Inflammatory Reprogramming Mediates Changes in Three-Dimensional Strain Capacity and Cardiac Function in Beagle Dogs with Doxorubicin-Related Cardiomyopathy.

Background: The cardiotoxicity of doxorubicin (DOX) limits its use in cancer treatment. To address this limitation, we developed a novel animal model that uses beagle dogs to investigate DOX-induced cardiac disorders. Unfortunately, the lack of effective cardioprotection strategies against DOX-induced cardiotoxicity poses a significant challenge. To establish a canine model for low-mortality DOX-induced cardiac dysfunction and explore the relationship between inflammatory reprogramming and DOX-related cardiotoxicity. Methods: Twenty male beagle dogs aged two years were randomly assigned into the DOX (N = 10) and control (CON) (N = 10) groups. DOX was infused (1.5 mg/kg) every two weeks until doses cumulatively reached 12 mg/kg. Serum biomarkers and myocardial pathology were evaluated, while real-time fluorescence-based quantitative polymerase chain reaction (RTFQ-PCR), two- and three-dimensional echocardiography (2DE and RT3DE), functional enrichment, and matrix correlation were also performed. Results: In the DOX group, high-sensitive cardiac troponin T (hs cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were significantly increased. Myocardial pathology indicated early to medium myocardial degeneration via a decreased cardiomyocyte cross-sectional area (CSA). Increased levels of inflammatory gene transcripts (interleukin 6 (IL6), tumor necrosis factor (TNF), transforming growth factor ß (TGF ß ), intercellular adhesion molecule 1 (ICAM1), interleukin 1 (IL1), interleukin 1 ß (IL1 ß ), and interleukin 8 (IL8)), of collagen metabolism and deposition regulatory genes (matrix metalloproteinase (MMP) family and tissue inhibitor of matrix metalloproteinase (TIMP) family), and the natriuretic peptide family (NPS) (natriuretic peptide A, B and C (NPPA, NPPB, and NPPC)) were observed. Strain abnormalities in the right ventricular longitudinal septal strain (RVLSS), right ventricular longitudinal free-wall strain (RVLFS), left ventricular global longitudinal strain (LVGLS), and left ventricular global circumferential strain (LVGCS) were detected at week 28 (vs. week 0 or CON group, p < 0.05, respectively). A significant decline in RVLSS and RVLFS occurred at week 16, which was earlier than in the corresponding left ventricular areas. A significant right ventricular ejection fraction (RVEF) decline was noted at week 16 (vs. week 0, 33.92 ± 3.59% vs. 38.58 ± 3.58%, p < 0.05), which was 12 weeks earlier than for the left ventricular ejection fraction (LVEF), which occurred at week 28 (vs. week 0, 49.02 ± 2.07% vs. 54.26 ± 4.38%, p < 0.01). The right ventricular strain and functional damages correlated stronger with inflammatory reprogramming (most R from 0.60 to 0.90) than the left ones (most R from 0.30 to 0.65), thereby indicating a more pronounced correlation. Conclusions: Inflammatory reprogramming mediated disorders of strain capacity and cardiac function predominantly in the right side of the heart in the newly established DOX-related cardiomyopathy beagle dog model.

Phase Behaviors and Photoresponsive Thin Films of Syndiotactic Side-Chain Liquid Crystalline Polymers with High Densely Substituted Azobenzene Mesogens.

