Spitzoid melanoma of childhood: a case series and review

Spitzoid melanomas (SM) and atypical Spitz tumors (AST) are rare pediatric neoplasms. We performed a retrospective, single-institution review and report our institutional experience. We identified 10 patients (median age: 12.5 years). A sentinel node biopsy (SNB) was performed in 8/10 (80%) patients, and interestingly 7/8 (87.5%) were found to be positive for malignant cells. A complete regional lymphadenectomy was performed in all SNB-positive patients, but only 2/8 (25%) were found to have additional lymph node spread. Adjuvant therapy was administered in 5/8 SLNB-positive and 2/2 (100%) regional LN-positive cases. All patients had excellent long-term outcomes (100% survival). This report highlights the excellent outcomes associated with SNB + pediatric SM and AST

Factors associated with a prolonged hospital stay during induction chemotherapy in newly diagnosed high risk pediatric acute lymphoblastic leukemia

Background High Risk (HR) or Very High Risk (VHR) acute lymphoblastic leukemia (ALL) treated with 4 drug induction chemotherapy is often associated with adverse events. The aim of this study was to identify risk factors associated with a prolonged inpatient length of stay LOS during induction chemotherapy. Procedure Data from patients (N = 73) (age<21 years) was collected through a retrospective chart review. Univariable and multivariable logistic regression was used to test for statistical significance. The overall survival and disease (leukemia)-free survival were analyzed using the Kaplan–Meier method and log-rank test. Results Of the 73 patients, 42 (57%) patients were discharged on day 4 of induction (short LOS, group A), while 31 (43%) patients (group B) experienced a prolonged LOS or an ICU stay (16 ± 27.7 days, median hospital stay = 8 days vs 4 days (group A), p = 0.02) due to organ dysfunction, infectious or metabolic complications. Group B patients were more likely to have a lower platelet count, serum bicarbonate, and a higher blood urea nitrogen (BUN) on day 4 of treatment (OR = 4.52, 8.21, and 3.02, respectively, p < 0.05). Multivariable analysis identified low serum bicarbonate (p = 0.002) and a platelet count<20,000/μL (p = 0.02) on day 4 of induction to be predictive of a prolonged LOS. Twenty six (group A (n = 16, 36%) and B (n = 11, 35%), p = 0.8) patients experienced unplanned admissions, within 30 days of discharge. Conclusions A significant proportion of newly diagnosed HR or VHR pediatric ALL patients experience a prolonged LOS and unplanned re-admissions. Aggressive discharge planning and close follow up is indicated in this cohort of patients

Effects of heavy metals on seed protein fractions in chickpea, Cicer arietinum (L.)

Worldwide, different abiotic stresses, such as drought, salinity, and heavy metals, harm crop productivity. Legumes, compared to cereals, are more susceptible to these stresses. The current work aimed to provide more insights into the effects of Cd and Pb on various seed protein characteristics of two cultivars of chickpea (Cicer arietinum), HC1 and HC5. At the highest concentrations of Cd, the total seed proteins decreased from 25.2% (control) to 7.1% (30 mg/kg soil), while in the case of the maximum concentration of Pb, 300 mg/kg soil, the protein content decreased to 16.1% from 25.2%. The content of each of the four seed protein fractions viz. albumins, globulins, glutelins and prolamins decreased with an increase in the concentration levels of both heavy metals. The dominating protein fraction, globulins, was reduced by 21.7% in HC1 under Cd stress, while it was reduced by 11.9% in Pb-treated genotype HC5. Electrophoretic analysis of four seed protein fractions on SDS-gels showed only quantitative changes in the polypeptide patterns under varying concentrations of Pb with few qualitative alterations under Cd treatment. The contents of the amino acids tryptophan, cysteine and methionine also decreased with increasing concentrations of heavy metals. Compared to Pb, Cd was found to be more detrimental concerning its influence on seed protein quality. Thus, our analysis revealed how heavy metals impact the quality of chickpea seed proteins by decreasing the content of essential amino acids

Asparagine: A Metabolite to Be Targeted in Cancers

Amino acids play central roles in cancer progression beyond their function as building blocks for protein synthesis. Thus, targeting amino acid acquisition and utilization has been proved to be therapeutically beneficial in various pre-clinical models. In this regard, depletion of circulating asparagine, a nonessential amino acid, by L-asparaginase has been used in treating pediatric acute lymphoblastic leukemia (ALL) for decades. Of interest, unlike most solid tumor cells, ALL cells lack the ability to synthesize their own asparagine de novo effectively. However, only until recently, growing evidence suggests that solid tumor cells strive to acquire adequate amounts of asparagine to support tumor progression. This process is subjected to the regulation at various levels, including oncogenic signal, tumor-niche interaction, intratumor heterogeneity and dietary accessibility. We will review the literature on L-asparaginase-based therapy as well as recent understanding of asparagine metabolism in solid tumor progression, with the hope of shedding light into a broader cancer therapeutic strategy by perturbing its acquisition and utilization

Histiocytic Sarcoma Associated with Coombs Negative Acute Hemolytic Anemia: A Rare Presentation

Histiocytic sarcoma (HS) rarely involves extranodal sites, such as the spleen. We report a unique pediatric case of massive splenomegaly and refractory Coombs negative hemolytic anemia (CNHA) secondary to HS. The CNHA resolved completely after an emergent splenectomy. Next generation sequencing (NGS) revealed novel ASXL1, PTPN11, KIT, and TP53 mutations, unmasking a clonal heterogeneity within the same neoplasm

Random glucose sampling as screening tool for diabetes among disadvantaged tuberculosis patients residing in urban slums in India.

