DLBCL. [ABSTRACT FROM AUTHOR]

Lung cancer is the second most common cancer and the leading cause of cancer-related deaths in 2022. The majority (80%) of lung cancer cases belong to the non-small cell lung carcinoma (NSCLC) subtype. Despite the increased screening efforts, the median five-year survival of metastatic NSCLC remains low at approximately 3%. Common treatment approaches for NSCLC include surgery, multimodal chemotherapy, and concurrent radio and chemotherapy. NSCLC exhibits high rates of resistance to treatment, driven by its heterogeneity and the plasticity of cancer stem cells (CSCs). Drug repurposing offers a faster and cheaper way to develop new antineoplastic purposes for existing drugs, to help overcome therapy resistance. The decrease in time and funds needed stems from the availability of the pharmacokinetic and pharmacodynamic profiles of the Food and Drug Administration (FDA)-approved drugs to be repurposed. This review provides a synopsis of the drug-repurposing approaches and mechanisms of action of potential candidate drugs used in treating NSCLC, including but not limited to antihypertensives, anti-hyperlipidemics, anti-inflammatory drugs, anti-diabetics, and anti-microbials. [ABSTRACT FROM AUTHOR]

Pulmonary embolism (PE) is defined as the obstruction of the pulmonary artery or one of its branches by a blood clot, tumor, air, or fat emboli originating elsewhere in the body. A saddle PE occurs when the obstruction affects the bifurcation of the main pulmonary artery trunk. We present a case of a 46-year-old man who presented to our hospital due to an episode of syncope. Computed tomography angiography (CTA) of the chest showed extensive PE and abdominal CT scan showed a large 8 cm left renal mass with inferior vena cava (IVC) thrombus. Emergent embolectomy, left total nephrectomy, and IVC tumor removal were performed yielding the diagnosis of clear cell renal cell carcinoma (RCC). Interestingly, our patient did not experience any symptoms related to his RCC until the diagnosis of PE due to syncope, and the asymptomatic tumor was found out to be the possible cause of this PE due to the presence of tumor cells constituting the tumor embolus. It is thus recommended to improve the early screening process for RCC. Besides, clinicians should pay attention to patients presenting with uncharacteristic symptoms of RCC who might present with symptoms of saddle PE. [ABSTRACT FROM AUTHOR]

Ataxia-telangiectasia is an autosomal recessive disorder that usually manifests in childhood due to mutations in the Ataxia-Telangiectasia Mutated (ATM) gene. It is believed that there is an association between this gene mutation/polymorphism and cancer risk, including breast, lung, and pancreatic cancers. We report a rare case of a 69-year-old woman who developed three different primary cancers, including non-small cell lung cancer (NSCLC) in both lungs and pancreatic adenocarcinoma, and was later found to have a rarely reported variant mutation in the ATM gene, namely Exon 39, c.5644 C > T. We hypothesize that the ATM gene, c.5644 C > T mutation could be a plausible contributor in the pathogenesis of these three cancers. This hypothesis has yet to be validated by larger studies that focus on a mechanistic approach involving DNA repair genes such as the ATM. More importantly, this paves the way to developing new patient-specific targeted therapies and inaugurating precision medicine as a cornerstone in cancer therapeutics. [ABSTRACT FROM AUTHOR]

