Background: The systemic inflammatory response syndrome (SIRS) criteria have not been validated in patients with hematologic malignancies (HM). Objective: To determine whether daily assessment of ...SIRS criteria allows early identification of HM patients who will develop septic shock (SS). Design: Observational, single-center, nested case-control study. Setting: Oncology unit of a tertiary care center. Patients: 547 consecutive, hospitalized, HM subject were enrolled. Using incidence-density sampling, 184 controls were matched to 46 SS cases. Measurements: The study exposure was the SIRS score. The study outcome was the development of SS during the hospitalization. Main Results: 8.4% of subjects developed SS. SIRS scores measured 24 hours prior to SS were significantly higher in cases than in controls (2.1 vs. 1.4, p
Tachycardia-induced cardiomyopathy (TIC) carries significant risk of morbidity and mortality, although full recovery is possible. Little is known about the myocardial recovery pattern.
The purpose of ...this study was to determine the time course and predictors of myocardial recovery in pediatric TIC.
An international multicenter study of pediatric TIC was conducted. Children ≤18 years with incessant tachyarrhythmia, cardiac dysfunction (left ventricular ejection fraction LVEF <50%), and left ventricular (LV) dilation (left ventricular end-diastolic dimension LVEDD z-score ≥2) were included. Children with congenital heart disease or suspected primary cardiomyopathy were excluded. Primary end-points were time to LV systolic functional recovery (LVEF ≥55%) and normal LV size (LVEDD z-score <2).
Eighty-one children from 17 centers met inclusion criteria: median age 4.0 years (range 0.0-17.5 years) and baseline LVEF 28% (interquartile range 19-39). The most common arrhythmias were ectopic atrial tachycardia (59%), permanent junctional reciprocating tachycardia (23%), and ventricular tachycardia (7%). Thirteen required extracorporeal membrane oxygenation (n = 11) or ventricular assist device (n = 2) support. Median time to recovery was 51 days for LVEF and 71 days for LVEDD. Two (4%) underwent heart transplantation, and 1 died (1%). Multivariate predictors of LV systolic functional recovery were age (hazard ratio HR 0.61, P = .040), standardized tachycardia rate (HR 1.16, P = .015), mechanical circulatory support (HR 2.61, P = .044), and LVEF (HR 1.33 per 10% increase, p=0.005). For normalization of LV size, only baseline LVEDD (HR 0.86, P = .008) was predictive.
Pediatric TIC resolves in a predictable fashion. Factors associated with faster recovery include younger age, higher presenting heart rate, use of mechanical circulatory support, and higher LVEF, whereas only smaller baseline LV size predicts reverse remodeling. This knowledge may be useful for clinical evaluation and follow-up of affected children.
Introduction: Febrile neutropenia, a commonly occurring entity in patients (pts) with HM, is treated empirically with antibiotics due to a high risk of developing septic shock. Currently, there is no ...way to predict which hospitalized pts with febrile neutropenia are at greatest risk of developing septic shock. Clinicians have traditionally used systemic inflammatory response syndrome (SIRS) criteria (≥ 2 of the following: RR > 20, HR >90, Temp > 38C or <36C, and WBC >12k or <4k) to facilitate the diagnosis of sepsis and to risk-stratify septic pts. However, it is unknown if SIRS criteria have any discriminatory value in pts with febrile neutropenia who, by definition, meet 2 of 4 of these criteria. Critical care guidelines recommend measuring serum lactate to assess sepsis severity. However, since malignancy itself may produce lactate, the utility of its measurement in this population is not clear. The purpose of this study was to determine the incremental predictive value of serum lactate in addition to the SIRS criteria to predict septic shock in HM pts with febrile neutropenia.
Methods: We tested the association of lactate, tachypnea, and tachycardia with the development of septic shock in hospitalized adult HM pts (age 18–83) in a nested, case-control design within a prospective, single-center, cohort study. Vital signs and lactate were measured during episodes of febrile neutropenia (Temp > 100.4 & ANC < 1000) during hospitalization. We defined an elevated lactate as a level ≥ 2.0 mmol/L. The study endpoint was the development of septic shock, defined as a document or suspected infection resulting in hypotension unresponsive to 1.5 L of IV fluids. The case-control design with incidence-density sampling allowed for maximal efficiency and minimal bias. Controls were matched on length of stay at the time of septic shock in a 4:1 ratio to achieve 80% power to detect an OR (odds ratio) of 2.5. Using multivariable logistic regression and receiver operating curve (ROC) analysis, we evaluated the association of SIRS and lactate with the development of septic shock within 48 hrs following their measurement.
