Exploring Novel Treatment Modalities for Type 1 Diabetes Mellitus: Potential and Prospects.

Despite the effectiveness of insulin injections in managing hyperglycemia in type 1 diabetes mellitus (T1DM), they fall short in addressing autoimmunity and regenerating damaged islets. This review aims to explore the potential and prospects of emerging treatment modalities for T1DM, including mesenchymal stem cells (MSCs), MSC-derived exosomes, gene therapy, islet allotransplantation, pancreatic islet cell transplantation, and teplizumab. We review emerging treatment modalities for T1DM, highlighting several promising strategies with varied mechanisms and outcomes. Mesenchymal stem cells demonstrate potential in modulating the immune response and preserving or restoring beta-cell function, although variability in sources and administration routes necessitates further standardization. Similarly, MSC-derived exosomes show promise in promoting beta-cell regeneration and immune regulation, supported by early-stage studies showing improved glucose homeostasis in animal models, albeit with limited clinical data. Gene therapy, utilizing techniques like CRISPR-Cas9, offers targeted correction of genetic defects and immune modulation; however, challenges in precise delivery and ensuring long-term safety persist. Islet allotransplantation and pancreatic islet cell transplantation have achieved some success in restoring insulin independence, yet challenges such as donor scarcity and immunosuppression-related complications remain significant. Teplizumab, an anti-CD3 monoclonal antibody, has demonstrated potential in delaying T1DM onset by modulating immune responses and preserving beta-cell function, with clinical trials indicating prolonged insulin production capability. Despite significant progress, standardization, long-term efficacy, and safety continue to pose challenges across these modalities. Conclusion: While these therapies demonstrate significant potential, challenges persist. Future research should prioritize optimizing these treatments and validating them through extensive clinical trials to enhance T1DM management and improve patient outcomes.

Molecular Basis of Hydatidiform Moles-A Systematic Review.

Gestational trophoblastic diseases (GTDs) encompass a spectrum of conditions characterized by abnormal trophoblastic cell growth, ranging from benign molar pregnancies to malignant trophoblastic neoplasms. This systematic review explores the molecular underpinnings of GTDs, focusing on genetic and epigenetic factors that influence disease progression and clinical outcomes. Based on 71 studies identified through systematic search and selection criteria, key findings include dysregulations in tumor suppressor genes such as p53, aberrant apoptotic pathways involving BCL-2 (B-cell lymphoma), and altered expression of growth factor receptors and microRNAs (micro-ribose nucleic acid). These molecular alterations not only differentiate molar pregnancies from normal placental development but also contribute to their clinical behavior, from benign moles to potentially malignant forms. The review synthesizes insights from immunohistochemical studies and molecular analyses to provide a comprehensive understanding of GTD pathogenesis and implications for personalized care strategies.

Molecular diagnosis of an unusual aetiology of chronic abdominal pain with ascites.

An immigrant woman in her 60s with a complex medical history and remote occupational exposure to patients with tuberculosis (TB) presented with abdominal pain, early satiety, bloating and weight loss. Physical exam showed abdominal distention and ascites. Diagnostic paracentesis revealed low serum ascites albumin gradient and elevated ascitic lymphocytic count. However, fluid cytology, bacterial and mycobacterial cultures were negative. An interferon-gamma release assay for TB was indeterminate. MRI of the abdomen and pelvis showed a thickened endometrial stripe. Endometrial biopsy demonstrated non-caseating granulomatous endometritis. No organisms were identified on Grocott methenamine silver or acid-fast bacilli special stains. A tissue block from the endometrial biopsy submitted for DNA sequencing was positive for mycobacterium tuberculosis (MTB) complex Urine mycobacterial cultures were obtained and the patient was started on isoniazid, rifampin, ethambutol and pyrazinamide, with significant improvement in her symptoms. Urine mycobacterial cultures were eventually positive for pansusceptible MTB.