Recently, a two-step diagnostic algorithm to diagnose diabetes among TB patients was proposed comprising random glucose and point-of-care HbA1c. This study evaluates the first part of this algorithm among disadvantaged TB patients. http://ow.ly/UI7d30nK1UN

Case Report Histiocytic Sarcoma Associated with Coombs Negative Acute Hemolytic Anemia: A Rare Presentation

Histiocytic sarcoma (HS) rarely involves extranodal sites, such as the spleen. We report a unique pediatric case of massive splenomegaly and refractory Coombs negative hemolytic anemia (CNHA) secondary to HS. The CNHA resolved completely after an emergent splenectomy. Next generation sequencing (NGS) revealed novel ASXL1, PTPN11, KIT, and TP53 mutations, unmasking a clonal heterogeneity within the same neoplasm

Development of a Fast SARS-CoV-2 IgG ELISA, Based on Receptor-Binding Domain, and Its Comparative Evaluation Using Temporally Segregated Samples From RT-PCR Positive Individuals

SARS-CoV-2 antibody detection assays are crucial for gathering seroepidemiological information and monitoring the sustainability of antibody response against the virus. The SARS-CoV-2 Spike protein's receptor-binding domain (RBD) is a very specific target for anti-SARS-CoV-2 antibodies detection. Moreover, many neutralizing antibodies are mapped to this domain, linking antibody response to RBD with neutralizing potential. Detection of IgG antibodies, rather than IgM or total antibodies, against RBD is likely to play a larger role in understanding antibody-mediated protection and vaccine response. Here we describe a rapid and stable RBD-based IgG ELISA test obtained through extensive optimization of the assay components and conditions. The test showed a specificity of 99.79% (95% CI: 98.82-99.99%) in a panel of pre-pandemic samples (n = 470) from different groups, i.e., pregnancy, fever, HCV, HBV, and autoantibodies positive. Test sensitivity was evaluated using sera from SARS-CoV-2 RT-PCR positive individuals (n = 312) and found to be 53.33% (95% CI: 37.87-68.34%), 80.47% (95% CI: 72.53-86.94%), and 88.24% (95% CI: 82.05-92.88%) in panel 1 (days 0-13), panel 2 (days 14-20) and panel 3 (days 21-27), respectively. Higher sensitivity was achieved in symptomatic individuals and reached 92.14% (95% CI: 86.38-96.01%) for panel 3. Our test, with a shorter runtime, showed higher sensitivity than parallelly tested commercial ELISAs for SARS-CoV-2-IgG, i.e., Euroimmun and Zydus, even when equivocal results in the commercial ELISAs were considered positive. None of the tests, which are using different antigens, could detect anti-SARS-CoV-2 IgGs in 10.5% RT-PCR positive individuals by the fourth week, suggesting the lack of IgG response

Systems Biology Approach Identifies Prognostic Signatures of Poor Overall Survival and Guides the Prioritization of Novel BET-CHK1 Combination Therapy for Osteosarcoma

Osteosarcoma (OS) patients exhibit poor overall survival, partly due to copy number variations (CNVs) resulting in dysregulated gene expression and therapeutic resistance. To identify actionable prognostic signatures of poor overall survival, we employed a systems biology approach using public databases to integrate CNVs, gene expression, and survival outcomes in pediatric, adolescent, and young adult OS patients. Chromosome 8 was a hotspot for poor prognostic signatures. The MYC-RAD21 copy number gain (8q24) correlated with increased gene expression and poor overall survival in 90% of the patients (n = 85). MYC and RAD21 play a role in replication-stress, which is a therapeutically actionable network. We prioritized replication-stress regulators, bromodomain and extra-terminal proteins (BETs), and CHK1, in order to test the hypothesis that the inhibition of BET + CHK1 in MYC-RAD21+ pediatric OS models would be efficacious and safe. We demonstrate that MYC-RAD21+ pediatric OS cell lines were sensitive to the inhibition of BET (BETi) and CHK1 (CHK1i) at clinically achievable concentrations. While the potentiation of CHK1i-mediated effects by BETi was BET-BRD4-dependent, MYC expression was BET-BRD4-independent. In MYC-RAD21+ pediatric OS xenografts, BETi + CHK1i significantly decreased tumor growth, increased survival, and was well tolerated. Therefore, targeting replication stress is a promising strategy to pursue as a therapeutic option for this devastating disease

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction