Optimal index for detecting splenic involvement on 18F-fluorodeoxyglucose positron emission tomography/computed tomography imaging in diffuse large B-cell lymphoma.

Accurate clinical staging is important in diffuse large B-cell lymphoma (DLBCL) to adapt to optimal therapy. Splenic involvement of DLBCL has been recently more detectable with the advancement of a diagnostic scan by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT). Our clinical question is whether splenic involvement was adequately diagnosed by FDG-PET/CT imaging. This retrospective study aimed to determine the optimal index for evaluating splenic involvement in patients with DLBCL. Patients with newly diagnosed DLBCL who were examined with FDG-PET/CT at diagnosis and the end of induction chemotherapy (EOI) was enrolled. The splenic involvement with the splenic FDG uptake value higher than that of the liver at diagnosis or with the decrease of splenic uptake at EOI by visual evaluation was evaluated as positive. The calculative evaluation of splenic involvement, based on the data of standardized uptake value (SUV) of the spleen, used maximum SUV (SUVmax), mean SUV (SUVmean), spleen total lesion glycolysis (spleen TLG), and spleen length. A change in each index following induction chemotherapy was expressed as an index. Receiver operating characteristic analysis was used to set the cutoff value for each index. This study included 52 patients. Spleen TLG (0.904) showed the best accuracy, followed by SUVmax (0.885) and SUVmean (0.885), among the 5 indexes for splenic involvement at diagnosis. Splenic involvement was predicted with a higher accuracy level (0.923) when selecting the cases with values higher than the cutoff level on both spleen TLG and SUVmax. The decision at EOI was more suitable by selecting both positive cases of ∆ TLG and ∆ SUVmax. Obtaining both the positive spleen TLG and SUVmax is recommended at diagnosis to predict splenic involvement. The assessment by ∆ spleen TLG and ∆ SUVmax seems to be optimal.

Male elite soccer players have a higher incidence of accessory ossicles in the foot and ankle.

PURPOSE: Accessory ossicles are caused by the failure of the fusion of secondary ossification centres and are more likely to occur due to heavy loading during the growth period or improper treatment after injury. This study aimed to investigate the incidence of foot and ankle accessory ossicles in male professional soccer players. METHODS: This study included male professional soccer players who underwent medical checkups at our hospital between 2017 and 2023 as the soccer group. Medical checkups included radiographs of bilateral anteroposterior and oblique foot, as well as bilateral anteroposterior and lateral ankle. Male patients age-matched with the soccer group who visited our hospital undergoing anteroposterior and oblique foot or anteroposterior and lateral ankle radiography were included in the control group. The incidence of accessory ossicles was investigated and compared between the soccer and control groups. RESULTS: In this study, 276 ankles and 276 feet, as well as 121 ankles and 79 feet, were included in the soccer and control groups, respectively. The incidence of accessory ossicles in the soccer and control groups was as follows: accessory navicular 35.9%, 24% (P = .049), os peroneum 8.0%, 2.5% (P = .09); os supranaviculare 7.6%, 1.3% (P = .039); os infranaviculare 1.4%, 1.3% (P = .090); os calcaneus secundarius 4.3%, 0% (P = .059); os vesalianum 0%, 0%; os subfiblare 12.7%, 2.5% (P < .001); os subtibiale 18.1%, 2.5% (P = .001); and os trigonum 89%, 24% (P < .001). CONCLUSIONS: Male professional soccer players had a higher incidence of accessory navicular, os supranaviculare, os subfiblare, os subtibiale, and os trigonum.

The lactate response to a second bout of exercise is not reduced in a concurrent lower-limb exercise program.

