Histopathological Examination Of Tissues Research Articles

Bilateral hip ochronosis, an unsuspected diagnosis in polyarticular pain: A case report

Alkaptonuria is a rare metabolic disorder characterized by the accumulation of homogentisic acid, leading to the deposition of blackish pigment in cartilage and soft tissue, known as ochronosis. This can mimic multiple joint pathologies and is a diagnosis of exclusion. We describe the case of a 52-year-old woman who had a total hip replacement after experiencing left hip pain for which oral medications were unable to provide relief. Unexpectedly, during the procedure, a blackish tissue was noticed. This led to a histological examination and the confirmation of the ochronosis diagnosis. The patient’s medical history revealed a number of malignancies, but no previous metabolic illness diagnoses. Subsequent follow-up revealed rapid-onset pain in other joints, leading to a similar diagnosis of polyarticular ochronosis in the right hip, knees, spine, and shoulders. This highlights how difficult it is to treat this condition. This case underscores the importance of considering ochronosis as a differential diagnosis in patients with chronic polyarticular pain. Current treatment consists of initial non-surgical measures, including physical therapy and analgesics. If there is no improvement, treatment would be joint arthroplasty. Awareness among orthopedic surgeons and histopathological examination of tissues is crucial for the accurate diagnosis and management of ochronosis.

Metastatic onset of prostate carcinoma: A clinical and pathological challenge.

Prostate cancer is the second most common cancer, following lung cancer, and the fifth leading cause of cancer death in men worldwide. The onset of the disease, characterized by symptoms or changes caused by distant metastases, is rare and poses a challenge for clinicians and pathologists. We aimed to present a series of prostate carcinoma (PC) with unusual, histologically confirmed distant metastases (pM1) at the time of diagnosis, which raised suspicions of other types or origins of the primary tumor. Patients diagnosed with PC and distant metastases within a five-year timeframe (2017-2022) were extracted from the hospital database. The following data were collected: patient's age, imaging data, serum PSA level, and histopathological evaluation results. Patients with unusual distant metastases were selected and analyzed. We identified 10 patients in whom the diagnosis of PC was established following histopathological examination of tissue taken from distant metastatic sites (pM1). In three patients, the location of distant metastases was unusual: retroperitoneal, cranial/dural/epicranial and supradiaphragmatic lymph nodes which posed diagnostic challenges. Establishing the prostate origin of the tumor relied on immunohistochemical (IHC) investigation guided by clinical-imaging information. A metastasis of PC may rarely present as a cranial/dural tumor, retroperitoneal, or supradiaphragmatic lymphadenopathies in a man over the age of 50, but it should be taken into consideration. In the absence of correlated clinical, imaging, and histopathological/IHC data, diagnosing distant metastasis from PC is difficult, especially considering its potentially confusing IHC profile.

Influence of Health Literacy on Cancer Prognosis; A Case Report of Childhood Fibrosarcoma

Background: Cancer is an emerging global public health threat in low- and middle-income countries, and poor health literacy has resulted into poor outcomes due to late diagnosis and care. Fibrosarcoma is among the rare - highly malignant tumor with poor prognosis when diagnosed late. Its survival rate is estimated to be around 20% in Low- and middle-income countries (LMICs) as compared to more than 80% in high-income countries. Case presentation: Herein we report a case of 14-years-old boy with a relapsing mass in his left hand. It was initially thought to be benign and it was resected, but later confirmed by tissue histopathological examination to be an infantile fibrosarcoma. Limb salvage surgery was not possible only to end up with forearm amputation. Discussion: Health literacy of healthcare workers and community at large has an influence on outcome of cancer treatments, it reduces incidences of late diagnoses as primary physicians will have an increased suspicion for malignancies whenever they encounter such a mass especially in children. Most of fibrosarcoma are deemed unresectable at diagnosis hence necessitating a multimodal approach including preoperative cytoreductive therapy and surgery. Conclusion: Fibrosarcoma has good prognosis when diagnosed early. To prevent unfavorable cancer-related outcomes and to have good oncological outcomes; health literacy on soft tissue sarcomas should be promoted especially at the community level as it is the case in other types of cancers.

Transarterial chemoembolization (TACE) combined with donafenib as first-line therapy for unresectable hepatocellular carcinoma (uHCC): A real-world clinical study.

e16145 Background: To evaluate the efficacy and safety of TACE combined with Donafenib, which is as a new tyrosine kinase inhibitors therapy recommended by the China liver cancer staging (CNLC) system for the treatment of unresectable hepatocellular carcinoma (uHCC). Methods: We conducted a single-center, retrospective study on patients diagnosed with uHCC treated by TACE plus Donafenib as the first-line therapy between May 2021 and September 2023 at The First Affiliated Hospital of Sun Yat-sen University. The primary outcomes evaluated in this study were progression-free survival (PFS) and overall survival (OS). Local response, one-year survival rate, safety and tolerability were the secondary outcomes. Results: All of 48 eligible patients by August, 2023, with the median age of 59 years. The clinical characteristics were as follows: BCLC stage A:2 (4.2%), B:16 (33.3%), and C:30 (62.5%); Child-Pugh class A:33 (68.8%) and B:15 (31.2%); ECOG PS 0: 27 (56.2%) and 1: 21 (43.7%). In this study, 10 (20.8%) patients had huge intrahepatic lesions, 15 (31.2%) subjects exhibited extrahepatic metastases at multiple sites, 19 (42.2%) patients presented with portal vein tumor thrombus, and 4 patients were diffuse-type HCC.107 TACE sessions were performed. Three patients had liver transplantation as frequent therapy, and histopathological examination of tissue from these subjects revealed complete necrotic foci. The median PFS was 12.8 months (95% CI: 8.66–NA) , mOS was not reached and the one-year OS rate was 87.5% (95% CI: 77%-97%) in the survival results. The tumor objective response rate was 58.3% with 14.5% complete response and 43.7% partial response based on mRECIST assessment. The disease control rate of the study group was 81.3%. The most common treatment-related adverse events (TRAEs) observed were elevated aspartate aminotransferase (AST) levels (75.0%), increase in bilirubin level (72.9%), elevated alanine aminotransferase (ALT) levels (54.2%), hand-foot syndrome (53.1%), diarrhea (29.1%), rashes (22.9%), hair loss (18.4%) and hypertension (12.5%). Twenty-three (46.9%) patients presented with grade 3 or 4 TRAEs including elevated AST levels (22.4%), elevated ALT levels (16.3%), increase in bilirubin level (4%), diarrhea (4%) and hypertension (2%). No Grade 5 TRAEs were observed. Conclusions: The combination of TACE and Donafenib presented good efficacy and tolerability, which could be potentially used as the first-line treatment of Chinese uHCC patients.

Abstract 1022: Integration of cerebrospinal fluid methylome and proteome can obviate the need for biopsy in central nervous system lymphoma

Abstract Background: The diagnosis of intra-axial brain tumors requires histopathological examination of tissue obtained by neurosurgery in current clinical practice, which comes with inherent risks. Some patients, particularly those with primary CNS lymphoma (PCNSL), only undergo surgery to obtain a diagnosis and do not derive any therapeutic benefit from surgical resection or debulking. Less-invasive techniques for diagnosis, such as liquid biopsy, therefore provides an opportunity to mitigate surgical risk in these patients. Methods: Patients with histopathology confirmed glioblastoma (GBM, IDH wild type), brain metastases (BM), and PCNSL with accompanying cerebrospinal fluid (CSF) samples were included in our study. Cell-free DNA methylation profiling and shotgun proteomics were obtained for all patients and used to train classifiers to distinguish each tumour entity from others. Specifically, binomial elastic net regression models were built by combining both data modalities using established early and late integration paradigms and performance was compared to classifiers built from individual data types alone. Each model was repeated 100 fold and performance assessed on an untouched testing subset. Results: Our cohort includes 20 patients with GBM, 17 with BM, and 14 with PCNSL, each with matching CSF cell-free DNA methylation and shotgun proteomic profiling. We show that these data can be integrated to fully discriminate PCNSL from its major diagnostic counterparts with a perfect median AUC of 1.00 (95% CI 1-1) and 100% specificity. Integrated "lymphoma vs other" models significantly outperform models trained on methylation or protein data alone, though the same dramatic improvement was not demonstrated in GBM or BM, suggesting synergistic biological information is specific to lymphoma. Conclusions: There is a critical need to diagnose patients with intra-axial tumours, particularly PCNSL, without relying on invasive and costly surgery. We present the most specific and accurate CNS lymphoma classifier to date by integrating the methylome and proteome of CSF. This has the potential for immediate clinical utility, eliminating the need for biopsy in an important subset of these patients. Citation Format: Alex P. Landry, Jeffrey A. Zuccato, Vikas Patil, Mathew Voisin, Justin Z. Wang, Yosef Ellenbogen, Chloe Gui, Andrew Ajisebutu, Farshad Nassiri, Gelareh Zadeh. Integration of cerebrospinal fluid methylome and proteome can obviate the need for biopsy in central nervous system lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1022.