Intramasseteric Solitary Myofibroma: A Case Report.

Solitary myofibroma or infantile myofibroma is a rare spindle cell neoplasm that generally affects infants before the age of 2 years but cases in young children and adults have been described. Although the location of infantile myofibroma in the oral and maxillofacial region has been described, the intramasseteric location of the lesion is very uncommon. A thorough assessment of histopathological and immunohistochemical characteristics is necessary to have a correct diagnosis. Treatment relies on surgical resection. In this article, we present a rare clinical case of a 15-year-old patient with a myofibroma of the masseteric muscle and its management.

Transcutaneous canine breast cancer detection in Tunisia: a pilot study.

BACKGROUND: Breast cancer in Tunisia is often diagnosed at a late stage with long delay in time to consultation and to diagnosis.The aim of this study is to estimate the sensitivity and specificity of the transcutaneous breast cancer detection by canine olfactionin Tunisian women and to identify the potential confounding factors. METHODS: This is a diagnostic case control study that took place from October 2021 to November 2022 in the Department of Medical Oncology at the University Hospital Farhat Hached of Sousse and in the security and training dog center located in Sousse (K9 Dog Center Security & Training). A two-year-old male Belgian Malinois was trained to detect breast cancer on skin secretion samples in compresses that had been worn overnight by women on their breast and then a double-blind testing was performed. There was no contact between women and the dog. From the mentioned responses of the dog, four parameters were calculated: sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV). RESULTS: Two hundred women were included in this trial: 100 breast cancer (BC) patients recruited from Farhat Hached University Hospital of Sousse and 100 healthy volunteers (HV).The calculated sensitivity was 84% (95% CI 78-89%) and the calculated specificity was 81% (95% CI 75-86%). The calculated predictive values were: PPV = 83,51% (95% CI 78,37-88,65%) and NPV = 81,55% (95% CI 76.17-86.93%). In the multivariate study, only four confounding factors of test's sensitivity were retained: age (OR = 1.210 [95% CI = 1.085-1.349]; p = 0.001), history of diabetes(OR = 0.017 [95% CI = 0.001-0.228]; p = 0.002), sampling at hospital (OR = 0.010 [95% CI = 0.003-0.464]; p = 0.010) and testing during chemotherapy courses (OR = 0.034 [95% CI = 0.003-0.404]; p = 0.007).For test's specificity, we retained the three following confounding factors: age (OR = 1,104 [95% CI = 1.021-1.195]; p = 0.014), history of benign mastopathy (OR = 0.243 [95% CI = 0.074-0.805]; p = 0.021)and history of arterial hypertension (OR = 0.194 [95% CI = 0.053-0.707]; p = 0.013). CONCLUSION: This is a pilot study that opens new avenues in developing a reliable cancer diagnostic tool that integrates the dog's olfactory ability to detect breast cancer using a transcutaneous sampling method. It could be a pre-test to select patients who are eligible to a screening mammogram, especially in low-income countries where there is no national mammography screening program. PACTR. ORG IDENTIFIER: PACTR202201864472288, registration date 11/01/2022.

Pulmonary Enteric Adenocarcinoma: A Very Rare Case Report from Qatar.

A 78-year-old male patient presented with dyspnea, loss of appetite, and weight loss. Workup and imaging showed suspected malignant lung lesion. Biopsy was done and showed features of pulmonary enteric adenocarcinoma (PEAC). This is a very rare disease and its diagnosis is challenging.

Heparin-induced Anaphylaxis shock.

