Fatal asphyxia due to large laryngeal granuloma.

Laryngeal granuloma, vocal process granuloma, or post-intubation granuloma are benign, inflammatory lesions of the arytenoid cartilage vocal process. The etiology of laryngeal granulomas is multifactorial, such as chronic irritation due to endotracheal intubation, vocal cord injury or trauma, and gastroesophageal reflux disease. They can arise postoperatively after mucosal injury due to orotracheal intubation. Clinical manifestations include voice change and dyspnea, which may start one to four months after extubation and may rarely lead to asphyxia. We presented a case of death due to glottic granuloma occurring after a surgical procedure to remove a laryngeal polyp attributed to previous laryngeal injuries by multiple intubations.

Characterization of tumors of jaw: Additive value of contrast enhancement and dual-energy computed tomography.

BACKGROUND: Currently, the differentiation of jaw tumors is mainly based on the lesion's morphology rather than the enhancement characteristics, which are important in the differentiation of neoplasms across the body. There is a paucity of literature on the enhancement characteristics of jaw tumors. This is mainly because, even though computed tomography (CT) is used to evaluate these lesions, they are often imaged without intravenous contrast. This study hypothesised that the enhancement characteristics of the solid component of jaw tumors can aid in the differentiation of these lesions in addition to their morphology by dual-energy CT, therefore improving the ability to differentiate between various pathologies. AIM: To evaluate the role of contrast enhancement and dual-energy quantitative parameters in CT in the differentiation of jaw tumors. METHODS: Fifty-seven patients with jaw tumors underwent contrast-enhanced dual-energy CT. Morphological analysis of the tumor, including the enhancing solid component, was done, followed by quantitative analysis of iodine concentration (IC), water concentration (WC), HU, and normalized IC. The study population was divided into four subgroups based on histopathological analysis-central giant cell granuloma (CGCG), ameloblastoma, odontogenic keratocyst (OKC), and other jaw tumors. A one-way ANOVA test for parametric variables and the Kruskal-Wallis test for non-parametric variables were used. If significant differences were found, a series of independent t-tests or Mann-Whitney U tests were used. RESULTS: Ameloblastoma was the most common pathology (n = 20), followed by CGCG (n = 11) and OKC. CGCG showed a higher mean concentration of all quantitative parameters than ameloblastomas (P < 0.05). An IC threshold of 31.35 × 100 µg/cm3 had the maximum sensitivity (81.8%) and specificity (65%). Between ameloblastomas and OKC, the former showed a higher mean concentration of all quantitative parameters (P < 0.001), however when comparing unilocular ameloblastomas with OKCs, the latter showed significantly higher WC. Also, ameloblastoma had a higher IC and lower WC compared to "other jaw tumors" group. CONCLUSION: Enhancement characteristics of solid components combined with dual-energy parameters offer a more precise way to differentiate between jaw tumors.

Visual, rapid, and cost-effective BK virus detection system for renal transplanted patients using gold nanoparticle coupled loop-mediated isothermal amplification (nanoLAMP).

A substantial percentage of kidney transplant recipients show transplant failure due to BK virus-induced nephropathy. This can be clinically controlled by the rapid and timely detection of BK virus infection in immune-compromised patients. We report a rapid (two hours from sample collection, processing, and detection), cost-effective (< 2$), highly sensitive and BKV-specific nanoLAMP (loop-mediated isothermal amplification) diagnostic methodology using novel primers and gold nanoparticles complex-based visual detection. The standardized nanoLAMP showed an analytical sensitivity of 25 copies/µl and did not cross-react with closely related JC and SV40 viruses. This nanoLAMP showed diagnostic sensitivity and specificity as 91% and 96%, respectively, taking 50 BK virus-negative (confirmed by qPCR from the plasma of healthy donors) and 57 positive BKV patient samples (confirmed by clinical parameters and qPCR assay). This simple two-step, low-cost, and quick (1-2 h/test) detection would be advantageous over the currently used diagnostic methodology. It may change the paradigm for polyomavirus infection-based failure of renal transplant.

Treatment outcomes in patients with Ewing sarcoma of the spine in a resource-challenged setting: 17-year experience from a single center in India.

