Morular Metaplasia of the Endometrium: A Case Report and Literature Review: Care Pathways based on Molecular Biology
Published on: 30th April, 2024
Background: Endometrial morular metaplasia, a clinical conundrum from a diagnostic and management angle given its rarity and low oncogenic potential, has been linked to endometrial hyperplasia and carcinoma. Case report: A 77-year-old woman with no significant past medical history, was found to have an asymptomatic thickened endometrium on pelvic imaging, after presenting with lower abdominal pain, 3yrs ago. Diagnostic hysteroscopy identified an endometrial polyp within a pyometra. Histopathology showed focal complex endometrial hyperplasia without atypia with superimposed morular metaplasia(EMM) with a negative microbiology assay.Following conservative management with multidisciplinary team(MDT) overview, as-per patient choice with 6-monthly follow-up hysteroscopy, endometrial biopsies and a short use of the Mirena® Intrauterine system (discontinued following poor tolerance), histopathology shows resolved hyperplasia with persistent EMM. Due to persistent disease, a hysterectomy is under consideration.Discussion: Current evidence suggests that a sub-type of EMM, a likely histological manifestation of beta-catenin (CTNNB1) gene mutation: could be a precursor of endometrial hyperplasia and low-grade endometrioid-endometrial carcinoma sub-type. Though low-grade in nature, the increased recurrence risk raises significant concerns.Prognostication following gene mutation identification can help with management options which include conservative, hormonal therapy with adjunct repeat endometrial sampling: or hysterectomy. The optimal frequency of endometrial sampling when uterine-sparing, is unclear, leading to a management conundrum, whilst persistent disease may require a hysterectomy.Conclusion: Management of endometrial morular metaplasia can be difficult but must reflect the woman’s choice with a MDT-overview. Immuno-histochemical tools utilizing new molecular biological advances, can simplify the diagnostic and prognostication processes, aiding clinical management.
Successful Management of a Giant Splenic Cyst during Pregnancy: A Rare Case
Published on: 27th May, 2024
Background: Maternal splenic cyst during pregnancy appears to be a rare pathology whose treatment is not codified. The most feared complication is rupture during pregnancy. It occurs in 60% of cases in the third trimester of pregnancy, leading to significant maternal-fetal morbidity and mortality. Case report: We describe the successful management of a 24-year-old patient, G1P0, with a history of a recurrent splenic cyst. She presented with a giant splenic cyst measuring 28 cm in diameter at 30 weeks of amenorrhea. A cesarean section was performed at 37 weeks gestation. A splenectomy was performed on day 21 postpartum.Conclusion: The incidence of splenic cysts is extremely rare during pregnancy. The diagnosis must be made as early as possible to undertake appropriate treatment before the appearance of maternal-fetal complications.
Germline BRCA1 Mutation inSquamous Cell Carcinoma of Oesophagus: Driver versus Passenger Mutation
Published on: 2nd July, 2024
We report a rare case of 62-year-old South Asian women who visited the Molecular Pathology and Genomics Department for hereditary germline cancer genetic testing after being diagnosed with oesophageal cancer, reported as invasive keratinizing squamous cell carcinoma metastasized to the lymph nodes. Her personal history revealed that she was diagnosed with triple-negative breast cancer five years before oesophageal cancer. Germline cancer testing showed pathogenic variants in BRCA1 gene c.68_69delAG, which proved it a hereditary breast and ovarian cancer syndrome. She was started on PARP inhibitors but developed some secondary respiratory failure and succumbed to death. Less than 10 cases have been reported in the literature of the association of germline BRCA1 and Squamous cell Carcinoma – the esophagus. The article focuses on the probable pathogenesis of BRCA1 mutation with non-classic malignancies and the response of Poly adenosine diphosphate ribose polymerase inhibitors (PARP) inhibitors in such a scenario. We report an unusual manifestation of the BRCA1 gene with second primary oesophageal squamous cell cancer occurring five years later to triple-negative breast cancer.
