Pathological Entity Research Articles

Neuronally Derived Soluble Abeta Evokes Cell-Wide Astrocytic Calcium Dysregulation in Absence of Amyloid Plaques in Vivo.

The key pathologic entities driving the destruction of synaptic function and integrity during the evolution of Alzheimer's disease (AD) remain elusive. Astrocytes are structurally and functionally integrated within synaptic and vascular circuitry and use calcium-based physiology to modulate basal synaptic transmission, vascular dynamics, and neurovascular coupling, which are central to AD pathogenesis. We used high-resolution multiphoton imaging to quantify all endogenous calcium signaling arising spontaneously throughout astrocytic somata, primary processes, fine processes, and capillary endfeet in the brain of awake APP/PS1 transgenic mice (11 male and 6 female mice). Endogenous calcium signaling within capillary endfeet, while surprisingly as active as astrocytic fine processes, was reduced ∼50% in the brain of awake APP/PS1 mice. Cortical astrocytes, in the presence of amyloid plaques in awake APP/PS1 mice, had a cell-wide increase in intracellular calcium associated with an increased frequency, amplitude, and duration of spontaneous calcium signaling. The cell-wide astrocytic calcium dysregulation was not directly related to distance to amyloid plaques. We could re-create the cell-wide intracellular calcium dysregulation in the absence of amyloid plaques following acute exposure to neuronally derived soluble Abeta from Tg2576 transgenic mice, in the living brain of male C57/Bl6 mice. Our findings highlight a role for astrocytic calcium pathophysiology in soluble-Abeta mediated neurodegenerative processes in AD. Additionally, therapeutic strategies aiming to protect astrocytic calcium physiology from soluble Abeta-mediated toxicity may need to pharmacologically enhance calcium signaling within the hypoactive capillary endfeet while reducing the hyperactivity of spontaneous calcium signaling throughout the rest of the astrocyte.SIGNIFICANCE STATEMENT Astrocytic calcium signaling is functionally involved in central pathologic processes of Alzheimer's disease. We quantified endogenous calcium signaling arising spontaneously in the brain of awake APP/PS1 mice, as general anesthesia suppressed astrocytic calcium signaling. Cell-wide astrocytic calcium dysregulation was not related to distance to amyloid plaques but mediated in part by neuronally derived soluble Abeta, supporting a role for astrocytes in soluble-Abeta mediated neurodegeneration. Spontaneous calcium signaling is largely compartmentalized and capillary endfeet were as active as fine processes but hypoactive in the presence of amyloid plaques, while the rest of the astrocyte became hyperactive. The cell-wide calcium pathophysiology in astrocytes may require a combination therapeutic strategy for hypoactive endfeet and astrocytic hyperactivity.

Benign incidental lesion of the calcaneus: the calcaneal vascular remnant.

The calcaneal vascular remnant, first described by Fleming et al. in 2005, is a benign intramedullary lesion of the calcaneus with a vascular origin. To determine the prevalence and magnetic resonance imaging (MRI) characteristics of incidental calcaneal vascular remnant on routine ankle MRI. We retrospectively reviewed 457 ankle MRI scans for the presence of calcaneal vascular remnant. MRI was considered positive when a focal cyst-like area was seen on a T2-weighted sequence, and a low signal intensity was identified on a T1-weighted image beneath the calcaneal sulcus. Patients with calcaneal vascular remnants were further evaluated for age, gender, right or left foot location, size, and lesion characteristics. The prevalence of incidental calcaneal vascular remnant was 21.7% on our consecutive ankle MR examinations. The average lesion size was 5.5 mm. No statistically significant difference was noted in the frequency of lesion detection between gender, age, and side of the lesions (P > 0.05). Multilobulated lesions were detected predominantly in women (P = 0.013) and classic type lesions were detected predominantly in men (P = 0.036). This report is the first to determine the prevalence and MRI characteristics of calcaneal vascular remnants. Detecting and reporting this lesion on routine MRI is essential to avoid confusion with other pathologic entities.