We aimed to evaluate the blood lactate level in response to two bouts of exercise. First, we hypothesized that blood lactate elevation in response to moderate-intensity aerobic exercise (MIAE) would be lower at the end of the second bout of MIAE than the first bout of MIAE. In this context, we also hypothesized that lactate accumulation at the end of resistance exercise (RE) would be reduced if MIAE is performed before RE (i.e., concurrent exercise; CE). If so, we hypothesized that the order of the CE (i.e., RE + MIAE vs. MIAE + RE) influences blood lactate kinetics. To test the hypotheses, forty-three healthy men participated in three studies. In study 1, 20 men (age 21 ± 2 years) performed two bouts of a 20-min MIAE separated by a 20-min rest interval. In study 2, 11 men (age 22 ± 1 years) performed RE only and CE (MIAE + RE; ARCE) with a 20-min rest interval in a crossover design. In study 3, 12 men (age 21 ± 2 years) performed both CEs, which were ARCE and RE + MIAE (RACE), with a 20-min rest interval in a crossover design. We measured blood lactate before and at the end of each exercise session. In study 1, the blood lactate response to the second bout of MIAE was lower than that of the first bout (P < 0.001, r = 0.68). However, the blood lactate response to the ARCE trial was not lower than the response to the RE trial in study 2 (P = 0.475, r = 0.22). The results of study 3 showed that the RACE and ARCE trials induced a similar lactate response (MIAE P = 0.423, r = 0.28; RE P = 0.766, d = 0.03). These observations indicate that whereas lactate accumulation might be diminished by a second bout of MIAE, a different type of exercise (i.e., aerobic/resistance) did not result in a diminished lactate accumulation in response to a second bout of exercise.

[Large-vessel vasculitis developed after use of long-acting granulocyte colony-stimulating factor in a patient with diffuse large B-cell lymphoma].

A 75-year-old man was diagnosed with diffuse large B-cell lymphoma originating from the paranasal sinuses. Curative induction chemotherapy was initiated and pegfilgrastim was administered on day5 of the first cycle as primary prophylaxis. The patient developed headache on day7 and fever on day11. These symptoms persisted despite treatment with antibiotics and antifungal agents. Computed tomography (CT) after admission revealed wall thickening in the aortic arch. Chest contrast-enhanced CT also revealed contrast enhancement in the thickened aortic wall. Results of blood cultures and serological tests for autoantibodies were negative, indicating that the clinical manifestations were not due to infection or a specific collagen disease. The final diagnosis was drag-induced large vessel vasculitis induced by long-acting granulocyte colony-stimulating factor (G-CSF). The patient's symptoms and large-vessel wall thickening immediately resolved after treatment with a glucocorticoid (prednisolone, 0.6 mg/kg/day). Aortitis should be considered as a differential diagnosis when fever is observed in a patient who received long-acting G-CSF during chemotherapy.

Investigating the Combined Effects of Mechanical Stress and Nutrition on Muscle Hypertrophic Signals Using Contractile 3D-Engineered Muscle (3D-EM).

Since 3D-EM closely resembles in vivo muscles, the aim of this study was to investigate the effects of exercise (electrical pulse stimulation (EPS)) and nutrition (maca), which contains triterpenes, on muscle hypertrophy by using 3D-EM for the first time. The 3D-EM was composed of C2C12 cells and type 1 collagen gel, was differentiated for 14 days, and was divided into four groups: control, maca, EPS, and maca + EPS. The medium was replaced every two days before each EPS intervention, and the concentration of maca in the culture solution was 1 mg/mL. The intervention conditions of the EPS were 30 V, 1 Hz, and 2 ms (24 h on, 24 h off, for one week). The expression levels of proteins were examined by Western blotting. The intervention of maca and EPS upregulated the expression of MHC-fast/slow (both p < 0.05) compared with the control group, and the addition of maca had no effect on the phosphorylation of mTOR (p = 0.287) but increased the AMPK phosphorylation (p = 0.001). These findings suggest that intervention with maca and EPS has a positive effect on muscle hypertrophy, which has a positive impact on sarcopenia. However, the underlying mechanisms remain to be further explored.

Breakpoints in complex chromosomal rearrangements correspond to transposase-accessible regions of DNA from mature sperm.

Constitutional complex chromosomal rearrangements (CCRs) are rare cytogenetic aberrations arising in the germline via an unknown mechanism. Here we analyzed the breakpoint junctions of microscopically three-way or more complex translocations using comprehensive genomic and epigenomic analyses. All of these translocation junctions showed submicroscopic genomic complexity reminiscent of chromothripsis. The breakpoints were clustered within small genomic domains with junctions showing microhomology or microinsertions. Notably, all of the de novo cases were of paternal origin. The breakpoint distributions corresponded specifically to the ATAC-seq (assay for transposase-accessible chromatin with sequencing) read data peak of mature sperm and not to other chromatin markers or tissues. We propose that DNA breaks in CCRs may develop in an accessible region of densely packaged chromatin during post-meiotic spermiogenesis.

