Fucosyltransferase 8 regulates adult neurogenesis and cognition of mice by modulating the Itga6-PI3K/Akt signaling pathway.

Fucosyltransferase 8 (Fut8) and core fucosylation play critical roles in regulating various biological processes, including immune response, signal transduction, proteasomal degradation, and energy metabolism. However, the function and underlying mechanism of Fut8 and core fucosylation in regulating adult neurogenesis remains unknown. We have shown that Fut8 and core fucosylation display dynamic features during the differentiation of adult neural stem/progenitor cells (aNSPCs) and postnatal brain development. Fut8 depletion reduces the proliferation of aNSPCs and inhibits neuronal differentiation of aNSPCs in vitro and in vivo, respectively. Additionally, Fut8 deficiency impairs learning and memory in mice. Mechanistically, Fut8 directly interacts with integrin α6 (Itga6), an upstream regulator of the PI3k-Akt signaling pathway, and catalyzes core fucosylation of Itga6. Deletion of Fut8 enhances the ubiquitination of Itga6 by promoting the binding of ubiquitin ligase Trim21 to Itga6. Low levels of Itga6 inhibit the activity of the PI3K/Akt signaling pathway. Moreover, the Akt agonist SC79 can rescue neurogenic and behavioral deficits caused by Fut8 deficiency. In summary, our study uncovers an essential function of Fut8 and core fucosylation in regulating adult neurogenesis and sheds light on the underlying mechanisms.

Influence of pulling direction on knot security: A laboratory research.

BACKGROUND: When tying knots, some surgeons do not pay particular attention to the direction in which they pull to lay down throws. We examine to what extent does pulling direction influence on knot security. METHODS: A total of 368 residents were instructed to tie knots with from 2 to 7 throws using silk braided suture in 3-0 gauge. The direction in which they pulled to lay down throws was recorded. Only the knots tied either by pulling in alternate directions (Group A) or in constant direction (Group C) from the first throw to the last were involved in statistical analysis. Tensile strength and untying rate of the knots were then measured for comparative analysis. RESULTS: For knots with from 2 to 7 throws, the tensile strength of the ones from Group A was significantly higher than that of the ones from Group C (p < 0.05), respectively. For knots with from 5 to 7 throws, the untying rate of the ones from Group A was significantly lower than that of the ones from Group C (p < 0.05), respectively. For the unraveled knots with from 2 to 7 throws (except for the ones with 5 throws), the tensile strength of the ones from Group A was significantly higher than that of the ones from Group C (p < 0.05), respectively. CONCLUSION: Pulling in constant direction results in inferior knot security. Surgeons must ascertain the influence of pulling direction on knot security, and try to achieve superior security with fewer throws to ensure patient safety.

Racial disparities in conditional survival of patients with bladder cancer: a population-based study.

BACKGROUND: Traditional estimates can only provide static predictions of cancer outcomes and cannot assess the evolving effect of race on patient survival. This study aims to reveal the dynamic survival of patients with bladder cancer and to explore the evolving effect of race on patient prognosis. METHODS: Using data from the Surveillance, Epidemiology, and End Results (SEER) registry, 99,590 white, 6,036 African American, and 4,685 Asian/Pacific Islander (API) patients with bladder cancer were identified. Conditional cancer-specific survival (CSS) rates, which could reflect the dynamic survival prediction of cancer patients, represented the primary outcomes, and were estimated by the Kaplan-Meier algorithm. The evolving effect of race on patient survival was evaluated by multivariable Cox regression in combination with conditional survival (CS) estimates. RESULTS: The 5-year CSS for African American patients who had survived 1, 2, 3, 4, or 5 years after definitive therapy improved from the baseline calculation by + 5.8 (84.4%), + 9.5 (87.4%), + 12.8 (90.0%), + 14.4 (91.3%), and + 14.7% (91.5%), respectively. The increasing trend also held for overall white and API patients, and for all patient subsets when CS was calculated according to different levels of sex, age, and disease stage. African Americans, despite having the worst survival at baseline, could have CSS comparable to their white and API counterparts after 4 years of survivorship. In addition, the risk of death for African Americans tended to decrease with increasing survival, and the risk was no longer significantly different from that of whites after 4 years of survival. CONCLUSIONS: While having the worst initial predicted outcomes, African Americans may eventually achieve comparable survival to white and API patients given several years of survivorship. As patient survival increases, African American race may lose its role as an indicator of poorer prognosis.