P77 A “GIANT” IN THE PANDORA’S BOX OF PARACARDIAC MASS

Abstract In this case report, we describe a giant coronary aneurysm (CAAs) of the right coronary artery occasionally found in a patient that underwent Bentall procedure 18 years earlier for acute aortic dissection. A 77–year–old man, former smoker, with type II diabetes, hypertension, dyslipidaemia, and obesity, was referred to our echo lab for echocardiography in December 2020. His medical history included anteroseptal non–Q–wave myocardial infarction (1983), type A acute aortic dissection treated with Bentall procedure and implantation of mechanical aortic valve (2002), and reparation of abdominal aortic aneurysm (2003). During the echocardiogram a paracardiac mass was incidentally found, in close contact to the right atrium and with a diameter of 60 mm in A4Ch–view, with the appearance of a cystic formation (Figure A). After a few days, a CT angiography was performed, with evidence of 61.6 mm–sized giant aneurysm located in the proximal right coronary artery, characterised by calcified walls, eccentric thrombosis, and compression of the right atrium (Figure B). The patient was subsequently evaluated by the Cardiac Surgery Division. Conservatively management with regular follow–up was performed, because of the high surgical risk of redo and the lack of symptoms. In November 2022 we performed a follow–up echocardiography with evidence of stability of the size of coronary artery aneurysm (Figure C). CAAs are defined as giant when the diameter of the vessel is greater than 20 mm. These pathological entities are extremely rare, with an incidence rate of 0.02%, and aetiologies are various. The most frequent aetiologies comprehend atherosclerosis (about 50% of cases), congenital (17%), arteritis (e.g., Kawasaki disease), connective tissue disease. Our case is characterised by the occasional diagnosis of CAA 18 years after Bentall Surgery, in absence of inflammatory vessels disease. To the best of our knowledge, It’s the largest giant CAA described in literature after Bentall cardiac surgery. Therefore, cardiologists should consider these rare entities when approaching an incidental echocardiographic finding of paracardiac mass, especially in patients with high burden of atherosclerotic disease. This case report underlines furthermore the importance of an integrated approach in the differential diagnosis of a paracardiac mass.

P402 PROSTHETIC MECHANICAL VALVE THROMBOSIS: THE EXPERIENCE OF SALAM CENTRE FOR CARDIAC SURGERY (EMERGENCY NGO)

Abstract Mechanical heart valve (MHV) replacement in patients with rheumatic valve disease is common in Africa. MHV requires long–life anticoagulation (OAT) and managing this can be difficult. Prosthetic valve thrombosis (VT) is a pathological entity characterized by thrombus formation on the prosthetic structures, with subsequent prosthesis dysfunction. Salam Centre for Cardiac Surgery was built in Khartoum Sudan by Emergency NGO. Since April 2007 high–quality and free–of–charge medical and cardio–surgical treatment has been offered to patients. More than 10000 cardiac surgery, 80% of which for MHV replacement, were performed. The aim of the work is to analyze the characteristics of patients with VT, the risk factors and clinical follow–up. From Aug 1, 2018 to Nov 30, 2022, 287 VT involving 237 patients were collected.The incidence is 1.36% p/y. The most relevant risk factor was the interruption of anticoagulant therapy and irregular INR control (N. 142; 49,5%). In 101 cases (35,2%) a clinical factor (infection, pregnancy, eosinophilia, heart failure) was the main cause of VT. The diagnosis, suspected with the Transthoracic Echo and confirmed with fluoroscopy, was done at the OPD visit (32,4%) in asymptomatic or at triage for symptomatic patients (67,6%). 236 patients were admitted to Salam Centre.The treatments of choice were thrombolysis, performed with 2 different protocols, fast and low dose–slow infusion (Alteplase 25 mg./6 hrs), followed by Triple Therapy (TT) (Warfarin, LMWH and Aspirin) (N.189–65,8%), TT alone (N.44– 15,3%) or Warfarin and Aspirin (N.54–18,8%). 210 events (73,2%) ended with unblocked valve,24 events ended with the death of the patient (8,3%); low dose/slow infusion regimen had less deaths. Thrombolysis was more effective (unblockage 79,9%). Warfarin and Aspirin and not admission to Salam Centre were linked to less unblokage and high mortality rate. Conclusions The incorrect conduct of OAT represents the most relevant risk factor for VT.Many are the underlying causes, from economic and social factors to insufficient patient awareness. MOH intervention to offer free of charge INR check, but also patient education must be improved. VT is caused also by intercurrent clinical events such as pregnancy, infection. Eosinophilia represents a chapter that deserves a detailed study.Patients with history of VT must be followed by a dedicated clinic that aims to increase patient loyalty in order to intercept risk factors as early as possible.

