Monocyte or white blood cell counts and β₂ microglobulin predict the durable efficacy of daratumumab with lenalidomide

BACKGROUND: Daratumumab is one of the most widely used treatments for relapsed/refractory multiple myeloma (MM) patients. However, not all patients achieve a lasting therapeutic response with daratumumab. OBJECTIVES: We hypothesized that a durable response to daratumumab could be predicted by the balance between the MM tumor burden and host immune status. DESIGN: We conducted a retrospective study using the real-world data in the Kansai Myeloma Forum (KMF) database. METHODS: We retrospectively analyzed 324 relapsed/refractory MM patients who were treated with daratumumab in the KMF database. RESULTS: In this study, 196 patients were treated with daratumumab, lenalidomide, and dexamethasone (DLd) regimen and 128 patients were treated with daratumumab, bortezomib, and dexamethasone (DBd) regimen. The median age at treatment, number of prior treatment regimens and time-to-next-treatment (TTNT) were 68, 4 and 8.02 months, respectively. A multivariate analysis showed that the TTNT under the DLd regimen was longer with either higher monocyte counts (analysis 1), higher white blood cell (WBC) counts (analysis 2), lower β2 microglobulin (B2MG < 5.5 mg/L) or fewer prior regimens (<4). No parameters were correlated with TTNT under the DBd regimen. CONCLUSION: We propose a simple scoring model to predict a durable effect of the DLd regimen by classifying patients into three categories based on either monocyte counts (0 points for ⩾200/μl; 1 point for <200/μl) or WBC counts (0 points for ⩾3500/μl; 1 point for <3500/μl) plus B2MG (0 points for <5.5 mg/L; 1 point for ⩾5.5 mg/L). Patients with a score of 0 showed significantly longer TTNT and significantly better survival compared to those with a score of 1 or 2 (both p < 0.001). To confirm this concept, our results will need to be validated in other cohorts

Early-phase changes of extravascular lung water index as a prognostic indicator in acute respiratory distress syndrome patients

Background: The features of early-phase acute respiratory distress syndrome (ARDS) are leakage of fluid into the extravascular space and impairment of its reabsorption, resulting in extravascular lung water (EVLW) accumulation. The current study aimed to identify how the initial EVLW values and their change were associated with mortality. Methods: This was a post hoc analysis of the PiCCO Pulmonary Edema Study, a multicenter prospective cohort study that included 23 institutions. Single-indicator transpulmonary thermodilution-derived EVLW index (EVLWi) and conventional prognostic factors were prospectively collected over 48 h after enrollment. Associations between 28-day mortality and each variable including initial (on day 0), mean, maximum, and Δ (subtracting day 2 from day 0) EVLWi were evaluated. Results: We evaluated 192 ARDS patients (median age, 69 years (quartile, 24 years); Sequential Organ Failure Assessment (SOFA) score on admission, 10 (5); all-cause 28-day mortality, 31%). Although no significant differences were found in initial, mean, or maximum EVLWi, Δ-EVLWi was significantly higher (i.e., more reduction in EVLWi) in survivors than in non-survivors (3.0 vs. ?0.3 mL/kg, p = 0.006). Age, maximum, and Δ-SOFA scores and Δ-EVLW were the independent predictors for survival according to the Cox proportional hazard model. Patients with Δ-EVLWi > 2.8 had a significantly higher incidence of survival than those with Δ-EVLWi ? 2.8 (log-rank test, χ2 = 7.08, p = 0.008). Conclusions: Decrease in EVLWi during the first 48 h of ARDS may be associated with 28-day survival. Serial EVLWi measurements may be useful for understanding the pathophysiologic conditions in ARDS patients. A large multination confirmative trial is required

CLINICAL AND BIOCHEMICAL STUDIES ON THE BASIS OF KETONE BODIES IN CATTLE : II. URINE KETONE BODIES IN NORMAL DAIRY CATTLE

These clinical and biochemical studies were made on the basis of the urine ketone bodies in 368 clinically healthy dairy cows. The results thus obtained may be summarized as follows. 1. The values for the urine ketone bodies of the clinically healthy cows varied so widely that they were statistically divided into 2 groups, viz., "normal and sub-normal groups". 2. The mean values for the ketone bodies of the normal group were 6.19 (2.12〜43.41) mg/100 ml in total ketone, and 1.25 (0.18〜24.95) mg/100 ml in free acetone. 3. The mean values for the ketone bodies of the sub-normal group were 122.50 (47.97〜258.00) mg/100 ml in total ketone, and 54.50 (25.83〜123.00) mg/100 ml in free acetone. 4 The values for free acetone, acetoacetic acid and β-hydroxybutyric acid increased in accordance with the increase of the total ketone. 5. All of the internal and external factors exerted influence upon the rise and fall of the total ketone, especially the stress of parturition, milk yield, season and feeding-management are very important. 6. The strength of the sugar and urobilinogen reaction in urine runs in parallel with the increase of the urine ketones. 7. In the sub-norml group, not only the increase of the ketone bodies but also increase of the blood sugar level and marked decrease in number of eosinophilic leucocytes were clarified

CLINICAL AND BIOCHEMICAL STUDIES ON THE BASIS OF KETONE BODIES IN CATTLE : I. BLOOD KETONE BODIES IN NORMAL DAIRY CATTLE

These clinical and biochemical studies were made on the basis of the blood ketone bodies in 368 clinically healthy dairy cows. The result thus obtained may be summarized as follows. 1. The values for the blood ketone bodies of the clinically healthy cows varied so widely that they were statistically divided into 2 groups, viz., "normal and sub-normal groups." 2. The mean values for the ketone bodies of the normal group were 3.11 (0.99〜11.17)mg/100ml in total ketone, and 0.79 (0.22〜4.53)mg/100ml in free acetone. 3. The mean values for the ketone bodies of the sub-normal group were 39.10 (12.30〜73.80)mg/100ml in total ketone, and 8.23 (5.20〜10.50)mg/100ml in free acetone. 4. The values for free acetone, acetoacetic acid and β-hydroxybutyric acid increased in accordance with the increase of the total ketone. 5. All of the internal and external factors exerted influence upon the rise and fall of the total ketone, especially, it may be supposed that the stress of parturition, milk yield, season and feeding-management were very important. 6. It was clarified that the sub-normal group showed not only the increase of the ketone bodies but also increase of the blood sugar level and marked decrease in number of eosinophilic leucocytes

Gene Mutations Responsible for Overexpression of AmpC β-Lactamase in Some Clinical Isolates of Enterobacter cloacae

AmpC regulatory genes in 21 ceftazidime-resistant clinical isolates of Enterobacter cloacae (MICs of ≥16 μg/ml) were characterized. All isolates exhibited AmpC overproduction due to AmpD mutation. Additionally, we found two AmpR mutants among the isolates. This is the first report of chromosomal ampR mutation in clinical isolates of E. cloacae