Host inflammatory response is the major factor in the progression of Chlamydia psittaci pneumonia.

Purpose: Chlamydia psittaci (C. psittaci) has caused sporadic, but recurring, fatal community-acquired pneumonia outbreaks worldwide, posing a serious threat to public health. Our understanding of host inflammatory responses to C. psittaci is limited, and many bronchitis cases of psittaci have rapidly progressed to pneumonia with deterioration. Methods: To clarify the host inflammatory response in psittacosis, we analyzed clinical parameters, and compared transcriptomic data, concentrations of plasma cytokines/chemokines, and changes of immune cell populations in 17 laboratory-confirmed psittacosis cases, namely, 8 pneumonia and 9 bronchitis individuals, in order to assess transcriptomic profiles and pro-inflammatory responses. Results: Psittacosis cases with pneumonia were found to have abnormal routine blood indices, liver damage, and unilateral pulmonary high-attenuation consolidation. Transcriptome sequencing revealed markedly elevated expression of several pro-inflammatory genes, especially interleukins and chemokines. A multiplex-biometric immunoassay showed that pneumonia cases had higher levels of serum cytokines (G-CSF, IL-2, IL-6, IL-10, IL-18, IP-10, MCP-3, and TNF-α) than bronchitis cases. Increases in activated neutrophils and decreases in the number of lymphocytes were also observed in pneumonia cases. Conclusion: We identified a number of plasma biomarkers distinct to C. psittaci pneumonia and a variety of cytokines elevated with immunopathogenic potential likely inducing an inflammatory milieu and acceleration of the disease progression of psittaci pneumonia. This enhances our understanding of inflammatory responses and changes in vascular endothelial markers in psittacosis with heterogeneous symptoms and should prove helpful for developing both preventative and therapeutic strategies.

Mitigation of block withholding attack based on zero-determinant strategy.

This article focuses on the mining dilemma of block withholding attack between the mining pools in the bitcoin system. In order to obtain the higher revenue, the rational mining pool usually chooses an infiltration attack, that is, the pool will falls into the mining dilemma of the PoW consensus algorithm. Thus the article proposes to apply zero-determinant strategies for optimizing the behavior selection of the mining pool under PoW consensus mechanism to increase the total revenues of the system, so as to solve the mining dilemma. After theoretically studying the set and extortionate strategy of zero-determinant, the article devises an adaptive zero-determinant strategy that the pool can change the corporation probability of the next round based on its previous revenues. To verify the effectiveness of zero-determinant strategies, based on the actual revenue of the mining pool defined and deduced in the paper, it simulates 30 sets of game strategies to illustrate the revenue variation of the mining pools. The simulation results show that the three zero-determinant strategies can effectively improve the convergence rate of cooperation, mitigate block withholding attack and maximize the total revenues of the system. Compared with the set and extortionate strategy, the adaptive strategy can ensure more stability and more revenue.

The prognostic value of the controlling nutritional status score in patients with myelodysplastic syndrome.

PURPOSE: To evaluate the prognostic value of the controlling nutritional status score (CONUT) in patients with myelodysplastic syndrome (MDS). METHODS: The clinical data of 81 newly diagnosed MDS patients treated with decitabine in the hematology ward of our hospital from October 2009 to September 2020 were analyzed retrospectively. According to the ROC curve of overall survival (OS), the best cutoff value of CONUT was obtained. MDS patients were divided into high CONUT score group and low CONUT score group according to the best cut-off value, and their clinical characteristics and survival were analyzed. RESULTS: Among the 81 patients with MDS, there were 32 cases in the high CONUT score group and 49 cases in low CONUT score group. Compared with the low CONUT group, the high CONUT group had lower levels of hemoglobin, lymphocyte count, albumin, and total cholesterol (P = 0.037, < 0.001, 0.009, < 0.001). The median OS of low and high CONUT groups were 17.2 and 11.0 months (P = 0.017). According to the results of univariate and multivariate survival analysis of OS, thrombocytopenia, high CONUT score, and medium and high risk IPSS-R score were independent prognostic factors. CONCLUSION: High CONUT score is associated with low hemoglobin in patients with MDS. High CONUT score indicates poor OS and it is an independent prognostic factor in patients with MDS.

Creation and application of war trauma treatment simulation software for first aid on the battlefield based on undeformed high-resolution sectional anatomical image (Chinese Visible Human dataset).