P94 LATE–ONSET POST–INFECTIVE AORTIC PSEUDO–ANEURYSM AFTER BIOPROSTETHIC AORTIC VALVE REPLACEMENT

Abstract A 74 year–old man was admitted three months after SAVR symptomatic for dyspnea. Past medical history: DM type 2, PAD and recent SAVR after diagnosis of severe aortic stenosis, complicated by Stafilococcus Epidermidis blood culture sternal wound dehiscence, requiring Robicsek technique treatment and long–term parenteral antibiotics. He was finally discharged to our cardiac rehab unit. Blood analysis: negative blood culture at admission with negative CPR. Late positivity (after 2 weeks) for a Staphylococcus epidermidis reinfection. EKG: normal atrio–ventricular and intra–ventricular conduction with regular repolarization. TTE: Normal left ventricular volume and ejection fraction with severe aortic regurgitation secondary to suspected partial bioprosthesis detachment. TOE: valvular detachment with a newly–formed pouch located in the mitro–aortic membrane. Bioprosthetic valvular failure (BVF) is a pathological entity arising from a variety of conditions affecting prosthetic heart valves. We present the case of a late–onset partial valvular bioprosthesis detachment associated with a newly–formed pseudoaneurysm due to late infective endocarditis occurred after cardiac surgery, initially manifested with negative cultural findings and suddenly evolved in severe aortic regurgitation. Valvular detachment is an infrequent complication of infective endocarditis. Surgery is the only option capable of restoring a proper anatomy and a correct function of the valvular apparatus. Patient underwent re–do surgery and a new SAVR was needed after confirmation of diagnosis with no residual aortic regurgitation after discharged. BVF is a fearsome and severe condition presenting with a wide spectrum of clinical presentation. Our experience highlights the need of a prompt diagnosis. Late positivity of blood cultures for Stafilococcus Epidermidis probably depend on prolonged antimicrobial therapy after sternal dehiscence treatment which have probably masked laboratoristic finding in early phase (negative CPR and blood cultures). An early intervention is mandatory in order to prevent systemic dissemination or acute decompensation secondary to severe aortic regurgitation. Surgical approach in this case guaranteed a radical treatment with no residual regurgitation or sub–acute microbial infection. 4–weeks parenteral antibiotics during cardiac–rehab efficacy–controlled relapse of CPR and blood–culture (negative before final discharge).

Repurposing Inhaled Ibuprofenate, a Non Steroidal Anti‐Inflammatory Drug, as a Potential Adjuvant Treatment for Pneumonia, CARDS and its Aetiological Agent SARS‐CoV‐2

AbstractIn this manuscript, we will describe and highlight the most important potential underlying mechanisms of action of the inhaled sodium ibuprofenate in hypertonic saline formulation‐NaIHS aerosolisable, as a probable adjuvant treatment for moderate and severe pneumonia and coronavirus disease 2019 (COVID‐19)‐associated acute respiratory distress syndrome in COVID‐19. In both pathological entities, we will refer exclusively to the pulmonary vasoplegic type and we will describe the following therapeutic effects of NaIHS: anti‐inflammatory, immunomodulatory and antiangiogenic. The synergistic action of these therapeutic effects anti‐inflammatory and immunomodulatory together may exert their action at the pulmonary level through the possible reversal of pulmonary vasoplegia and may thereby restore hypoxic pulmonary vasoconstriction, correcting the uncoupling of the ventilation/perfusion ratio and vasoplegic intrapulmonary shunting and, above all, it may reverse severe hypoxaemia and acute respiratory failure. We will also mention the potential virucidal effects of NaIHS on severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2).There are available three retrospective observational studies in moderate and severe COVID‐19 pneumonia, carried out in Argentina, with all three studies concluding that there was a significant reduction in mortality. The most important of these was conducted with the approval of the Institutional Review Board of the National Bureau of Economic Research of Harvard and Columbia Universities, which analysed data from 5146 patients and concluded that NaIHS reduced mortality by 48.7%, although randomized clinical trials are still needed to confirm these emerging data and enable the rise of NaIHS as a new adjuvant treatment.Conclusively, we deem essential to reuse known drugs, such as ibuprofen, in COVID‐19, due to the constant emergence of variants and subvariants of concern secondary to mutations and immune escape mechanisms of (SARS‐CoV‐2), since effective medical treatments are currently scarce and many of them are controversial or not available worldwide.

