Parotid gland leiomyosarcoma in a child: an extremely unusual neoplasm.

We report the case of an 8-year-old boy with a parotid mass diagnosed to be a leiomyosarcoma. Considering the unresectable extent of the mass, the patient was subjected to radiotherapy. The patient developed distant metastasis following the course of radiotherapy and was put on chemotherapy. The child was lost to further follow up. To our knowledge, this is the first reported case in the English-language literature of such an entity in the pediatric age group.     

Decision-making in pediatric blunt solid organ injury: A deep learning approach to predict massive transfusion,need for operative management,and mortality risk

BackgroundThe principal triggers for intervention in the setting of pediatric blunt solid organ injury (BSOI) are declining hemoglobin values and hemodynamic instability. The clinical management of BSOI is, however, complex. We therefore hypothesized that state-of-art machine learning (computer-based) algorithms could be leveraged to discover new combinations of clinical variables that might herald the need for an escalation in care. We developed algorithms to predict the need for massive transfusion (MT), failure of non-operative management (NOM), mortality, and successful non-operative management without intervention, all within 4 hours of emergency department (ED) presentation.MethodsChildren (≤ 18 years) who sustained a BSOI (liver, spleen, and/or kidney) between 2009 and 2018 were identified in the trauma registry at a pediatric level 1 trauma center. Deep learning models were developed using clinical values [vital signs, shock index-pediatric adjusted (SIPA), organ injured, and blood products received], laboratory results [hemoglobin, base deficit, INR, lactate, thromboelastography (TEG)], and imaging findings [focused assessment with sonography in trauma (FAST) and grade of injury on computed tomography scan] from pre-hospital to ED settings for prediction of MT, failure of NOM, mortality, and successful NOM without intervention. Sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC) were used to evaluate each model's performance.ResultsA total of 477 patients were included, of which 5.7% required MT (27/477), 7.2% failed NOM (34/477), 4.4% died (21/477), and 89.1% had successful NOM (425/477). The accuracy of the models in the validation set was as follows: MT (90.5%), failure of NOM (83.8%), mortality (91.9%), and successful NOM without intervention (90.3%). Serial vital signs, the grade of organ injury, hemoglobin, and positive FAST had low correlations with outcomes.ConclusionDeep learning-based models using a combination of clinical, laboratory and radiographic features can predict the need for emergent intervention (MT, angioembolization, or operative management) and mortality with high accuracy and sensitivity using data available in the first 4 hours of admission. Further research is needed to externally validate and determine the feasibility of prospectively applying this framework to improve care and outcomes.Level of EvidenceIIIStudy TypeRetrospective comparative study (Prognosis/Care Management).     

High order interactions of xenobiotic metabolizing genes and P53 codon 72 polymorphisms in acute leukemia

Polymorphisms in xenobiotic metabolizing genes are associated with altered metabolism of carcinogens in acute leukemia (AL). This study applied two data mining approaches to explore potential interactions among P53 and xenobiotic metabolizing genes in 230 AL patients [131 acute myeloid leukemia (AML) and 99 acute lymphoblastic leukemia (ALL)] and 199 controls. Individually, none of the genotypes showed significant associations with AML risk. However, in ALL the CYP1A12A TC genotype was associated with increased risk (OR = 2.02; 95% CI = 1.14–3.58; P = 0.01), whereas the GSTM1 null genotype imparted reduced risk (OR = 0.55; 95% CI = 0.31–0.96; P = 0.03). In classification and regression tree analysis, combinations of GSTM1 present, CYP1A12C AA or GG, EPHX1 exon3 TC, and EPHX1 exon4 AA or GG genotype strongly enhanced the risk of AML (OR = 5.89; 95% CI = 1.40–26.62; P = 0.01). In ALL, combinations of CYP1A12A TT, P53 GG or CC and GSTP1 AG genotypes conferred the highest risk (OR = 4.19; 95% CI = 1.45–12.25; P = 0.004). In multifactor dimensionality reduction analysis, a four locus model (GSTP1, P53, EPHX1 exon3, and CYP1A12A) was the best predictor model for ALL risk. The association between this model and ALL risk remained true even at low prior probabilities of 0.01% (false positive report probability = 0.05). Interaction entropy interpretations of the best model of ALL revealed that two‐way interactions were mostly synergistic. These results suggest that high order gene–gene interactions play an important role in AL risk. Environ. Mol. Mutagen., 2012. © 2012 Wiley Periodicals, Inc.     

Ellagic acid ameliorates cisplatin induced hepatotoxicity in colon carcinogenesis

The clinical application of cisplatin (CP), one of the most extensively used antineoplastic drug, is restricted by its numerous side effects. CP's antitumor potential resides in the free generation of reactive oxygen species leading to oxidative stress. This stress is a source of the side effects associated with its use. Ellagic acid (EA), a polyphenol is known to possess multiple health benefits owing to its antioxidant properties. EA is largely metabolized by the colon microbiota of different mammals and therefore was a polyphenol of choice in the present study. The present study was thus carried out to explore the protective potential of EA on CP induced hepatotoxicity in colon tumor bearing mice. The administration of EA (10 mg/kg bwt po daily for 6 weeks) significantly ameliorated the toxicity caused by CP (5 mg/kg bwt ip once a week for 4 weeks). Activities of liver marker enzymes and lactate dehydrogenase were brought back to normal. EA cotreatment also led to a marked reduction in the extent of peroxidative damage to liver tissue as was evident from the improvement in the histopathological changes observed and FT‐IR analysis. The present study, therefore, suggests that the administration of EA reduces the CP‐induced hepatotoxicity, thereby emerging out as a potential candidate for chemopreventive action.     