BACKGROUND: Effective first aid on the battlefield is vital to minimize deaths caused by war trauma and improve combat effectiveness. However, it is difficult for junior medical students, which have relatively poor human anatomy knowledge and first aid experience. Therefore, we aim to create a treatment simulation software for war trauma, and to explore its application for first aid training. METHODS : This study is a quantitative post-positivist study using a survey for data collection. First, high-resolution, thin-sectional anatomical images (Chinese Visible Human (CVH) dataset) were used to reconstruct three-dimensional (3D) wound models. Then, the simulation system and the corresponding interactive 3D-PDF, including 3D models, graphic explanation, and teaching videos, were built, and used for first aid training in army medical college. Finally, the interface, war trauma modules, and training effects were evaluated using a five-point Likert scale questionnaire. All measurements are represented as mean and standard deviations. Moreover, free text comments from questionnaires were collected and aggregated. RESULTS: The simulation software and interactive 3D-PDF were established. This included pressure hemostasis of the vertex, face, head-shoulder, shoulder-arm, upper forearm, lower limb, foot, and punctures of the cricothyroid membrane, pneumothorax, and marrow cavity. Seventy-eight medical students participated in the training and completed the questionnaire, including 66 junior college students and 12 graduate students. The results indicated that they were highly satisfied with the software (score: 4.64 ± 0.56). The systems were user-friendly (score: 4.40 ± 0.61) and easy to operate (score: 4.49 ± 0.68). The 3D models, knowledge of hemostasis, and puncture were accurate (scores: 4.41 ± 0.67, and 4.53 ± 0.69) and easily adopted (scores: 4.54 ± 0.635, and 4.40 ± 0.648). They provided information about hemostasis and puncture (all scores > 4.40), except for cricothyroid membrane puncture (scores: 4.39 ± 0.61), improved the learning enthusiasm of medical students (score: 4.55 ± 0.549), and increased learning interest (score: 4.54 ± 0.57). CONCLUSION: Our software can effectively help medical students master first aid skills including hemostasis, cricothyroid membrane and bone marrow puncture, and its anatomy. This may also be used for soldiers and national first aid training.

Human-to-human transmission of Chlamydia psittaci in China, 2020: an epidemiological and aetiological investigation.

BACKGROUND: Chlamydia psittaci can infect a wide range of avian species, occasionally causing psittacosis (also known as parrot fever) in humans. Most human psittacosis cases are associated with close contact with pet birds or poultry. In December, 2020, an outbreak of severe community-acquired pneumonia of unknown aetiology was reported in a hospital in Shandong province, China, and some of the patients' close contacts had respiratory symptoms. Our aims were to determine the causative agent of this epidemic and whether there had been human-to-human transmission. METHODS: For this epidemiological and aetiological investigation study, we enrolled patients who had community-acquired pneumonia confirmed by chest CT at two local hospitals in Shandong Province in China. We collected sputum, bronchoalveolar lavage fluid, and nasopharyngeal swab samples from participants and detected pathogens by surveying for 22 target respiratory microbes using a commercial assay, followed by metagenomic next-generation sequencing, specific nested PCR, and qPCR tests. We excluded individuals who were C psittaci-negative on both tests. We recruited close contacts of the C psittaci-positive patients, and tested nasopharyngeal swabs from the close contacts and samples from ducks from the processing plant where these patients worked. We then integrated the epidemiological, clinical, and laboratory data to reveal the potential chain of transmission of C psittaci that characterised this outbreak. FINDINGS: Between Dec 4 and 29, 2020, we used metagenomic next-generation sequencing and different PCR-based approaches to test 12 inpatients with community-acquired pneumonia, of whom six (50%) were workers at a duck-meat processing plant and two (17%) were unemployed people, who were positive for C psittaci and enrolled in this study. We contacted 61 close contacts of the six patients who worked at the duck-meat processing plant, of whom 61 (100%) were enrolled and tested, and we determined that the community-acquired pneumonia outbreak was caused by C psittaci. Within the outbreak cluster, 17 (77%) of 22 participants had confirmed C psittaci infections and five (23%) of 22 participants were asymptomatic C psittaci carriers. The outbreak had begun with avian-to-human transmission, and was followed by secondary and tertiary human-to-human transmission, which included transmission by several asymptomatic carriers and by health-care workers. In addition, some of the participants with confirmed C psittaci infection had no identified source of infection, which suggested cryptic bacterial transmission. INTERPRETATION: Our study data might represent the first documented report of human-to-human transmission of C psittaci in China. Therefore, C psittaci has the potential to evolve human-to-human transmission via various routes, should be considered an elevated biosecurity and emergent risk, and be included as part of the routine diagnosis globally, especially for high-risk populations. FUNDING: Academic Promotion Programme of Shandong First Medical University, National Science and Technology Major Project, ARC Australian Laureate Fellowship.