Relationship between the morphology of osteophytes and cartilage lesions in anterior ankle impingement in athletes: a cross-sectional study.

BACKGROUND: The present study aimed to describe the frequency and severity of tram-track lesions in anterior ankle impingement in athletes and to evaluate the association between osteophyte morphology and severity of tram-track lesions, the distinctive cartilage lesions associated with tibial osteophytes in anterior ankle impingement syndrome. METHODS: We evaluated 34 athletes who underwent arthroscopic osteophyte resection for anterior ankle impingement between January 2017 and March 2021. RESULTS: We found tram-track lesions in 26 athletes (76.5%). Arthroscopic findings revealed the distribution of the International Cartilage Repair Society grades of tram-track lesions (grade 0, eight; grade 1, seven; grade 2, ten; grade 3, nine; grade 4, zero). These findings indicate that athletes with anterior ankle impingement syndrome may have more severe cartilage lesions than non-athletes. There was a positive correlation between the International Cartilage Repair Society grade and osteophyte size (r = 0.393, p = 0.021). We divided athletes into two groups according to the presence or absence of osteophyte protrusion into the joint space. Osteophyte protrusion was present in 14 athletes (41.2%). All athletes in the protrusion-type group had tram-track lesions; seven (50%) had International Cartilage Repair Society grade 3. The protrusion-type group's International Cartilage Repair Society grade was significantly higher than that of the non-protrusion-type group (p = 0.008). The osteophyte sizes in the two groups were not significantly different (p = 0.341). CONCLUSIONS: Based on these findings, osteophyte protrusion should be assessed when an indication of arthroscopic treatment for anterior ankle impingement syndrome is considered, particularly in athletes.

Unexpected appearance of KMT2A::MLLT10 fusion transcript in acute myeloid leukemia with t(5;11)(q31;q23.3).

As an uncommon but nonrandom translocation in acute myeloid leukemia (AML) t(5;11)(q31;q23) results in fusion between KMT2A at 11q23 and ARHGAP26 at 5q31. The 5q31 region has another KMT2A partner, AFF4, which was identified in acute lymphoblastic leukemia harboring ins(5;11)(q31;q13q23). We report here a 65-year-old woman with AML M5b. G-banding and spectral karyotyping demonstrated 46,XX,t(5;11)(q31;q23.3). Fluorescence in situ hybridization revealed not only separated 5' and 3' KMT2A signals but a faint 5' KMT2A signal. Reverse transcription polymerase chain reaction (RT-PCR), using a KMT2A sense primer and ARHGAP26 antisense primer, detected no band whereas RT-PCR with a AFF4 antisense primer revealed an amplified band. However, sequence analysis unexpectedly disclosed that KMT2A exon 6 was connected with MLLT10 exons 15 to 18. This may be due to cross-hybridization between MLLT10 exon 18 and AFF4 antisense primer derived from AFF4 exon 10 since both exons had eight identical bases (AAGCAGCT). The MLLT10 gene is located at 10p12.31; a faint 5' KMT2A signal was probably present at this locus. These findings indicate that in AML the 5' KMT2A fragment containing exons 1 to 6 may be cryptically inserted into MLLT10 intron 14 when a reciprocal translocation t(5;11)(q31;q23.3) involving KMT2A occurred.

Clinical application of long-read nanopore sequencing in a preimplantation genetic testing pre-clinical workup to identify the junction for complex Xq chromosome rearrangement-related disease.