Ewing sarcoma (ES) of the spine is a rare childhood cancer with sparse literature on treatment outcomes. We aimed to describe survival outcomes and prognostic factors in patients with spinal ES treated at a single institute in a resource-challenged setting. We conducted a retrospective analysis of patients with spinal ES registered at a tertiary care oncology center between 2003-2019. Clinical patient data was retrieved from hospital records. Cox regression analysis was used to identify the association of baseline clinical parameters with event free survival (EFS) and overall survival (OS). A cohort of 85 patients was analyzed including 38 (45%) patients with metastatic disease. The median age was 15 years with 73% being male. Local therapy was administered in 62 (72.9%) patients with surgery alone in 8 (9.4%), radiotherapy alone in 36 (42.4%) and both in 18 (21.2%) patients. A higher proportion of males received local therapy than females (80.3% versus 59.1%; p = 0.049). The median EFS and OS were 20.1 and 28.6 months, respectively. On univariable analysis, age ≤ 15 years, female sex, serum albumin ≤3.5 g/dL and hemoglobin ≤11 g/dL were associated with inferior EFS while younger age, female sex, hypoalbuminemia and metastatic disease were associated with inferior OS. On multivariable analysis, only hypoalbuminemia was predictive for inferior EFS (HR:2.41; p = 0.005) while hypoalbuminemia (HR:2.06;p = 0.033) and female sex (HR:1.83; p = 0.046) were associated with inferior OS. We concluded that hypoalbuminemia confers poor prognosis in ES spine. Survival outcomes are poorer in females treated in our setting, possibly due to prevailing sex-based biases.

Fatal asphyxia due to large laryngeal granuloma

ABSTRACT Laryngeal granuloma, vocal process granuloma, or post-intubation granuloma are benign, inflammatory lesions of the arytenoid cartilage vocal process. The etiology of laryngeal granulomas is multifactorial, such as chronic irritation due to endotracheal intubation, vocal cord injury or trauma, and gastroesophageal reflux disease. They can arise postoperatively after mucosal injury due to orotracheal intubation. Clinical manifestations include voice change and dyspnea, which may start one to four months after extubation and may rarely lead to asphyxia. We presented a case of death due to glottic granuloma occurring after a surgical procedure to remove a laryngeal polyp attributed to previous laryngeal injuries by multiple intubations.

Fibro-Adipose Vascular Anomaly (FAVA): Not Another Vascular Anagram.

Background. Fibro-adipose vascular anomaly (FAVA) is a rare benign mesenchymal lesion. Characterized primarily by intramuscular vascular malformation with secondary overgrowth of other mesenchymal elements, particularly fibro-adipose tissue, the condition is sometimes complicated by nonspecific clinical and imaging features, causing diagnostic dilemma. Herein, we attempted to outline and correlate the clinical characteristics, imaging findings, and histopathological features of this unusual entity. Method. The study design was retrospective in nature. Computerized database of our institute was searched for tumors, and archived slides were reviewed. Pertinent clinical data including imaging findings and treatment details were also recovered for correlation. Result. Among total of 24 patients identified, mean age was approximately 16 years, with the presence of nearly equal gender distribution. Pain along with swelling was most common symptoms with the presence of movement limitation, in few. Most lesions were long-standing and anatomically confined to lower limb with no side predilection. Using imaging, the majority of the lesions were identified as vascular anomaly or venous malformation, with FAVA being a differential diagnosis in few lesions. However, in a couple of patients, likelihood of mesenchymal tumors was also suggested, radiologically. On histology, the lesions showed the presence of clustered back to back, abnormal thin-walled, variably dilated, blood-filled sac-like vessels amid skeletal muscle bundles, along with extensive fibro-adipose tissue and variably atrophic skeletal muscle bundles, at the periphery, diagnostic of FAVA. Conclusion. Owing to the presence of overlapping clinical and imaging features, FAVA is often misdiagnosed, causing dilemma in clinical management. Clinical, radiological, and histopathological correlation is thereby warranted for clinching the correct diagnosis.

Chemotherapy response evaluation using diffusion weighted MRI in Ewing Sarcoma: A single center experience.