Introduction: Anaphylaxis is a fatal condition that can be easily managed if discovered early. Only a few examples of anaphylaxis-like reactions caused by heparin have been documented, and immediate-type hypersensitivity reactions to heparin are extremely uncommon. Case Presentation: We report a case of a 53-yearold gentleman known to have an End Stage Renal Disease (ESRD) on Hemodialysis for two years, who went to the dialysis facility in his usual state of health. After two hours of dialysis, a new lock of taurolidine/heparin was installed; one minute later, the patient started to vomit and became restless, blood pressure dropped to 60/47 mmHg, and urticarial hives and a reddish rash developed on his skin, covering his trunk and limbs. He was immediately given three doses of epinephrine intramuscularly, which he did not respond to. Therefore, an epinephrine infusion was started. IV hydrocortisone and diphenhydramine were given for symptomatic relief. The patient was shifted to the emergency department, where he became vitally stable and returned to baseline. Heparininduced anaphylaxis was assumed based on the quick response to the above medications. Conclusion: This case can be added to the growing literature regarding this rare reaction, and more studies should be done to understand the nature of the reaction better. We recommend that the healthcare team becomes vigilant of heparin as a possible cause of anaphylaxis.

Endomyocardial Fibrosis With Bilateral Ventricular Thrombus: A Case Report and Literature Review.

Endomyocardial fibrosis (EMF) is a rare restrictive cardiomyopathy in non-tropical areas. It is seen in most of the patients living in or coming from tropical areas, and is rarely seen in patients who have never visited these areas. It is characterized by fibrotic thickening of the endocardium, predominantly affecting the ventricular apices and inflow tracts. Although thrombus formation is a known complication in various cardiac conditions such as atrial fibrillation, atrial flutter, ventricular heart disease, and patent foramen ovale, the occurrence of bilateral thrombus in EMF is exceptionally rare. We present a case report describing a unique finding of bilateral ventricular thrombus in a patient diagnosed with EMF, highlighting the clinical presentation, diagnostic approach, and management challenges associated with this rare phenomenon.

A Challenging Case of Adult-Onset Still's Disease Complicated by Macrophage Activation Syndrome With Multiorgan Failure.

Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disease that involves the excessive production of proinflammatory cytokines. Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune-mediated disorder that can be primary or secondary to malignancy, infections, and autoimmune diseases. We present an interesting case of a young female with adult-onset Still's disease that commenced during pregnancy. Whole-body fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scan showed diffuse uptake in the spleen and bone marrow with widespread lymphadenopathy. During the delayed diagnostic process to exclude lymphoproliferative malignancy, she developed severe HLH/macrophage activation syndrome (MAS) with multiorgan failure. In this case report, we described the challenges faced during the diagnosis of AOSD. We also highlighted the importance of using clinical criteria to aid in the early diagnosis and management of AOSD patients and the role of FDG-PET/CT scans in patients with AOSD. Additionally, we discussed the management aspects for patients with macrophage activation syndrome.

A Subacute Presentation of Isolated Tuberculous Septic Hip Arthritis.

Tuberculous septic arthritis is a rare type of septic arthritis that is caused by Mycobacterium tuberculosis. However, it can lead to devastating complications if not diagnosed and treated correctly. We hereby report a 41-year-old female with no medical history who presented with a three-week history of right hip pain and inability to bear weight, found to have moderate to severe tenderness at the right anterior hip and gluteal area and limitation of joint movement. Magnetic resonance imaging (MRI) of the hip showed features of right hip septic arthritis with synovitis and anteromedial and posteromedial small collections. She was diagnosed with tuberculosis (TB) after joint fluid aspiration, and she was started on anti-TB treatment including isoniazid, rifampicin, ethambutol, and pyrazinamide directly after. Considering the case and the subacute presentation that can mimic bacterial septic arthritis, clinicians should always consider TB infection in their differential diagnosis upon assessing a suspected patient with septic arthritis even with a subacute presentation to achieve the correct diagnosis and start appropriate treatment to avoid its harmful complications.

Differential distribution of actual and surrogate oncotype DX recurrence scores in breast cancer patients by age, menopausal status, race, and body mass index.