OBJECTIVE: Xq chromosome duplication with complex rearrangements is generally acknowledged to be associated with neurodevelopmental disorders, such as Pelizaeus-Merzbacher disease (PMD) and MECP2 duplication syndrome. For couples who required a PGT-M (pre-implantation genetic testing for monogenic disease) for these disorders, junction-specific PCR is useful to directly detect pathogenic variants. Therefore, pre-clinical workup for PGT-M requires the identification of the junction of duplicated segments in PMD and MECP2 duplication syndrome, which is generally difficult. METHODS: In this report, we used nanopore long-read sequencing targeting the X chromosome using an adaptive sampling method to identify breakpoint junctions in disease-causing triplications. RESULTS: By long-read sequencing, we successfully identified breakpoint junctions in one PMD case with PLP1 triplication and in another MECP2 triplication case in a single sequencing run. Surprisingly, the duplicated region involving MECP2 was inserted 45 Mb proximal to the original position. This inserted region was confirmed by FISH analysis. With the help of precise mapping of the pathogenic variant, we successfully re-established STR haplotyping for PGT-M and avoided any potential misinterpretation of the pathogenic allele due to recombination. CONCLUSION: Long-read sequencing with adaptive sampling in a PGT-M pre-clinical workup is a beneficial method for identifying junctions of chromosomal complex structural rearrangements.

The age-related required number of zygotes estimated from prior clinical studies of preimplantation genetic testing for aneuploidy (PGT-A).

Women who are undergoing preimplantation genetic testing for aneuploidy (PGT-A) often wish to know how many eggs will be required to optimize the chances of a live birth. However, no precise data on this can yet be provided during genetic counseling for this procedure. On the basis of PGT-A data from related studies and current databases, we have estimated that the number of zygotes required for a 50% chance of a live birth is 8 at age 40 but increases markedly to 21 at age 43. PGT-A markedly reduces the miscarriage rate per embryo transfer but does not alleviate the extremely high number of zygotes required for a live birth in women of an advanced maternal age. Detailed genetic counseling will therefore be desirable prior to undergoing this procedure.

Acute Effect of Caffeine Supplementation on 100-m Sprint Running Performance: A Field Test.

PURPOSE: No study has assessed the acute effect of caffeine supplementation on 100-m sprint running in athletics and caffeine's net ergogenicity on 100-m sprint running remains unclear. We investigated the acute effects of caffeine supplementation on 100-m sprint running performance in a field test. METHODS: Thirteen male collegiate sprinters were subjected to 100-m sprint running time trials (TT) after the ingestion of 6 mg·kg -1 body weight caffeine or placebo supplementation in a double-blind, counterbalanced, randomized, and crossover design. Sprint velocity was measured with a laser system, and sprint time was calculated from the data in which the effects of environmental factors that would act as confounding factors on sprint time during TT were eliminated. RESULTS: The corrected 100-m sprint time was significantly shortened by 0.14 s with caffeine supplementation compared with placebo (placebo: 11.40 ± 0.39 s, caffeine: 11.26 ± 0.33 s; P = 0.007, g = -0.33). The corrected sprint time up to 60 m during TT was also significantly shorter with caffeine supplementation than with placebo ( P = 0.002). Furthermore, the mean sprint velocity for splits of 0-10 and 10-20 m was significantly increased by caffeine supplementation (all P < 0.05). CONCLUSIONS: Acute caffeine supplementation enhanced the corrected 100-m sprint time by improving the sprint performance in the first 60 m after more explosive acceleration in the early stage of the acceleration phase. Thus, for the first time, we directly demonstrated caffeine's ergogenicity on 100-m sprint performance in athletics.

Maternal high-fat diet promotes calcified atherosclerotic plaque formation in adult offspring by enhancing transformation of VSMCs to osteochondrocytic-like phenotype.