Results: Of the 547 pts enrolled, 46 (8.4%; 95% confidence interval CI: 6.2–10.9) developed septic shock. Baseline characteristics including age, vital signs, ANC, medications, and lactate were similar between the groups. The mean baseline lactate (1.0 mmol/L; 95% CI: 0.5–2.0) for the cohort was similar to our hospital's normal range (.7–2.1mmol/L). In univariate analysis of HR, RR and lactate, only tachypnea (RR>20) (OR 5.9; 95% CI: 2.0–16.9, p =.001) and elevated lactate level (OR 18.4; 95% CI: 4.1–81.6, p <.001) were significantly associated with the subsequent development of septic shock. In multivariate analysis, lactate and RR remained independent predictors of septic shock (lactate, OR=12.1; 95% CI: 2.1–70.1, p=.005; tachypnea, OR=7.6; 95%CI: 1.6–35.5, p=.01). The area under the ROC curve for the SIRS+LA model was significantly higher than that of the SIRS model alone (0.75 and .69 respectively, p=.02).
Conclusions: In febrile neutropenic pts, measurement of tachypnea is the only SIRS criteria with independent prognostic importance for the development of septic shock. In addition to RR, measurement of serum lactate (a valid, inexpensive, readily available laboratory test) at the time of febrile neutropenia, adds significant value in the prediction of which HM pts are at increased risk of developing septic shock. Although further study is required to validate these results, routine measurement of lactate may help identify pts who may benefit from increased monitoring and early intervention strategies.
There is limited evidence regarding the impact of cardiology involvement in the care of cancer patients.
This study evaluated the impact of cardiology involvement on guideline-adherent cardiovascular ...monitoring and risk factor management in patients with breast cancer treated with trastuzumab.
In a single-center retrospective cohort study, electronic health records from 1,047 patients with breast cancer receiving trastuzumab between January 2009 and July 2018 were evaluated. A visit to a cardiology provider beginning from the 3 months before cancer therapy initiation until the last contact date defined cardiology involvement. Guideline-adherent monitoring, defined by echocardiography assessment within the 4 months before trastuzumab initiation and follow-up echocardiography at least every 4 months during therapy, was compared in patients with and without cardiology involvement before treatment initiation. Multivariable associations between cardiology involvement and the time-varying risk factors blood pressure and body mass index (BMI) were assessed by using generalized estimating equations.
Cardiology involvement occurred in 293 (28%) patients. A higher proportion of patients with cardiology involvement before trastuzumab initiation had guideline-adherent monitoring (76.4% vs. 60.1%; p = 0.007). Cardiology involvement was associated with an average 1.5 mm Hg (95% CI: –2.9 to –0.1; p = 0.035) lower systolic blood pressure, which was more pronounced in those with hypertension (–2.7 mm Hg; 95% CI: –4.6 to –0.7; p = 0.007). Cardiology involvement was associated with a lower BMI in patients with baseline BMI ≥25 kg/m2 (mean difference: –0.5 kg/m2; 95% CI: –1.0 to –0.1; p = 0.027).
Cardiology involvement in patients with breast cancer treated with trastuzumab is associated with greater adherence to cardiovascular monitoring and modest improvements in risk factor control.
