Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ganciclovir, an acyclic nucleoside with improved activity against cytomegalovirus in vitro, was used to treat 15 marrow transplant patients with symptomatic cytomegalovirus infection of the gastrointestinal tract. Eleven of the 15 had improvement in one or more of their clinical signs or symptoms during treatment. No clinical relapses were observed. Viral excretion from throat, urine and blood stopped at a median of 6 days of treatment, but six patients had recurrence of viral excretion 7-25 days after treatment was stopped. The only toxicity was the development of reversible neutropenia in eight of 15 patients after 10-19 days of treatment. Neutropenia was not related to duration of treatment, plasma drug levels or to the neutrophil count at the beginning of treatment. Although treatment with ganciclovir may be associated with marrow suppression, the serious nature of gastrointestinal infection due to cytomegalovirus in the immunocompromised host, the antiviral effect and the possible clinical improvement observed in vivo, and the lack of other effective treatments justify further controlled studies with this agent in immunocompromised patients with serious cytomegalovirus infection.
 ...
PMID:Ganciclovir treatment of cytomegalovirus infection of the gastrointestinal tract after marrow transplantation. 284 43

9-(1,3-dihydroxy-2-propoxymethyl) guanine (ganciclovir) was used to treat 41 patients (median age, 37 years) with the acquired immunodeficiency syndrome and cytomegalovirus gastrointestinal infection. Sites of infection were the colon in 31, the esophagus in 5, the rectum in 4, and the small bowel in 1. Patients received ganciclovir, 5 mg/kg body weight, intravenously every 12 hours for 14 days. Clinical improvement was seen in 30 patients and virologic response in 32. Mainly hematologic toxicity occurred: moderate leukopenia (1000 to 1900/mm3) was seen in 7 patients and severe (less than 1000/mm3) in 1, and moderate neutropenia (500 to 1000/mm3) in 5 and severe (less than 500/mm3) in 1. A cutaneous rash developed in 2 patients. Median overall survival was 16 weeks (range, 2 to 56). Cytomegalovirus recurred in 13 patients; median time to recurrence was 9 weeks from the start of treatment. Ganciclovir may be effective in treating cytomegalovirus gastrointestinal disease in patients with the acquired immunodeficiency syndrome.
 ...
PMID:9-(1,3-Dihydroxy-2-propoxymethyl)guanine (ganciclovir) in the treatment of cytomegalovirus gastrointestinal disease with the acquired immunodeficiency syndrome. 303 60

Candida albicans systemic dissemination in immunocompromised patients is thought to develop from initial gastrointestinal (GI) colonisation. It is unclear what components of the innate immune system are necessary for preventing C. albicans dissemination from the GI tract, but studies in mice have indicated that both neutropenia and GI mucosal damage are crucial for allowing widespread invasive C. albicans disease. Mouse models, however, provide limited applicability to genome-wide screens for pathogen or host factors - factors that might influence systemic dissemination following GI colonisation. For this reason we developed a Drosophila model to study intestinal infection by Candida. We found that commensal flora aided host survival following GI infection. Candida provoked extensive JNK-mediated death of gut cells and induced antimicrobial peptide expression in the fat body. From the side of the host, nitric oxide and blood cells influenced systemic antimicrobial responses. The secretion of SAP4 and SAP6 (secreted aspartyl proteases) from Candida was also essential for activating systemic Toll-dependent immunity.
 ...
PMID:Pathogen and host factors are needed to provoke a systemic host response to gastrointestinal infection of Drosophila larvae by Candida albicans. 2154 Feb 43