Background: The most common cause of infectious pulmonary granulomas worldwide is Mycobacterium tuberculosis. The diagnosis is based on clinical presentation, histopathologic findings, detection of acid-fast bacilli (AFB) in tissue or sputum using special stains, and/or isolation of mycobacteria in cultures or via PCR-based methods. Different studies have shown that high levels of discrepancy exist between these diagnostic approaches in lung tissue specimens. Objective: To assess the degree of concordance between the results of special stains and cultures on lung tissue specimens in the diagnosis of mycobacterial infections. Methodology: Eighty-seven patients with a diagnosis of granulomas (necrotizing and non-necrotizing) on lung tissue specimens were identified. Cohen's kappa was used to measure the general concordance between the results of the histopathological examination (special stains) and bacteriological tissue cultures. Results: With Kinyoun acid-fast stains, 8/48 (16.7%) cases were positive for AFB. With FITE stains, 10/57 (17.5%) cases were positive for AFB. There was strong agreement between Kinyoun acid-fast and FITE stains (Kappa = 0.806; p-value < 0.001). Tissue cultures were performed on 38/87 cases (43.7%), and 10/38 (26.3%) of the cultures were positive for mycobacteria. There was no concordance between Kinyoun acid-fast stains or FITE stains and tissue cultures results. Conclusion: Our observations represent an initial step in the process of reviewing the two methods used at our institution to diagnose mycobacterial infections on lung tissue specimens and highlight the need of incorporating more advanced diagnostic methods such as PCR to confirm mycobacterial infections and improve patient management. Importantly, species-level identification of mycobacteria is necessary to guide treatment. [ABSTRACT FROM AUTHOR]

Miller–Dieker syndrome (MDS) is a rare genetic disorder characterized by congenital lissencephaly (absent or diminished cerebral gyri), facial dysmorphisms, neurodevelopmental retardation, intrauterine fetal demise, and death in early infancy or childhood. We present a case of a 4-year-old girl with MDS (17p13.3p13.2 deletion) who was admitted to the hospital due to fever and increased secretions from her nose, mouth, and tracheostomy tube (as she had been on a ventilator and G-tube dependent since birth). During the course of hospitalization, she developed multiorgan failure, third spacing, and significant lactic acidosis. The patient had a cardiorespiratory arrest and expired after 4 months and 8 days of hospitalization. We provide a synopsis of the main autopsy findings, with a focus on the neuropathologic anomalies. [ABSTRACT FROM AUTHOR]

Medulloblastoma is the most common malignant brain tumor of childhood accounting for about 60% of all pediatric embryonal tumors. Despite improvements in the overall survival rate, this tumor still lacks an efficient, reliable, and less toxic therapeutic approach. Characterization of the molecular mechanisms involved in medulloblastoma initiation and progression is a crucial step for the development of effective therapies. Signal transducer and activator of transcription 3 is a convergence point for several signaling cascades that are implicated in medulloblastoma tumorigenesis. Accumulated evidence has revealed the pivotal role of signal transducer and activator of transcription 3 in medulloblastoma pathogenesis such as proliferation, survival, angiogenesis, and immunosuppression as well as maintenance, drug resistance, and recurrence. In this review, we focus on the role of signal transducer and activator of transcription 3 in medulloblastoma tumorigenesis and discuss the recent advances of signal transducer and activator of transcription 3 inhibition as a promising developed strategy for medulloblastoma therapy. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is an uncommon subcategory of non-Hodgkin lymphoma (NHL). Pathogenesis primarily includes overexpression of CCND1 and SOX11 along with other molecular aberrations. Lutetium 177Lu-DOTATATE is a radiolabeled somatostatin analogue used for the treatment of gastrointestinal neuroendocrine tumors. There are no clinical data supporting the use of Lutetium 177Lu-DOTATATE in the treatment of lymphoma. We describe the case of an 84-year-old man with a history of MCL and carcinoid tumor of the lung. Following progression of the carcinoid malignancy, the patient was treated with Lutetium 177Lu-DOTATATE. After treatment, there was an overall improvement of the patient's MCL that was demonstrated by stable lymphadenopathy on serial CT scans and down-trend of the absolute lymphocyte count. Therefore, we hypothesize that 177Lu-DOTATATE might have a role and can be repurposed for treating MCL. [ABSTRACT FROM AUTHOR]