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Oroxylum indicum
is traditional herbal medicine in India, China and Japan used for its anti-diarrhoeal/anti-dysenteric activity, also found to be active against experimentally induced (DNBS induced) ...inflammatory bowel disease in rats with potential reduction in diarrhoea. It promotes us to evaluate effects of
Oroxylum indicum
on intestinal motility, both in vitro and in vivo, in rodents. Flavonoids rich fraction of
O. indicum
was obtained and the effect of extract on contraction of acetylcholine, barium chloride and electrical field stimulation was studied on isolated rabbit ileum. Anti-diarrhoeal activities were investigated using castor oil and magnesium sulphate-induced diarrhoeal models in mice. Effect on intestinal motility was studied using gastrointestinal motility and antienteropooling assay methods. Antimicrobial activity of extract was evaluated using disc diffusion assay method. Extract inhibited the contractions induced by acetylcholine, barium chloride and electrical field stimulation. Verapamil potentiates inhibitory effect of extract. Extract showed significant and dose-dependent anti-diarrhoeal effect devoid of altering gastrointestinal motility in normal animals. It also inhibited the microbial growth in disc diffusion assay method. Extract normalized intestinal motility altered by inflammatory stimulus and possesses antidiarrhoeal activity. Alteration of intestinal motility may involve modification in L-type Ca
2+
channels.
Oroxylum indicum is traditional herbal medicine in India, China and Japan used for its anti-diarrhoeal/anti-dysenteric activity, also found to be active against experimentally induced (DNBS induced) ...inflammatory bowel disease in rats with potential reduction in diarrhoea. It promotes us to evaluate effects of Oroxylum indicum on intestinal motility, both in vitro and in vivo, in rodents. Flavonoids rich fraction of O. indicum was obtained and the effect of extract on contraction of acetylcholine, barium chloride and electrical field stimulation was studied on isolated rabbit ileum. Anti-diarrhoeal activities were investigated using castor oil and magnesium sulphate-induced diarrhoeal models in mice. Effect on intestinal motility was studied using gastrointestinal motility and antienteropooling assay methods. Antimicrobial activity of extract was evaluated using disc diffusion assay method. Extract inhibited the contractions induced by acetylcholine, barium chloride and electrical field stimulation. Verapamil potentiates inhibitory effect of extract. Extract showed significant and dose-dependent antidiarrhoeal effect devoid of altering gastrointestinal motility in normal animals. It also inhibited the microbial growth in disc diffusion assay method. Extract normalized intestinal motility altered by inflammatory stimulus and possesses antidiarrhoeal activity. Alteration of intestinal motility may involve modification in L-type $Ca^{2+}$ channels.
Idecabtagene vicleucel (ide-cel, also called bb2121), a B-cell maturation antigen-directed chimeric antigen receptor (CAR) T-cell therapy, has shown clinical activity with expected CAR T-cell toxic ...effects in patients with relapsed and refractory multiple myeloma.
In this phase 2 study, we sought to confirm the efficacy and safety of ide-cel in patients with relapsed and refractory myeloma. Patients with disease after at least three previous regimens including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody were enrolled. Patients received ide-cel target doses of 150 × 10
to 450 × 10
CAR-positive (CAR+) T cells. The primary end point was an overall response (partial response or better); a key secondary end point was a complete response or better (comprising complete and stringent complete responses).
Of 140 patients enrolled, 128 received ide-cel. At a median follow-up of 13.3 months, 94 of 128 patients (73%) had a response, and 42 of 128 (33%) had a complete response or better. Minimal residual disease (MRD)-negative status (<10
nucleated cells) was confirmed in 33 patients, representing 26% of all 128 patients who were treated and 79% of the 42 patients who had a complete response or better. The median progression-free survival was 8.8 months (95% confidence interval, 5.6 to 11.6). Common toxic effects among the 128 treated patients included neutropenia in 117 patients (91%), anemia in 89 (70%), and thrombocytopenia in 81 (63%). Cytokine release syndrome was reported in 107 patients (84%), including 7 (5%) who had events of grade 3 or higher. Neurotoxic effects developed in 23 patients (18%) and were of grade 3 in 4 patients (3%); no neurotoxic effects higher than grade 3 occurred. Cellular kinetic analysis confirmed CAR+ T cells in 29 of 49 patients (59%) at 6 months and 4 of 11 patients (36%) at 12 months after infusion.
Ide-cel induced responses in a majority of heavily pretreated patients with refractory and relapsed myeloma; MRD-negative status was achieved in 26% of treated patients. Almost all patients had grade 3 or 4 toxic effects, most commonly hematologic toxic effects and cytokine release syndrome. (Funded by bluebird bio and Celgene, a Bristol-Myers Squibb company; KarMMa ClinicalTrials.gov number, NCT03361748.).
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