Effect of Clinical Typing on Serum Urate Targets of Benzbromarone in Chinese Gout Patients: A Prospective Cohort Study

IntroductionAchieving a goal of serum urate levels in patients with gout is an important way to prevent gout and its complications while it remains difficult with a low targeting rate worldwidely. Currently, hyperuricemia classification has not been widely applied to the management of gout owing to insufficient clinical evidences. This study aimed to evaluate the effectiveness of achieving target urate based on hyperuricemia classification in Chinese patients with gout.MethodsIn this prospective study, patients with gout receiving urate lowering therapy with benzbromarone were assigned to two groups, a renal underexcretion and an unclassified type. The primary endpoint was the proportion of patients achieving the serum urate target (<360 μmol/L) during the 12-week study. The frequency of acute gout attacks as well as physical and chemical indicators were secondary endpoints.ResultsTarget serum urate level was achieved in 60.5% of underexcretors compared with 39.0% of patients of the unclassified type at week 12 (P = 0.002). Blood glucose and cholesterol levels were lower in the underexcretor group compared with the unclassified type group at the end of the trial, without significant different frequencies in gout flare during the study. In subgroup analysis, stratified by body mass index and estimated glomerular filtration rate, the proportion of patients with serum urate <360 μmol/L was greater in the underexcretion compared with the unclassified type group.ConclusionsThe increased achievement of target serum urate in the underexcretion group supports the use of a clinical hyperuricemia typing treatment strategy for gout.

Newly identified HMO-2011-type phages reveal genomic diversity and biogeographic distributions of this marine viral group

Viruses play critical roles in influencing biogeochemical cycles and adjusting host mortality, population structure, physiology, and evolution in the ocean. Marine viral communities are composed of numerous genetically distinct subfamily/genus-level viral groups. Among currently identified viral groups, the HMO-2011-type group is known to be dominant and broadly distributed. However, only four HMO-2011-type cultivated representatives that infect marine SAR116 and Roseobacter strains have been reported to date, and the genetic diversity, potential hosts, and ecology of this group remain poorly elucidated. Here, we present the genomes of seven HMO-2011-type phages that were isolated using four Roseobacter strains and one SAR11 strain, as well as additional 207 HMO-2011-type metagenomic viral genomes (MVGs) identified from various marine viromes. Phylogenomic and shared-gene analyses revealed that the HMO-2011-type group is a subfamily-level group comprising at least 10 discernible genus-level subgroups. Moreover, >2000 HMO-2011-type DNA polymerase sequences were identified, and the DNA polymerase phylogeny also revealed that the HMO-2011-type group contains diverse subgroups and is globally distributed. Metagenomic read-mapping results further showed that most HMO-2011-type phages are prevalent in global oceans and display distinct geographic distributions, with the distribution of most HMO-2011-type phages being associated with temperature. Lastly, we found that members in subgroup IX, represented by pelagiphage HTVC033P, were among the most abundant HMO-2011-type phages, which implies that SAR11 bacteria are crucial hosts for this viral group. In summary, our findings substantially expand current knowledge regarding the phylogenetic diversity, evolution, and distribution of HMO-2011-type phages, highlighting HMO-2011-type phages as major ecological agents that can infect certain key bacterial groups.

Meta-Analysis of D-Dimer, hsCRP and Cytokines in COVID-19 Severe/Critical Patients in China