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyper-inflammatory disorder that occurs due to immunologic dysregulation. HLH can be primary (hereditary) or secondary to infections, autoimmune diseases, immune deficiencies, metabolic diseases, drugs, or malignancies. Lymphoid neoplasms mostly accompany malignancy-associated HLH. We present a case of a 12-year-old boy with a history of precursor B lymphoblastic leukemia (B-ALL), who subsequently developed chemotherapy-induced acute myeloid leukemia (t-AML). The patient was admitted for febrile neutropenia and initial laboratory tests revealed hemophagocytic lymphohistiocytosis (HLH). The hospital course was complicated by multiple infections and septic shock. The patient received several broad-spectrum antimicrobials, dexamethasone, as well as a pericardial drain to drain the hemorrhagic pericardial effusion. Despite intervention, the patient expired, and an autopsy was performed. We provide a synopsis of the main autopsy findings. [ABSTRACT FROM AUTHOR]

Opinion Statement: Medulloblastoma (MB) is the most frequent pediatric brain tumor. Despite conventional therapy, MB patients have high mortality and morbidity rates mainly due to the incomplete understanding of the molecular and cellular processes involved in development of this cancer. Similar to other solid tumors, MB demonstrated high endothelial cell proliferation and angiogenic activity, wherein new blood vessels arise from the pre-existing vasculature, a process named angiogenesis. MB angiogenesis is considered a hallmark for MB development, progression, and metastasis emphasizing its potential target for antitumor therapy. However, angiogenesis is tightly regulated by a set of angiogenic factors making it a complex process to be targeted. Although agents targeting these factors and their receptors are early in development, the potential for their targeting may translate into improvement in the clinical care for MB patients. In this review, we focus on the most potent angiogenic factors and their corresponding receptors, highlighting their basic properties and expression in MB. We describe their contribution to MB tumorigenesis and angiogenesis and the potential therapeutic targeting of these factors. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite improvements in standardized screening methods and the development of promising therapies for colorectal cancer (CRC), survival rates are still low. Drug repurposing offers an affordable solution to achieve new indications for previously approved drugs that could play a protagonist or adjuvant role in the treatment of CRC. In this review, we summarize the current data supporting drug repurposing as a feasible option for patients with CRC. Colorectal cancer (CRC) is the third most common cancer in the world. Despite improvement in standardized screening methods and the development of promising therapies, the 5-year survival rates are as low as 10% in the metastatic setting. The increasing life expectancy of the general population, higher rates of obesity, poor diet, and comorbidities contribute to the increasing trends in incidence. Drug repurposing offers an affordable solution to achieve new indications for previously approved drugs that could play a protagonist or adjuvant role in the treatment of CRC with the advantage of treating underlying comorbidities and decreasing chemotherapy toxicity. This review elaborates on the current data that supports drug repurposing as a feasible option for patients with CRC with a focus on the evidence and mechanism of action promising repurposed candidates that are widely used, including but not limited to anti-malarial, anti-helminthic, anti-inflammatory, anti-hypertensive, anti-hyperlipidemic, and anti-diabetic agents. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical's mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An alternative way to treat PCa is by repurposing of existing drugs that were initially intended for other conditions. By extrapolating the effects of previously approved drugs to the intracellular processes of PCa, treatment options will expand. In addition, drug repurposing is cost-effective and efficient because it utilizes drugs that have already demonstrated safety and efficacy. This review catalogues the drugs that can be repurposed for PCa in preclinical studies as well as clinical trials. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), acknowledged as the most common progressive neurodegenerative disorder, is the leading cause of dementia in the elderly. The characteristic pathologic hallmarks of AD—including the deposition of extracellular senile plaques (SP) formation, intracellular neurofibrillary tangles, and synaptic loss, along with prominent vascular dysfunction and cognitive impairment—have been observed in patients. Fibroblast growth factors (FGFs), originally characterized as angiogenic factors, are a large family of signaling molecules that are implicated in a wide range of biological functions in brain development, maintenance and repair, as well as in the pathogenesis of brain-related disorders including AD. Many studies have focused on the implication of FGFs in AD pathophysiology. In this review, we will provide a summary of recent findings regarding the role of FGFs and their receptors in the pathogenesis of AD, and discuss the possible opportunities for targeting these molecules as novel treatment strategies in AD. [ABSTRACT FROM AUTHOR]