Consensus guidelines for the management of adult low-grade gliomas for low and middle-income countries.

Low-grade gliomas (LGG) are brain tumors of glial cells origin. They are grade 1 and grade 2 tumors according to the WHO classification. Diagnosis of LGG is made through imaging, histopathological analysis, and use of molecular markers. Imaging alone does not establish the grade of the tumor and thus a histopathological examination of tissue is crucial in establishing the definite histopathological diagnosis. Clinical presentation varies according to the location and size of the tumor. Surgical resection is strongly recommended in LGG over observation to improve overall survival as surgery leads to greater benefit due to progression-free survival. Radiation has shown benefits in LGG patients in randomized controlled trials and chemotherapy with temozolomide has also shown good results. This paper covers the principles of low-grade gliomas management and summarizes the recommendations for the LMICs.

Improved intervertebral fusion in LLIF rabbit model with a novel titanium cage

BACKGROUND CONTEXTThere is no established small animal approach model for the strict simulation of lateral lumbar interbody fusion (LLIF) surgery. PURPOSEThis study aims to establish a reliable LLIF rabbit model that strictly simulates the procedure and to preliminarily evaluate the differences in fusion outcomes with different graft materials. STUDY DESIGNA controlled laboratory. METHODSFifty-four 4-month-old white New Zealand female and male rabbits were selected and divided into five groups: Group A (dissection group) consisted of 9 rabbits, Group B (normal approach group) consisted of 9 rabbits, Group C (autogenous iliac bone group) consisted of 12 rabbits, Group D (BMP-2 carrier material group) consisted of 12 rabbits, and Group E (allograft bone group) consisted of 12 rabbits. Based on data from Group A, a novel titanium metal fusion device was designed. Postoperatively, at the 12-week mark, manual palpation was employed to compare the interbody fusion status among Groups B, C, D, and E. Specimens from Groups C, D, and E were subjected to Micro-CT scanning to compare various parameters such as trabecular bone volume (BV), bone volume fraction (BV/TV, BVF), and bone surface area (BS). Furthermore, a tissue histopathological examination was performed to observe the structure and morphology of newly formed bone within the fusion mass as well as the remodeling of the graft in each group. RESULTSBased on the measurements obtained from the dissection group, we designed a U-shaped interbody fusion device with dimensions of 10 mm in length, 2.5 mm in width, and 1.3 mm in height. In Group B, 9 cases exhibited intervertebral mobility. In Group C, 1 case showed nonfusion. In Group D, all cases achieved fusion. In Group E, 4 cases did not achieve fusion. Additionally, the Micro-CT results showed that the interbody fusion index scores were 4.64±0.50 in Group C, 4.33±0.65 in Group D, and 3.36±0.81 in Group E. There was no statistically significant difference in fusion index scores between Groups C and D (p=.853). Notably, Groups C and D had higher scores than Group E (p<.001). The trabecular bone volume (BV) in Groups C and D also showed no significant difference but was significantly higher than in Group E (p<.001). Furthermore, the histopathological results revealed that the specimens from Group E had less newly formed cartilage and bone compared to Groups C and D. CONCLUSIONSThis study successfully established a strict simulation of the clinical LLIF procedure in a rabbit model. Moreso, we conducted a preliminary validation indicating that the BMP-2 carrier material achieved interbody fusion outcomes similar to autogenous iliac bone. CLINICAL SIGNIFICANCEThe findings of this investigation from animal models provide a theoretical basis for the clinical use of BMP-2 to promote early spinal fusion in LLIF procedures. Importantly, the study provides a small animal model foundation for research related to LLIF surgery.