Azobenzene-containing polymers (azopolymers) are a kind of fascinating stimuli-responsive materials with broad and versatile applications. In this work, a series of syndiotactic C1 type azopolymers of Pm-Azo-Cn with side-chain azobenzene mesogens of varied length alkoxy tails (n=1, 4, 8, 10) and different length alkyl spacers (m=6, 10) have been prepared via Rh-catalyzed carbene polymerization. The thermal properties and ordered assembly structures of thus synthesized side chain liquid crystalline polymers (SCLCPs) have been systematically investigated with differential scanning calorimetry (DSC), polarized optical microscopy (POM) and variable-temperature small/wide-angle X-ray scattering (SAXS/WAXS) analyses. P10-Azo-C1 and P10-Azo-C4 with shorter alkoxy tails exhibited hierarchical structures SmB/Colob and transformed into SmA/Colob at a higher temperature, while P10-Azo-C8 and P10-Azo-C10 with longer alkoxy tails only displayed side group dominated layered SmB phase and transformed into SmA phase at higher temperatures. For P6-Azo-C4 with a shorter spacer only showed a less ordered SmA phase owing to interference by partly coupling between the side chain azobenzene mesogens and the helical backbone. More importantly, the series high densely substituted syndiotactic C1 azopolymer thin films, exhibited evidently and smoothly reversible photoresponsive properties, which demonstrated promising photoresponsive device applications.

Advantages of single-site laparoscopic orchiopexy for palpable undescended testes in children: a prospective comparison study.

PURPOSE: To evaluate the feasibility of single-site laparoscopic orchiopexy for palpable undescended testes in children. METHODS: We prospectively studied patients with undescended testes between July 2021 and June 2022. In total, 223 patients were included in our study: 105 underwent single-site laparoscopic orchiopexy and 118 underwent conventional laparoscopic orchiopexy. During single-site laparoscopic orchiopexy, 3 ports were inserted within the umbilicus. RESULTS: No differences were observed between the groups in terms of age and laterality. For unilateral undescended testes, the operating time was longer in the single site group than in the conventional group at the early stages (55.31 ± 12.04 min vs. 48.14 ± 14.39 min, P = 0.007), but it was similar to the conventional group at the later stages (48.82 ± 13.49 min vs. 48.14 ± 14.39 min, P = 0.78). Testicular ascent occurred in one patient from each group. There was no significant difference in the success rate between the single-site group and the conventional group (99.0% vs. 99.2%, P = 0.93). In the single-site group, no visible abdominal scarring was observed, while in the conventional group, there were two noticeable scars on the abdomen. CONCLUSION: Single-site laparoscopic orchiopexy offers superior cosmetic results and comparable success rates compared to conventional laparoscopic orchiopexy for palpable undescended testes.

Combined assessment of health hazard and odour impact of soils at a contaminated site: a case study on a defunct pharmaceuticals factory in China.

Surveys and assessments of contaminated sites primarily focus on hazardous pollutants in the soil with less attention paid to odorants. This makes the management of contaminated sites difficult. In this study, hazardous and odorous pollutants in the soil were assessed for a large site that was previously used for production of pharmaceuticals to determine the degree and characteristics of soil contamination at pharmaceutical production sites, for undertaking rational remediation measures. The main hazardous pollutants at the study site were triethylamine, n-butyric acid, benzo(a)pyrene (BaP), N-nitrosodimethylamine (NDMA), dibenzo(a,h)anthracene (DBA), total petroleum hydrocarbons (C10-C40) (TPH), and 1,2-dichloroethane; TEA, BA, and isovaleric acid (IC) were the main odorants. As the type and distribution of hazardous and odorous pollutants differ, it is necessary to separately assess the impact of these pollutants at a contaminated site. Soils in the surface layer pose significant non-carcinogenic (HI = 68.30) and carcinogenic risks (RT = 3.56E-5), whereas those in the lower layer only pose non-carcinogenic risks (HI > 7.43). Odorants were found at considerable concentrations both in the surface and lower layers, with the maximum concentrations being 29,309.91 and 41.27, respectively. The findings of this study should improve our understanding of soil contamination at former pharmaceutical production sites and should inform the assessment of the risks posed by contaminated sites, with problems associated with odour, and possible remediation strategies.

Facile Synthesis of Liquid Crystal Dimers Bridged with a Phosphonic Group.