Radiomics by Quantitative Diffusion-weighted MRI for Predicting Response in Patients with Extremity Soft-tissue Undifferentiated Pleomorphic Sarcoma
Published on: 9th July, 2024
Purpose: This study aimed to determine the relevance of first- and high-order radiomic features derived from Diffusion-Weighted Imaging (DWI) and Apparent Diffusion Coefficient (ADC) maps for predicting treatment response in patients with Undifferentiated Pleomorphic Sarcoma (UPS).Methods: This retrospective study included 33 extremity UPS patients with pre-surgical DWI/ADC and surgical resection. Manual volumetric tumor segmentation was performed on DWI/ADC maps acquired at Baseline (BL), Post-Chemotherapy (PC), and Post-Radiation Therapy (PRT). The percentage of pathology-assessed treatment effect (PATE) in surgical specimens categorized patients into responders (R; PATE ≥ 90%; 16 patients), partial-responders (PR; 89% - 31% PATE; 10 patients), and non-responders (NR; PATE ≤ 30%; 7 patients). 107 radiomic features were extracted from BL, PC, and PRT ADC maps. Statistical analyses compared R vs. PR/NR.Results: Pseudo-progression at PC and universal stability at PRT were observed in R and PR/NR based on RECIST, WHO, and volumetric assessments. At PRT, responders displayed a 35% increase in ADC mean (p = 0.0034), a 136% decrease in skewness (p = 0.0001), and a 363% increase in the 90th percentile proportion (p = 0.0009). Comparing R vs. PR/NR at BL, statistically significant differences were observed in glrlm_highgraylevelrunemphasis (p = 0.0081), glrlm_shortrunhighgraylevelemphasis (p = 0.0138), gldm_highgraylevelemphasis (p = 0.0138), glcm_sumaverage (p = 0.0164), glcm_jointaverage (p = 0.0164), and glcm_autocorrelation (p = 0.0193). At PC, firstorder_meanabsolutedeviation (p = 0.0078), firstorder_interquartilerange (p = 0.0109), firstorder_variance (p = 0.0109), and firstorder_robustmeanabsolutedeviation (p = 0.0151) provided statistically significant differences.Conclusion: Observing a high post-therapeutic ADC mean, low skewness, and high 90th percentile proportion with respect to baseline is predictive of successfully treated UPS patients presenting > 90% PATE. Highly significant higher-order radiomic results include glrlm-highgraylevelrunemphasis (BL) and first-order-mean absolute deviation (PC).
Neuroprotective Effect of 7,8-dihydroxyflavone in a Mouse Model of HIV-Associated Neurocognitive Disorder (HAND)
Published on: 18th September, 2024
Treatment for HIV-associated neurocognitive disorders (HAND) remains elusive. 7,8-dihydroxyflavone (DHF), an analog of brain-derived neurotrophic factor (BDNF) and a high-affinity TrkB agonist, has been proposed as a viable therapeutic alternative to BDNF in crossing the Blood-Brain Barrier (BBB) and promoting growth, differentiation, maintenance, and survival of neurons. Here, we expand on our previous study investigating the therapeutic role of DHF on the cortical and hippocampal brain regions of the Tg26 mice, an animal model of HAND. We detected increased immunoreactivity for ion channels (SUR1, TRPM4) and the water channel aquaporin-4 (AQP4), suggesting an ionic and osmotic imbalance in the brains of Tg26 mice. Tg26 mice also exhibited loss of synaptic stability (SYN, SYP) and nicotinamide metabolism (NAMPT, SIRT1) that were associated with astrogliosis. Furthermore, Tg26 mice demonstrated increased iNOS and reduced HO-1/NRF2 expressions, implicating increased ER and oxidative stress. DHF treatment in Tg26 mice reversed these pathological changes. These data suggest crosstalk among TrkB, Akt, and related transcription factors (NF-κB, STAT3, and NRF2) as an underlying mechanism of Tg26-associated pathology in the brain. Finally, taken together with our prior study, these results further highlight a therapeutic role of DHF in promoting neuroprotection in HAND that may be applied in conjunction with current antiviral therapies.