Inadequate use of statistics in biomedical research might not only affect science but also harm human beings if applied in medical practice. Biostatistics is fundamental to improve understanding and appraising of evidence-based medicine (EBM); yet, it is still not well understood and appreciated by medical students. Therefore, early exposure of medical students and physicians-in-training to research tools including Biostatistics is of utmost importance. The aim of this study is to determine the perception of Biostatistics by medical students at a private medical school in Beirut, Lebanon, and to identify its best implementation time in the medical curriculum. This is a cross-sectional study based on a self-administered questionnaire distributed among medical students in their pre-clerkship years (first three years of a 6-year program) who undertook Biostatistics. The assessment of perception was based on the 5-point Likert scale anchored by Strongly disagree = 1 and Strongly agree = 5 including 36 questions distributed into four domains to assess the course value, difficulty, behavioral, and expectations. 186 of 269 students responded to the questionnaire, yielding a response rate of 69.14%. Around 60% of students declared that the knowledge gained from biostatistics courses is useful to their future career, and almost 70% understood the main concepts of biostatistics. 57.7% of students perceived that lack of practicing exercises might contribute to making the course more difficult. The mean score of domains was higher in females but did not significantly differ within the three academic years. Only 35.1% of the students positively perceived the importance of biostatistics modules, mostly third-year students. Although the majority of medical students perceived biostatistics modules negatively, they were aware of the relevance of biostatistics to their medical career and real-life health issues. [ABSTRACT FROM AUTHOR]

Brain tumors in adults may be infrequent when compared with other cancer etiologies, but they remain one of the deadliest with bleak survival rates. Current treatment modalities encompass surgical resection, chemotherapy, and radiotherapy. However, increasing resistance rates are being witnessed, and this has been attributed, in part, to cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells that reside within the tumor bulk and have the capacity for self-renewal and can differentiate and proliferate into multiple cell lineages. Studying those CSCs enables an increasing understanding of carcinogenesis, and targeting CSCs may overcome existing treatment resistance. One approach to weaponize new drugs is to target these CSCs through drug repurposing which entails using drugs, which are Food and Drug Administration–approved and safe for one defined disease, for a new indication. This approach serves to save both time and money that would otherwise be spent in designing a totally new therapy. In this review, we will illustrate drug repurposing strategies that have been used in brain tumors and then further elaborate on how these approaches, specifically those that target the resident CSCs, can help take the field of drug repurposing to a new level. [ABSTRACT FROM AUTHOR]

Opinion Statement: Neuroblastoma (NB) is a heterogeneous solid tumor of the pediatric population that originates from neural crest cells and affects the developing sympathetic nervous system. It is the most common neuroblastic tumor accounting for approximately 10% of all childhood cancers and 10-15% of pediatric tumor mortalities. The outcomes range from spontaneous tumor regression in low-risk groups to metastasis and death even after multimodal therapy in high-risk groups. Hence, the detection of NB at an early stage improves outcomes and provides a better prognosis for patients. Early detection and prognosis of NB depend on specific molecules termed biomarkers which can be tissue-specific or circulating. Certain biomarkers are employed in the classification of NB into different groups to improve the treatment and prognosis, and others can be used as therapeutic targets. Therefore, novel biomarker discovery is essential for the early detection of NB, predicting the course of the disease, and developing new targeted treatment strategies. In this review, we aim to summarize the literature pertinent to some important biomarkers of NB and discuss the prognostic role of these biomarkers as well as their potential role in targeted therapy. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma (SCC) arising in a Zenker diverticulum (ZD) is an extremely rare entity. Approximately 50 cases have been reported worldwide. We report a case of a 74-year-old man who presented to our institution with chronic regurgitation, dysphagia and halitosis. The patient was initially seen in 2015 at which point he reported a 10-year history of these symptoms and was diagnosed with ZD. A barium swallow was done revealing a large posterior esophageal diverticulum with significant residual contrast within the diverticulum lumen. Given these findings, he was taken for open surgical excision where a SCC was identified. Although it is extremely rare for a SCC to occur in a ZD, patients with ZD must undergo regular surveillance endoscopy of the esophagus and the diverticulum itself to identify any suspicious mass or lesion arising in within. [ABSTRACT FROM AUTHOR]