Liquid crystal (LC) dimers with well-defined composition and structure arouse broad attentions for their exhibiting LC properties beyond conventional low molar mass mesogens and serving as fascinating model compounds for LC polymers. Here in this work, a series of LC dimers bridged with a phosphonic group have been synthesized through a facile free radical mediated addition reaction between hypophosphorous acid and vinyl terminated cyanobiphenyl mesogens with variant length alkyl spacers. In addition, two esterified derivatives and a group of mono-addition homologues with a terminal phosphonic acid group have also been prepared for comparison study. All the newly synthesized compounds exhibit monotropic nematic (N) phase with typical schlieren textures except for the LC dimer with the longest eleven-methylene spacer, which surprisingly shows twist-bend nematic (NTB ) phase directly from the isotropic state upon cooling. Moreover, the thermal transition properties such as the nematic-isotropic transition temperatures and associated entropy changes of the series LC dimers display a modest odd-even effect. Furthermore, both the LC dimers and the mono-addition homologues in N phase are quite easy to achieve homeotropic alignment upon annealing thanks to the supramolecular interactions between the introduced phosphonic acid group and the hydroxylated glass surface. This work thus provides a novel synthesis strategy for a class of LC materials bridged with a phosphonic acid group prone to further functionalization, which may serve as promising vertical alignment agents and pave the way for developing a new kind of functionalized LC materials of NTB phase.

Design, synthesis and antifungal activity of threoninamide carbamate derivatives via pharmacophore model.

Thirty-six novel threoninamide carbamate derivatives were designed and synthesised using active fragment-based pharmacophore model. Antifungal activities of these compounds were tested against Oomycete fungi Phytophthora capsici in vitro and in vivo. Interestingly, compound I-1, I-2, I-3, I-6 and I-7 exhibited moderate control effect (>50%) against Pseudoperonospora cubensis in greenhouse at 6.25 µg/mL, which is better than that of control. Meanwhile most of these compounds exhibited significant inhibitory against P. capsici. The other nine fungi were also tested. More importantly, some compounds exhibited remarkably high activities against Sclerotinia sclerotiorum, P. piricola and R. solan in vitro with EC50 values of 3.74-9.76 µg/mL. It is possible that the model is reliabile and this method can be used to discover lead compounds for the development of fungicides.

The provenance of deep groundwater and its relation to arsenic distribution in the northwestern Hetao Basin, Inner Mongolia.

High-arsenic (As) groundwater has been widely found throughout the world. The source of groundwater would determine spatial distribution of groundwater As. In order to trace the source of high-As deep groundwater (DGW, depths > 50 m), groundwater, sediments, and local bedrock samples were taken to investigate chemical and isotopic compositions in the Hetao Basin, China. Results showed that 87Sr/86Sr in DGW gradually decreased with the increase in As concentrations along the approximate flow path. In recharge-oxic zone (Zone I), DGW was mainly recharged by fissure water, influenced mostly by weathering of phyllite bedrock and meta-basalt. In groundwater flow-moderate reducing zone (Zone II), DGW was mainly related to incongruent dissolution of feldspar. However, in groundwater flow-reducing zone (Zone III), DGW was partly recharged from shallow groundwater (SGW) with depths < 50 m. The mixing contributions of SGW to DGW in Zone III mostly exceeded 80% during groundwater irrigation season. In Zone I, DGW As concentrations were mostly lower than 50 µg/L due to oxic conditions. In Zone II, the weakly alkaline pH and the decreasing Ca/Na resulting from incongruent dissolution of feldspar caused As desorption, which was the major contribution to As mobilization (As mostly > 200 µg/L). In Zone III, the recharge of SGW introduced labile organic matter to support reduction of Fe(III) oxyhydroxides/oxides and predominantly led to As release into groundwater (As > 300 µg/L). This study has provided insights into the source of high-As DGW and the effect of SGW mixing on As mobilization.

Humanised effector-null FcγRIIA antibody inhibits immune complex-mediated proinflammatory responses.