BACKGROUND: Non-invasive biomarkers for early chemotherapeutic response in Ewing sarcoma family of tumors (ESFT) are useful for optimizing existing treatment protocol. PURPOSE: To assess the role of diffusion-weighted magnetic resonance imaging (MRI) in the early evaluation of chemotherapeutic response in ESFT. MATERIAL AND METHODS: A total of 28 patients (mean age = 17.2 ± 5.6 years) with biopsy proven ESFT were analyzed prospectively. Patients underwent MRI acquisition on a 1.5-T scanner at three time points: before starting neoadjuvant chemotherapy (baseline), after first cycle chemotherapy (early time point), and after completion of chemotherapy (last time point). RECIST 1.1 criteria was used to evaluate the response to chemotherapy and patients were categorized as responders (complete and partial response) and non-responders (stable and progressive disease). Tumor diameter, absolute apparent diffusion coefficient (ADC), and normalized ADC (nADC) values in the tumor were measured. Baseline parameters and relative percentage change of parameters after first cycle chemotherapy were assessed for early detection of chemotherapy response. RESULTS: The responder:non-responder ratio was 21:7. At baseline, ADC ([0.864 ± 0.266 vs. 0.977 ± 0.246]) × 10-3mm2/s; P = 0.205) and nADC ([0.740 ± 0.254 vs. 0.925 ± 0.262] × 10-3mm2/s; P = 0.033) among responders was lower than the non-responders and predicted response to chemotherapy with AUCs of 0.6 and 0.735, respectively. At the early time point, tumor diameter (27% ± 14% vs. 4.6% ± 10%; P = 0.002) showed a higher reduction and ADC (75% ± 44% vs. 52% ± 72%; P = 0.039) and nADC (81% ± 44% vs. 48% ± 67%; P = 0.008) showed a higher increase in mean values among responders than the non-responders and identified chemotherapy response with AUC of 0.890, 0.723, and 0.756, respectively. CONCLUSION: Baseline nADC and its change after the first cycle of chemotherapy can be used as non-invasive surrogate markers of early chemotherapeutic response in patients with ESFT.

Contrast-enhanced multidetector computed tomography features and histogram analysis can differentiate ameloblastomas from central giant cell granulomas.

BACKGROUND: No qualitative or quantitative analysis of contrast-enhanced computed tomography (CT) images has been reported for the differentiation between ameloblastomas and central giant cell granulomas (CGCGs). AIM: To describe differentiating multidetector CT (MDCT) features in CGCGs and ameloblastomas and to compare differences in enhancement of these lesions qualitatively and using histogram analysis. METHODS: MDCT of CGCGs and ameloblastomas was retrospectively reviewed to evaluate qualitative imaging descriptors. Histogram analysis was used to compare the extent of enhancement of the soft tissue. Fisher's exact tests and Mann-Whitney U test were used for statistical analysis (P < 0.05). RESULTS: Twelve CGCGs and 33 ameloblastomas were reviewed. Ameloblastomas had a predilection for the posterior mandible with none of the CGCGs involving the angle. CGCGs were multilocular (58.3%), with a mixed lytic sclerotic appearance (75%). Soft tissue component was present in 91% of CGCGs, which showed hyperenhancement (compared to surrounding muscles) in 50% of cases, while the remaining showed isoenhancement. Matrix mineralization was present in 83.3% of cases. Ameloblastomas presented as a unilocular (66.7%), lytic (60.6%) masses with solid components present in 81.8% of cases. However, the solid component showed isoenhancement in 63%. No matrix mineralization was present in 69.7% of cases. Quantitatively, the enhancement of soft tissue in CGCG was significantly higher than in ameloblastoma on histogram analysis (P < 0.05), with a minimum enhancement of > 49.05 HU in the tumour providing 100% sensitivity and 85% specificity in identifying a CGCG. CONCLUSION: A multilocular, lytic sclerotic lesion with significant hyperenhancement in soft tissue, which spares the angle of the mandible and has matrix mineralization, should indicate prospective diagnosis of CGCG.

Ultracellular Imaging of Bronchoalveolar Lavage from Young COVID-19 Patients with Comorbidities Showed Greater SARS-COV-2 Infection but Lesser Ultrastructural Damage Than the Older Patients.

In this study, we examined the cellular infectivity and ultrastructural changes due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the various cells of bronchoalveolar fluid (BALF) from intubated patients of different age groups (≥60 years and <60 years) and with common comorbidities such as diabetes, liver and kidney diseases, and malignancies. BALF of 79 patients (38 cases >60 and 41 cases <60 years) were studied by light microscopy, immunofluorescence, scanning, and transmission electron microscopy to evaluate the ultrastructural changes in the ciliated epithelium, type II pneumocytes, macrophages, neutrophils, eosinophils, lymphocytes, and anucleated granulocytes. This study demonstrated relatively a greater infection and better preservation of subcellular structures in these cells from BALF of younger patients (<60 years compared with the older patients (≥60 years). The different cells of BALF from the patients without comorbidities showed higher viral load compared with the patients with comorbidities. Diabetic patients showed maximum ultrastructural damage in BALF cells in the comorbid group. This study highlights the comparative effect of SARS-CoV-2 infection on the different airway and inflammatory cells of BALF at the subcellular levels among older and younger patients and in patients with comorbid conditions.