Opinion Statement: Medulloblastoma (MB) is the most common pediatric brain malignancy, with a 5-year overall survival (OS) rate of around 65%. The conventional MB treatment, comprising surgical resection followed by irradiation and adjuvant chemotherapy, often leads to impairment in normal body functions and poor quality of life, especially with the increased risk of recurrence and subsequent development of secondary malignancies. The development and progression of MB are facilitated by a variety of immune-evading mechanisms such as the secretion of immunosuppressive molecules, activation of immunosuppressive cells, inhibition of immune checkpoint molecules, impairment of adhesive molecules, downregulation of the major histocompatibility complex (MHC) molecules, protection against apoptosis, and activation of immunosuppressive pathways. Understanding the tumor-immune relationship in MB is crucial for effective development of immune-based therapeutic strategies. In this comprehensive review, we discuss the immunological aspect of the brain, focusing on the current knowledge tackling the mechanisms of MB immune suppression and evasion. We also highlight several key immunotherapeutic approaches developed to date for the treatment of MB. [ABSTRACT FROM AUTHOR]

Purpose: Campylobacter species are currently the most common cause of bacterial gastroenteritis. In Lebanon, Campylobacter infection occurrence is underdiagnosed owing to the lack of specific culture and rapid test kits, particularly among children. This study aimed to evaluate the prevalence, laboratory findings, and clinical characteristics of Campylobacter infection in hospitalized children with acute gastroenteritis in South Lebanon. Methods: We conducted a 6-month retrospective cohort study between January and June 2018, including 291 children aged between 1 month and 12 years, who were admitted to a tertiary healthcare center in South Lebanon. The medical files of the patients were reviewed to retrieve the required clinical information, including clinical and laboratory data. Results: The prevalence of campylobacteriosis agents in pediatric patients with acute gastroenteritis is 12.02%. Patients infected with Campylobacter had more severe acute gastroenteritis than Campylobacter-negative patients and often presented with high-grade fever, diarrhea episodes more than six times per day, diarrhea lasting for more than five days, and dehydration. Indeed, children with high-grade fever (≥38.5°C) were five times more likely to test positive for Campylobacter than those with low-grade fever. In addition, the results showed a higher Vesikari score for the majority of Campylobacter-positive patients with severe acute gastroenteritis compared to a moderate profile for Campylobacter-negative patients. Conclusion: The present study findings highlight that Campylobacter infection is frequent among children with acute gastroenteritis. Therefore, the detection of Campylobacter should be carried out for the diagnosis of human gastroenteritis in Lebanon, along with the detection of routine enteropathogens. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is by far the most commonly diagnosed cancer in men worldwide. Despite sensitivity to androgen deprivation, patients with advanced disease eventually develop resistance to therapy and may die of metastatic castration-resistant prostate cancer (mCRPC). A key challenge in the management of PCa is the clinical heterogeneity that is hard to predict using existing biomarkers. Defining molecular biomarkers for PCa that can reliably aid in diagnosis and distinguishing patients who require aggressive therapy from those who should avoid overtreatment is a significant unmet need. Mechanisms underlying the development of PCa are not confined to cancer epithelial cells, but also involve the tumor microenvironment. The crosstalk between epithelial cells and stroma in PCa has been shown to play an integral role in disease progression and metastasis. A number of key markers of reactive stroma has been identified including stem/progenitor cell markers, stromal-derived mediators of inflammation, regulators of angiogenesis, connective tissue growth factors, wingless homologs (Wnts), and integrins. Here, we provide a synopsis of the stromal-epithelial crosstalk in PCa focusing on the relevant molecular biomarkers pertaining to the tumor microenvironment and their role in diagnosis, prognosis, and therapy development. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a complex and multifactorial neurodevelopmental disorder characterized by the presence of restricted interests and repetitive behaviors besides deficits in social communication. Syndromic ASD is a subset of ASD caused by underlying genetic disorders, most commonly Fragile X Syndrome (FXS) and Rett Syndrome (RTT). Various mutations and consequent malfunctions in core signaling pathways have been identified in ASD, including glycogen synthase kinase 3 (GSK3). A growing body of evidence suggests a key role of GSK3 dysregulation in the pathogenesis of ASD and its related disorders. Here, we provide a synopsis of the implication of GSK3 in ASD, FXS, and RTT as a promising therapeutic target for the treatment of ASD. [ABSTRACT FROM AUTHOR]