OBJECTIVE: Immune complexes (ICs) play a critical role in the pathology of autoimmune diseases. The aim of this study was to generate and characterise a first-in-class anti-FcγRIIA antibody (Ab) VIB9600 (previously known as MEDI9600) that blocks IgG immune complex-mediated cellular activation for clinical development. METHODS: VIB9600 was humanised and optimised from the IV.3 Ab. Binding affinity and specificity were determined by Biacore and ELISA. Confocal microscopy, Flow Cytometry-based assays and binding competition assays were used to assess the mode of action of the antibody. In vitro cell-based assays were used to demonstrate suppression of IC-mediated inflammatory responses. In vivo target suppression and efficacy was demonstrated in FcγRIIA-transgenic mice. Single-dose pharmacokinetic (PK)/pharmacodynamic study multiple dose Good Laboratory Practice (GLP) toxicity studies were conducted in non-human primates. RESULTS: We generated a humanised effector-deficient anti-FcγRIIA antibody (VIB9600) that potently blocks autoantibody and IC-mediated proinflammatory responses. VIB9600 suppresses FcγRIIA activation by blocking ligand engagement and by internalising FcγRIIA from the cell surface. VIB9600 inhibits IC-induced type I interferons from plasmacytoid dendritic cells (involved in SLE), antineutrophil cytoplasmic antibody (ANCA)-induced production of reactive oxygen species by neutrophils (involved in ANCA-associated vasculitis) and IC-induced tumour necrosis factor α and interleukin-6 production (involved in rheumatoid arthritis). In FcγRIIA transgenic mice, VIB9600 suppressed antiplatelet antibody-induced thrombocytopaenia, acute anti-GBM Ab-induced nephritis and anticollagen Ab-induced arthritis. VIB9600 also exhibited favourable PK and safety profiles in cynomolgus monkey studies. CONCLUSIONS: VIB9600 is a specific humanised antibody antagonist of FcγRIIA with null effector function that warrants further clinical development for the treatment of IC-mediated diseases.

The advantages of transumbilical single-site laparoscopic percutaneous extraperitoneal closure for inguinal hernia in 1583 children.

BACKGROUND: There have been numerous surgical procedures for inguinal hernia in children, and recently the novel technique of single-site laparoscopic procedure was introduced. This study aimed to analyze the safety and efficacy of single-site laparoscopic hernia repair in a large number of children, while compared with the traditional open surgery. METHODS: From January 2012 to June 2015, we performed transumbilical single-site laparoscopic percutaneous extraperitoneal closure (TSLPEC) in 1583 patients, including bilateral hernia in 135 cases, and unilateral hernia in 1448 cases (left side in 582, right side in 866). From January 2007 to January 2010, we performed open inguinal hernia repair in 355 patients, including bilateral hernia in 52 cases, and unilateral hernia in 303 cases. Operating time, recurrence rate, incidence of contralateral hernia, and prevalence of contralateral patent processus vaginalis (cPPV) were recorded and compared. RESULTS: A total of 1583 patients underwent TSLPEC, without conversion to open surgery. For unilateral repair, the average operating time in TSLPEC group was shorter than open repair group (19.3 ± 6.1 vs. 28.0 ± 8.9, p < 0.05), and it was much shorter than open repair group for bilateral repair (26.2 ± 9.5 vs. 49.8 ± 12.9, P p < 0). The left hernia had higher prevalence of cPPV than right hernia (48.1% vs. 38.5%, p < 0.05). The wound recovered well with good cosmetic appearance in TSLPEC group. Hernia recurrence occurred in seven cases (0.4%) of TSLPEC group, and six cases (1.7%) of open repair group ( p < 00.05). No contralateral hernia developed in TSLPEC group, while 17 cased (5.6%) had contralateral hernia in open repair group ( p < 00.05). CONCLUSIONS: TSLPEC is an effective and safe procedure for inguinal hernias with lots of advantages, including short operating time, simultaneous management of cPPV, excellent cosmetic appearance, low incidence of contralateral hernia, and low recurrence rate. This procedure could be recommended as a routine treatment for inguinal hernias in children.

