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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The overproduction of reactive oxygen species (ROS) has been associated with various human diseases. ROS exert a multitude of biological effects with both physiological and pathological consequences. Monosodium glutamate (MSG), a sodium salt of the natural amino acid glutamate, is a flavor-enhancing food additive, which is widely used in Asian cuisine and is an ingredient that brings out the "umami" meat flavor. MSG consumption in rats is associated with ROS generation. Owing to its consumption as part of the fast-food culture and concerns about its possible effects on pregnancy, we aimed to study the impact of MSG on placental trophoblast cells. MSG exposure influenced trophoblast invasion and differentiation, two of the most critical functions during placentation through enhanced production of ROS. Similar findings were also observed on MSG-treated placental explants, as confirmed by elevated Nrf2 levels. Ultrastructural studies revealed signs of subcellular injury by MSG exposure. Mechanistically, MSG-induced oxidative stress with endoplasmic reticulum stress pathways involving Xbp1s and IRE1α was observed. The effect of MSG through an increased ROS production indicates that its long-term exposure might have adverse health effect by compromising key trophoblast functions. [ABSTRACT FROM AUTHOR]

Hypertensive disorders of pregnancy (HDP) are one of the commonest maladies, affecting 5%–10% of pregnancies worldwide. The American College of Obstetricians and Gynecologists (ACOG) identifies four categories of HDP, namely gestational hypertension (GH), Preeclampsia (PE), chronic hypertension (CH), and CH with superimposed PE. PE is a multisystem, heterogeneous disorder that encompasses 2%–8% of all pregnancy‐related complications, contributing to about 9% to 26% of maternal deaths in low‐income countries and 16% in high‐income countries. These translate to 50 000 maternal deaths and over 500 000 fetal deaths worldwide, therefore demanding high priority in understanding clinical presentation, screening, diagnostic criteria, and effective management. PE is accompanied by uteroplacental insufficiency leading to vascular and metabolic changes, vasoconstriction, and end‐organ ischemia. PE is diagnosed after 20 weeks of pregnancy in women who were previously normotensive or hypertensive. Besides shallow trophoblast invasion and inadequate remodeling of uterine arteries, dysregulation of the nonimmune system has been the focal point in PE. This results from aberrant immune system activation and imbalanced differentiation of T cells. Further, a failure of tolerance toward the semi‐allogenic fetus results due to altered distribution of Tregs such as CD4+FoxP3+ or CD4+CD25+CD127(low) FoxP3+ cells, thereby creating a cytotoxic environment by suboptimal production of immunosuppressive cytokines like IL‐10, IL‐4, and IL‐13. Also, intracellular production of complement protein C5a may result in decreased FoxP3+ regulatory T cells. With immune system dysfunction as a major driver in PE pathogenesis, it is logical that therapeutic targeting of components of the immune system with pharmacologic agents like anti‐inflammatory and immune‐modulating molecules are either being used or under clinical trial. Cholesterol synthesis inhibitors like Pravastatin may improve placental perfusion in PE, while Eculizumab (monoclonal antibody inhibiting C5) and small molecular inhibitor of C5a, Zilucoplan are under investigation. Monoclonal antibody against IL‐17(Secukinumab) has been proposed to alter the Th imbalance in PE. Autologous Treg therapy and immune checkpoint inhibitors like anti‐CTLA‐4 are emerging as new candidates in immune horizons for PE management in the future. [ABSTRACT FROM AUTHOR]