Thiophene-Based Ligands: Design, Synthesis and Their Utilization for Optical Assignment of Polymorphic-Disease-Associated Protein Aggregates.

The development of ligands for detecting protein aggregates is of great interest, as these aggregated proteinaceous species are the pathological hallmarks of several devastating diseases, including Alzheimer's disease. In this regard, thiophene-based ligands have emerged as powerful tools for fluorescent assessment of these pathological entities. The intrinsic conformationally sensitive photophysical properties of poly- and oligothiophenes have allowed optical assignment of disease-associated protein aggregates in tissue sections, as well as real-time in vivo imaging of protein deposits. Herein, we recount the chemical evolution of different generations of thiophene-based ligands, and exemplify their use for the optical distinction of polymorphic protein aggregates. Furthermore, the chemical determinants for achieving a superior fluorescent thiophene-based ligand, as well as the next generation of thiophene-based ligands targeting distinct aggregated species are described. Finally, the directions for future research into the chemical design of thiophene-based ligands that can aid in resolving the scientific challenges around protein aggregation diseases are discussed.

Colorectal Cancer-The "Parent" of Low Bowel Obstruction.

Introduction: Despite the improvement of early diagnosis methods for multiple pathological entities belonging to the digestive tract, bowel obstruction determined by multiple etiologies represents an important percentage of surgical emergencies. General data: Although sometimes obstructive episodes are possible in the early stages of colorectal cancer, the most commonly installed intestinal obstruction has the significance of an advanced evolutionary stage of neoplastic disease. Development of Obstructive Mechanism: The spontaneous evolution of colorectal cancer is always burdened by complications. The most common complication is low bowel obstruction, found in approximately 20% of the cases of colorectal cancer, and it can occur either relatively abruptly, or is preceded by initially discrete premonitory symptoms, non-specific (until advanced evolutionary stages) and generally neglected or incorrectly interpreted. Success in the complex treatment of a low neoplastic obstruction is conditioned by a complete diagnosis, adequate pre-operative preparation, a surgical act adapted to the case (in one, two or three successive stages), and dynamic postoperative care. The moment of surgery should be chosen with great care and is the result of the experience of the anesthetic-surgical team. The operative act must be adapted to the case and has as its main objective the resolution of intestinal obstruction and only in a secondary way the resolution of the generating disease. Conclusions: The therapeutic measures adopted (medical-surgical) must have a dynamic character in accordance with the particular situation of the patient. Except for certain or probably benign etiologies, the possibility of colorectal neoplasia should always be considered, in low obstructions, regardless of the patient's age.

Abstract #1398160: A Rare Case of Water Clear Cell Parathyroid Adenoma Escaping Sestamibi Scan and Neck Ultrasound – A Diagnostic Conundrum of a Rare Pathological Intity with a Rare Presentation

