Molecular Tumor Board for Unicorns: Outcomes for rare and ultra-rare cancers using an N-of-One personalized treatment strategy.

Treatment of rare/ultra-rare tumors is an unmet need due to a lack of standardized therapies and clinical trials. We developed the Molecular Tumor Board (MTB), a multidisciplinary team that integrates molecular profiling to generate personalized, N-of-One treatments for advanced cancers. This study evaluates 112 patients with rare/ultra-rare tumors who presented to the MTB and were evaluable for clinical therapeutic outcome. Overall, 46/112 patients (41%) received a treatment regimen with a high degree of matching between tumor molecular alterations and drugs given (reflected by a high Matching Score (≥50%)). Patients with a high versus low Matching Score experienced significantly longer progression-free survival (p = 0.005) and overall survival (p = 0.047), and higher rates of clinical benefit (stable disease ≥6 months, partial response, or complete response) (54% vs. 32% p = 0.027). The MTB facilitated personalized N-of-One matching of drugs to tumor molecular alterations, which was associated with improved clinical outcomes in patients with rare/ultra-rare cancers.

Bacteria.guru: Comparative Transcriptomics and Co-Expression Database for Bacterial Pathogens.

While bacteria can be beneficial to our health, their deadly pathogenic potential has been an ever-present concern exacerbated by the emergence of drug-resistant strains. As such, there is a pressing urgency for an enhanced understanding of their gene function and regulation, which could mediate the development of novel antimicrobials. Transcriptomic analyses have been established as insightful and indispensable to the functional characterization of genes and identification of new biological pathways, but in the context of bacterial studies, they remain limited to species-specific datasets. To address this, we integrated the genomic and transcriptomic data of the 17 most notorious and researched bacterial pathogens, creating bacteria.guru, an interactive database that can identify, visualize, and compare gene expression profiles, coexpression networks, functionally enriched clusters, and gene families across species. Through illustrating antibiotic resistance mechanisms in P. aeruginosa, we demonstrate that bacteria.guru could potentially aid in discovering multi-faceted antibiotic targets and, overall, facilitate future bacterial research. AVAILABILITY: The database and coexpression networks are freely available from https://bacteria.guru/. Sample annotations can be found in the supplemental data.

Acne Vulgaris: Treatment Made Easy for the Primary Care Physician.

Acne is the most common skin condition observed in adolescent and preadolescent patients. Pediatric providers are on the forefront of managing the disease, often as a secondary concern in a busy practice. Therefore, every provider needs to have an acne treatment plan that is effective, easy to communicate, and simple to follow. This article provides treatment rationale and guidelines-based recommendations for the initial treatment of acne, tips for troubleshooting any side effects, and a plan for subsequent follow-up to maintain good control. [Pediatr Ann. 2020;49(3):e109-e115.].

Analysis of Tissue and Circulating Tumor DNA by Next-Generation Sequencing of Hepatocellular Carcinoma: Implications for Targeted Therapeutics.

Hepatocellular carcinoma (HCC) has limited treatment options. Molecular analysis of its mutational landscape may enable the identification of novel therapies. However, biopsy is not routinely performed in HCC. The utility of analyzing cell-free circulating tumor DNA (ctDNA) by next-generation sequencing (NGS) is not established. We performed 32 ctDNA NGS analyses on 26 patients; 10 of these patients had tissue NGS (236 to 626 genes). ctDNA was evaluated using an assay that detects single nucleotide variants, amplifications, fusions, and specific insertion/deletion alterations in 54 to 70 genes. The ctDNA demonstrated that 23 of 26 patients (88.5%) had ≥1 characterized alteration, and all these individuals had ≥1 potentially actionable alteration. The most frequently mutated gene was TP53 (16 of 26 patients, 61.5%). There were 47 unique characterized molecular alterations among 18 total gene alterations [variants of unknown significance (VUS) excluded)]. ctDNA and tissue NGS frequently showed different profiles, perhaps due to length of time between tissue and blood samples [median = 370 days (range, 29 to 876 days)]. Serial ctDNA evaluation in an illustrative patient treated with capecitabine demonstrated emergence of a new TP53 alteration after progression. In conclusion, ctDNA profiling is feasible in advanced HCC, and serial assessment using ctDNA NGS can reveal genomic changes with time. NGS of ctDNA provides a minimally invasive alternative for identifying potentially actionable gene alterations and potential molecular targeted therapies. Dynamic changes in molecular portfolio associated with therapeutic pressure in difficult-to-biopsy patients can be observed. Mol Cancer Ther; 17(5); 1114-22. ©2018 AACR.

Changes in lung function in Republic of Singapore Navy divers.

BACKGROUND: It is recognized that diving may result in long-term adverse effects on the lungs, In the Republic of Singapore Navy (RSN), divers undergo an annual examination, which includes spirometry to detect early any deterioration in lung function, to ensure that personnel are fit to continue their duties. There are a few Asian studies on lung function, and none on Asian divers. OBJECTIVES: To analyze the lung function of a group of RSN divers over a five-year period. METHODOLOGY: This was a retrospective study based on the spirometric results of RSN divers during their annual recertification in 2001 and in 2006. There were 116 subjects who underwent the spirometry at the same centre in both 2001 and 2006. RESULTS: The divers showed a statistically significant increase in mean forced vital capacity (FVC) from 86.1% to 89.5% of predicted (P < 0.01) over the five-year period. In addition, the mean forced expiratory volume in one second (FEV1) improved significantly from 87.2% to 90.2% of predicted (P < 0.01). However, there was a statistically significant decrease in FEV1/FVC ratio from 87.0% to 85.0% of predicted (P < 0.01). Mean peak expiratory flow rose from 100.1% to 111.00% of predicted (P < 0.01). We did not find any statistically significant relationship between years of service or smoking history and changes in lung function for the divers. CONCLUSION: Despite being statistically significant, these findings are probably of minimal clinical significance, but do demonstrate that there is no decline in lung function in these divers over this period of time.