Budesonide – Oral Galenic Formulations for Crohn Disease
Published on: 11th October, 2024
The aim of this work is to verify the pharmaceutical form in the galenic field of oral Budesonide compounded used in Crohn’s disease: capsules delay release or oral suspension. In particular ways the kinds of excipients or bases-vehicle used in the galenic pharmacy practice. The therapeutic need for Crohn’s disease requires a release of the API in delayed-release DR. The Budesonide molecule shows low systemic impacts due to its hepatic metabolism vs. a topical effect useful in this pathology. In this work, the oral pharmaceutical forms are analyzed: modified-release capsules and oral suspension with specific advantages for each one. Some formulations provided by various pharmacies are reported in this work as well as new technology like the 3D-PRINTING systems for colonic targeting tablets.
The Pores of Kohn, an Overlooked Pulmonary Structure: A Review
Published on: 25th October, 2024
Many studies from the early 20th century on the significance of the pores of Kohn were assessed based on the pathogenesis and pathology of pneumococci pneumonia occurring in man. The pneumococci were carried in the edema fluid directly from alveolus to alveolus through the pores of Kohn and from bronchiole to bronchiole as a result of repeated aspirations, aided by breathing, coughing, and gravity. With the emerging minimally invasive and non-invasive techniques experimentations and the current medications; tackling exacerbations and improving the pulmonary function in various lung diseases remains a dilemma for clinicians and researchers. In this article, we aim to review specifically the pores of Kohn as this is the portal for the spread of infection but also lung recruitment during breathing.
Changes in Private Psychiatric Outservice Related to SARS-CoV-2 Pandemic
Published on: 8th November, 2024
The SARS-CoV-2 pandemic, which began in late 2019, initially manifested with acute respiratory symptoms, including bilateral pneumonia, and later emerged as a systemic disease. This brief report assesses changes in the clinical profiles of psychiatric outpatients before, during, and after the pandemic’s most severe periods, focusing on mood, anxiety, and cognitive symptoms. Data from a private psychiatric facility in Rome reveal that both pandemic-related stressors and SARS-CoV-2 infection itself may contribute to enduring affective and cognitive symptoms in both older and younger adult subgroups. Notably, during the pandemic, older patients showed elevated psychopathology scores (BPRS-24) compared to younger individuals. In the post-pandemic period, younger adults exhibited increased positive symptoms on the PANSS Positive subscale, suggesting a gradual worsening in symptoms post-pandemic ( = 0.47). Cognitive assessments (MMSE and PM38) further highlighted fluctuating performance over time, with older adults showing two distinct declines during the pandemic and in 2024. This work underscores the importance of sustained mental health interventions to address the pandemic’s psychosocial and neuroinflammatory legacy. This perspective also considers new data on the CNS effects of “toxin-like peptides” synthesized by microbiome bacteria.
Adult Neurogenesis: A Review of Current Perspectives and Implications for Neuroscience Research
Published on: 12th November, 2024
Background: The study of new neuron formation in the adult brain has sparked controversy and ignited interest among scientists in recent times, these include its occurrence and location in the adult human brain, functional significance, variation in study methods, translation from animal model to human, and ethical challenges involving neural stem cell research. Aim: To provide a comprehensive understanding of adult neurogenesis, functional significance, and challenges and explore the latest advances in the study of adult neurogenesis. Methodology: An extensive and systematic search of electronic databases (Medline, Scopus, Web of Science) was conducted using keywords related to adult neurogenesis and techniques involved in its study. Results: The mechanism of adult neurogenesis was found to occur in specific brain regions such as the subgranular zone of the dentate gyrus and subventricular zone of the lateral ventricle. Adult neurogenesis is vital neural plasticity, providing a potential mechanism for the brain to adapt and reorganize in response to environmental cues and experiences. Cutting-edge research and sophisticated imaging techniques, such as two-photon microscopy, MRI, optogenetic, and stem-cell-based therapies have provided deeper insight into the study of adult neurogenesis. Conclusion: The study of neurogenesis is important for understanding nervous system development, physiology, pathology, and exploring neuroplasticity. Its advancement is challenged by some ethical concerns regarding embryonic, pluripotent stem cells, and the need for safe, and noninvasive study methods. Although recent breakthroughs in neuroimaging, microscopic techniques, and genetic tools are aiding real-time study of adult neurogenesis.