Design, synthesis, and fungicidal activities of imino diacid analogs of valine amide fungicides.

The novel imino diacid analogs of valine amides were synthesized via several steps, including the protection, amidation, deprotection, and amino alkylation of valine, with the resulting structures confirmed by (1)H and (13)C NMR and HRMS. Bioassays showed that some of these compounds exhibited good fungicidal activity. Notably, isopropyl 2-((1-((1-(3-fluorophenyl)ethyl)amino)-3-methyl-1-oxobutan-2-yl)amino)propanoate 5i displayed significant levels of control, at 50%, against Erysiphe graminis at 3.9µM as well as a level of potency very similar to the reference azoxystrobin, which gave 60% activity at this concentration. The present work demonstrates that imino diacid analogs of valine amides could be potentially useful key compounds for the development of novel fungicides against wheat powdery mildew.

Design, synthesis, and fungicidal activity of novel carboxylic acid amides represented by N-benzhydryl valinamode carbamates.

Carboxylic acid amide (CAA) fungicides are an important class of agricultural fungicide with oomycete activity and low toxicity toward mammalian cells. To find CAA analogues with high activity against resistant pathogens, a series of substituted N-benzhydryl valinamide carbamate derivatives were designed and synthesized by introducing substituted aromatic rings into valinamide carbamate leads. Bioassays showed that some title compounds exhibited very good in vitro fungicidal activity against Phytophthora capsici and in vivo fungicidal activities against Pseudoperonospora cubensis. Topomer CoMFA was performed to explore the structure-activity relationship on the basis of the in vitro data. The dimethoxy substituted aromatic analogue 9e was found to display higher in vitro fungicidal activity against Phytophthora capsici than iprovalicarb but lower activity than mandipropamid, and higher in vivo fungicidal activity against Pseudoperonospora cubensis than dimethomorph at a dosage of 6.25 µg mL(-1).

Open-Pose 3D zero-shot learning: Benchmark and challenges.

With the explosive 3D data growth, the urgency of utilizing zero-shot learning to facilitate data labeling becomes evident. Recently, methods transferring language or language-image pre-training models like Contrastive Language-Image Pre-training (CLIP) to 3D vision have made significant progress in the 3D zero-shot classification task. These methods primarily focus on 3D object classification with an aligned pose; such a setting is, however, rather restrictive, which overlooks the recognition of 3D objects with open poses typically encountered in real-world scenarios, such as an overturned chair or a lying teddy bear. To this end, we propose a more realistic and challenging scenario named open-pose 3D zero-shot classification, focusing on the recognition of 3D objects regardless of their orientation. First, we revisit the current research on 3D zero-shot classification and propose two benchmark datasets specifically designed for the open-pose setting. We empirically validate many of the most popular methods in the proposed open-pose benchmark. Our investigations reveal that most current 3D zero-shot classification models suffer from poor performance, indicating a substantial exploration room towards the new direction. Furthermore, we study a concise pipeline with an iterative angle refinement mechanism that automatically optimizes one ideal angle to classify these open-pose 3D objects. In particular, to make validation more compelling and not just limited to existing CLIP-based methods, we also pioneer the exploration of knowledge transfer based on Diffusion models. While the proposed solutions can serve as a new benchmark for open-pose 3D zero-shot classification, we discuss the complexities and challenges of this scenario that remain for further research development. The code is available publicly at https://github.com/weiguangzhao/Diff-OP3D.

Combined pretreatment of malic acid and kraft pulping for the production of fermentable sugars and highly active lignin.