Multinucleated giant cells are commonly encountered in histopathology and are mostly a clue to diagnosis but sometimes pose a diagnostic confusion. The present study elucidates a case series of giant cell lesions (GCL) with emphasis on differential diagnosis and other investigations that contribute towards arriving at a final diagnosis. We also intended to devise an algorithmic approach for the accurate pathological characterization of these lesions. All the cases reported in the department from January 2018 to June 2019 were reviewed by pathologists and the total number of lesions where giant cells were diagnostic or an additional finding were included in this study. Twenty-five cases out of 1000 biopsies were diagnosed based on giant cell morphology. The most frequent lesions were central giant cell granuloma, followed by cherubism, hyperparathyroidism, peripheral giant cell granuloma, tuberculosis, and hybrid lesion. A systematic approach towards differential diagnosis for such cases and a diagnostic algorithm was devised which is being followed as per the reported spectrum of GCL. Radiological, serology, and sometimes ancillary staining techniques are essential for the accurate histopathological diagnosis of giant cell lesions. Our diagnostic algorithm helps narrow down the spectrum of investigations necessary to characterize these lesions, enabling for a swifter and more confident identification of the pathologies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Secretory carcinoma (SC) of the salivary gland is considered to be a low-intermediate grade tumor with the potential of locally aggressive behavior. This tumor is similar both genetically (ETV6-NTRK3 fusion) and histologically to secretory carcinoma of the breast. We intent to share our experience of four cases of SC in terms of clinical behavior, pathological features, and treatment outcome. Medical records of four cases of SC were retrieved and analyzed for clinical presentation, surgical treatment, and outcome. Pathological data was reanalyzed along with immunohistochemistry. Out of the four identified SC cases, three were men. Two lesions originated from the parotid gland and two from minor salivary glands. Two of these cases exhibited features of locally aggressive pattern. SC of salivary gland origin has distinct histological and immunohistochemical features apart from the characteristic genetic translocation and fusion. Surgery with or without adjuvant radiotherapy is the treatment of choice. To establish the biological behavior of this tumor, larger case series with long-term follow-up is desirable. [ABSTRACT FROM AUTHOR]

Misdiagnosed PAS confirmed at medicolegal autopsy Pulmonary artery sarcoma (PAS) is a rare disease and usually indistinguishable from acute or chronic thromboembolic disease of the pulmonary arteries. We present a case of pulmonary artery sarcoma in a 54‐year‐old male, who was clinically misdiagnosed as pulmonary thromboembolism. The patient died of disease; however, the actual diagnosis of PAS was made after a medicolegal autopsy. PAS can be a diagnostic challenge for both clinicians and pathologists. In an autopsy case with a clinical suspicion of pulmonary thromboembolism, if there is an abnormal gross appearance in the pulmonary artery, the forensic pathologist should have a high index of suspicion of PAS, which should be ruled out by a histopathologic examination. [ABSTRACT FROM AUTHOR]

Study Design: Prospective, comparative. Purpose: To compare the histopathological and electron microscopic changes in the ligamentum flavum (LF) between degenerative lumbar canal stenosis (LCS) and lumbar disk herniation (LDH). Overview of Literature: The LF has been implicated as a key structure in the pathogenesis of LCS. With aging, the LF undergoes morphological changes-a decrease in the elastic component and an increase in the collagen component, in addition to other focal changes. By comparing the histopathological and electron microscopic picture of the LF in elderly patients with LCS with that in young patients with LDH, the role of this ligament in the pathogenesis of LCS may be clarified. Methods: Forty patients were prospectively recruited and divided into two groups: group 1 included 20 patients with degenerative LCS aged >55 years and group 2 included patients with LDH aged <35 years. The ligament flava were collected during the patients' surgery. The features noted on histopathological examination included the fibrosis score, the loss of elastic fibers, calcification, chondroid metaplasia, mucinous degeneration, vascularization, long septa, clefts, granulation tissue, and ganglion-like cysts. The features noted on electron microscopic examination included the elastic fiber thickness, the quality of elastic fibers, the elastic:collagen ratio, calcification, melanin fibers, remnants of necrotic cells, and electron-dense material in the LF. All parameters were compared between group 1 and group 2. Results: On histopathological examination, the two groups exhibited significant differences regarding three parameters: chondroid metaplasia, long septa, and ganglion-like cysts. On electron microscopy examination, significant differences were observed between the two groups regarding two parameters: the quality of elastic fibers and the elastic:collagen ratio. Conclusions: Characteristic morphological changes may be noted on histopathological and electron microscopic examination that mark the degenerative changes in the LF that contribute to the occurrence and pathogenesis of degenerative LCS. [ABSTRACT FROM AUTHOR]