Parathyroid water-clear cell hyperplasia (WCCH) and water-clear cell adenoma (WCCA) are extremely rare causes of primary hyperparathyroidism (PHPT). WCCH contributes to < 1% of all PHPT however WCCA is exceptionally rare and has been reported only in less than 30 case reports. We are presenting a very rare indolent pathological entity with a very rare presentation escaping common diagnostic measures of Sestamibi scan and neck ultrasound. A 63-year-old female presented for evaluation of severe osteoporosis with a T-score of -3.6. Laboratory workup revealed elevated parathyroid hormone (PTH) of 122 pg/ml (reference range 12-88 pg/ml), Normal calcium 9.8 mg/dl, Normal vitamin D 50 ng/ml, and normal magnesium 2.2 mg/dl. 24-hour urine calcium was 421 mg/24H. Diagnosis was consistent with normocalcemic PHPT and meeting surgical criteria with osteoporosis and high urine calcium. Sestamibi scan did not identify any focal activity. CT H&N revealed an 8 mm mass inferior and posterior to right thyroid lobe with partial washout and slightly different enhancement compared to thyroid gland. Neck ultrasound (US) reported that previously noted tissue activity on the CT H&N is not visualized and most likely represents normal thyroid tissue. Patient was referred to otolaryngology surgery and underwent four gland explorations, including right inferior and left superior parathyroidectomy. Pathology of superior parathyroid gland revealed parathyroid water clear cell adenoma. 3-month Postoperative PTH 29.4 pg/ml and calcium level of 9.3 mg/dl. Solitary parathyroid adenoma (SPA) attributes to 80-85% of PHPT. Majority of cases is due to Chief cell adenomas, less frequent pathologies include oxyphil cell adenoma, lipoadenoma, WCCA or mixed type. Scientific literature regarding WCCA presentation and diagnosis is blurred due to its rarity. Clinical presentation of WCCA resembles other etiologies of PHPT, though some data suggest that is frequently indolent and manifests with mild PHPT. Literature suggests that WCCA has low biochemical activity and most cases had normal to mildly elevated calcium-our patient support this hypothesis-. Hypercalcemia does not manifest until significant growth of the adenoma, though few reported cases manifested with hypercalcemia. Unlike other SPA where Sestamibi scan sensitivity is 91%, literature suggests possibility of false-negative results with WCCA which is hypothesized to be attributed to its different histology of glycogen-rich vacuolized cytoplasm that leads to fast Sestamibi wash-out, for the same reason data suggest that US is more decisive given high water content of cells -Our patient didn’t follow this rule and escaped Sistamibi and US though seen on CT- which still makes the diagnosis of WCCA a conundrum. Some cases underwent surgical excision based on clinical diagnosis which led to revision of PHPT and/or hypercalcemia. There is no available data suggesting different long-term follow-up regimens for WCCA compared to other SPA. Further literature with longer follow-up is needed for this extremely rare entity for a comprehensive understanding of its natural course.

Coexistence of multiple clear cell papillary renal cell carcinoma with renal oncocytoma: a case report.

The authors report a case of a female 65-year-old suffering from end-stage kidney failure for 10 years, who presented with a double left renal tumor, composed by an oncocytoma associated to multiple CCPRCC, a very rare entity. A radical left nephrectomy was realized by lumbotomy, with an uneventful postoperative course. Histological examination was challenging. Immunohistological examination showed diffuse positivity of cytokertain 7. No local recurrence nor metastatic progression were found during the 12 months of follow-up. CCPRCC, is a new entity, previously known as the unclassified rena cell carcinoma, is a malignant renal tumor, initially reported in patients at end-stage kidney failure. Oncocytoma is a well-known rare benign renal tumor. The association of both is rare, and should be kept in mind, especially when scanoguided diagnosis biopsy is realized. Histopathological confirmation may be challenging, given the recent identification of CCPRCC. The nuclei disposal toward the luminal surface is a characteristic pathological landmark of CCPRCC. Immunohistopathological examination is of great help, showing a distinctive profile: diffuse staining for cytokertain 7 and carbonic anhydrase IX. CCPRCC is a new malignant pathological entity in renal tumors. It can be associated with other benign renal lesions. This should be taken into consideration while histopathological examination, mainly of scanoguided biopsy cores.

Paratracheal air cysts; a rare cause of recurrent hemoptysis

Paratracheal air cysts (PTACs) refer to small collections of air, present at the level of the thoracic inlet, adjacent to the trachea. PTACs encompass a variety of pathological entities and are usually encountered incidentally on computed tomography (CT) of the chest. Clinically, most patients remain asymptomatic; while a minority, may be associated with cough, dyspnea and hemoptysis probably as a result of pooled secretions and secondary infections. We report one such case of recurrent hemoptysis in a 30-year-old male, as a result of a right paratracheal air cyst.

OPTN: A Possible Genetic Cause of Both CBS and ALS (P9-11.013)