The separation and utilization of cellulose, hemicellulose, and lignin in lignocellulosic biorefineries present significant challenges. This study proposes a pretreatment method for biomass refining by combining acid and kraft pulping. Firstly, the biomass was pretreated by malic acid, resulting in the isolation of xylo-oligosaccharides (XOS) with a yield of 86.26 % with optimized conditions of 180 °C, 1 wt% concentration, 40 min. Secondly, a mixture of 12.98 wt% NaOH and 1.043 wt% Na2S is employed to achieve lignin removal efficiency up to 63.42 %. Physical refinement techniques are then applied to enhance the enzyme digestion efficiency of cellulose, resulting in an increase from 55.03 % to 91.4 % for efficient cellulose conversion. The reacted samples exhibit a lignin composition rich in ß-O-4 ether bonds, facilitating their high-value utilization. The results indicated that the combined pretreatment approach demonstrates high efficiency in separating cellulose, hemicellulose, and lignin while obtaining XOS, highly active lignin, and enzyme-digested substrates.

The microbiota and renal cell carcinoma.

Renal cell carcinoma (RCC) accounts for about 2% of cancer diagnoses and deaths worldwide. Recent studies emphasized the critical involvement of microbial populations in RCC from oncogenesis, tumor growth, and response to anticancer therapy. Microorganisms have been shown to be involved in various renal physiological and pathological processes by influencing the immune system function, metabolism of the host and pharmaceutical reactions. These findings have extended our understanding and provided more possibilities for the diagnostic or therapeutic development of microbiota, which could function as screening, prognostic, and predictive biomarkers, or be manipulated to prevent RCC progression, boost anticancer drug efficacy and lessen the side effects of therapy. This review aims to present an overview of the roles of microbiota in RCC, including pertinent mechanisms in microbiota-related carcinogenesis, the potential use of the microbiota as RCC biomarkers, and the possibility of modifying the microbiota for RCC prevention or treatment. According to these scientific findings, the clinical translation of microbiota is expected to improve the diagnosis and treatment of RCC.

Design, synthesis, and fungicidal activities of novel piperazine thiazole derivatives containing oxime ether or oxime ester moieties.

BACKGROUND: To study the effect of changing the piperidine ring of oxathiapiprolin on the fungicidal activity, we designed and synthesized novel piperazine thiazole derivatives containing oxime ether or oxime ester moieties, and studied their fungicidal activities against Phytophthora capsici in vitro. RESULTS: These derivatives showed moderate to good fungicidal activities against Phytophthora capsici, two oxime ether derivatives showed higher fungicidal activity in vitro than dimethomorph (EC50  = 0.1331 µg mL-1 ) and comparable to oxathiapiprolin (EC50  = 0.0042 µg mL-1 ). Oxime ester derivatives showed significantly reduced activities compared with oxime ether derivatives. Most of these derivatives showed broad-spectrum fungicidal activity against the other eight kinds of fungi. Moreover, four derivatives exhibited good antifungal activities in vivo against Phytophthora capsici, Pseudoperonospora cubensis, and Phytophthora infestans. The hyphae morphology study showed that compound 10d might cause mycelial abnormalities of Phytophthora capsici. CONCLUSION: The activity of 10b against Phytophthora infestans was better than that of mandipropamid, and compound 10d exhibited higher fungicidal activities against Pseudoperonospora cubensis and Phytophthora infestans than mandipropamid. These two derivatives emerged as promising candidates for antifungal drugs. © 2023 Society of Chemical Industry.

Stem cells implanted with nanofibrous mats for injured endometrial regeneration and immune-microenvironment remodeling.