PURPOSE: The Oncotype DX Recurrence Score (RS) is a widely used prognostic tool for estrogen receptor-positive breast cancer patients. Multiple surrogate models can predict RS with good accuracy. In this study we aimed to determine whether the RS and two surrogate indices were differentially distributed by age, menopausal status, race, and body mass index (BMI). METHODS: 516 breast cancer cases treated at a single institution were analyzed. Epidemiologic data, RS, tumor size, grade, and biomarker data were abstracted. Breast Cancer Prognostic Score (BCPS) and modified Magee equation 2 were used to calculate surrogate RS. Patients were stratified into different groups based on age, menopausal status, race, BMI, or a combination of strata. Mean and standard deviation were calculated for each group/subgroup. RESULTS: Age below median (< 63) was associated with higher RS, especially in obese and Black patients. RS was also higher in obese and Black patients in the premenopausal subgroup. Black patients had a higher RS compared to White women in the premenopausal and non-obese subgroups. BMI < 30 was associated with higher RS, especially in older, postmenopausal, and Black patients. Some of these observations were replicated by the two surrogate models. The surrogate recurrence scores were higher in the younger age group, in non-obese older/postmenopausal women, and in younger/premenopausal obese individuals. CONCLUSIONS: Higher RS was observed in younger and premenopausal breast cancer patients, especially among the Black and obese subgroups, and in non-obese patients, especially among Black and older/postmenopausal women, suggesting more aggressive disease in these subgroups. Some statistical differences could be replicated by both surrogate models, suggesting that they may have utility in breast cancer epidemiology studies that do not have access to Oncotype DX RS or patient outcome data.

Diagnostic value of intraoperative fine-needle aspiration cytologic diagnosis versus frozen section-based histopathologic diagnosis in thoracic malignancies: A single institution's experience.

BACKGROUND: Primary lung cancer is the leading cause of cancer death in the United States. Most lung cancers are diagnosed in an outpatient setting, but a subset requires intraoperative diagnosis. Two intraoperative diagnostic methods are available, frozen section (FS) and fine needle aspiration (FNA) cytology. This study compares intraoperative FNA cytology and FS based diagnosis in thoracic malignancies within the same clinical practice. METHODS: Pathology reports from thoracic intraoperative FNA cytology or FS (January 2017-December 2019) were reviewed. Resection diagnosis was the gold standard. If unavailable, concurrent biopsy and final FNA cytology diagnosis were the gold standard. RESULTS: Of 300 FNA specimens (155 patients), 142 (47%) cases were benign, and 158 (53%) were malignant. Adenocarcinoma was the most common malignant diagnosis (40%), followed by squamous cell carcinoma (26%), neuroendocrine tumors (18%), and other (16%). Intraoperative FNA yielded 88% sensitivity, 99% specificity, and 92% accuracy (p < .001). Of 298 FS specimens (252 patients), 215 (72%) cases were malignant and 83 (28%) were benign. Adenocarcinomas was the most common malignant diagnosis (48%), followed by squamous cell carcinoma (25%), metastatic carcinomas (13%), and other (14%). FS yielded 97% sensitivity, 99% specificity, and 97% accuracy (p < .001). CONCLUSION: Our findings confirm FS is the gold standard for intraoperative diagnosis. FNA cytology may be useful as a non-invasive, inexpensive initial diagnostic tool intraoperatively, given the similar specificity (99% FNA, 99% FS) and accuracy (92% FNA, 97% FS). Negative FNA could be followed by the costlier and invasive FS. We encourage surgeons to utilize intraoperative FNA first.

Race-Related Differences in the Clinical Presentation and Histopathologic Features of Phyllodes Tumor.