Aim: Maternal high-fat diet (HFD) is associated with the development of cardiovascular disease (CVD) in adult offspring. Atherosclerotic vascular calcification is well documented in patients with CVD. We examined the effect of maternal HFD on calcified plaque formation. Methods and results: Seven-week-old female apo-E-/- mice (C57BL6/J) were nourished either an HFD or a normal diet (ND) a week before mating, and during gestation and lactation. Offspring of both the groups were fed a high-cholesterol diet (HCD) from 8 weeks of age. Osteogenic activity of the thoracic aorta, assessed using an ex vivo imaging system, was significantly increased after 3 months of HCD in male offspring of HFD-fed dams (O-HFD) as compared with those of ND-fed dams (O-ND). Alizarin-red-positive area in the aortic root was significantly increased after 6 months of HCD in male O-HFD as compared to that of O-ND. Plaque size and Oil Red O-positive staining were comparable between the two groups. Primary cultured vascular smooth muscle cells (VSMCs) of the thoracic aorta were treated with phosphate and interleukinL-1ß (IL-1ß) to transform them into an osteochondrocytic-like phenotype. Intracellular calcium content and alkaline phosphatase activity were markedly higher in the VSMCs of O-HFD than in O-ND. IL-1ß concentration in the supernatant of bone marrow-derived macrophages was markedly higher in O-HFD than in O-ND. Conclusion: Our findings indicate that maternal HFD accelerates the expansion of atherogenic calcification independent of plaque progression. In vitro phosphate- and IL-1ß-induced osteochondrocytic transformation of VSMCs was augmented in O-HFD. Inhibition of VSMCs, skewing toward osteochondrocytic-like cells, might be a potential therapeutic strategy for preventing maternal HFD-associated CVD development.

Effects of Maca on Muscle Hypertrophy in C2C12 Skeletal Muscle Cells.

With aging, sarcopenia and the associated locomotor disorders, have become serious problems. The roots of maca contain active ingredients (triterpenes) that have a preventive effect on sarcopenia. However, the effect of maca on muscle hypertrophy has not yet been investigated. The aim of this study was to examine the effects and mechanism of maca on muscle hypertrophy by adding different concentrations of yellow maca (0.1 mg/mL and 0.2 mg/mL) to C2C12 skeletal muscle cell culture. Two days after differentiation, maca was added for two days of incubation. The muscle diameter, area, differentiation index, and multinucleation, were assessed by immunostaining, and the expression levels of the proteins related to muscle protein synthesis/degradation were examined by Western blotting. Compared with the control group, the muscle diameter and area of the myotubes in the maca groups were significantly increased, and the cell differentiation index and multinucleation were significantly higher in the maca groups. Phosphorylation of Akt and mTOR was elevated in the maca groups. Maca also promoted the phosphorylation of AMPK. These results suggest that maca may promote muscle hypertrophy, differentiation, and maturation, potentially via the muscle hypertrophic signaling pathways such as Akt and mTOR, while exploring other pathways are needed.

Investigation of Brain Function-Related Myokine Secretion by Using Contractile 3D-Engineered Muscle.

Brain function-related myokines, such as lactate, irisin, and cathepsin B (CTSB), are upstream factors that control brain-derived neurotrophic factor (BDNF) expression and are secreted from skeletal muscle by exercise. However, whether irisin and CTSB are secreted by muscle contraction remains controversial. Three-dimensional (3D)-engineered muscle (3D-EM) may help determine whether skeletal muscle contraction leads to the secretion of irisin and CTSB, which has never been identified with the addition of drugs in conventional 2D muscle cell cultures. We aimed to investigate the effects of electrical pulse stimulation (EPS)-evoked muscle contraction on irisin and CTSB secretion in 3D-EM. The 3D-EM, which consisted of C2C12 myoblasts and type-1 collagen gel, was allowed to differentiate for 2 weeks and divided into the control and EPS groups. EPS was applied at 13 V, 66 Hz, and 2 msec for 3 h (on: 5 s/off: 5 s). Irisin and CTSB secretion into the culture medium was measured by Western blotting. Irisin secretion was significantly increased following EPS (p < 0.05). However, there was no significant difference in CTSB secretion between the two groups. The present study suggests that irisin may be a contractile muscle-derived myokine, but CTSB is not secreted by EPS-evoked muscle contractile stimulation in 3D-EM.

Treatment of sick sinus syndrome in a patient with cardiac lymphoma via chemotherapy without pacemaker implantation: A case report.

Successful treatment of the acute phase of bradycardia in patients with cardiac lymphoma via medical therapy alone has not been reported. This case report describes the successful treatment of sick sinus syndrome in an 84-year-old man with cardiac lymphoma via chemotherapy without pacemaker implantation.

Mechanical unloading of 3D-engineered muscle leads to muscle atrophy by suppressing protein synthesis.