Varied etiology in patients presenting with non-puerperal mastitis: an observational study

Abstract Introduction: The etiology of nonpuerperal mastitis is more diverse varying from infections to autoimmune disorders. Most of them are misdiagnosed as pyogenic mastitis and are treated with routine antibiotics. In this study the various causes of nonpuerperal mastitis which required surgical intervention were evaluated. It was observed that some of the pre-malignant and malignant conditions were also presented as nonpuerperal mastitis. Materials and methods: All non-lactating women who presented with symptoms and signs of mastitis and did not respond to single course of antibiotics (active against staphylococcus) treated in tertiary care Hospital and in private practice of primary author between June 2021 to December 2022 and in those in whom the ultrasound of breast was also suggestive of inflammatory breast disease were included in the study and rest were excluded from study. The final etiological diagnosis of these patients is given by the histopathological examination of tissue taken from the wall of abscess cavity or of breast mass. Results: Total 21 patients were included in the study of which 7 patients had nonspecific infection, 3 patients were diagnosed to have tuberculous mastitis, 3 patients with idiopathic granulomatous mastitis, 2 patients with periductal mastitis, 1 patient with fat necrosis, 3 patients with atypical ductal hyperplasia and 2 patients were diagnosed to have invasive duct cell carcinoma. Conclusion: The etiology of nonpuerperal mastitis is diverse. Not only the benign conditions but premalignant conditions like ADH, DCIS and even invasive carcinoma can present with clinical symptoms and signs of inflammatory breast disease.

Texture analysis using short-tau inversion recovery magnetic resonance images to differentiate squamous cell carcinoma of the gingiva from medication-related osteonecrosis of the jaw.

Despite the difficulty in distinguishing between squamous cell carcinoma (SCC) and medication-related osteonecrosis of the jaw (MRONJ) on the basis of medical imaging examinations, the two conditions have completely different treatment methods and prognoses. Therefore, differentiation of SCC from MRONJ on imaging examinations is very important. This study aimed to distinguish SCC from MRONJ by performing texture analysis using magnetic resonance imaging (MRI) short-tau inversion recovery images. This retrospective case-control study included 14 patients with SCC of the lower gingiva and 35 with MRONJ of the mandible who underwent MRI and computed tomography (CT) for suspected SCC or MRONJ. SCC was identified by histopathological examination of tissues excised during surgery. The radiomics features of SCC and MRONJ were analyzed using the open-access software MaZda version 3.3 (Technical University of Lodz, Institute of Electronics, Poland). CT was used to evaluate the presence or absence of qualitative findings (sclerosis, sequestrum, osteolysis, periosteal reaction, and cellulitis) of SCC and MRONJ. Among the 19 texture features selected using MaZda feature-reduction methods, SCC of the gingiva and MRONJ of the mandible revealed differences in two histogram features, one absolute gradient feature, and 16Gy level co-occurrence matrix features. In particular, the percentile, angular second moment, entropy, and difference entropy exhibited excellent diagnostic performance. Non-contrast-enhanced MRI texture analysis revealed differences in texture parameters between mandibular SCC and mandibular MRONJ. MRI texture analysis can be a new noninvasive quantitative method for distinguishing between SCC and MRONJ.