Efficacy and outcomes of osteosynthesis depend on various factors including types of injury and repair, host factors, characteristics of implant materials and type of implantation. One of the most important host factors appears to be the extent of bone damage due to the mechanical force and thermal injury which are produced at cutting site during bone drilling. The temperature above the critical temperature (47 °C) produces thermal osteonecrosis in the bones. In the present work, experimental investigations were performed to determine the effect of drilling parameters (rotational speed, feed rate and drill diameter) and techniques (conventional surgical bone drilling and rotary ultrasonic bone drilling) on cutting force and temperature generated during bone drilling. The drilling experiments were performed by a newly developed bone drilling machine on different types of human bones (femur, tibia and fibula) having different biological structure and mechanical behaviour. The bone samples were procured from male cadavers with the age of second to fourth decades. The results revealed that there was a significant difference (p < 0.05) in cutting force and temperature rise for rotary ultrasonic bone drilling and conventional surgical bone drilling. The cutting force obtained in rotary ultrasonic bone drilling was 30%–40%, whereas temperature generated was 50%–55% lesser than conventional surgical bone drilling process for drilling in all types of bones. It was also found that the cutting force increased with increasing feed rate, drill diameter and decrease in rotational speed, whereas increasing rotational speed, drill diameter and feed rate resulted in higher heat generation during bone drilling. Both the techniques revealed that the axial cutting force and the temperature rise were significantly higher in femur and tibia compared with the fibula for all combinations of process parameters. [ABSTRACT FROM AUTHOR]

The giant cell tumor of tendon sheath (GCTTS) or nodular tenosynovitis arises as discrete solitary nodule in the tendon sheath near joints of toes and fingers. Multifocal giant cell tumor of tendon sheath is a rare entity, of which the etiology is not yet fully understood and it is different from diffuse type of GCTTS. Diffuse type of GCTTS occurs around large joints having a main mass from which a small satellite nodule may arise. Multifocal GCTTS along a single tendon is a more rare entity. Herein, we describe a case of multifocal GCTTS along the tendon sheath of flexor digitorum profundus tendon of index finger. The patient was managed by surgical excision of the tumor swellings with no recurrence at two years follow up. [ABSTRACT FROM AUTHOR]

Cutting force and torque are important factors in the success of the bone drilling process. In the recent past, many attempts have been made to reduce the cutting force and torque in the bone drilling process. In this work, drilling on human cadaver bones has been performed using rotary ultrasonic bone drilling process to investigate the effect of drilling parameters on cutting force and torque. The experimental work was carried on a recently developed rotary ultrasonic bone drilling machine for surgical operations. The experimental work was performed in two phases. The first phase includes a comparative study between rotary ultrasonic bone drilling and conventional surgical bone drilling, to study the influence of various drilling parameters (rotational speed, drill diameter, and drilling tool feed rate) on the cutting force and torque. The results revealed that the cutting force and torque produced during drilling operations in rotary ultrasonic bone drilling were lesser (30%-40%) than conventional surgical bone drilling. In the second phase, response surface methodology was used to perform the statistical modeling of cutting force and torque in rotary ultrasonic bone drilling process. Analysis of variance was performed at a confidence interval of 95% to analyze the significant contribution (p < 0.05) of process parameters (drilling speed, feed rate, drill diameter, and abrasive particle size) on the responses (cutting force and torque). The confirmatory experiments were performed to validate the developed statistical models. It was found that both cutting force and torque decrease with increase in drilling speed and increases with the increasing drill diameter, feed rate, and abrasive particle size. [ABSTRACT FROM AUTHOR]