Opinion Statement: Medulloblastoma is the most frequently diagnosed primary malignant brain tumor among children. Currently available therapeutic strategies are based on surgical resection, chemotherapy, and/or radiotherapy. However, majority of patients quickly develop therapeutic resistance and are often left with long-term therapy-related side effects and sequelae. Therefore, there remains a dire need to develop more effective therapeutics to overcome the acquired resistance to currently available therapies. Unfortunately, the process of developing novel anti-neoplastic drugs from bench to bedside is highly time-consuming and very expensive. A wide range of drugs that are already in clinical use for treating non-cancerous diseases might commonly target tumor-associated signaling pathways as well and hence be of interest in treating different cancers. This is referred to as drug repurposing or repositioning. In medulloblastoma, drug repurposing has recently gained a remarkable interest as an alternative therapy to overcome therapy resistance, wherein existing non-tumor drugs are being tested for their potential anti-neoplastic effects outside the scope of their original use. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) is the most commonly diagnosed cancer and the second leading cause of cancer-related deaths among adult males globally. The poor prognosis of PCa is largely due to late diagnosis of the disease when it has already progressed to an advanced stage marked by androgen-independence, thus necessitating new strategies for early detection and treatment. We construe that these direly needed advances are limited by our poor understanding of early events in the progression of PCa and that would thus represent ideal targets for early intervention. To begin to fill this void, we interrogated molecular "oncophenotypes" that embody the transition of PCa from an androgen-dependent (AD) to–independent (AI) state. Methods: To accomplish this aim, we used our previously established AD and AI murine PCa cell lines, PLum-AD and PLum-AI, respectively, which recapitulate primary and progressive PCa morphologically and molecularly. We statistically surveyed global gene expressions in these cell lines by microarray analysis. Differential profiles were functionally interrogated by pathways, gene set enrichment and topological gene network analyses. Results: Gene expression analysis of PLum-AD and PLum-AI transcriptomes (n = 3 each), revealed 723 differentially expressed genes (392 upregulated and 331 downregulated) in PLum-AI compared to PLum-AD cells. Gene set analysis demonstrated enrichment of biological functions and pathways in PLum-AI cells that are central to tumor aggressiveness including cell migration and invasion facilitated by epithelial-to-mesenchymal transition (EMT). Further analysis demonstrated that the p38 mitogen-activated protein kinase (MAPK) was predicted to be significantly activated in the PLum-AI cells, whereas gene sets previously associated with favorable response to the p38 inhibitor SB203580 were attenuated (i.e., inversely enriched) in the PLum-AI cells, suggesting that these aggressive cells may be therapeutically vulnerable to p38 inhibition. Gene set and gene-network analysis also alluded to activation of other signaling networks particularly those associated with enhanced EMT, inflammation and immune function/response including, but not limited to Tnf, IL-6, Mmp 2, Ctgf, and Ptges. Accordingly, we chose SB203580 and IL-6 to validate their effect on PLum-AD and PLum-AI. Some of the common genes identified in the gene-network analysis were validated at the molecular and functional level. Additionally, the vulnerability to SB203580 and the effect of IL-6 were also validated on the stem/progenitor cell population using the sphere formation assay. Conclusions: In summary, our study highlights pathways associated with an augmented malignant phenotype in AI cells and presents new high-potential targets to constrain the aggressive malignancy seen in the castration-resistant PCa. [ABSTRACT FROM AUTHOR]