Immunohistochemical investigation of FIPV3-70 antigen expression in the ileum of cats with effusive feline infective peritonitis

Abstract One of the most common infectious causes of cat mortality is feline infective peritonitis (FIP), along with panleukopenia and viral upper respiratory tract infections. FIP is more likely to affect cats whose immune system is weak or suppressed. It is thought that the infection of macrophages and monocytes plays a major role in the pathogenic process. In order to set a definitive diagnosis for this infectious disease, a histopathological examination of tissues, and feline coronavirus (FCoV) detection by immunohistochemistry (IHC) is necessary. In this investigation, 15 cats between the ages of 5 and 24 months with clinical suspicion of FIP, underwent post-mortem necropsy, pathohistological and immunohistochemical examination. The results showed that all the cats had abdominal effusion with pyogranulomas throughout the abdominal serosa. Ten out of fifteen cats were FIP positive using immunohistochemical methods. This method also showed the antigen deposition in the macrophages thus confirming their role in the pathogenesis of FIP.

Diagnostic capacity for cutaneous fungal diseases in the African continent.

Cutaneous fungal infections are very common, especially in poorer communities and with intercurrent HIV infection. Determining the fungal pathogen in skin-related fungal neglected tropical diseases (NTDs) determines optimal therapy. We undertook a country survey across many African countries to determine the diagnostic capacity for skin fungal diseases. A detailed questionnaire was delivered to country contacts to collect data on availability, frequency, and location of testing for key diagnostic procedures and followed up with 2 rounds of validation by video call and by confirmation of individual country data confirmation by email. Of 47 countries with data, seven (15%) and 21 (45%) do not offer skin biopsy in the public or private sector, respectively, but 22 (46%) countries do it regularly, mostly in university hospitals. Direct microscopy is often performed in 20 of 48 (42%) countries in the public sector and not done in 10 (21%). Fungal cultures are often performed in 21 of 48 (44%) countries in the public sector but not done in nine (20%) or 21 (44%) in either public or private facilities. Histopathological examination of tissue is frequently used in 19 of 48 (40%) countries but not in nine (20%) countries in the public sector. The cost of diagnostics to patients was a major limiting factor in usage. Major improvements in the availability and use of diagnostic tests for skin, hair, and nail fungal disease are urgently needed across Africa.

Unveiling the Enigmatic Nature of Disseminated Rhinosporidiosis: Insights and Challenges of the recurrent menace.

Rhinosporidiosis is an endemic condition in India that is difficult to treat when it is disseminated. This condition commonly affects the nasal cavity and nasopharynx mucosa, accounting for 75% of the clinical cases. Although rare, rhinosporidiosis can present with only cutaneous involvement without mucosal disease. Symptoms of this condition include complaints of nasal obstruction and episodic nasal bleeding. Diagnosis is achieved through histopathological examination of tissue and demonstration of the sporangium. Rhinosporidiosis tends to recur as it spreads through autoinoculation. Therefore, during endonasal endoscopic excision of the mass, it is essential not to injure the surrounding mucosa. A trial of medical therapy with dapsone is advised, but it is mostly ineffective in cases of disseminated disease. Here, we present a case report of a patient who underwent seven surgeries for the same condition over 12 years but was unable to get rid of the recurrent menace.

Deletion of Emc1 in photoreceptor cells causes retinal degeneration in mice.

The endoplasmic reticulum membrane protein complex (EMC) plays a critical role in the synthesis of multi-pass membrane proteins. Genetic studies indicated that mutations in EMC1 gene were associated with retinal degeneration diseases, however the role of EMC1 in photoreceptor has not been proved. Here, we show that Emc1 ablation in the photoreceptor cells of mice recapitulated the retinitis pigmentosa (RP) phenotypes, including an attenuated scotopic electroretinogram (ERG) response and the progressive degeneration of rod cells and cone cells. Histopathological examination of tissues from rod-specific Emc1 KO (RKO) mice revealed mislocalized rhodopsin and irregularly arranged cone cells at the age of 2 months. Further immunoblotting analysis revealed decreased levels of membrane proteins and ER chaperones in 1-month-old RKO retinae, and this led us to speculate that the loss of membrane proteins is the main cause of the degeneration of photoreceptors. EMC1 most likely regulated the membrane protein levels at an earlier step in the biosynthetic process before the proteins translocated into the ER. Our study demonstrates the essential roles of Emc1 in photoreceptor cells, and reveals the mechanism through which EMC1 mutations are linked to RP.