<h3>Objective:</h3> To report a patient with a mutation typically associated with familial amyotrophic lateral sclerosis (ALS), but instead presenting with the corticobasal syndrome (CBS) phenotype. <h3>Background:</h3> CBS is defined by atypical parkinsonism and specific examination findings indicating cortical dysfunction. In contrast, corticobasal degeneration (CBD) is a pathological entity and is the principal pathology underlying CBS. CBD and frontotemporal dementia (FTD) often involve tau deposition, but in different topographical distributions, and also in different molecular forms. Many cases of CBD and FTD may, in addition, overlap clinically. By comparison, there is significantly less clinical overlap between ALS and the pathologies that cause CBS. Here we report a case of CBS linked to a mutation in the OPTN gene. This individual has several close relatives diagnosed with familial ALS who also have been found to carry the same OPTN mutation. <h3>Design/Methods:</h3> NA <h3>Results:</h3> We report a 49-year-old man with 6 months of involuntary movements of the right upper extremity, followed by gait unsteadiness and memory changes. Family history was notable for two siblings with ALS linked to a mutation in the OPTN gene. On exam, we noted right hemidystonia, as well as bradykinesia and brisk reflexes in the right arm. There was gait ataxia, as well as right-sided astereognosis, agraphesthesia, tactile extinction, and ideomotor apraxia. No ocular abnormalities, orthostasis, or other upper-motor neuron features were seen. MRI showed left peri-Rolandic fissure atrophy. Gene testing revealed homozygosity for a loss of function splice-site mutation in the OPTN gene. <h3>Conclusions:</h3> This case illustrates differential effects of the same gene mutation in different family members. It is interesting that the pathology causing CBS in this patient shares the same mutation with an inherited form of ALS. The heterogeneity of OPTN phenotypes may be a consequence of the same neuropathology, but with differential topographical distribution in the nervous system. <b>Disclosure:</b> Dr. Feldman has nothing to disclose. Dr. Benatar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. The institution of Dr. Benatar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Arrowhead. Dr. Benatar has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Alexion. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Annexon. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UniQure. Dr. Benatar has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Immunovant. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alector. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Benatar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Benatar has received intellectual property interests from a discovery or technology relating to health care. Dr. Benatar has received intellectual property interests from a discovery or technology relating to health care. Dr. Saraf Lavi has nothing to disclose. Dr. Latchman has nothing to disclose. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amneal. Dr. Singer has received personal compensation in the range of $10,000-$49,999 for serving as a Video Panel with CNS Ratings LLC. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Course Organiztion with Omniprex Scientific Medical Eduaction. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Reviewer with Health Monitor Network. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Speaker with Movement Disorders Society. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Workshop Moderator with International Neurotoxin Association Inc. Dr. Singer has received personal compensation in the range of $500-$4,999 for serving as a Lecturer with CME Outfitteres LLC.

Anorexia Nervosa in Juvenile Systemic Lupus Erythematosus (SLE): A Causality Dilemma.

Juvenile-onset systemic lupus erythematosus (jSLE) is an autoimmune disorder with multifaceted clinical findings in different organ systems. Neuropsychiatric manifestations affect more than half of SLE patients, and there is increasing evidence that anorexia nervosa (AN), a feeding and eating disorder (FED) characterized by significantly reduced energy intake, is among them. Herein, a review of the literature on the potential association between jSLE and AN was performed. Reported clinical cases were identified, and putative pathophysiological mechanisms were sought that could potentially explain the observed relationship between these two pathological entities. Four reports of isolated cases and a case series including seven patients were identified. In this limited patient pool, the diagnosis of AN preceded that of SLE in the majority of cases, whereas in all cases both entities were diagnosed within a time span of two years. Many explanations for the observed relationships have been proposed. AN has been associated with the stress of chronic disease diagnosis; on the other hand, the chronic inflammation associated with AN may contribute to the development/appearance of SLE. Adverse childhood experiences, concentrations of leptin, shared autoantibodies, and genetic traits appear to be important factors in this well-established interplay. In essence, it seems important to increase clinician awareness of the concomitant development of AN and SLE and invite further research on the subject.

SARS-CoV-2-Induced Myocarditis: A State-of-the-Art Review.

