Real-world effectiveness and safety analysis of carfilzomib-lenalidomide-dexamethasone and carfilzomib-dexamethasone in relapsed/refractory multiple myeloma: a multicenter retrospective analysis

Background: Little is known about the real-world survival benefits and safety profiles of carfilzomib-lenalidomide-dexamethasone (KRd) and carfilzomib-dexamethasone (Kd). Methods: We performed a retrospective analysis to evaluate their efficacy and safety in 157 patients registered in the Kansai Myeloma Forum database. Results: A total of 107 patients received KRd. Before KRd, 99% of patients had received bortezomib (54% were refractory disease), and 82% had received lenalidomide (57% were refractory disease). The overall response rate (ORR) was 68.2%. The median progression-free survival (PFS) and overall survival (OS) were 8.8 and 29.3 months, respectively. Multivariate analysis showed that reduction of the carfilzomib dose and non-IgG M protein were significantly associated with lower PFS and reduction of the carfilzomib dose and refractoriness to prior bortezomib-based regimens were significantly associated with lower OS. A total of 50 patients received Kd. Before Kd, 96% of patients had received bortezomib (54% were refractory disease). The ORR was 62.0%. The median PFS and OS were 7.1 and 20.9 months, respectively. Based on the multivariate analysis, reduction of the carfilzomib dose and International Staging System Stage III (ISS III) were significantly associated with lower PFS. Grade III or higher adverse events were observed in 48% of KRd cases and 54% of Kd cases. Cardiovascular events, cytopenia, and infections were frequent, and 4 KRd patients died due to heart failure, arrhythmia, cerebral hemorrhage, and pneumonia. Conclusion: Our analysis showed that an adequate dose of carfilzomib is important for achieving the best survival benefits in a real-world setting. Adverse effects after KRd and Kd therapy should also be considered

Associations between Sleep-Disordered Breathing and Metabolic Risk Factors beyond Obesity

金沢大学附属病院代謝内科Objective. Individuals with multiple metabolic risk factors often experience concomitant sleep-disordered breathing (SDB). We aimed to determine the associations of SDB with individual components of metabolic syndrome independent of obesity. Methods. A cross-sectional study was conducted in 1137 employees aged 30–64 years. Apnea-hypopnea index (AHI) was assessed using a portable monitor for obstructive sleep apnea by admission. Of these, 451 participants took an oral glucose tolerance test to assess homeostatic model assessment of insulin resistance (HOMA-IR) and Matsuda insulin sensitivity index (ISI). Results. The odds ratio (OR) of the highest category of the AHI (≥15 episodes per hour) compared to the lowest one (<5 episodes per hour) was significantly elevated for hypertension, for hypertriglyceridemia, and for low HDL-cholesterolemia when adjusted for age, sex, and alcohol and smoking status (). After further adjustment for body mass index (BMI) or waist circumference, the associations for hypertension still remained statistically significant () while those for hypertriglyceridemia and low HDL-cholesterolemia were no longer significant. The association between higher insulin resistance as assessed by HOMA-IR and Matsuda ISI and higher categories of the AHI was also lost after adjustment for BMI. Conclusion. Obesity was a strong confounding factor in the association between SDB and most metabolic risk factors including insulin resistance, except for hypertension. Further longitudinal study is needed to examine the temporal or causal relationships between SDB and metabolic risk factors. This trial is registered with UMIN-CTR UMIN000028067

Feeding habits of juvenile slime flounder Microstomus achne in the coastal area of southern Hokkaido

A total of 45 juvenile [30.0–57.4 mm total length (TL)] slime flounder Microstomus achne were collected in the coastal area of southern Hokkaido from April to July in 2001 and April to June in 2002. Their diets were analyzed. Slime flounder juveniles of 30.0–39.9 mm TL fed predominantly on small crustaceans (gammarid amphipods, harpacticoids and cumaceans) and those of 40.0–57.4 mm TL on gammarid amphipods, cumaceans and polychaetes. The major prey items changed with growth from small crustaceans (e.g., harpacticoids) to polychaetes, although gammarid amphipods were the major prey items throughout the juvenile period (30.0–57.4 mm TL)

Embryonic development and effect of water temperature on hatching of Lophius litulon

Most Lophiiformes including Lophius species are considered to spawn egg masses called an "egg veil" or "egg ribbon" composed of numerous mucoid chambers. However, Lophius eggs have been rarely collected in the field and thus little is known about their biological features. Here we examined the embryonic development of Lophius litulon and also the effects of water temperature on the embryonic development of eggs from egg veils collected in the field. Embryonic development was observed from the late cleavage stage to hatching. Low rates of mortality and deformity of embryos and early larvae were observed at 13-21 degrees C. The estimated appropriate water temperature range closely approximated the range of temperatures (12-20 degrees C) at which egg veils of L. litulon have been found in the field. Embryonic development accelerated with increased water temperatures. These results will enable estimation of the origin of and passive movement of egg veils and subsequently larvae and will help to reveal the spatiotemporal distribution of the spawning and nursery grounds of L. litulon

Differences in body proportions between hatchery-reared- and wild Pacific herring, Clupea pallasii (Actinopterygii: Clupeiformes: Clupeidae)

The body proportions of 0-group Pacific herring, Clupea pallasii, were compared between hatchery-reared- and wild fish and significant differences were observed. There were fewer vertebrae (Mean ± SD) in hatchery-reared- (52.5 ± 2.15) than in wild fish (53.7 ± 0.92). For both the hatchery-reared- and the wild individuals, the correlations between number of vertebrae and vertebral column length (VCL) per standard length (SL) were positive. Head length (HL) was approximated as SL minus VCL. Therefore, the proportion of HL in relation to SL became lower with the higher number of vertebrae. Their vertebral number may relate to the difference of body proportions between hatchery-reared- and wild fish