Objective: To analyze the relationship between D-dimer, inflammatory markers, cytokines and disease severity, and the possibility of early identification of COVID-19 critical type patients. Methods: PubMed, EMBASE and CNKI databases were searched by computer, and references of related reviews and systematic reviews were manually searched as supplements. The retrieval deadline is February 9, 2021. According to the inclusion and exclusion criteria, the literatures were screened and the quality was evaluated, and then the data were extracted for meta-analysis. The fixed/random effects model was used to calculate the weighted mean difference (WMD) and 95% CI to evaluate whether the levels of D-dimer, hsCRP, IL-6, IL-8, IL-10 and TNF-α in critical type patients were statistically different from those in severe type patients. If there were statistical differences, logistic regression analysis was used, and establish the receiver operating characteristic curve (ROC) and area under the curve (AUC) of each index for the diagnosis of critical type patients. The best diagnostic value of COVID-19 critical type patients was calculated by Youden index. Results: A total of 3519 literatures entered the screening process. According to the inclusion and exclusion criteria, 40 articles were finally included in this study, and all of them were high-quality studies after evaluation. The results of meta-analysis showed that the levels of D-dimer, hsCRP, IL-6, IL-8 and IL-10 in critical type group were significantly higher than those in severe type group (P<0.05). Based on ROC curve, the AUC of D-dimer was 0.785 (95% CI: 0.671-0.899), AUC of hsCRP was 0.884 (95% CI: 0.632-1.000), AUC of IL-6 was 0.819 (95% CI: 0.700-0.939), which had diagnostic significance for critical type patients (P<0.05). The optimal diagnostic threshold of D-dimer was ≥2.00 mg/L (sensitivity 89.3%, specificity 64.0%); the optimal diagnostic threshold of hsCRP was ≥64.22 mg/L (sensitivity 75.0%, specificity 100%); the optimal diagnostic threshold of IL-6 was ≥33.01 ng/L (sensitivity 68.0%, specificity 92.0%). Conclusion: The levels of D-dimer, hsCRP, IL-6, IL-8 and IL-10 in COVID-19 critical type patients were significantly higher than those in severe type patients. Our results might be helpful in identify and risk reduction of mortality in critical types patients infected with COVID-19. Disclosures No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation Conditioned with Myeloablative Regimens Containing Total Body Irradiation in Adolescent and Young Adult Patients with Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia Who Were Treated with Pediatric-Type Chemotherapy