Protocol for Developing a Femur Osteotomy Model in Wistar Albino Rats.

Fracture healing is a physiological process resulting in the regeneration of bone defects by the coordinated action of osteoblasts and osteoclasts. Osteoanabolic drugs have the potential to augment the repair of fractures but have constraints like high costs or undesirable side effects. The bone healing potential of a drug can initially be determined by in vitro studies, but in vivo studies are needed for the final proof of concept. Our objective was to develop a femur osteotomy rodent model that could help researchers understand the development of callus formation following fracture of the shaft of the femur and that could help establish whether a potential drug has bone healing properties. Adult male Wistar albino rats were used after Institutional Animal Ethics Committee clearance. The rodents were anesthetized, and under aseptic conditions, complete transverse fractures at the middle one-third of the shafts of the femurs were created using open osteotomy. The fractures were reduced and internally fixed using intramedullary K-wires, and secondary fracture healing was allowed to take place. After surgery, intraperitoneal analgesics and antibiotics were given for 5 days. Sequential weekly x-rays assessed callus formation. The rats were sacrificed based on radiologically pre-determined time points, and the development of the fracture callus was analyzed radiologically and using immunohistochemistry.

Role of MDM2, CDK4, BCL2, Parafibromin and Galectin 1 in Differentiating Osteosarcoma from its Benign Fibro-osseous Lesions.

Benign fibro-osseous lesions (BFOLs) are a diverse group of lesions showing considerable degree of overlap with low grade osteosarcoma (LGOS). Further, de-differentiated osteosarcoma (DOS) is usually indistinguishable from conventional high-grade OS (COS) if LGOS foci are not identified. Thus, there is a need for adjunctive immunohistochemical markers to differentiate OS from benign FOLs as well as DOS from COS. This study evaluated the role of immunohistochemical expression of MDM2, CDK4, parafibromin, BCL-2 and Galectin-1 (Gal-1) in accurate characterization of benign FOLs and in differentiating them from OS. From our archives, we retrieved 101 tissue samples which were diagnosed as osteosarcoma (OS) /ossifying fibroma (OF) / fibrous dysplasia (FD) or fibrous hyperplasia (FH) and examined their immunohistochemical staining pattern with the aforementioned antibodies. MDM2 showed 100% specificity for diagnosing OS. CDK4 and Gal-1 showed linear increase in immunoexpression from benign BFOLs to OS. BCL-2 showed equivocal immunopositivity in OF and OS, but the positivity was higher than that observed in FD. The highest immunoexpression for parafibromin was seen in FD followed by OF and OS cases. Thus, MDM2 is most specific, and Gal-1 is most sensitive of all the markers studied in differentiating OS from benign mimics. Combination of these two markers can be used as an adjunct to conventional imaging and microscopy in accurate characterization of these lesions. Further MDM2 overexpression can differentiate DOS and COS.

Scanning Electron Microscopy of Giant Cells from Giant Cell Tumor of Bone.

Surface ultrastructures of giant cells (GCs) may help distinguish an aggressive tumor from an indolent giant cell tumor (GCT). This protocol describes a better way for ultrastructural surface imaging of GC from GCT of bone by scanning electron microscope (SEM). Fresh GCT samples collected in Dulbecco's modified Eagle medium (DMEM) are thoroughly washed to remove the blood and treated with collagenase to isolate the GCs. The collagenase-treated and critical point dried (CPD) samples yield a greater number of isolated GCs with better surface morphology, including membrane folding and micro-vesicular structures on the surface. Collagenase digestion and CPD should be performed for ultrastructural surface imaging of individual giant cells.

Malignancy mimics- diagnostic perplexities for oral and maxillofacial pathologists.