Severe endometrial injury caused by invasive uterine operation and/or endometritis often results in intrauterine adhesions (IUAs), which are named Asherman's syndrome (AS), further leading to menstrual disorders, infertility and severe complications during pregnancy and delivery. IUAs or AS has been a challenging medical problem. Stem cells are a promising therapeutic modality for endometrial regeneration in patients with refractory AS. Here, we developed a new system of adipose-derived mesenchymal stem cells (ADMSCs) implantation on silk fibroin/polycaprolactone (SF/PCL) electrospun nanofibers (ADMSCs-SF/PCL) and used it in the damaged endometrium of a rat model. After SF/PCL enhanced the proliferation of transplanted ADMSCs, the results showed that the ADMSCs-SF/PCL system could recover morphology, promote regeneration of the glands and angiogenesis by increasing CD31 expression, and reverse endometrial fibrosis by decreasing TGF-ß/Smad expression. In addition, the ADMSCs-SF/PCL system also increased the expression of differentiation and decidualization markers, including HOXA11, HAND2 and FOXO1. Most importantly, the ADMSCs-SF/PCL system could remodel the special immune microenvironment, resulting in dominant NK infiltration and a normal Th1/Th2 bias in the endometrium. Moreover, this treatment had a lower but more persistent effect than estrogen. Thus, the ADMSCs-SF/PCL system enhanced endometrial restoration, suggesting a promising strategy for damaged endometrial regeneration and immune microenvironment remodeling.

Targeting the Inducible T-cell Costimulator (ICOS) in Patients with Relapsed/Refractory T-follicular Helper Phenotype Peripheral T-cell and Angioimmunoblastic T-cell Lymphoma.

PURPOSE: Proliferation of T-follicular helper (TFH) CD4+ T cells is a postulated pathogenic mechanism for T-cell non-Hodgkin lymphomas (T-NHL). The inducible T-cell costimulator (ICOS) is highly expressed by TFH, representing a potential target. MEDI-570 is a monoclonal antibody against ICOS, which eliminates ICOS+ cells in preclinical models. PATIENTS AND METHODS: We report the safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical activity of MEDI-570 in T-NHL. NCI-9930 is a phase I, first-in-human study of MEDI-570 in relapsed/refractory malignant T-NHL known to express ICOS. MEDI-570 was administered intravenously every 3 weeks for up to 12 cycles. Primary endpoints were safety, dose-limiting toxicities (DLT), and recommended phase II dose (RP2D). Secondary and exploratory endpoints included efficacy parameters and various correlative studies. This study is supported by the National Cancer Institute (NCT02520791). RESULTS: Twenty-three patients were enrolled and received MEDI-570 at five dose levels (0.01-3 mg/kg). Sixteen (70%) had angioimmunoblastic T-cell lymphoma (AITL); median age was 67 years (29-86) and the median prior lines of therapies was 3 (1-16). Most common grade 3 or 4 adverse events were decreased CD4+ T cells (57%), lymphopenia (22%), anemia (13%), and infusion-related reactions (9%). No DLTs were observed. The RP2D was determined at 3 mg/kg. Analysis of T-cell subsets showed reductions in CD4+ICOS+ T cells reflecting its effects on TFH cells. The response rate in AITL was 44%. CONCLUSIONS: MEDI-570 was well tolerated and showed promising clinical activity in refractory AITL. MEDI-570 resulted in sustained reduction of ICOS+ T lymphocytes.

Characteristics of Deep Venous Thrombosis in Isolated Lower Extremity Fractures and Unsolved Problems in Guidelines: A Review of Recent Literature.

Deep venous thrombosis (DVT) has been characterized by a disorder of venous return caused by abnormal blood clotting in deep veins. It often occurs in the lower limbs and is a common complication in orthopaedics. Therefore, relevant professional organizations domestic and overseas had formulated and constantly updated relevant guidelines to prevent the occurrence of DVT. According to the management strategy of the guidelines, the incidence of DVT can be significantly reduced. However, due to the variety of fractures types, the guidelines cannot expound precautions and characteristics of DVT for all fracture types at present, and there are other related unresolved problems. For example, there is still a lack of consistent optimal strategies for the management of DVT following isolated lower extremity fractures with a higher incidence. The best anticoagulant strategies for patients with upper limb fractures, pediatric fractures, and those combined with other injuries are rarely described in orthopaedic guidelines, but such fractures are common in clinical orthopaedics. The long-term complications after DVT, such as post-thrombotic syndrome, are not well-understood. In the absence of clear guidance, orthopaedic surgeons often resort to empiric anticoagulation or conservative treatment, so the prevention effects of DVT are inconsistent. The purpose of this review is to summarize the characteristics of DVT events after isolated lower extremity fractures and to discuss the unsolved issues in the guidelines by reviewing the previous literature and tracing the history of DVT discovery, to provide more scientific and comprehensive recommendations for the prediction and prevention of DVT.