Purpose: There is no study till date determining the spectrum of adverse events of pazopanib in Indian patients with advanced sarcoma.Materials and Methods: We conducted a retrospective study by analyzing the case records of metastatic sarcoma patients treated with pazopanib from January 2016 to July 2017 in sarcoma medical oncology clinic. Toxicity was assessed according to CTCAE v.4.03 criteria. SPSS version 23 was used for statistical evaluation.Results: A total of 33 patients received pazopanib. The median age was 41 years (range, 19-75 years), with a male predominance (54.5%). Twenty-six patients (78.8%) had ECOG performance status 1 at the time of pazopanib initiation. The most common type of sarcoma was synovial sarcoma, and the mean duration of pazopanib intake in patients was 4.12 months. The median follow-up was 13 months. Median progression-free survival was 5 months, and median overall survival was 18 months. Overall response rate was 6.0%. Out of the 33 patients, 42.4% (n = 14) received it after first line of therapy. Six patients (18.2%) required dose reductions due to toxicity. Thirteen (39.4%) patients experienced CTCAE grade 3 or 4 toxicities. Most common grade 3 and 4 toxicities experienced among patients were hand-foot skin reaction (18.2%) and proteinuria (9.1%). No significant difference was seen when analyzed for variables such as age, sex, ECOG performance status, comorbidities, and number of previous lines received in patients experiencing grade 3 and 4 toxicities.Conclusions: The spectrum of adverse events in Indian patients at doses lower than the recommended dose is distinctly different from the western population. However, this unique toxicity profile needs to be validated in prospective studies. [ABSTRACT FROM AUTHOR]

Purpose: Adipose tissue dysfunction is at the center of metabolic dysfunctions associated with obesity. Through studies in isolated adipocytes and mouse models, ATP-binding cassette transporter A1 (ABCA1) expression in the adipose tissue has been shown to regulate high-density lipoprotein (HDL) cholesterol levels in the circulation and insulin sensitivity at both adipose tissue and whole-body levels. We aimed to explore the possible link between ABCA1 expression in the adipose tissue and metabolic derangements associated with obesity in humans. Patients and methods: This exploratory study among individuals who were lean (body mass index [BMI]: 22.3±0.34 kg/m2, n=28) and obese (BMI: 44.48±5.3 kg/m2, n=34) compared the expression of ABCA1, adiponectin and GLUT4 (SLC2A4) in visceral and subcutaneous adipose tissue using quantitative real-time PCR and immunohistochemistry. Homeostatic model assessment for insulin resistance (HOMA-IR) and adipose tissue insulin resistance (adipo-IR) were used as insulin resistance markers. Results: Visceral adipose tissue from individuals who were obese had significantly lower ABCA1 (P=0.04 for mRNA and protein) and adiponectin (P=0.001 for mRNA) expression compared to that from lean individuals. Subcutaneous adipose tissue did not show any significant difference in the expression. When individuals were divided into insulin-sensitive (IS) and insulin-resistant (IR) groups based on HOMA-IR, IR individuals had lower ABCA1 (P=0.0001 for mRNA and P=0.009 for protein) expression compared to IS individuals in visceral adipose tissue, but not in subcutaneous adipose tissue. The difference was significant after adjusting for age, gender and BMI. ABCA1 mRNA expression in visceral adipose tissue correlated negatively with both HOMA-IR (r=–0.44, P=0.0003) and adipo-IR (r=–0.35, P=0.005) after adjusting for age, gender and BMI. ABCA1 expression in either visceral or subcutaneous adipose tissue did not have any significant correlation with HDL cholesterol levels or mean adipocyte area. Conclusion: Obesity and insulin resistance are associated with lower expression of ABCA1 in visceral adipose tissue in humans. [ABSTRACT FROM AUTHOR]

Nodular fasciitis is a benign, self-limiting proliferative disorder of fibroblast of uncertain aetiology, occurs frequently in the forearm. Nodular fasciitis in hand inducing carpal tunnel syndrome is exceptional. There are four cases of non-intraneural nodular fasciitis causing peripheral neuropathy that has been reported previously. We present the case of a 38-year- old man with features of unilateral carpal tunnel syndrome. Decompression of the median nerve performed subsequently along with excision of the lesion in a piecemeal fashion. Histopathological and immunohistochemical findings were consistent with nodular fasciitis. There were complete resolution of symptoms and no sign of recurrence at the end of 1 year after surgery. [ABSTRACT FROM AUTHOR]