Three-dimensional (3D)-engineered muscle is an useful approach to a more comprehensive understanding of molecular mechanisms underlying unloading-induced muscle atrophy. We investigated the effects of mechanical unloading on molecular muscle protein synthesis (MPS)- and muscle protein breakdown (MPB)-related signaling pathways involved in muscle atrophy in 3D-engineered muscle, and to better understand in vitro model of muscle disuse. The 3D-engineered muscle consisting of C2C12 myoblasts and type-1 collagen gel was allowed to differentiate for 2 wk and divided into three groups: 0 days of stretched-on control (CON), 2 and/or 7 days of stretched-on (ON), in which both ends of the muscle were fixed with artificial tendons, and the stretched-off group (OFF), in which one side of the artificial tendon was detached. Muscle weight (-38.1% to -48.4%), length (-67.0% to -73.5%), twitch contractile force (-70.5% to -75.0%), and myosin heavy chain expression (-32.5% to -50.5%) in the OFF group were significantly decreased on days 2 and 7 compared with the ON group (P < 0.05, respectively), despite that ON group was stable over time. Although determinative molecular signaling could not be identified, the MPS rate reflected by puromysin-labeled protein was significantly decreased following mechanical unloading (P < 0.05, -38.5% to -51.1%). Meanwhile, MPB, particularly the ubiquitin-proteasome pathway, was not impacted. Hence, mechanical unloading of 3D-engineered muscle in vitro leads to muscle atrophy by suppressing MPS, cell differentiation, and cell growth rather than the promotion of MPB.NEW & NOTEWORTHY Three-dimensional (3D)-engineered muscles have recently been shown to closely replicate the in vivo architecture. We found that mechanical unloading of 3D-engineered muscle led to muscle disuse atrophy accompanied by reduced functional properties and contractile protein expression via suppression of muscle protein synthesis. This novel model may improve the in vitro testing of modalities with the potential to reduce mechanical unloading-induced atrophy.

Repeated Social Defeat Enhances CaCl2-Induced Abdominal Aortic Aneurysm Expansion by Inhibiting the Early Fibrotic Response via the MAPK-MKP-1 Pathway.

Depression is an independent risk factor for cardiovascular disease and is significantly associated with the prevalence of abdominal aortic aneurysm (AAA). We investigated the effect of repeated social defeat (RSD) on AAA development. Eight-week-old male wild-type mice were exposed to RSD by being housed with larger CD-1 mice in a shared cage. They were subjected to vigorous physical contact. After the confirmation of depressive-like behavior, calcium chloride was applied to the infrarenal aorta of the mice. At one week, AAA development was comparable between the defeated and control mice, without any differences being observed in the accumulated macrophages or in the matrix metalloproteinase activity. At two weeks, the maximum diameter and circumference of the aneurysm were significantly increased in the defeated mice, and a significant decrease in periaortic fibrosis was also observed. Consistently, the phosphorylation of the extracellular signal-regulated kinase and the incorporation of 5-bromo-2'-deoxyuridine in the primarily cultured aortic vascular smooth muscle cells were significantly reduced in the defeated mice, which was accompanied by a substantial increase in mitogen-activated protein kinase phosphatase-1 (MKP-1). The MKP-1 mRNA and protein expression levels during AAA were much higher in the defeated mice than they were in the control mice. Our findings demonstrate that RSD enhances AAA development by suppressing periaortic fibrosis after an acute inflammatory response and imply novel mechanisms that are associated with depression-related AAA development.

The association of high Vancomycin trough concentration with acute kidney injury during combination therapy of Piperacillin/Tazobactam and Vancomycin.