Incidence and risk factors of preoperative isolated calf deep venous thrombosis following hip fractures.

ABSTRACT: There is still a lack of data on isolated calf deep vein thrombosis (ICDVT) following hip fractures surgery. The study aimed to determine the incidence of preoperative ICDVT and the associated risk factors in patients with hip fractures requiring surgery.The 289 patients who required hip surgery were included, duplex ultrasonography was routinely used to make a definite diagnosis of preoperative ICDVT located in unilateral or bilateral calf. Data on demographics and laboratory-associated blood biomarkers results were included. Univariate analyses were used to analyse the data of demographics, comorbidities, personal history operation related indexes and laboratory biomarkers, then the multivariate logistic regression analysis was employed to identify the independent risk factors associated with ICDVT.Sixty-eight (23.5%) patients were diagnosed with preoperative ICDVTs. The univariate analyses showed significant differences regarding ICDVT were age, current smoking, alcohol consumption, time from injury to operation, albumin, white blood cells, lymphocyte, red blood cells, hemoglobin, hematocrit, and activated partial thromboplastin time level among the 44 factors. The multivariable model confirmed 3 risk factors were significantly independent in association with preoperative ICDVTs, including current smoking, time delay from injury to operation and activated partial thromboplastin time ( < 28seconds).The incidence of preoperative ICDVT in hip fracture was 23.5%, and patients with associated risk factors are prone to form ICDVTs, identification of these factors may help to reduce the incidence of ICDVT with hip fractures by taking early prevention measures.

Incidence and risk factors of preoperative deep venous thrombosis following pelvic and acetabular fractures: a retrospective case-control study.

The objective of this study was to investigate the prevalence of preoperative deep venous thrombosis (DVT) in the pelvic cavity and lower extremities following pelvic and acetabular fractures and to identify the risk factors of the occurrence of DVT. Duplex ultrasound (DUS) screening and blood tests were conducted in patients admitted from June 2012 to December 2020 for surgical treatment of pelvic and acetabular fractures. Univariate analyses were performed on data of demographics, comorbidities, time from injury to surgery, injury mechanism, accompanied injury, and laboratory results. The optimal cutoff values of continuous variables with statistical significance were obtained by using the receiver operating characteristic (ROC) curve. A multivariate logistic regression analysis was then employed to examine the independent values in terms of predicting preoperative DVT. A total of 607 patients with pelvic and acetabular fractures were included, among whom 82 (13.5%) patients sustained preoperative DVTs. Specifically, 31.7% (26/82) were diagnosed with proximal DVTs. Fifty-two (63.4%) patients had DVT within 7 days after injury, and 67 (81.7%) patients within 10 days. The multivariate logistic regression analysis identified 6 factors independently associated with the presence of preoperative DVT, including age > 46 years (odds ratio [OR] = 2.94), BMI > 26.73 kg/m2 (OR = 3.91), time from injury to surgery > 9 days (OR = 5.39), associated injury (OR = 7.85), ALB < 32.8 g/L (OR = 2.71) and FIB > 3.095 g/L (OR = 3.34). Despite the modern prophylactic regimen, the preoperative DVT in patients with pelvic and acetabular fractures still draws the attention of orthopaedic surgeons. Better understanding these risk factors can help surgeons refine the risk stratification profile and perform early interdisciplinary management for patients at high risk of DVT.