Clinical Response Failure Research Articles

The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients

Bispecific Tcell engagers (TCEs) have shown promise in the treatment of various cancers, but the immunological mechanism and molecular determinants of primary and acquired resistance to TCEs remain poorly understood. Here, we identify conserved behaviors of bone marrow-residing Tcells in multiple myeloma patients undergoing BCMAxCD3 TCE therapy. We show that the immune repertoire reacts to TCE therapy with cell state-dependent clonal expansion and find evidence supporting the coupling of tumor recognition via major histocompatibility complex class I (MHC class I), exhaustion, and clinical response. We find the abundance of exhausted-like CD8+ Tcell clones to be associated with clinical response failure, and we describe loss of target epitope and MHC class I as tumor-intrinsic adaptations to TCEs. These findings advance ourunderstanding of the invivo mechanism of TCE treatment in humans and provide the rationale for predictive immune-monitoring and conditioning of the immune repertoire to guide future immunotherapy in hematological malignancies.

Implications of Antibiotic Resistance for Patients' Recovery From Common Infections in the Community: A Systematic Review and Meta-analysis.

Antibiotic use is the main driver for carriage of antibiotic-resistant bacteria. The perception exists that failure of antibiotic treatment due to antibiotic resistance has little clinical impact in the community. We searched MEDLINE, EMBASE, PubMed, Cochrane Central Register of Controlled Trials, and Web of Science from inception to 15 April 2016 without language restriction. We included studies conducted in community settings that reported patient-level data on laboratory-confirmed infections (respiratory tract, urinary tract, skin or soft tissue), antibiotic resistance, and clinical outcomes. Our primary outcome was clinical response failure. Secondary outcomes were reconsultation, further antibiotic prescriptions, symptom duration, and symptom severity. Where possible, we calculated odds ratios with 95% confidence intervals by performing meta-analysis using random effects models. We included 26 studies (5659 participants). Clinical response failure was significantly more likely in participants with antibiotic-resistant Escherichia coli urinary tract infections (odds ratio [OR] = 4.19; 95% confidence interval [CI] = 3.27-5.37; n = 2432 participants), Streptococcus pneumoniae otitis media (OR = 2.51; 95% CI = 1.29-4.88; n = 921 participants), and S. pneumoniae community-acquired pneumonia (OR = 2.15; 95% CI = 1.32-3.51; n = 916 participants). Clinical heterogeneity precluded primary outcome meta-analysis for Staphylococcus aureus skin or soft-tissue infections. Antibiotic resistance significantly impacts on patients' illness burden in the community. Patients with laboratory-confirmed antibiotic-resistant urinary and respiratory-tract infections are more likely to experience delays in clinical recovery after treatment with antibiotics. A better grasp of the risk of antibiotic resistance on outcomes that matter to patients should inform more meaningful discussions between healthcare professionals and patients about antibiotic treatment for common infections.

Failure to respond to IV metoclopramide at gastric emptying scan does not predict failure of clinical response to oral prokinetics

Failure to respond to IV metoclopramide at gastric emptying scan does not predict failure of clinical response to oral prokinetics

Postpartum ovarian vein thrombosis after vaginal delivery: A report of 11 cases

To review and characterize the presentation of postpartum ovarian vein thrombosis after vaginal delivery. We reviewed medical records of patients with the prior diagnosis of septic pelvic thrombophlebitis, deep vein thrombosis, and pulmonary embolism associated with pregnancy. The study covered the 10-year period from July 1984 through August 1994 and included women hospitalized at E.H. Crump Women's Hospital, Regional Medical Center, University of Tennessee, Memphis, Tennessee. During the study period, there were 76,858 deliveries: 13,109 cesareans and 63,749 vaginal deliveries. Eleven patients had documented postpartum ovarian vein thrombosis after vaginal delivery. Ten patients were readmitted an average of 7.6 days after delivery (range 3-17). The diagnosis was documented by computed tomography (CT) scan or ultrasound in ten women and laparotomy in one. Nine patients were readmitted with the presumptive diagnosis of endometritis, the other two with the presumptive diagnosis of pyelonephritis. Nine were treated initially with ampicillin, gentamicin, and clindamycin. Heparin therapy was added when failure of clinical response was noted. No patient defervesced within 24 hours of beginning heparin therapy; only two patients defervesced within 48 hours, and the remaining patients became afebrile at an average of 6.8 days (range 4-18, median 5). The diagnosis of ovarian vein thrombosis should be considered early in the care of patients readmitted with a diagnosis of endometritis after vaginal delivery. If prompt defervescence does not occur with aggressive intravenous antibiotic therapy, a CT scan should be obtained in a timely manner for prompt diagnosis and therapy. Our findings do not support the time-honored rule that septic pelvic thrombophlebitis and ovarian vein thrombosis respond within 24-48 hours to therapeutic anticoagulation with heparin.

Management of postoperative infections in obstetrics and gynecology.

A discussion of postoperative infections in obstetrics and gynecology has been presented with particular emphasis on soft tissue infections involving the operative site. It has been emphasized that the offending organisms are those normally found in the vagina and cervix and that mixed infections are common. The immediate life threats to the patient are endotoxin shock and clostridial sepsis; therefore, initial therapy should include coverage for those organisms. Because of the potential toxicity of clindamycin and chloramphenicol, as well as the usual protracted course of Bacteroides infections, the addition of one of these drugs can generally be deferred until its use is dictated by microbiologic data or a failure of clinical response. Persistent fever generally indicates a lack of the appropriate antibiotic, an undrained collection of pus, or concomitant pelvic thrombophlebitis, the latter being a special concern with anaerobic infections. Specific infections and their management have also been discussed as have urinary tract and pulmonary infections and drug fever.