Application of a three-dimensional visualization model in intraoperative guidance of percutaneous nephrolithotomy.

OBJECTIVES: To establish a three-dimensional visualization model of percutaneous nephrolithotomy, apply it to guiding intraoperative puncture in a mixed reality environment, and evaluate its accuracy and clinical value. METHODS: Patients with percutaneous nephrolithotomy indications were prospectively divided into three-dimensional group and control group with a ratio of 1:2. For patients in three-dimensional group, positioning markers were pasted on the skin and enhanced computed tomography scanning was performed in the prone position. Holographic three-dimensional models were made and puncture routes were planned before operation. During the operation, the three-dimensional model was displayed through HoloLens glass and visually registered with the patient's body. Puncture of the target renal calyx was performed under three-dimensional-image guiding and ultrasonic monitoring. Patients in the control group underwent routine percutaneous nephrolithotomy in the prone position under the monitoring of B-ultrasound. Deviation distance of the kidney, puncture time, puncture attempts, channel coincidence rate, stone clearance rate, and postoperative complications were assessed. RESULTS: Twenty-one and 40 patients were enrolled in three-dimensional and control group, respectively. For three-dimensional group, the average deviation between virtual and real kidney was 3.1 ± 2.9 mm. All punctures were performed according to preoperative planning. Compared with the control group, the three-dimensional group had shorter puncture time (8.9 ± 3.3 vs 14.5 ± 6.1 min, P < 0.001), fewer puncture attempts (1.4 ± 0.6 vs 2.2 ± 1.5, P = 0.009), and might also have a better performance in stone clearance rate (90.5% vs 72.5%, P = 0.19) and postoperative complications (P = 0.074). CONCLUSIONS: The percutaneous nephrolithotomy three-dimensional model manifested acceptable accuracy and good value for guiding puncture in a mixed reality environment.

NAD+ Modulates the Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells via Akt Signaling Pathway.

Nicotinamide adenine dinucleotide hydrate (NAD+) acts as the essential component of the tricarboxylic citric acid (TCA) cycle and has important functions in diverse biological processes. However, the roles of NAD+ in regulating adult neural stem/progenitor cells (aNSPCs) remain largely unknown. Here, we show that NAD+ exposure leads to the reduced proliferation and neuronal differentiation of aNSPCs and induces the apoptosis of aNSPCs. In addition, NAD+ exposure inhibits the morphological development of neurons. Mechanistically, RNA sequencing revealed that the transcriptome of aNSPCs is altered by NAD+ exposure. NAD+ exposure significantly decreases the expression of multiple genes related to ATP metabolism and the PI3k-Akt signaling pathway. Collectively, our findings provide some insights into the roles and mechanisms in which NAD+ regulates aNSPCs and neuronal development.

Association between baseline Controlling Nutritional Status score and clinical outcomes of patients with multiple myeloma.

BACKGROUND: The Controlling Nutritional Status (CONUT) score, a novel immuno-nutritional index, was reported as a predictor of overall survival (OS) in some tumors. OBJECTIVE: We aimed to investigate the association between baseline CONUT Score and clinical outcomes in patients with multiple myeloma (MM). METHODS: We performed a retrospective analysis of 245 patients with MM. The CONUT score was determined prior to therapy. RESULTS: Among the entire cohort, the complete remission rate was markedly higher in the low-CONUT (⩽ 3) group compared to the mid-CONUT (4-9) group or high-CONUT (> 9) group (44.1% vs 25.8%, P= 0.039; 44.1% vs 12.5%, P= 0.002). Patients with CONUT score > 9 had significant poor prognosis, and CONUT score ⩽ 3 group showed better survival outcome than other groups in OS (P< 0.001). Besides, we stratified the patients by combining International Staging System (ISS) stage and CONUT score in a model, and found that CONUT score could improve the prognostic impact of ISS stages on OS. In multivariate analysis, older age (⩾ 70 years) and a high CONUT score (⩾ 4) were independent prognostic risk factors for OS. CONCLUSIONS: The CONUT score was a predictor of OS in MM patients especially in cases with both low ISS staging and CONUT score. The baseline CONUT score may be an early and practical indicator of the efficacy of anti-myeloma treatment.