Background: Although introduction of pediatric-type Berlin-Frankfurt-Munster (BFM) chemotherapy has markedly improved the prognosis of adolescent and young adult (AYA) patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph-negative ALL), their higher toxicity has become an emerging issue with an increased post-remission mortality in AYA patients than pediatric patients. Allogeneic stem cell transplantation (allo-SCT) with myeloablative conditioning (MAC) regimens containing total body irradiation (TBI) is recognized as an important treatment option for patients with higher risk diseases. However, safety and efficacy of allo-SCT with TBI-MAC have not been fully investigated among AYA patients who received pediatric-type chemotherapy. Patients and methods: AYA was defined as 16 to 39 years old. Of the 143 AYA patients with Ph-negative ALL who underwent the first allo-SCT in the first remission between 2007 and 2016 at the 20 institutions, 106 patients who were treated with one BFM chemotherapy regimen before transplant and were conditioned with MAC regimens containing more than or equal to 8 Gy of TBI dose. The reasons for the transplant were surveyed with a multi-answer questionnaire. Overall survival (OS) was defined as the interval from the date of transplant to the date of death. Fisher's exact test was used to compare binary variables. The cumulative incidence (CI) of non-relapse mortality (NRM) and relapse were evaluated with Gray's test, considering relapse and NRM as a competing risk, respectively. OS was estimated with the Kaplan-Meier method and compared using the log-rank test. Factors associated with at least borderline significance (p < 0.20) in univariate analyses were subjected to multivariate analysis. The Fine-Gray and Cox proportional hazard model were used for multivariate analysis of risk factors and prognostic factors, respectively. Values of p < 0.05 were considered to indicate statistical significance. Results: Of the 106 patients included in this study, 61 were male, and 45 were female. The median age at transplant was 29 years (range, 16-39 years). Donor types were related, unrelated, and cord blood in 47 (44%), 47 (44%), and 12 (12%) patients, respectively. The difficulty of continuing chemotherapy due to side effects as the reason for transplant was included in 13 patients (12%). As chemotherapy before transplant, pediatric-type and adult-type regimens were used in 56 (53%) and 50 patients (47%), respectively. There was no significant difference in baseline characteristics and transplant procedures between the pediatric-type group and the adult-type group, except for proportion of patients over 30 years (14% vs. 64%, respectively; p < 0.01), those with more than or equal to 2 of hematopoietic cell transplant comorbidity index (13% vs. 36%, respectively; p < 0.01), and transplant between 2007 and 2011 (36% vs. 64%, respectively; p < 0.01). The CI of NRM, the OS rates, and the CI of relapse were not significantly different between two groups (NRM: 4% vs. 12% at three years after transplant, respectively; p = 0.26), (OS: 86% vs. 70%, respectively; p = 0.14), and (relapse: 16% vs. 24%, respectively; p = 0.32), respectively. Multivariate analysis for NRM revealed that more than or equal to 1 of performance status at transplant (hazard ratio [HR] = 4.8; p < 0.01) and transplant due to side effects of chemotherapy (HR = 3.5; p = 0.04) were identified as independent risk factors, but not pediatric-type chemotherapy (HR = 0.48; p = 0.23). The proportions of transplant due to side effects of chemotherapy were similar between two groups (13% vs. 12%, respectively; p = 1). No independent prognostic factor for OS was found, while transplant between 2007 and 2011 (HR = 2.5; p = 0.04) was extracted as an independent risk factor of relapse. Regarding transplant complications, significant differences were not shown in CI of grade II to IV acute graft-versus-host disease (GVHD), chronic GVHD, bacteremia, cytomegalovirus reactivation, hemorrhagic cystitis, and avascular necrosis between two groups. No characteristic cause of NRM was found in the pediatric-type group. Conclusion: These findings suggested that conventional allo-SCT with TBI-MAC can be performed without increasing NRM in AYA patients with Ph-negative ALL even after pediatric-type chemotherapy. Disclosures Kimura: MSD: Honoraria; Sumitomo Dainippon Pharma: Honoraria; Astellas: Honoraria; Pfizer: Honoraria; Kyowa Kirin: Honoraria; Chugai Pharmaceutical: Honoraria; Bristol-Myers Squibb: Honoraria; Ono Pharmaceutical: Honoraria; Eisai: Honoraria; Nippon Kayaku: Honoraria; Takeda Pharmaceutical: Honoraria; SymBio Pharmaceutical: Honoraria. Usuki: MSD: Speakers Bureau; Alexion: Speakers Bureau; Pfizer: Research Funding; Kyowa Kirin: Research Funding, Speakers Bureau; Eisai: Speakers Bureau; Nippon shinyaku: Research Funding, Speakers Bureau; Astellas-Amgen-Biopharma: Research Funding; Nippon Boehringer Ingelheim: Research Funding; Takeda: Research Funding, Speakers Bureau; Celgene: Research Funding, Speakers Bureau; Janssen: Research Funding; Ono: Research Funding, Speakers Bureau; Brisol-Myers Squibb: Research Funding, Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Otsuka: Research Funding, Speakers Bureau; Sumitomo Dainippon: Research Funding; Daiichi Sankyo: Research Funding, Speakers Bureau; Symbio: Research Funding, Speakers Bureau; Gilead: Research Funding; Abbvie: Research Funding; Astellas: Research Funding, Speakers Bureau; Mundipharma: Research Funding; Yakult: Speakers Bureau; PharmaEssentia: Speakers Bureau. Sakaida: Bristol Myers Squibb: Research Funding; Chugai: Research Funding; Ono: Research Funding; Kyowa Kirin: Research Funding. Fujisawa: Novartis: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Otsuka: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding. Handa: Abbvie: Honoraria; MSD: Research Funding; Shionogi: Research Funding; Sanofi: Honoraria, Research Funding; Ono: Honoraria; BMS: Honoraria; Janssen: Honoraria; Daiichi Sankyo: Research Funding; Celgene: Honoraria, Research Funding; Chugai: Research Funding; Kyowa Kirin: Research Funding; Takeda: Honoraria, Research Funding. Hatta: Bristol-Myers Squibb: Honoraria; Novartis KK: Honoraria; Pfizer Japan Inc.: Honoraria; Otsuka Pharmaceutical.: Honoraria. Kanda: Otsuka Pharmaceutical: Honoraria, Research Funding; Sanofi: Research Funding; MSD: Honoraria.