Bilateral Trigeminal Neuralgia Refractory to Medical Therapy: Importance of A Multi-Therapeutic Approach
Published on: 10th January, 2025
Bilateral trigeminal neuralgia refractory to medical therapy is a rare occurrence and it is mandatory to choose therapeutic procedures minimizing possible bilateral sensitive deficit due to the employment of bilateral mininvasive ablative techniques. A patient affected by bilateral trigeminal neuralgia refractory to medical therapy secondary to multiple sclerosis is presented. Multiple therapeutic tools were employed in this challenging pathology. The second and third left trigeminal divisions were involved by the neuralgia, while the third division was involved in the right facial side. Controlled radiofrequency thermocoagulation was employed for the isolated right third division, then radiosurgery was conducted for the left hemifacial side. After one month, because of the persistence of pain attacks of the left second trigeminal division, peripheral authorizations were performed. Control of pain, with the withdrawal of medical therapy (BNI scale class I), was achieved in this patient with a multi-therapeutic approach. Radiofrequency thermorizotomy was performed for the right third division because neuralgia was very acute, and immediate pain relief was achieved. Pain in the left third trigeminal division regressed after radiosurgery, while pain in the left second division continued after radiosurgery, then peripheral alcoholization was performed with pain control.Bilateral trigeminal neuralgia refractory to medical therapy should be treated by the dedicated neurosurgeon, avoiding bilateral ablative techniques for the same division and using neurosurgical techniques according to the trigeminal division interested by the neuralgia and according to the intensity of pain.
Evolution of the Mineralocorticoid Receptor and Gender Difference in Cardiovascular Pathology
Published on: 28th January, 2025
Retracing the evolution of Mineralocorticoid Receptors (MR) obliges us to take an instructive as well as fascinating leap back in time. This journey teaches us that the relationship between MRs and what we consider their natural ligand, aldosterone, has not always been an exclusive one. MRs operated for a very long time in the oceans and, in any case, in an aquatic environment, stimulated by ligands other than aldosterone, and exercising functions that we still do not know well but which were certainly different from those they currently perform in terrestrial vertebrates, where they maintain normal sodium and body fluids. The history of MRs was initially intertwined with that of female sexual hormones, in particular with progesterone, which was one of the first agonists for MRs, before becoming, with the transition to the terrestrial environment, an important antagonist. This initial intertwining could be the cause of the sexual dimorphism that can be glimpsed when these receptors are overstimulated, as emerges from many experimental studies and some clinical data and/or when antagonistic drugs for these receptors are studied. This must be taken into account in the planning of clinical studies, especially randomized controlled trials, in which the presence of the two sexes must always be well balanced and in the interpretation of the results which must always be performed being well aware of the gender of participants. This does not always happen, however.
Clinical and Histopathological Mismatch: A Case Report of Acral Fibromyxoma
Published on: 7th April, 2025
Background: Acral Fibromyxoma (AFM) is a rare benign soft tissue tumour which is described as a fibromatous and myxoid tumour of skin and soft tissue. Case details: A 40-year-old male presented to the Dermatology outpatient department with swelling over the wrist of one year duration. The swelling was associated with mild pain, and it gradually increased in size to reach its present size. Cutaneous examination revealed a 2x2 cm mobile, cystic to firm, non-tender swelling over the dorsum of the right wrist. Based on its location and clinical features, it was provisionally diagnosed as a ganglion cyst and excision biopsy was done. Histology showed stellate-shaped cells in a myxoid background with round to oval nuclei having a small, inconspicuous nucleolus. Acral fibromyxoma presents a distinct histopathology including a myxoid stroma and spindle-shaped cells, which are essential for accurate diagnosis and management.
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