Platelet reactivity in patients and recurrent events post-stenting: results of the PREPARE POST-STENTING Study.

OBJECTIVES: We investigated the relation of high ex vivo platelet reactivity, rapid fibrin generation, and high thrombin-induced clot strength to postdischarge ischemic events in patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: High platelet reactivity and rapid fibrin generation may affect the incidence of ischemic events after PCI. However, limited data is available to link these ex vivo markers to the occurrence of events. METHODS: We measured platelet reactivity to adenosine diphosphate (ADP) by light transmittance aggregometry (LTA) in patients undergoing PCI (n = 192). Clot strength, a measure of thrombin-induced fibrin and platelet interactions, and the time to initial fibrin generation, a marker of thrombin activity, were measured by thrombelastography. The relation of these measurements to ischemic event occurrence was prospectively examined over six months. RESULTS: A total of 100% and 84% of patients were on aspirin and clopidogrel therapy, respectively, at the time of the initial event. Posttreatment ADP-induced aggregation by LTA (63 +/- 12% vs. 56 +/- 15%, p = 0.02) and clot strength (MA) were higher (74 +/- 5 mm vs. 65 +/- 4 mm, p < 0.001) and time to initial fibrin generation was shorter (4.3 +/- 1.3 min vs. 5.9 +/- 1.5 min, p < 0.001) in patients with events (n = 38). The event rates in the highest quartiles of LTA and MA were 32% and 58%, respectively. CONCLUSIONS: High platelet reactivity and clot strength, and rapid fibrin formation are novel risk factors for ischemic events after PCI. Clot strength is more predictive than ADP-induced platelet aggregation and may explain the occurrence of events despite treatment with cyclooxygenase-1 and P2Y12 inhibitors.     

Clinico-immunological profile in a case of hepatic tubercular abscess: A rare manifestation of extrapulmonary TB in an immunocompetent child

Tubercular liver abscess is a rare entity even in an endemic area for TB. We report here a rare case of pediatric tuberculous liver abscess, the etiology of which was established using recently introduced Cartridge based nucleic acid amplification test (CBNAAT). A 7 years old male child presented with vomiting, pain abdomen and fever. Hepatomegaly was found on examination. Ultrasound of abdomen revealed two liver abscesses in the right lobe. Patient remained symptomatic even after empirical antimicrobial therapy. On diagnostic tap Gram stained smear of the pus showed polymorphs with negative culture. CBNAAT was positive for Mycobacterial tuberculosis and sensitive to rifampicin. Subjecting difficult extrapulmonary specimens to relevant microbiological investigations along with CBNAAT and other newer methods may improve diagnosis of tuberculosis in such rare cases thus leading to an early management and decrease in morbidity.     

Aloe vera affects changes induced in pulmonary tissue of mice caused by cigarette smoke inhalation

This study was undertaken to determine the influence of Aloe vera (AV) on changes induced in pulmonary tissue of cigarette smoke (CS) inhaling mice. CS inhalation for 4 weeks caused pulmonary damage as evident by histoarchitectural alterations and enhanced serum and tissue lactate dehydrogenase (LDH) activities. CS inhalation also led to increased mucin production as revealed by mucicarmine and Alcian Blue‐Periodic Acid Schiff (AB‐PAS) staining. Studies on bronchoalveolar lavage fluid (balf) of CS exposed animals revealed structural changes in phospholipids and increase in surface tension when compared with control counterparts. These changes were accompanied by enhanced nitric oxide (NO) levels, citrulline levels, peroxidative damage, and differential modulation of antioxidant defense system. AV administration (seven weeks, 500 mg/kg b.w. daily) to CS inhaling mice led to modulation of CS induced pulmonary changes as revealed by lesser degree of histoarchitectural alterations, lesser mucin production, decreased NO levels, citrulline levels, peroxidative damage, and serum LDH activity. AV treatment to CS inhaling mice was associated with varying response to antioxidant defense system, however balf of CS + AV treated animals did not exhibit appreciable changes when compared with that of CS exposed animals. These observations suggest that AV has the potential to modulate CS induced changes in the pulmonary tissue which could have implications in management of CS associated pulmonary diseases, however, further investigations are required to explore its complete mechanism of action. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 999–1013, 2015.     

Matrix detachment and proteasomal inhibitors diminish Sulf-2 expression in breast cancer cell lines and mouse xenografts

Sulfatase 2 (Sulf-2) has been previously shown to be upregulated in breast cancer. Sulf-2 removes sulfate moieties on heparan sulfate proteoglycans which in turn modulate heparin binding growth factor signaling. Here we report that matrix detachment resulted in decreased Sulf-2 expression in breast cancer cells and increased cleavage of poly ADP-ribose polymerase. Silencing of Sulf-2 promotes matrix detachment induced cell death in MCF10DCIS cells. In an attempt to identify Sulf-2 specific inhibitor, we found that proteasomal inhibitors such as MG132, Lactacystin and Bortezomib treatment abolished Sulf-2 expression in multiple breast cancer cell lines. Additionally, we show that Bortezomib treatment of MCF10DCIS cell xenografts in mouse mammary fat pads significantly reduced tumor size, caused massive apoptosis and more importantly reduced Sulf-2 levels in vivo. Finally, our immunohistochemistry analysis of Sulf-2 expression in cohort of patient derived breast tumors indicates that Sulf-2 is significantly upregulated in autologous metastatic lesions compared to primary tumors (p < 0.037, Pearson correlation, Chi-Square analysis). In all, our data suggest that Sulf-2 might play an important role in breast cancer progression from ductal carcinoma in situ into an invasive ductal carcinoma potentially by resisting cell death.