Analysis of global stock markets' connections with emphasis on the impact of COVID-19.

We explore global stock markets' connections during the financial crises or risks since 1995 with emphasis on the situation under COVID-19. We choose 40 countries/regions and take one index from each of them, and then compute the correlation coefficients and distances between each pair of the indices with a sliding window. We construct the complexes and carry out topological data analysis mainly through persistence landscapes and their L p -norms, which exhibit the complexes' daily changes. We establish a critical dates' detection system based on the persistence landscapes. Topological features of the complex networks are shown on the critical dates and dates before them. All the results show clearly that the connections became even closer among the markets when COVID-19 spread worldwide than those of any other risk. The robustness and effectiveness of these methods provide guidance for the analysis of financial crises in the future.

Fto-modulated lipid niche regulates adult neurogenesis through modulating adenosine metabolism.

Adult neurogenesis is regulated by diverse factors including the local environment, i.e. the neurogenic niche. However, whether the lipid in the brain regulates adult neurogenesis and related mechanisms remains largely unknown. In the present study, we found that lipid accumulates in the brain during postnatal neuronal development. Conditional knockout of Fto (cKO) in lipid not only reduced the level of lipid in the brain but also impaired the learning and memory of mice. In addition, Fto deficiency in lipid did not affect the proliferation of adult neural stem cells (aNSCs), but it did inhibit adult neurogenesis by inducing cell apoptosis. Mechanistically, specific deleting Fto in lipid altered gene expression and increased adenosine secretion of adipocytes. The treatment of adenosine promoted the apoptosis of newborn neurons. As a whole, these results reveal the important function of the lipid niche and its associated mechanism in regulating adult neurogenesis.

Single-Use Versus Reusable Digital Flexible Ureteroscopes for the Treatment of Renal Calculi: A Prospective Multicenter Randomized Controlled Trial.

Objective: To compare the efficacy and safety of a single-use digital flexible ureteroscope (f-URS) and a reusable digital f-URS (URF-V) for the treatment of renal stones in adults. Patients and Methods: In this randomized open-label noninferiority trial, we randomly selected patients with renal stones to receive ureteroscopy through a single-use digital f-URS (ZebraScope™; Happiness Workshop, Beijing, China) or a URF-V (Olympus, Tokyo, Japan). The primary endpoint was the 1-month postsurgical stone-free rate (SFR). The secondary efficacy endpoints assessed were the high-quality rate of images, the eligible rate of operability, the operative time, and the length of hospital stay. The safety outcomes assessed were the presence of postoperative complications, adverse events (AEs), and serious AEs (SAEs). The noninferiority margin was set at -10%. Results: In total, 126 patients completed the study (i.e., 63 patients in each group). The demographic and preoperative parameters were comparable between the two groups. The 1-month SFR was 77.78% for the ZebraScope group and 68.25% for the URF-V group (two-sided 95% confidence interval [CI]: -5.95 to 25.01). The high-quality rate of images and the eligible rate of operability were 100% in both groups (two-sided 95% CI: -5.27 to 5.35). There was no difference between the two groups in the operative time (p = 0.687), the length of hospital stay (p = 0.430), the presence of postoperative complications (p = 0.310), the presence of AEs (p = 0.709), and the presence of SAEs (p = 0.648). The most important and fatal SAE was acute urinary tract obstruction. Conclusion: The single-use digital f-URS (ZebraScope) appears to be at least noninferior to URF-V regarding the 1-month SFR, the high-quality rate of images, and the eligible rate of operability. Single-use digital f-URSs are an effective and safe alternative to URF-V.

Association of CD117 and HLA-DR expression with shorter overall survival and/or progression-free survival in patients with multiple myeloma treated with bortezomib and thalidomide combination treatment without transplantation.