Analysis of bronchial and vascular patterns in left upper lobes to explore the genesis of mediastinal lingular artery and its influence on pulmonary anatomical variation

Background For thoracic surgeons, three-dimensional computed tomography bronchography and angiography (3-DCTBA) is a convenient way to analyze pulmonary variations before segmentectomy. Mediastinal lingular artery (MLA) is one of the representative variations. Methods The 3-DCTBA data of left upper lobe (LUL) were collected from patients who underwent pulmonary surgery from January 2018 to December 2019. We reviewed the patterns of bronchi and pulmonary vessels and grouped them according to different classifications. Results Among all the 404 cases of 3-DCTBA, mediastinal lingular artery (MLA) was found in 107 cases (26.49%). The patterns of B3 and the vein in left upper division (LUD) are distinct between mediastinal (M-type) group and interlobar (IL-type) group. The patterns of bronchi and veins in lingular division, as well as the pattern of pulmonary artery in LUD, have no differences between M-type and IL-type groups. Conclusions Mediastinal lingular artery is speculated to originate from the variation of B3, and the MLA independently influences the venous pattern in LUD in turn.

Knudsen type group for time in ℝ and related Boltzmann type equations

We consider certain Boltzmann type equations on a bounded physical and a bounded velocity space under the presence of both reflective as well as diffusive boundary conditions. We introduce conditions on the shape of the physical space and on the relation between the reflective and the diffusive part in the boundary conditions such that the associated Knudsen type semigroup can be extended to time [Formula: see text]. Furthermore, we provide conditions under which there exists a unique global solution to a Boltzmann type equation for time [Formula: see text] or for time [Formula: see text] for some [Formula: see text] which is independent of the initial value at time 0. Depending on the collision kernel, [Formula: see text] can be arbitrarily small.

“Holographic Implementations” in the Complex Fluid Dynamics through a Fractal Paradigm

Assimilating a complex fluid with a fractal object, non-differentiable behaviors in its dynamics are analyzed. Complex fluid dynamics in the form of hydrodynamic-type fractal regimes imply “holographic implementations” through velocity fields at non-differentiable scale resolution, via fractal solitons, fractal solitons–fractal kinks, and fractal minimal vortices. Complex fluid dynamics in the form of Schrödinger type fractal regimes imply “holographic implementations”, through the formalism of Airy functions of fractal type. Then, the in-phase coherence of the dynamics of the complex fluid structural units induces various operational procedures in the description of such dynamics: special cubics with SL(2R)-type group invariance, special differential geometry of Riemann type associated to such cubics, special apolar transport of cubics, special harmonic mapping principle, etc. In such a manner, a possible scenario toward chaos (a period-doubling scenario), without concluding in chaos (nonmanifest chaos), can be mimed.

Clinical Course and Outcome of Patients with SARS-CoV-2 Alpha Variant Infection Compared to Patients with SARS-CoV-2 Wild-Type Infection Admitted to the ICU

The alpha variant of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is associated with higher transmissibility and possibly higher mortality compared with wild-type SARS-CoV-2. However, few data are available on the clinical course of infections with the alpha variant compared with wild-type SARS-CoV-2 in critically ill patients in intensive care units (ICUs). Therefore, we retrospectively analyzed patients admitted to our ICU due to SARS-CoV-2 Alpha variant infection and compared characteristics and course to patients with SARS-CoV-2 wild-type infection. The median age of patients with Alpha variant infections was 57 years compared to 62 years in the wild-type group. ICU survival was 41/80 (51%) in the Alpha variant group and 35/80 (44%) in the wild-type group (p = 0.429). Results of a matched-pair analysis based on age and sex illustrated that 45/58 patients (77.6%) in the Alpha variant group and 38/58 (65.5%) patients in the wild-type group required mechanical ventilation (p = 0.217). ICU survival was documented for 28/58 patients (48.3%) in the Alpha variant group and 27/58 patients (46.6%) in the wild-type group (p = 1). Thus, ICU mortality among patients with SARS-CoV-2 infections remains high. Although the Alpha variant group included younger patients requiring mechanical ventilation, no significant differences between patients with the SARS-CoV-2 Alpha variant and the SARS-CoV-2 wild-type, respectively, were detected with respect to clinical course and ICU mortality. For future VOCs, we believe it would be important to obtain valid and rapid data on the clinical course of critically ill patients who test positive for COVID-19 in order to perform appropriate epidemiological planning of intensive care capacity.

