Ileal Adenocarcinoma with Liver Metastasis in Patient with Crohn\u27s Disease: A 9-Year Survival.

Small bowel adenocarcinoma is a rare but well-known complication of Crohn\u27s disease. The diagnosis of small bowel adenocarcinoma remains difficult since its presentation is highly variable and mimics active or obstructive Crohn\u27s disease. The diagnosis is often delayed and typically detected only at surgery in an advanced stage with a poor prognosis. We report a case of metastatic ileal adenocarcinoma in a patient with Crohn\u27s disease with prolonged survival. Our case describes serial promising treatment options of these advanced malignancies and raises a possible role for checkpoint immunotherapy

Proteogenomic landscape of breast cancer tumorigenesis and targeted therapy

The integration of mass spectrometry-based proteomics with next-generation DNA and RNA sequencing profiles tumors more comprehensively. Here this "proteogenomics" approach was applied to 122 treatment-naive primary breast cancers accrued to preserve post-translational modifications, including protein phosphorylation and acetylation. Proteogenomics challenged standard breast cancer diagnoses, provided detailed analysis of the ERBB2 amplicon, defined tumor subsets that could benefit from immune checkpoint therapy, and allowed more accurate assessment of Rb status for prediction of CDK4/6 inhibitor responsiveness. Phosphoproteomics profiles uncovered novel associations between tumor suppressor loss and targetable kinases. Acetylproteome analysis highlighted acetylation on key nuclear proteins involved in the DNA damage response and revealed cross-talk between cytoplasmic and mitochondrial acetylation and metabolism. Our results underscore the potential of proteogenomics for clinical investigation of breast cancer through more accurate annotation of targetable pathways and biological features of this remarkably heterogeneous malignancy

Acute Hepatitis A Causing Severe Hemolysis and Renal Failure in Undiagnosed Glucose-6-Phosphate Dehydrogenase Deficient Patient: A Case Report and Review of the Literature

Infection with hepatitis A virus is usually a self-limited illness that rarely results in fulminant liver failure. Severe hemolysis is an uncommon complication but has been reported in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency. Here, we report a case with undiagnosed G6PD deficiency who presented with hyperbilirubinemia, severe hemolysis, and acute renal failure precipitated by acute hepatitis A infection

A systematic review of randomized controlled trials for the prevention of bronchopulmonary dysplasia in infants

OBJECTIVE: Bronchopulmonary dysplasia (BPD) is the most common cause of pulmonary morbidity in premature infants and is associated with life-long morbidities. Developing drugs for the prevention of BPD would improve public health. We sought to determine characteristics of favorable randomized controlled trials (RCTs) of drugs for BPD prevention. EVIDENCE REVIEW: We searched MEDLINE and EMBASE from 1992–2014 using the MeSH terms “BPD” and “respiratory distress syndrome, newborn.” We included a Cochrane Library search to ensure inclusion of all available RCTs. We identified RCTs with BPD as a primary or secondary outcome and determined the definition of BPD used by the study. We determined whether a phase I or phase II study—to determine drug safety, efficacy, or optimal dose—was performed prior to the RCT. Finally, we searched the Cochrane Library for meta-analyses for each drug and used the results of available meta-analyses to define a favorable versus unfavorable RCT. FINDINGS: We identified 2026 articles; 47 RCTs met our inclusion criteria encompassing 21 drugs; 5 of the drugs reduced the incidence of BPD. We found data from phase I or II studies for 16 of the drugs, but only 1 demonstrated a reduction of BPD. CONCLUSIONS AND RELEVANCE: The majority of the drugs studied in RCTs failed to reduce the incidence of BPD. Performing early-phase studies prior to phase III trials might provide necessary information on drugs and drug doses capable of preventing BPD, thus informing the development of future RCTs

Proteogenomic and metabolomic characterization of human glioblastoma

Glioblastoma (GBM) is the most aggressive nervous system cancer. Understanding its molecular pathogenesis is crucial to improving diagnosis and treatment. Integrated analysis of genomic, proteomic, post-translational modification and metabolomic data on 99 treatment-naive GBMs provides insights to GBM biology. We identify key phosphorylation events (e.g., phosphorylated PTPN11 and PLCG1) as potential switches mediating oncogenic pathway activation, as well as potential targets for EGFR-, TP53-, and RB1-altered tumors. Immune subtypes with distinct immune cell types are discovered using bulk omics methodologies, validated by snRNA-seq, and correlated with specific expression and histone acetylation patterns. Histone H2B acetylation in classical-like and immune-low GBM is driven largely by BRDs, CREBBP, and EP300. Integrated metabolomic and proteomic data identify specific lipid distributions across subtypes and distinct global metabolic changes in IDH-mutated tumors. This work highlights biological relationships that could contribute to stratification of GBM patients for more effective treatment. Wang et al. perform integrated proteogenomic analysis of adult glioblastoma (GBM), including metabolomics, lipidomics, and single nuclei RNA-Seq, revealing insights into the immune landscape of GBM, cell-specific nature of EMT signatures, histone acetylation in classical GBM, and the existence of signaling hubs which could provide therapeutic vulnerabilities

Glucocorticoid Treatment for Bronchopulmonary Dysplasia

Although there is supporting evidence that glucocorticoids improve the short-term pulmonary outcome of newborns, studies indicate significant long-term side effects with neurological sequelae. Corticosteroids can be administered by any route and the licensed products differ significantly in their pharmacological properties and (side) effects. Treatment schedules and dosing regimens vary significantly. Consequently, studies are difficult to compare and to summarise. However, to date, there is no dosing strategy which can always considered to be safe. This provides a dilemma for the treating clinician, who has to balance possible benefits against probable harms in individual patients. This book chapter will first highlight the general mechanism of action of corticosteroids both as natural hormones and as newly synthetised drugs. We will then focus on the function of corticoids during inflammation and their special role in lung development. We will present the clinical data and summarise the current evidence for glucocorticoid treatment strategies ranging from intravenous application to inhalation. Key aspects are the different treatment strategies with dexamethasone and hydrocortisone, because these are the most heavily used substances in newborns. We will take into account different modes of administration, different substances and dosing schedules before ending with some conclusions

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma

To explore the biology of lung adenocarcinoma (LUAD) and identify new therapeutic opportunities, we performed comprehensive proteogenomic characterization of 110 tumors and 101 matched normal adjacent tissues (NATs) incorporating genomics, epigenomics, deep-scale proteomics, phosphoproteomics, and acetylproteomics. Multi-omics clustering revealed four subgroups defined by key driver mutations, country, and gender. Proteomic and phosphoproteomic data illuminated biology downstream of copy number aberrations, somatic mutations, and fusions and identified therapeutic vulnerabilities associated with driver events involving KRAS, EGFR, and ALK. Immune subtyping revealed a complex landscape, reinforced the association of STK11 with immune-cold behavior, and underscored a potential immunosuppressive role of neutrophil degranulation. Smoking-associated LUADs showed correlation with other environmental exposure signatures and a field effect in NATs. Matched NATs allowed identification of differentially expressed proteins with potential diagnostic and therapeutic utility. This proteogenomics dataset represents a unique public resource for researchers and clinicians seeking to better understand and treat lung adenocarcinomas