Certain immunophenotypes in multiple myeloma (MM), including CD56 and CD117, have been reported to be associated with overall survival (OS). However, previous reports have ignored the impact of different treatment regimens and the long-term prognostic value of immunophenotyping in MM when treated with novel agents, including thalidomide and bortezomib, in the absence of transplantation for autologous stem cell transplantation and allo-hematopoietic stem cell transplantation. To further understand the long-term prognostic value of immunophenotyping in MM, when treated with bortezomib combined with thalidomide-based regimens without transplantation, 80 patients who were newly diagnosed between January 2007 and December 2015, were analyzed retrospectively. In contrast to previous studies, no significant survival time difference was observed between CD56+/CD117+ and CD56-/CD117- groups. Multivariate analysis suggested that human leukocyte antigen-antigen D-related (HLA-DR)+ was independently associated with shorter OS and progression-free survival (PFS), while CD117+ was an independent prognostic factor for decreased PFS. In addition, the myeloma prognostic index (MPI), defined by HLA-DR+, age ≥65 years and international staging system stage III, was suitable for risk stratification of patients treated with novel agents for OS and PFS. The results of the current study suggested that HLA-DR+ patients had a shorter OS and PFS and CD117+ patients had shorter PFS. HLA-DR+ or CD117+ was sufficient to affect survival. Evaluating these markers may reveal valuable prognostic factors for MM in patients receiving bortezomib combined with thalidomide-based regimens without autologous stem cell transplantation and allo-hematopoietic stem cell transplantation). MPI may describe an accessible tool to predict the prognosis of patients with MM.

Real-World Clinical Outcomes in Elderly Chinese Patients with Multiple Myeloma: A Single-Center Experience.

BACKGROUND Recently, improvement in overall survival (OS) was demonstrated in elderly patients with multiple myeloma (MM). Our aim here was to analyze treatment outcomes in elderly Chinese patients with MM in real-world practice. MATERIAL AND METHODS This retrospective study enrolled 122 newly diagnosed MM patients ages 65-84 between January 2007 and December 2015 in a single hematology department. RESULTS The median age of patients was 70.5 years. The median OS period of the entire cohort was 33 months; the 5-year OS estimate was 30.4%. The median OS of the 65-69, 70-74, and ≥75 years old groups were 43, 36, and 6 months, respectively. Female patients had better OS than male patients (40 and 28 months, P=0.026). Patients who received short-course bortezomib-containing regimens during their course of disease had a significantly longer median OS of 37 months compared with 28 months for patients without bortezomib treatment (P=0.029). Patients with age-adjusted Charlson comorbidity index (aaCCI) <5 showed longer median OS compared to those with aaCCI ³5 (45 months vs. 23 months, P<0.001). Multivariate analysis revealed that male sex, high aaCCI, and LDH were independent prognostic factor for OS. CONCLUSIONS The marked survival improvement in the elderly patients was associated with the increased use of short-course bortezomib. CCI and LDH are important clinical prognostic factors for survival in elderly MM patients.

Early mortality in elderly patients undergoing treatment for multiple myeloma in real-world practice.

Objectives This study was performed to analyze the risk factors for early mortality (EM) in elderly patients undergoing treatment for multiple myeloma (MM) in real-world clinical practice. Methods Retrospective data from 108 elderly patients who were newly diagnosed with MM from January 2007 to July 2015 were analyzed in a single hematology center. EM was defined as death of any cause within 12 months after diagnosis. A multivariate regression model was used to evaluate EM. Results EM occurred in 16 (14.8%) elderly patients with newly diagnosed MM. The most common cause of death was infection (10/16, 62.5%). In the multivariate analysis, only an age of ≥75 years, International Staging System (ISS) stage III disease, and high lactate dehydrogenase concentration were significantly and independently associated with EM. Conclusion Our results suggest that infection is the leading cause of EM in elderly patients with MM. An age of ≥75 years, ISS stage III disease, and a high lactate dehydrogenase concentration are significant predictors of EM. We should further target this higher-risk patient population to define personalized therapy with which to improve outcomes.

Evaluation of neutrophil-to-lymphocyte ratio in newly diagnosed patients receiving borte- zomib-based therapy for multiple myeloma.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) at diagnosis has been identified as an independent prognostic marker in several malignancies. Recently, a few studies have reported that an elevated pretreatment NLR is associated with poor survival among multiple myeloma (MM) patients. However, the role of NLR at diagnosis in patients with MM treated with regimens containing bortezomib has been less explored. OBJECTIVE: We aimed to investigate the relationships between NLR and overall survival (OS) in newly diagnosed patients receiving bortezomib-based therapy for MM. METHODS: A total of 76 newly diagnosed patients with MM treated with bortezomib-based regimes were analyzed retrospectively. NLR was calculated from whole blood counts prior to therapy and subsequently correlated with OS. RESULTS: Complete remission (CR) was seen in 39.2% of patients with NLR < 2.95 compared to 20% in the group with NLR ⩾ 2.95 (P= 0.094). NLR was lower in CR patients in comparison to Non-CR subjects (P= 0.044). Patients with a NLR ⩾ 2.95 experienced inferior median survival compared to those with NLR < 2.95 (4-year OS rates were 30.9% and 64.8%, respectively, P= 0.029). In multivariate analysis, only elevated LDH and IgA MM were factors predicting inferior OS. CONCLUSIONS: Elevated NLR was associated with poor OS in MM patients receiving induction therapy with bortezomib-based regimens, but it was not an independent prognostic factor in this patient cohort.