BACKGROUND: Co-administration of Piperacillin/Tazobactam (PIPC/TAZ) and Vancomycin (VCM) as an antibiotic therapy for severe infectious diseases increases the risk of nephrotoxicity. We retrospectively investigated the utility of monitoring VCM trough concentration in early stage of developing acute kidney injury (AKI) on this combination therapy. METHODS: We enrolled all infectious disease patients who were managed with concurrent PIPC/TAZ and VCM. The record of dosage and the administration interval of each antibiotic and its clinical parameters, as well as the VCM trough concentrations, blood culture for bacteria, and serum creatinine values, were collected. VCM trough concentration was measured during the initial 48-72 h of VCM administration. Nephrotoxicity was evaluated as the degree of AKI. RESULTS: A total of 47 patients fulfilling the criteria were registered, and AKI developed in 10 patients. There was no statistical difference between the AKI and non-AKI groups with regard to age, height, weight, basal creatinine level, body surface area, body mass index, PIPC/TAZ dose, VCM dose, gender, artificial management, and death within around 30 days. The VCM trough level was increased significantly in the AKI group (mean [standard deviation {SD}]: 25.9 [7.8] µg/mL) compared to that in the non-AKI group (mean [SD]: 15.7 [6.9] µg/mL) (p = 0.003). During the clinical course, renal function returned to normal levels in three out of four AKI stage 2 patients, whereas only partial recovery was achieved in all AKI stage 3 patients. CONCLUSIONS: A high VCM trough concentration may have an influence on the occurrence of AKI during combination therapy of PIPC/TAZ and VCM. Careful monitoring of VCM trough concentration will be required to prevent AKI progression.

Bone Marrow Infiltration Is a Distinctive Risk Factor for Rituximab Infusion-Related Reactions in CD20-Positive B-Cell Non-Hodgkin Lymphoma.

BACKGROUND: Bone marrow infiltration of lymphoma cells is a candidate risk factor for infusion-related reactions (IRRs) in patients with CD20-positive B-cell non-Hodgkin lymphoma (B-NHL). However, despite with the lack of sufficient data, the effect of bone marrow infiltration of B-NHL cells on the incidence rate of grade 2 or higher IRRs with the administration of rituximab has been retrospectively studied in this paper. METHODS: Patients with CD20-positive B-NHL who received the rituximab induction therapy for the first time were enrolled in this study. To evaluate the bone marrow infiltration of B-NHL cells, May-Giemsa stain of bone marrow films and flow cytometry examination of bone marrow aspiration samples were performed. IRR grade was determined using the IRR criteria in the Common Terminology Criteria for Adverse Events version 4.0. RESULTS: A total of 127 patients were eligible for this study. Grade 2 or higher IRRs were observed in 43 (34%) patients. In univariate analysis, use of glucocorticoid before rituximab infusion was a strong risk-avoiding factor for grade 2 or higher IRRs. Advanced stage of disease (Ann Arbor: stages III and IV) or bone marrow infiltration of B-NHL cells revealed the risk factors, regardless of glucocorticoid premedication. Using multivariate analysis, bone marrow infiltration was found to be an independent risk factor for patients without prior glucocorticoid use. CONCLUSION: Bone marrow infiltration of B-NHL cells is a risk factor for grade 2 or higher IRRs at the first rituximab induction therapy without glucocorticoid premedication.

Target enrichment long-read sequencing with adaptive sampling can determine the structure of the small supernumerary marker chromosomes.

Structural analysis of small supernumerary marker chromosomes (sSMCs) has revealed that many have complex structures. Structural analysis of sSMCs by whole genome sequencing using short-read sequencers is challenging however because most present with a low level of mosaicism and consist of a small region of the involved chromosome. In this present study, we applied adaptive sampling using nanopore long-read sequencing technology to enrich the target region and thereby attempted to determine the structure of two sSMCs with complex structural rearrangements previously revealed by cytogenetic microarray. In adaptive sampling, simple specification of the target region in the FASTA file enables to identify whether or not the sequencing DNA is included in the target, thus promoting efficient long-read sequencing. To evaluate the target enrichment efficiency, we performed conventional pair-end short-read sequencing in parallel. Sequencing with adaptive sampling achieved a target enrichment at about a 11.0- to 11.5-fold higher coverage rate than conventional pair-end sequencing. This enabled us to quickly identify all breakpoint junctions and determine the exact sSMC structure as a ring chromosome. In addition to the microhomology and microinsertion at the junctions, we identified inverted repeat structure in both sSMCs, suggesting the common generation mechanism involving replication impairment. Adaptive sampling is thus an easy and beneficial method of determining the structures of complex chromosomal rearrangements.