Objective: In pathology practice, one frequently encounters benign lesions which superficially resemble malignancy clinically and histopathologically. The diagnostic pitfalls can be avoided if the approach exemplified in the present study is followed. We expect that familiarity of these cases will be helpful for pathologists at the beginning of their career. Methods: Clinical case records of all the pathological specimens reported in our laboratory from January 2018 to September 2019 were queried. Cases displaying pseudotumor features were reviewed along with the special stains were performed and immunohistochemistry (IHC) studies. A working classification of pseudotumors presenting in the oral cavity was proposed. Results: Immunoglobulin G4-related disease, nodular fasciitis, fibrolipoma, odontogenic keratocyst with giant cell granuloma, juvenile ossifying fibroma with central giant cell granuloma and tumor-induced osteomalacia were the most common diagnoses where the tissue specimens resembled malignancies on routine clinicoradiological evaluation and light microscopy of tissue specimens. Their differential diagnosis and the pathological diagnostic dilemmas are explained. We have also highlighted the importance of correlating clinical, radiological and microscopic details with the findings deduced from advanced pathological aids to establish the final diagnosis. Conclusions: Pathologists should be aware of the conditions where the diagnosis of malignancy needs stricter evaluation to rule out malignant mimics. In such scenarios, correlation of light microscopy findings with clinical and radiological details cannot be overemphasized. Advanced pathological aids such as IHC, where necessary are often indispensable for reaching the accurate diagnosis in these cases.

Thermal changes during drilling in human femur by rotary ultrasonic bone drilling machine: A histologic and ultrastructural study.

Undue heat production in surgical bone drilling leads to osteonecrosis and can be an important cause of failure of osteosynthesis, impaired healing, and loosening of implants following orthopedic surgery. The present work aims to minimize heat production below the critical temperature for thermal osteonecrosis (i.e., 47°C) and obviate thermal bone damage due to drilling. A total of 20 samples from the shaft of the human femur were obtained at autopsies and drilling was performed at room temperature by an operation theater (OT) compatible rotary ultrasonic bone drilling (RUBD) machine. K-type thermocouples were used to measure the temperature rise during drilling and the physical changes of the bone samples were observed by infrared gama camera. Light microscopic and transmission electron microscopic studies were performed to evaluate the bone cell damage. The maximum temperature recorded in RUBD (40.6 ± 1.3°C) was much below the critical temperature for thermal osteonecrosis (p < .05) at the rotational speed of 2000 rpm. Light microscopic and ultrastructural studies also revealed that there was no appreciable damage to the bone cells. Conventional bone drilling (CD) on the other hand recorded much higher temperature (66.6 ± 3.2°C), tissue burn and bone cell necrosis. Hence, RUBD machine has a potentiality for its use in orthopedic surgery and may provide better results.

Sudden death of an egg donor during oocyte retrieval due to ovarian hyperstimulation syndrome

ABSTRACT Ovarian Hyperstimulation Syndrome (OHSS) is uncommon among oocyte donors during in vitro fertilization (IVF) procedure and is rarely associated with death. We report a case of a 23-year-old oocyte donor who suddenly died on the operation table during oocyte retrieval. She had no risk factors in her menstrual history, laboratory, or clinical parameters. The antagonist cycle, triggered with the GnRH agonist protocol, was carried out. The cause of death at autopsy was attributed to respiratory failure due to acute massive pulmonary edema, which developed due to the complication of OHSS. Only a few autopsy cases associated with OHSS have been published, but, as far as we know, no clinical or autopsy cases of sudden death caused by OHSS have been reported.

Oxidative stress-induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathway.

Pre-eclampsia (PE) is a pregnancy-specific disorder, characterized by hypertension and proteinuria. In PE, trophoblasts mediated inadequate remodeling of uterine spiral arteries seem to interrupt uteroplacental blood flow, one of the hallmarks in the early onset of PE (EO-PE). This, in turn, results in placental ischemia-reperfusion injury during hypoxia and reoxygenation episodes, leading to the generation of reactive oxygen species (ROS) and oxidative stress (OS). But still it is debatable if OS is a cause or consequence of PE. In this present study, we have investigated the effects of OS on PE placentae and trophoblast cell functions using BeWo and HTR8/SVneo cell lines. PE placental tissues showed abnormal ultrastructure, high level of reactive oxygen species (ROS) with altered unfolded protein responses (UPR) in compare with term placental tissues. Similar to PE placentae, during OS induction, the trophoblast cells showed altered invasion and migration properties with significantly variable expression of differentiation and invasion markers, e.g., syncytin and MMPs. The effect was rescued by antioxidant, N-acetyl cysteine, thereby implying a ROS-specific effect and in the trophoblast cells, OS triggers UPR pathway through IRE1α-XBP1 axis. Taken together, these findings highlight the harmful effect of unfolded protein response, which was induced due to OS on trophoblast cells and deformed invasion and differentiation programme and can be extended further to clinical settings to identify clinically approved antioxidants during pregnancy as a therapeutic measure to reduce the onset of PE.