Evaluation of the Application Effect of Contrast-Enhanced Ultrasound Image Technology Based on Three-Dimensional Image Fusion Algorithm in the Diagnosis of Adenomyosis

In this paper, the effect of ultrasound images based on a 3-dimensional image fusion algorithm in the diagnosis of adenomyosis was evaluated. 88 patients with adenomyosis who were treated in the hospital from February 2019 to May 2020 were selected as the research subjects. They were rolled into localized type (Group A), with 40 cases, and diffuse type (Group B), with 48 cases. At the same time, 45 women of normal childbearing age who underwent physical examination in the outpatient clinic were rolled into the control group (Group C). Three-dimensional ultrasound scans of the uterus were performed on all patients, to observe the enhancement methods and characteristics. Then, the image characteristics of adenomyosis were studied through the time-intensity curve (TIC). Arise time ATs of three groups of patients were not different greatly ( P > 0.05 ). It was found that the enhancement method, enhancement uniformity, and enhancement level of ultrasound scan in Groups A and B were significantly different from Group C ( P < 0.05 ). In contrast with Group C, the rise time (RT) of the ultrasound scan of the two groups was less, the time-to-peak (TTP) was faster, and the image maximum (IMAX) was higher ( P < 0.05 ). What is more, contrast-enhanced ultrasonic (CEUS) detection in patients with adenomyosis showed centrality and nonuniform high enhancement. Besides, less RT, faster TTP, and higher IMAX than the normal population can be the key evidence for the clinical diagnosis of adenomyosis. In conclusion, according to the blood supply characteristics of adenomyosis and other gynecological diseases, the enhancement method and enhancement time of ultrasound images are significantly different. TIC can reflect the hemodynamic difference between the lesion and the normal ones. Therefore, the CEUS based on the three-dimensional image fusion algorithm can be applied to the image diagnosis of adenomyosis.

Effectivity of V4 and v4C implantable contact lenses in the treatment of complications after vitreoretinal surgery: A comparative study

Objective This study aims to analyze and compare the postoperative ocular parameters of two different types of implantable contact lenses (ICLs) (for retinal detachment) to provide a clinical reference for vitreoretinal surgery. Methods From March 2016 to March 2021, 24 patients (24 eyes) with rhegmatogenous retinal detachment following ICL implantation at the Eye Center of Taizhou Central Hospital were recruited. Based on the different types of ICL, they were divided into the V4 type ICL implantation group (V4 type group) and v4C type ICL implantation group (v4C type group), with 12 cases (12 eyes) in each group. Both groups were treated with pars plana vitrectomy; differences in postoperative ocular complications between the two groups were compared. Results The postoperative uncorrected and best corrected visual acuity for both groups were significantly higher than those preoperatively (P < 0.001); the same applied to the intraocular pressures (P < 0.05). Fluctuation in intraocular pressure was higher in the V4 group than in the v4C group (P < 0.05). The arch height, measured using anterior segment optical coherence tomography on the first day after operation, was lower in the V4 group than in the v4C group (P < 0.05). There was also no significant difference between the two groups before and after the operation (P > 0.05). Conclusion For patients with V4 type ICL implantation and mesh removal, stimulation of the ciliary body and the risk factors for pupil block caused by ciliary muscle spasm should be reduced as much as possible during pars plana vitrectomy. If postoperative complications such as decreased arch height and increased intraocular pressure occur, the application of compound tropicamide eye drops is an effective method to activate the pupil.