The importance of history in pediatric soft tissue swellings: a case of rhabdomyosarcoma with initial diagnosis of hemangioma

Clinicians often encounter soft tissue swellings in children, which can be benign or malignant in nature. Significant emphasis placed on radiological findings may skew clinical judgement. This cascade often leads to overlooking other differential diagnoses and the natural history of these soft tissue masses. We discuss the case of a 2-year-old child with a swelling over her left upper back. Swelling was first noticed at 6 months old, and grew progressively larger after age of one. Two ultrasounds performed reported the mass as an infantile hemangioma. It reached a point where the child could no longer lie supine due to the huge size of the mass. MRI of the back was ordered, and findings were suggestive of a posterior chest wall soft tissue sarcoma with lung metastases. Histopathological examination of tissue obtained from trucut biopsy confirmed the diagnosis of embryonal rhabdomyosarcoma stage 4. In this scenario, the natural history of soft tissue swelling was atypical of hemangioma. However, there was lapse in clinical judgement, as radiological findings were consistent with diagnosis, not once but twice. This conglomeration of factors led to unfortunate delay in diagnosis. When faced with soft tissue swellings in children, a thorough correlation between history, clinical examination, and imaging studies required to form holistic picture, for betterment of patient outcome.

Autoantibody screening of plasma and peritoneal fluid of patients with endometriosis.

Are there specific autoantibody profiles in patients with endometriosis that are different from those in controls? This study did not reveal a significantly higher prevalence of autoantibodies in the studied groups of patients. Various inflammatory factors are postulated to be involved in the pathomechanisms of endometriosis, and a potential link exists with autoimmune diseases, which may also play an important role. As the diagnosis of endometriosis remains invasive, it can only be confirmed using laparoscopy with histopathological examination of tissues. Numerous studies have focused on identifying useful biomarkers to confirm the disease, but without unequivocal effects. Autoantibodies are promising molecules that serve as potential prognostic factors. A multicentre, cross-sectional study was conducted over 18 months (between 2018 and 2019), at eight Departments of Obstetrics and Gynaecology in several cities across Poland on 137 patients undergoing laparoscopic examination for the diagnosis of endometriosis. During laparoscopy, we obtained plasma samples from 137 patients and peritoneal fluid (PF) samples from 98 patients. Patients with autoimmune diseases were excluded from the study. Autoantibody profiling was performed using HuProt v3.1 human proteome microarrays. We observed no significant differences in the expression of autoantibodies in the plasma or PF between the endometriosis and control groups. The study revealed that in the PF of women with Stage II endometriosis, compared with other stages, there were significantly higher reactivity signals for ANAPC15 and GABPB1 (adj. P < 0.016 and adj. P < 0.026, respectively; logFC > 1 in both cases). Comparison of the luteal and follicular phases in endometriosis patients revealed that levels of NEIL1 (adj. P < 0.029), MAGEB4 (adj. P < 0.029), and TNIP2 (adj. P < 0.042) autoantibody signals were significantly higher in the luteal phase than in the follicular phase in PF samples of patients with endometriosis. No differences were observed between the two phases of the cycle in plasma or between women with endometriosis and controls. Clustering of PF and plasma samples did not reveal unique autoantibody profiles for endometriosis; however, comparison of PF and plasma in the same patient showed a high degree of concordance. Although this study was performed using the highest-throughput protein array available, it does not cover the entire human proteome and cannot be used to study potentially promising post-translational modifications. Autoantibody levels depend on numerous factors, such as infections; therefore the autoantibody tests should be repeated for more objective results. Although endometriosis has been linked to different autoimmune diseases, it is unlikely that autoimmune responses mediated by specific autoantibodies play a pivotal role in the pathogenesis of this inflammatory disease. Our study shows that in searching for biomarkers of endometriosis, it may be more efficient to use higher-throughput proteomic microarrays, which may allow the detection of potentially new biomarkers. Only research on such a scale, and possibly with different technologies, can help discover biomarkers that will change the method of endometriosis diagnosis. This study was funded by a grant from the Polish Ministry of Health (grant no. 6/6/4/1/NPZ/2017/1210/1352). It was also funded by the Estonian Research Council (grant PRG1076) and the Horizon 2020 Innovation Grant (ERIN; grant no. EU952516), Enterprise Estonia (grant no. EU48695), and MSCA-RISE-2020 project TRENDO (grant no. 101008193). The authors declare that there is no conflict of interest. N/A.

