Combined use of noninvasive tests is useful in the initial diagnostic approach to a child with suspected inflammatory bowel disease

OBJECTIVE: To assess the effectiveness of the combined use of fecal calprotectin (FC), anti-Saccharomyces cerevisiae antibody (ASCA), perinuclear staining antineutrophil antibody (pANCA), small intestinal permeability test (IP), and bowel wall ultrasonography measurement (BWUS) in the diagnostic work-up of children with suspected inflammatory bowel disease (IBD). METHODS: All children referred for initial assessment of possible IBD were eligible. Patients with symptoms or signs (right-lower quadrant mass, perianal disease, or hematochezia) mandating a complete work-up for IBD were excluded. All enrolled patients underwent a clinical, laboratory, radiographic, and endoscopic evaluation including biopsy examinations. The immunoglobulin (Ig)G and IgA ASCA, IgG pANCA, FC, IP, and BWUS were tested in all patients at the initial assessment. RESULTS: A final diagnosis of IBD was made in 27 patients: 17 Crohn disease and 10 ulcerative colitis. Eighteen children had other gastrointestinal diagnoses (8 functional bowel disorders, 5 food allergy-mediated diseases, 4 infectious enterocolitis, 1 familial Mediterranean fever). In patients with simultaneous abnormal values of FC, BWUS, and ASCA/pANCA, the estimated probability of having IBD was 99.47%. Patients with negative results on all tests had a 0.69% of probability of IBD. CONCLUSIONS: The incorporation of noninvasive diagnostic tests into the initial diagnostic approach may avoid unnecessary invasive procedures and facilitate clinical decision-making when the diagnosis of IBD in children is initially uncertain.     

Scrotal hematoma due to neonatal adrenal hemorrhage: the value of ultrasonography in avoiding unnecessary surgery

Scrotal hematoma is an uncommon presentation of neonatal adrenal hemorrhage. Nine previous cases of such an association have been reported in the literature, and unnecessary surgery was carried out in five of these cases. The authors report three new cases observed during a 3-year period and stress the critical role of scrotal and abdominal ultrasonography in order to avoid unnecessary surgical exploration. Received: 13 June 1996 Accepted: 28 January 1997     

The sphingosine kinase 2 inhibitor ABC294640 displays anti‐non‐small cell lung cancer activities in vitro and in vivo

Non‐small cell lung cancer (NSCLC) accounts for about 85‐90% of lung cancer cases, and is the number one killer among cancers in the United States. The majorities of lung cancer patients do not respond well to conventional chemo‐ and/or radio‐therapeutic regimens, and have a dismal 5‐year survival rate of ～15%. The recent introduction of targeted therapy and immunotherapy gives new hopes to NSCLC patients, but even with these agents, not all patients respond, and responses are rarely complete. Thus, there is still an urgent need to identify new therapeutic targets in NSCLC and develop novel anti‐cancer agents. Sphingosine kinase 2 (SphK2) is one of the key enzymes in sphingolipid metabolism. SphK2 expression predicts poor survival in NSCLC patients, and is associated with Gefitinib‐resistance. In this study, the anti‐NSCLC activities of ABC294640, the only first‐in‐class orally available inhibitor of SphK2, were explored. The results obtained indicate that ABC294640 treatment causes significant NSCLC cell apoptosis, cell cycle arrest and suppression of tumor growth in vitro and in vivo. Moreover, lipidomics analyses revealed the complete signature of ceramide and dihydro(dh)‐ceramide species in the NSCLC cell‐lines with or without ABC294640 treatment. These findings indicate that sphingolipid metabolism targeted therapy may be developed as a promising strategy against NSCLC.     

Successful Treatment of Kaposi Sarcoma–Associated Herpesvirus Inflammatory Cytokine Syndrome After Kidney–Liver Transplant: Correlations With the Human Herpesvirus 8 miRNome and Specific T Cell Response

After transplant, patient infection with human herpesvirus 8 (HHV‐8) and Kaposi sarcoma–associated herpesvirus (KSHV) is known to cause aggressive tumors and severe nonneoplastic complications. These latter syndromes are driven by HHV‐8/KSHV lytic reactivations and related hyperinflammatory host responses typically characterized by high viral loads, elevated levels of cytokines and other inflammation biomarkers, cytopenia, organ failure, high fever, and worsening conditions (with no evidence of B cell neoplasias). These disorders are associated with a high mortality rate, often due to lack of prompt diagnosis, effective therapeutic approaches, and adequate follow‐up. These features resemble most of those defining the so‐called KSHV‐associated inflammatory cytokine syndrome (KICS), which was recently recognized in patients positive for human immunodeficiency virus (HIV). In this report, we describe—for the first time—a case of a KICS‐like nonneoplastic recurrent complication occurring after transplant in an HIV‐negative patient that was successfully treated by a combination of anti‐CD20 monoclonal therapy, antivirals, and modification of the immunosuppressive regimen. In addition to clinical and laboratory findings collected during 3‐year follow‐up, we report novel experimental data on HHV‐8–specific T cell dynamics and circulating microRNA profile, showing correlations with clinical course and other laboratory markers (including viral load, C‐reactive protein, and cytokine levels), providing useful information about abnormal cellular and cytokine dynamics underlying HHV‐8–associated inflammatory disorders in posttransplant patients.