Interannual growth differences and growth-selective survival in larvae and juveniles of marbled sole Pseudopleuronectes yokohamae

Flatfishes drastically change their habitat, body form, and feeding during metamorphosis; thus, the early juvenile and larval stages are viewed as being critical for early survival. However, to the best of our knowledge, no studies have tested the growth-mortality hypothesis for both larval and juvenile stages of flatfishes. Therefore, we investigated the relationship between growth rate and environmental factors and tested the hypothesis for both larval and juvenile stages of marbled sole Pseudopleuronectes yokohamae in Hakodate Bay, Japan from 2001 to 2003. For both larval and juvenile stages, otolith growth correlated with water temperature. Eye-migrating larvae were defined as survivors of planktonic life (SV pelagic). Large juveniles captured in late June and July were defined as survivors of shrimp predation (SVjuvenile). To test the growth-mortality hypothesis, otolith growth was compared between the SV and the original population. During the pelagic larval stage, growth-selective survival was not detected in any of the 3 yr. During the early juvenile stage, fast-growing individuals survived selectively in 2002 but not in 2003. In 2002, population growth of juveniles was slow because water temperatures were low. Thus, juveniles in 2002 required time to exceed the size spectrum that is vulnerable to shrimp predation; consequently, the individuals that grew more rapidly were able to survive selectively. Our results show the importance of the early juvenile stage for the survival of flatfishes

Maternal effects and larval survival of marbled sole Pseudopleuronectes yokohamae

Maternal effects of animals are the phenotypic influences of age, size, and condition of spawners on the survival and phenotypic traits of offspring. To clarify the maternal effects for marbled sole Pseudopleuronectes yokohamae, we investigated the effects of body size, nutrient condition, and growth history of adult females on egg size, larval size, and starvation tolerance, growth, and feeding ability of offspring. The fecundity of adult females was strongly dependent on body size. Path analysis revealed that the mother's total length positively affected mean egg diameter, meaning that large females spawned large eggs. In contrast, the relative growth rate of adult females negatively affected egg diameter. Egg diameters positively affected both notochord length and yolk sac volume of the larvae at hatching. Under starvation conditions, notochord length at hatching strongly and positively affected days of survival at 14 °C but not at 9 °C. Under adequate food conditions (1000 rotifers L− 1), the notochord length of larvae 5 days after hatching positively affected feeding rate, implying that large larvae have high feeding ability. In addition, the mean growth rate of larvae between 0 and 15 days increased with increasing egg diameter under homogenous food conditions, suggesting that larvae hatched from large eggs might have a growth advantage for at least to 15 days after hatching. In marbled sole, these relationships (i.e., mother's body size-egg size-larval size-larval resistance to starvation-larval feeding ability) may help explain recruitment variability

Annual variation of potential predation impacts on larval and juvenile marbled sole Pseudopleuronectes yokohamae by sand shrimp Crangon uritai in Hakodate Bay, Hokkaido

An investigation was conducted to evaluate the annual variation in potential predation impact (PPI) on larval and juvenile Pseudopleuronectes yokohamae by Crangon uritai in Hakodate Bay using predator–prey size relationships. Laboratory experiments were designed to estimate the favorable prey size of C. uritai through back-calculation of body length (BL) of P. yokohamae from sagittal otolith diameter observed in the stomachs of C. uritai. The most favorable prey–predator size ratio (BL of P. yokohamae–total length (TL) of C. uritai) class was 0.15–0.19, and ranged from 0.12–0.31. There was a significant positive correlation between the BL increase of P. yokohamae and the bottom water temperature in the field, such that BLs stagnated during the cold year of 1999 from April to June, and increased during the warm year of 2002. In contrast, no significant correlation was found between the TL increase of C. uritai and the bottom water temperature. Moreover, there were no significant differences in the mean TL of C. uritai between months (April–June) or years (1998–2002). Variation of PPI depended on the relationships between the growth rates of P. yokohamae and bottom water temperature. Therefore, the warm year of 2002 resulted in higher potential predation impact (PPI ≥ 20), and it was at least 20 days shorter than that of the cold year of 1999. These results suggest that increased bottom water temperature in the nursery area was one of the most important factors for cumulative predation loss

Spatial distribution and feeding habits of the shrimp Crangon uritai as a predator on larval and juvenile marbled sole Pleuronectes yokohamae

To examine predation on larval and juvenile Pleuronectes yokohamae by Crangon uritai, the spatial distribution and feeding habits of C. uritai were studied. Crangon uritai fed on various prey, including P. yokohamae. Density-dependent predation on juvenile Crangon spp., larval and juvenile gobiid fish Chaenogobius heptacanthus, mysids, and gammarids was observed. The abundance of alternative prey might, therefore, play an important role in reducing the pressure of predation on P. yokohamae. In each year, C. uritai migrated from depths of 10 m in March to depths of 3 m in May. There was a significant negative correlation between the weighted mean depth (WMD) of C. uritai and the weighted mean bottom water temperature (WMBWT). The migration was, therefore, delayed in the cold spring, during which C. uritai occupied depths of approximately 10 m. In contrast, no significant correlation was found between the WMD of P. yokohamae and WMBWT. Settlement of P. yokohamae began at depths of 15 m, mainly during early April. The spatial distributions of these two organisms show greater overlap during the cold spring, resulting in increased opportunities for predation