In this review, we investigated whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can directly cause myocarditis with severe myocardial damage induced by viral particles. A review of the major data published from 2020 to 2022 was performed by consulting the major databases alongside first-hand experiences that emerged from the cardiac biopsies and autopsy examinations of patients who died of SARS-CoV-2 infections. From this study, a significantly large amount of data suggests that the Dallas criteria were met in a residual percentage of patients, demonstrating that SARS-CoV-2 myocarditis was a rare clinical and pathological entity that occurred in a small percentage of subjects. All cases described here were highly selected and subjected to autopsies or endomyocardial biopsies (EMBs). The most important discovery, through the detection of the SARS-CoV-2 genome using the polymerase chain reaction, consisted in the presence of the viral genome in the lung tissue of most of the patients who died from COVID-19. However, the discovery of the SARS-CoV-2 viral genome was a rare event in cardiac tissue from autopsy findings of patients who died of myocarditis It is important to emphasize that myocardial inflammation alone, as promoted by macrophages and T cell infiltrations, can be observed in noninfectious deaths and COVID-19 cases, but the extent of each cause is varied, and in neither case have such findings been reported to support clinically relevant myocarditis. Therefore, in the different infected vs. non-infected samples examined, none of our findings provide a definitive histochemical assessment for the diagnosis of myocarditis in the majority of cases evaluated. We report evidence suggesting an extremely low frequency of viral myocarditis that has also been associated with unclear therapeutic implications. These two key factors strongly point towards the use of an endomyocardial biopsy to irrefutably reach a diagnosis of viral myocarditis in the context of COVID-19.

Stump appendicitis: challenging diagnosis with serious complication: a case report

Stump appendicitis is a rare complication of appendectomy because of recurrent inflammation of the residual appendix. The diagnosis is often delayed because of low index of suspicious, which may result in serious complications. Twenty-three-year-old male patient presented with right lower quadrant abdominal pain after 7month of appendectomy done at a hospital. On physical examination, he has right lower quadrant tenderness and rebound tenderness. Abdominal ultrasound was done with finding of blind-ended tubular noncompressible 2cm long part of appendix with wall-to-wall diameter of 10mm. There is also focal defect with surrounding fluid collection. With this finding, perforated stump appendicitis was diagnosed. He was operated with similar intra operative finding. The patient discharged improved after 5days of hospital. This is first reported case in Ethiopia as far as our search is concerned. Despite past medical history of appendectomy, the diagnosis was made by means of ultrasound scan. Stump appendicitis is a rare but important complication of appendectomy, often misdiagnosed. Prompt recognition is important to avoid serious complications. This pathologic entity should always be kept in mind in case of right lower quadrant pain in patient with previous history of appendectomy.

An enduring debate on gliomatosis cerebri

Gliomatosis cerebri (GC) is a unique glial tumor that extensively invades the cerebral white matter and has been recognized as an entity of neuroepithelial tumors since the first edition of the WHO classification of brain tumors in 1979. Thereafter, in the fourth edition of the WHO classification in 2007, it was clearly defined as a specific type of astrocytic tumor. However, in the WHO 2016 classification, which was based on the concept of integrated diagnosis using molecular genetics, GC was deleted as it was considered to be only one growth pattern of diffuse glioma and not a specific pathological entity. Since then, there has been criticism by many neuro-oncologists and the establishment of the GC working group at the NIH, and many activities in the world arguing that GC should not be deleted from the clinical discussion of brain tumors. In Japan, positive activities toward multicenter research on GC pathology should be performed, and molecular pathological evidence that can contribute to the WHO classification in the future should be developed. In this article, the author outlined the pathological characteristics of GC, which has been repeated changing since its conception, and also describes his opinion on GC as a neuro-oncologist.

Comparative evaluation of podoplanin in odontogenic cysts and tumours to determine their proliferative potential-An immunohistochemical study.

Odontogenic cysts and tumours are a wide array of complex pathological entities ranging from mild indolent to aggressive detrimental in nature, which occur as a result of anomalous alterations in normal odontogenesis. Hence, these odontogenic lesions need to be evaluated extensively by using potential immunohistochemical markers. To evaluate and compare the expression of podoplanin, a lymphoendothelial IHC marker in odontogenic cysts and odontogenic tumours to determine their proliferative potential. All the study samples were retrieved from the archives of the Department of Oral Pathology and Microbiology, PIDS&RC, Hyderabad. The study samples were selected as per the standard histopathological diagnostic criteria and subjected for IHC analysis using podoplanin. Seventy paraffin-embedded tissue specimens of OKC, OOC, dentigerous cyst (DC) and ameloblastoma (AM) include study sample, which were stained with podoplanin IHC marker and staining properties were evaluated. All the cases were categorized as high, moderate, weak or negatively reactive on the basis of the composite scoring. Statistical analysis was done using SPSS version 14, and then results were compared by ANOVA post hoc test and Kruskal Wallis Test. In the comparison of composite scores of OKCs and AM, there was no significant statistical difference. The present study contributes to the significant association of podoplanin expression with cellular proliferation, cystic expansion and local invasiveness of odontogenic cysts and tumours through cytoskeletal reorganization and cell migration.