BACKGROUND: Phyllodes tumor (PT) is a rare fibroepithelial lesion of the breast with variable malignant potential. Black women have a higher incidence of a related benign tumor, fibroadenoma, but there are limited epidemiological data on PT. The aim of our study was to evaluate race-related differences in the clinicopathologic features and outcomes of PT. METHODS: Our institutional pathology database was queried for breast specimen reports from 01/2009 to 10/2019 to identify patients with a pathologic diagnosis of PT. Chart review and detailed slide review were performed to obtain clinical and histopathologic variables, respectively. RESULTS: Among twelve patients, two had malignant PT, three had borderline PT, and seven had benign PT. All patients with malignant and borderline PT were black, compared with 29% of those with benign PT. There were no apparent race-related differences in specific histopathologic features among black vs. non-black women with benign PT. Malignant and borderline PT were relatively larger than benign PT, with mean tumor sizes of 9.0 cm (standard deviation [SD] 4.7 cm), 12.2 cm (SD 9.4 cm), and 5.4 cm (SD 5.8 cm), respectively. Two women had a local recurrence, both of whom were black. DISCUSSION: In this single-institution retrospective study, we observed disproportionate rates of aggressive histopathologic features and disparate outcomes among black women with PT. A multi-institutional PT registry would facilitate improved knowledge about race-related differences in the presentation and outcomes of this rare tumor.

Prospecting for candidate molecules from Conus virgo toxins to develop new biopharmaceuticals.

Background: A combination of pharmacological and biomedical assays was applied in this study to examine the bioactivity of Conus virgo crude venom in order to determine the potential pharmacological benefit of this venom, and its in vivo mechanism of action. Methods: Two doses (1/5 and 1/10 of LC50, 9.14 and 4.57 mg/kg) of the venom were used in pharmacological assays (central and peripheral analgesic, anti-inflammatory and antipyretic), while 1/2 of LC50 (22.85 mg/kg) was used in cytotoxic assays on experimental animals at different time intervals, and then compared with control and reference drug groups. Results: The tail immersion time was significantly increased in venom-treated mice compared with the control group. Also, a significant reduction in writhing movement was recorded after injection of both venom doses compared with the control group. In addition, only the high venom concentration has a mild anti-inflammatory effect at the late inflammation stage. The induced pyrexia was also decreased significantly after treatment with both venom doses. On the other hand, significant increases were observed in lipid peroxidation (after 4 hours) and reduced glutathione contents and glutathione peroxidase activity, while contents of lipid peroxidation and nitric oxide (after 24 hours) and catalase activity were depleted significantly after venom administration. Conclusion: These results indicated that the crude venom of Conus virgo probably contain bioactive components that have pharmacological activities with low cytotoxic effects. Therefore, it may comprise a potential lead compound for the development of drugs that would control pain and pyrexia.

A Quantitative and Qualitative Assessment of Frozen Section Diagnosis Accuracy and Deferral Rate Across Organ Systems.

OBJECTIVES: Monitoring of frozen section diagnostic performance provides an important quality improvement measure. METHODS: Surgical specimens involving a frozen section diagnosis over a 3-year period were retrospectively reviewed. Glass slides were reviewed on cases with discordance. Discordance and deferral rates were calculated. RESULTS: Of 3,675 frozen section diagnoses included, 96 (2.7%) were discordant with the final diagnosis. Additionally, 114 frozen section diagnoses (3.1%) were deferred. The organ-specific discordance rates were lowest in breast and genitourinary specimens and highest for pancreas, lymph node, and gynecologic specimens. Deferral rates were highest in musculoskeletal, breast, and hepatobiliary cases and lowest in thyroid, parathyroid, and neuropathology cases. Discordance was explained by block-sampling error (45%), specimen-sampling error (27%), or interpretation error (27%). Discordant frozen section diagnoses from gynecologic specimens were responsible for 81% of specimen-sampling errors; frozen section diagnoses of lymph nodes, head and neck, and pancreas were responsible for 54% of interpretation errors; 51% of block-sampling errors involved lymph node evaluation for metastatic carcinoma. CONCLUSIONS: Careful gross evaluation and microscopic examination of multiple levels should minimize specimen-sampling error and block-sampling error, respectively. Periodic review of accuracy and deferral rates may help reduce errors and improve the overall performance of this essential procedure.