Microbiology Profile of COVID-19-Associated Rhino-Orbital Mucormycosis Pathogens in South India.

This study describes the microbiological and histopathological features of patients with COVID-19-associated rhino-orbital mucormycosis (ROM) seen at the L V Prasad Eye Institute between May and August 2021. Diagnosed clinically and radiologically, 24 patients with ROM were included in the study. Deep nasal swabs or endoscopically collected nasal swabs or orbital tissues were submitted for microbiological evaluation and invitro susceptibility testing by microbroth dilution for natamycin, amphotericin B, caspofungin, posaconazole, ketoconazole, and voriconazole. Cultures were processed by 28S ribosomal DNA polymerase chain reaction and molecular sequencing. A portion of orbital tissues was also sent for histopathological evaluation. The age of the patients ranged from 27 to 75 (mean 48.58 ± 14.09) years and the majority (79%) were male. Nineteen patients were known to be diabetic prior to developing ROM and 18 patients had recovered from active COVID-19 infection. Thirteen patients had a history of hospitalization during COVID-19 infection and eight received steroids. Of the 24 samples, microbiological evaluation identified Rhizopus arrhizus in 12, Rhizopus microsporus in 9, Lichtheimia ramosa in 2, and Rhizopus delemar in 1. Twelve isolates were tested for antifungal susceptibility and all were susceptible to natamycin and amphotericin B. The susceptibility to posaconazole was high, with minimum inhibitory concentration (MIC) < 2 µg/mL for 10/12 (84%) isolates, whereas the MIC of other drugs varied. Histopathological examination of tissues showed acute fulminant disease, granuloma formation, and vascular invasion by the fungal pathogens in these specimens. Rhizopus arrhizus was predominantly associated with ROM and most isolates were susceptible to amphotericin B and posaconazole. Further studies are needed to corroborate the findings and explain possible underlying links.

Natural infection with Toxoplasma gondii, Neospora caninum and Sarcocystis species in domestic pigeons (Columba livia domestica) in Iran

Pigeons are common birds around the world and may act as intermediate hosts of the tissue cyst-forming apicomplexan parasites Toxoplasma gondii, Neospora caninum and Sacrocystis spp. This study aimed to provide an overview on the prevalence of and exposure to these parasites in Iranian domestic rock pigeon (Columba livia domestica) through molecular, serological and histopathological examination. Blood and tissue samples (i.e., brain, heart, gizzard, neck, thigh, and pectoral muscles) were taken from 100 pigeons. Sera were screened by agglutination tests for detection of anti- T. gondii and N. caninum antibodies, genomic DNA from tissue samples were assessed by respective species-specific PCRs, and histopathological examination of tissues was carried out. A seroprevalence of 45 % to anti-T. gondii and 35 % to anti-N. caninum IgG was recorded. PCR detected T. gondii DNA in 28 pigeons. Sacrocystis spp. was detected in one animal, but sequencing of the 28 S rRNA gene product did not reveal the identity of the species. Histopathology revealed myocarditis, myositis, and gliosis in the heart, skeletal muscles, and brain, respectively. No Sarcocystis tissue-cysts were detected, but T. gondii tissue cyst-like structures in the brain (i.e., 4 %) and heart (i.e., 3 %) were found by histology. Data reported herein demonstrate that pigeons from Iran are infected with tissue cyst-forming apicomplexans, particularly T. gondii. Since domestic pigeons are in close contact with human populations, and consumption of their meat and egg is popular in different societies, control strategies for minimizing the risk of infection in both pigeons and humans are suggested.