We conducted an observational study to assess the etiology, clinical features and outcomes of bloodstream infection (BSI) in 172 hematopoietic SCT (HCST) recipients. One hundred episodes of BSI in the pre-engraftment period (early onset) were compared with 89 episodes in the post-engraftment phase (late onset). More patients with late-onset BSI received an allogeneic HSCT, had GVHD and had received corticosteroids, whereas patients with early-onset BSI were more likely to have neutropenia, severe mucositis and a central venous catheter (CVC) in place. CVC was the most frequent site of infection, followed by an endogenous source. Pneumonia and gastrointestinal infection were particularly frequent in late-onset BSI, whereas mucositis was more frequent in the early-onset group. Gram-positive organisms predominated over Gram negatives. Streptococcus pneumoniae was more frequent in patients with late-onset BSI. Patients with late-onset BSI presented worse outcomes regarding septic shock, intensive care unit admission and early and overall case-fatality rates. Early-onset BSI was mainly related to the presence of neutropenia, mucositis and CVC, whereas late-onset BSI mainly affected severely immunosuppressed allogeneic HSCT recipients with GVHD and corticosteroids. Late-onset BSI caused high case-fatality rates. BSI due to S. pneumoniae was especially frequent late after transplantation. The development of better vaccination strategies is needed.
...
PMID:Etiology, clinical features and outcomes of pre-engraftment and post-engraftment bloodstream infection in hematopoietic SCT recipients. 2466 20

This study aimed at comparing bortezomib, thalidomide, and lenalidomide in patients with multiple myeloma (MM) for safety and efficacy using meta-analysis. This meta-analysis identified 17 randomized controlled trials (RCTs) including 6742 patients. These RCTs were separated according to the different agent-based regimens and to autologous stem-cell transplantation (ASCT). Complete response (CR), progression-free survival (PFS), overall survival (OS), and adverse events (AE) were combined. The total weighted risk ratio (RR) of CR was 3.29 [95% confidence interval (95% CI): 2.22-4.88] (P < 0.0001) for the novel agent-based regimens. These novel agent-based regimens showed greater benefit in terms of PFS of all subgroups irrespective of whether the patient received ASCT or not. The hazard ratio (HR) for PFS was 0.64 [95% CI: 0.60-0.69] (P < 0.00001). Improvements of OS could be found only in the bortezomib- and thalidomide-based regimens without ASCT. The pooled HRs were 0.74 [95% CI: 0.65-0.86] (P < 0.0001) and 0.80 [95% CI: 0.70-0.90] (P = 0.0004), respectively. Several AEs were shown more frequently in the novel agent-based regimens compared with controls such as hematologic events (neutropenia, anemia, and thrombocytopenia), gastrointestinal infection, peripheral neuropathy, thrombosis, and embolism events. In conclusion, in spite of the AEs, novel agent-based regimens are safe and effective for the treatment of MM.
...
PMID:Efficacy and Safety of Novel Agent-Based Therapies for Multiple Myeloma: A Meta-Analysis. 2694 4

OBJECTIVETo identify predictors of disagreement with antimicrobial stewardship prospective audit and feedback recommendations (PAFR) at a free-standing children's hospital.DESIGNRetrospective cohort study of audits performed during the antimicrobial stewardship program (ASP) from March 30, 2015, to April 17, 2017.METHODSThe ASP included audits of antimicrobial use and communicated PAFR to the care team, with follow-up on adherence to recommendations. The primary outcome was disagreement with PAFR. Potential predictors for disagreement, including patient-level, antimicrobial, programmatic, and provider-level factors, were assessed using bivariate and multivariate logistic regression models.RESULTSIn total, 4,727 antimicrobial audits were performed during the study period; 1,323 PAFR (28%) and 187 recommendations (15%) were not followed due to disagreement. Providers were more likely to disagree with PAFR when the patient had a gastrointestinal infection (odds ratio [OR], 5.50; 95% confidence interval [CI], 1.99-15.21), febrile neutropenia (OR, 6.14; 95% CI, 2.08-18.12), skin or soft-tissue infections (OR, 6.16; 95% CI, 1.92-19.77), or had been admitted for 31-90 days at the time of the audit (OR, 2.08; 95% CI, 1.36-3.18). The longer the duration since the attending provider had been trained (ie, the more years of experience), the more likely they were to disagree with PAFR recommendations (OR, 1.02; 95% CI, 1.01-1.04).CONCLUSIONSEvaluation of our program confirmed patient-level predictors of PAFR disagreement and identified additional programmatic and provider-level factors, including years of attending experience. Stewardship interventions focused on specific diagnoses and antimicrobials are unlikely to result in programmatic success unless these factors are also addressed.Infect Control Hosp Epidemiol 2018;806-813.
 ...
PMID:Predictors of Antimicrobial Stewardship Program Recommendation Disagreement. 2970 81