Exposure to anesthetic agents in early childhood or late intrauterine life might be associated with neurotoxicity and long-term neurocognitive decline in adulthood. This could be attributed to induction of neuroapoptosis and inhibition of neurogenesis by several mechanisms, with a pivotal role of microRNAs in this milieu. MicroRNAs are critical regulators of gene expression that are differentially expressed in response to internal and external environmental stimuli, including general anesthetics. Through this systematic review, we aimed at summarizing the current knowledge apropos of the roles and implications of deregulated microRNAs pertaining to anesthesia-induced neurotoxicity in animal models and derived neuronal cultures. OVID/Medline and PubMed databases were lastly searched on April 1st, 2019, using the Medical Subject Heading (MeSH) or Title/Abstract words ("microRNA" and "anesthesia"), to identify all published research studies on microRNAs and anesthesia. During the review process, data abstraction and methodological assessment was done by independent groups of reviewers. In total, 29 studies were recognized to be eligible and were thus involved in this systematic review. Anesthetic agents studied included sevoflurane, isoflurane, propofol, bupivacaine, and ketamine. More than 40 microRNAs were identified to have regulatory roles in anesthesia-induced neurotoxicity. This field of study still comprises several gaps that should be filled by conducting basic, clinical, and translational research in the future to decipher the exact role of microRNAs and their functions in the context of anesthesia-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

In the pediatric population, brain tumors represent the most commonly diagnosed solid neoplasms and the leading cause of cancer-related deaths globally. They include low-grade gliomas (LGGs), medulloblastomas (MBs), and other embryonal, ependymal, and neuroectodermal tumors. The mainstay of treatment for most brain tumors includes surgical intervention, radiation therapy, and chemotherapy. However, resistance to conventional therapy is widespread, which contributes to the high mortality rates reported and lack of improvement in patient survival despite advancement in therapeutic research. This has been attributed to the presence of a subpopulation of cells, known as cancer stem cells (CSCs), which reside within the tumor bulk and maintain self-renewal and recurrence potential of the tumor. An emerging promising approach that enables identifying novel therapeutic strategies to target CSCs and overcome therapy resistance is drug repurposing or repositioning. This is based on using previously approved drugs with known pharmacokinetic and pharmacodynamic characteristics for indications other than their traditional ones, like cancer. In this review, we provide a synopsis of the drug repurposing methodologies that have been used in pediatric brain tumors, and we argue how this selective compilation of approaches, with a focus on CSC targeting, could elevate drug repurposing to the next level. [ABSTRACT FROM AUTHOR]

Inherent characteristics, such as height, are essential parameters for the identification of an unknown individual from dismembered remains by forensic anthropometrics. Clinically, in certain situations that impede a person from standing or in diseases that affect vertebral column length, stature estimation using hand anthropometric measures might confer a simpler, easier, more reliable, and less time-consuming alternative method to directly measure the standing height. The objective of this study is to correlate between hand anthropometric measures and measured heights of adult Lebanese individuals and to formulate regression equations to predict the height from these anthropometric measures. We conducted an age-proportionate randomized cross-sectional study using a consecutive sample of 394 participants from central Beirut and its suburbs. Participants were randomly divided into a development sample and a cross-validation sample. Linear regression models were used to formulate the different equations specific for height estimation. Regression equations of predicted heights from right- and left-hand measurements were obtained. Body mass index (BMIs) calculated from the measured heights and BMIs predicted by the regression equations showed no significant difference between the development and the cross-validation samples. Similarly, the measured and predicted heights showed no difference between the two samples. On the other side, a very strong correlation was demonstrated between the measured and predicted heights and BMIs in males and females and in both the development and the cross-validation samples. In conclusion, the formulated regression equations using hand anthropometric measures, age, and sex provide a statistically valid estimation of height and might indeed be useful in the clinical context. [ABSTRACT FROM AUTHOR]