Acquired hemophilia

Acquired hemophilia (AH) is an autoimmune hemostatic disorder mediated by autoantibodies directed against factor FVIII:C. In 52 % of cases, the cause is unknown or is not associated with other pathological entities; in the rest, there are concomitant factors: lupus, rheumatoid arthritis, cancer, pregnancy, and medications. In Mexico, there is not a registry of AH, and awareness of the disease among health personnel is low. The groups with the highest incidence are women of childbearing age and individuals older than 70 years. It is characterized by severe bleeding, especially after trauma and normal childbirth or cesarean delivery, and large ecchymoses in the trunk and extremities. The suspicion is simple, it just takes for sudden, severe hemorrhage and a prolonged aPTT that is not corrected with plasma to concur in an individual. Treatment involves achieving hemostasis and eradicating the antibody. The former is achieved with recombinant activated factor VII or activated prothrombin complex concentrate. Cyclophosphamide, prednisone or rituximab are used to eradicate the antibody. Most cases of AH are not diagnosed, which translates into a high mortality rate. Given that awareness about the disease among physicians is low, it is not suspected, neither diagnosed, and nor is it treated. This document reviews the most recent data on AH and expands on its diagnosis and treatment.

A COMPARATIVE STUDY OF DEXMEDETOMIDINE AND MAGNESIUM SULPHATE AS AN ADJUVANT TO BUPIVACAINE FOR POSTOPERATIVE EPIDURAL ANALGESIA IN LOWER LIMB SURGERIES

Background:Pain is pathologic entity,noxious stimulus and a most common problems challenging the anaesthetist.Regional anaesthesia is a safe,inexpensive technique that inhibits the nerve transmission to relieve pain and also provide postoperative analgesia.Magnesium is N-methyl D-aspartate receptor and physiological calcium antagonist.Dexmedetomedine is α2 receptor antagonist with analgesic and sedative properties. Objectives: To compare the duration of postoperative analgesia,time of administration of first rescue analgesia,systemic side effects of epidural bupivacaine with Magnesium sulphate and dexmedetomidine. Methods: After approval of ethical committee and informed written consent A prospective randomised study was conducted with Sixty ASA grade I and II patients aged between 18-60 years undergoing lower limb surgeries were divided into two groups of 30 each .Group BM and Group BD received 10ml of 0.125% bupivacaine with 100mg of 20%MgSo4 and 12.5mcg of dexmedetomidine respectively.Heart rate,mean arterial pressure,VAS score,time for first rescue analgesia were recorded postoperatively.Epidural analgesia was given when VAS score was more than 4. Results:VAS was significantly less in group BM,time for first rescue analgesia was more in group BM compared to group BD without any systemic side effects . Conclusion:Administration of Magnesium sulphate with bupivacaine provides prolonged postoperative analgesia compared with Dexmedetomidine without any systemic side effects.

IgG4 Related Sclerosing Inflammatory Pseudotumor Simulating Cholesteatoma Of The Temporal Bone

Introduction Sclerosing inflammatory pseudotumor of the temporal bone is a rare fibro-inflammatory, benign albeit locally aggressive pathological entity. Case Report We report a case of Sclerosing inflammatory pseudotumor of the temporal bone, simulating a cholesteatoma. A 61-year-old female presented with right otalgia, hearing loss, facial pain and imbalance. Ear microscopy revealed a pulsatile mass in the external auditory canal. HRCT temporal bone and MRI reported soft tissue mass in the right middle ear and mastoid air cells, causing attenuation of the ossicles with erosion through the tegmen and mastoid cortex. The patient underwent canal wall down tympanomastoidectomy. The histopathology with immunohistochemistry was consistent with IgG4 related sclerosing inflammatory pseudotumor. Discussion This case report explores the similarities as well as the clinical differences between cholesteatoma and IgG4 sclerosing inflammatory pseudotumor of temporal bone, along with the diagnostic and treatment challenges. It is often mistaken for neoplasm or cholesteatoma, hence should be considered as a differential diagnosis.