Evaluation of pretreatment red cell distribution width in patients with multiple myeloma.

BACKGROUND: Red blood cell distribution width (RDW) has been reported as an inflammatory biomarker and a predictor of prognosis in different types of cancer. However, the role of RDW at diagnosis in patients with multiple myeloma (MM) has been less explored. OBJECTIVE: We aimed to investigate the association between RDW and the response to treatment and overall survival (OS) in patients with MM. METHODS: We retrospectively analyzed the data for 196 MM patients between January 1, 2007 and December 31, 2015. Kaplan-Meier analysis and Cox regression model were used. RESULTS: High RDW values were associated with lower platelet count, lower hemoglobin levels, lower albumin levels, and higher lactate dehydrogenase (LDH) level. Among the entire cohort, the overall response rates (ORR) and complete response (CR) rate of initial therapy were markedly higher in the low-RDW group compared to the high-RDW group. RDW was significant lower in CR in comparison to Non-CR groups in patients treated with bortezomib-based regimens as induction therapy. The patients with low-RDW at diagnosis had better OS when compared to those with high-RDW. CONCLUSIONS: Elevated RDW was associated with worse survival in patients with MM and could predict treatment responses. Further larger and prospective studies are required.

[Influence of Chromosome Abnormality on Therapeutic Efficacy and Prognosis of Newly Diagnosed Multiple Myeloma Treated with Bortezomib].

OBJECTIVE: To explore the influence of chromosome abnormality on therapeutic efficacy and prognosis of patients with newly diagnosed multiple myeloma(MM) treated with bortezomib. METHODS: The clinical data of 152 patients with newly diagnosed MM were collected from January 2008 to December 2011. All patients received bortezo-mib-based chemotherapy and the therapeutic efficacy were investigated for 4 cycles later. The R banding and DNA probe were used to analyze the chromosome and gene (RB1 deletion, D13S319 deletion, P53 deletion, IgH rearrangement and 1q21 amplification) of chromosome specimens. Moreover, the therapeutic efficacy and long-term survival data were analyzed among the patients with different types of chromosomal abnormality. The Kaplan-Meier was applied to analyze survival, and COX risk proportional model was used for multivariate analysis. RESULTS: Among 152 patients with MM, there were 47 cases(30.92%) of abnormal karyotype, 43 cases(28.29%) of abnormal RB1,49 cases (32.24%) of abnormal D13S319, 30 cases (19.74%) of abnormal P53, 58 cases (38.16%) of abnormal IgH and 33 cases (21.71%) of abnormal chromosome 1q21. All the patients were evaluable for the therapeutic efficacy, including 24 CR, 54 nCR, 21 PR, 14 MR and 39 PD with response rate of 74.34% and remission rate of 50.66%. Compared with normal controls, the response and remission rate were lower than that in the patients with abnormal karyotype of D13S319, P53 or IgH, and remission rate was lower in the patients with RB1 or 1q21 (P<0.05). All the patients were followd-up (median: 52.0 months, range: 22-72 months), but median overall survival(OS) was not yet reached at the end of the follow-up. The median OS was in the patients with different chromosome versus the normal subjects (P<0.05). The chromosome abnormality was found to affect the prognosis of MM by COX multivariate analysis. In regard to the normal subjects, the risk for poor prognosis increased by 1.177, 2.639, 6.552, 3.124, 2.045 and 7.264 fold in the patients with abnormal Karyotype of RB1, D13S319, P53, IgH and 1q21, respectively. CONCLUSION: The abnormality of chromosome can influence the efficacy and prognosis of newly diagnosed MM patients treated with bortezomib. The detection of chromosomal abnormalities has a certain reference value for the treatment of primary MM.