Clinical Diagnosis of Pleuroparenchymal Fibroelastosis

Pleuroparenchymal fibroelastosis (PPFE) is an extremely rare interstitial lung disease (ILD) characterised by fibroelastotic changes predominating in the subpleural lung parenchyma with visceral pleural fibrosis involving the upper lobes. It has distinctive clinical, radiological, and pathological manifestations. Diagnosis constitutes literally a stalemate because of its rarity, unavailability of an agreed diagnostic consensus, and requirement of tissue biopsy for an accurate final diagnosis that can not be performed in most of the patients owing to the comorbid complications of the disease itself. Identification of PPFE may also pose great difficulties due to the coexistence of other interstitial lung diseases. PPFE usually exhibits a persistently deteriorating prognostic course culminating in fatal complications including respiratory failure, pulmonary hypertension, cor pulmonale, or pneumothorax. Presence of disease relevant complications frequently preclude invasive tissue biopsy interventions in these patients leading to a diagnostic challenge for clinicians. This review aims to provide a definitive diagnosis based on entirely the clinical manifestatins of PPFE by shedding light on the pathogenesis, clinical, and radiologic findings of the disease. Histopathological tissue evaluation was also included in the diagnostic approach for patients whose condition was suitable for an invasive biopsy intervention. With this review, it is concluded that an approach consisting of exclusively clinical manifestations will ensure adequate support for an accurate PPFE diagnosis without any requirement for histopathological tissue examination.

Timing and mid-term outcomes of using leadless pacemakers as replacement for infected cardiac implantable electronic devices.

Cardiac implantable electronic device (CIED) infections have a high morbidity and mortality and are an indication of device extraction. As a replacement, leadless pacemakers (LPs) may be preferable due to a low infection risk, but mid-term data on reinfections is lacking. Moreover, early LP reimplantation in pacemaker-dependent patients would circumvent the need for temporary pacemakers. We included all patients with LP implantation as a replacement for an infected CIED, between January 2013 and December 2021. The occurrence of reinfection was assessed during standard follow-up visits. Twenty-nine patients (mean age 81 ± 9years) were included, of which 21 (73%) had a pocket infection, 7 (24%) endocarditis, and 1 (3%) a systemic infection without endocarditis. All LP implantations were successful. LPs were implanted before extraction (n = 4, 13%), simultaneously with extraction (n = 5, 17%) and after extraction (n = 20, 70%). No reinfection occurred during the follow-up of median 32months (IQR 13-66months). Repeat blood cultures obtained in 9 (30%) patients and transthoracic echocardiography in all 7 patients with pacemaker endocarditis were negative for reinfection. In a subset of 6 LPs extracted during follow-up due to early battery depletion, prophylactically after the battery advisory or due to non-capture (median 36months (range 0-67months) post-implantation), histopathologic examination of tissues around the LPs showed no signs of infection. After replacing infected CIEDs for an LP, no reinfections occurred in over 2.5years follow-up. These results confirm that in case of CIED infection, the LP is an appealing replacement device. LP implantation before CIED extraction is feasible.

C ase Series of C ardiac M etastasis in Experience, Tertiary Care Centre

The incidence of secondary cardiac tumouris 2.3% in previous autopsies studies. Common metastasizing tumours to the heart are lung, esophagus, breast, stomach, pancreas, melanoma, and colon. The oral sqaumous cell carcinoma metastasizing to the heart are r eported in few cases. we are presenting three cases, Out of which two cases of a 51yearold and 59yearold deceased male previously diagnosed with upper esophagus and Larynx squamous cell carcinoma, found having multiple metastatic lesions of lung, liver as well as metastatic foci to the heart in histopathological examination of tissues received after conducting autopsy. Another single case of 28 yearold female of adenocarcinoma of unknown origin,possibility of ovarian origin, which shows metastasis to all major organs including heart. The involvement was limited to the myocardium with a normal pericardium and endocardium, which is not common. The case details and relevant clinical discussion of all three cases are described to highlight asymptomatic, me tastatic foci of oral as well as laryngeal squamous cell carcinoma to myocardium and one case of adenocarcinoma of unknown origin. Keywords: Cardiac metastasis, secondary cardiac tumors 140 /pISSN:22316140, eISSN:23957859 Case Series