Efficacy of daratumumab on multiple myeloma patients with renal insufficiency: a systematic review and meta-analysis.

BACKGROUND: Renal insufficiency (RI) is a key factor affecting the prognosis of multiple myeloma (MM) patients. Because the benefit of daratumumab for treating MM patients with RI remains unclear, our objective was to evaluate the efficacy of daratumumab on MM patients with RI. METHODS: We conducted a systematic search of the PubMed, EMBASE, and Cochrane Library databases as of October 24, 2023. Two independent reviewers screened the article titles, abstracts, and full text to identify the randomized controlled trials (RCTs) meeting the inclusion and exclusion criteria. Meta-analyses were performed using RevMan version 5.4. Outcomes of interest were progression-free survival (PFS), overall survival (OS), complete response or better (≥CR), and minimal residual disease (MRD) negativity, all calculated as hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs). RESULTS: A total of 10 RCTs with 5003 patients were included. Add-on daratumumab improved PFS and OS among newly diagnosed MM (NDMM) patients with RI (HR 0.48 [95% CI: 0.36, 0.64, I2 = 65%] and HR 0.63 [95% CI: 0.48, 0.82, I2 = 0%]) as well as relapsed/refractory MM (RRMM)-RI patients, compared with the control group (HR 0.46 [95% CI: 0.37, 0.58, I2 = 0%] and HR 0.68 [95% CI: 0.51, 0.92, I2 = 0%]). In terms of the renal status, the efficacy of add-on daratumumab for MMRI patients was similar to that for MM patients with normal renal function. A prolonged PFS benefit for add-on daratumumab treatment versus the control was evident across all RRMM-RI subgroups, and the benefits tended to increase with the follow-up time. CONCLUSIONS: Our results indicate that MM patients with RI could benefit from a daratumumab-added regimen regardless of MM status. Additional high-quality RCTs are still warranted to confirm our findings.

Daratumumab, bortezomib, melphalan, and prednisone versus bortezomib, melphalan, and prednisone alone in transplant-ineligible Asian patients with newly diagnosed multiple myeloma: final analysis of the phase 3 OCTANS Study.

The superiority and tolerability of daratumumab plus bortezomib/melphalan/prednisone (D-VMP) versus bortezomib/melphalan/prednisone (VMP) in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) was previously described in the global phase 3 ALCYONE study. The primary analysis of the phase 3 OCTANS study further demonstrated the superiority and tolerability of D-VMP (n = 144) versus VMP (n = 71) in transplant-ineligible Asian patients with NDMM. The current analysis describes the final efficacy and safety outcomes for D-VMP versus VMP in OCTANS, with a follow-up of > 3 years. D-VMP demonstrated a benefit versus VMP with regard to the rate of very good partial response or better (80.1% vs. 47.3%), median progression-free survival (38.7 vs. 19.2 months), median time to next treatment (46.8 vs. 20.6 months), rate of complete response or better (46.6% vs. 18.9%), median duration of response (41.3 vs. 18.5 months), achievement of minimal residual disease (MRD) negativity (40.4% vs. 10.8%), and sustained MRD negativity for ≥ 12 months (24.7% vs. 1.4%) and ≥ 18 months (15.1% vs. 1.4%). Median progression-free survival was longer among patients who achieved MRD negativity and sustained MRD negativity. The progression-free survival benefit observed with D-VMP was preserved across most clinically relevant subgroups, including patients with high-risk cytogenetics. No new safety concerns were identified with extended follow-up. This final analysis of OCTANS continues to demonstrate a clinical benefit for D-VMP versus VMP in transplant-ineligible Asian patients with NDMM, consistent with the global ALCYONE study, and supports the use of daratumumab combinations in this population. Trial registration: ClinicalTrials.gov Identifier NCT03217812 submitted July 13, 2017.

Electrostimulation-Based Decellularized Matrix Bladder Patch Promotes Bladder Repair in Rats.

Bladder tissue engineering offers significant potential for repairing defects resulting from congenital and acquired conditions. However, the effectiveness of engineered grafts is often constrained by insufficient vascularization and neural regeneration. This study utilized four primary biomaterials─gelatin methacryloyl (GelMA), chitin nanocrystals (ChiNC), titanium carbide (MXene), and adipose-derived stem cells (ADSC)─to formulate two types of bioinks, GCM0.2 and GCM0.2-ADSC, in specified proportions. These bioinks were 3D printed onto bladder acellular matrix (BAM) patches to create BAM-GCM0.2 and BAM-GCM0.2-ADSC patches. The BAM-GCM0.2-ADSC patches underwent electrical stimulation to yield GCM0.2-ADSC-ES bladder patches. Employed for the repair of rat bladder defects, these patches were evaluated against a Control group, which underwent partial cystectomy followed by direct suturing. Our findings indicate that the inclusion of ADSC and electrical stimulation significantly enhances the regeneration of rat bladder smooth muscle (from [24.052 ± 2.782] % to [57.380 ± 4.017] %), blood vessels (from [5.326 ± 0.703] % to [12.723 ± 1.440] %), and nerves (from [0.227 ± 0.017] % to [1.369 ± 0.218] %). This research underscores the superior bladder repair capabilities of the GCM0.2-ADSC-ES patch and opens new pathways for bladder defect repair.

A bilayer bioengineered patch with sequential dual-growth factor release to promote vascularization in bladder reconstruction.

Bladder tissue engineering holds promise for addressing bladder defects resulting from congenital or acquired bladder diseases. However, inadequate vascularization significantly impacts the survival and function of engineered tissues after transplantation. Herein, a novel bilayer silk fibroin (BSF) scaffold was fabricated with the capability of vascular endothelial growth factor (VEGF) and platelet derived growth factor-BB (PDGF-BB) sequential release. The outer layer of the scaffold was composed of compact SF film with waterproofness to mimic the serosa of the bladder. The inner layer was constructed of porous SF matrix incorporated with SF microspheres (MS) loaded with VEGF and PDGF-BB. We found that the 5% (w/v) MS-incorporated scaffold exhibited a rapid release of VEGF, whereas the 0.2% (w/v) MS-incorporated scaffold demonstrated a slow and sustained release of PDGF-BB. The BSF scaffold exhibited good biocompatibility and promoted endothelial cell migration, tube formation and enhanced endothelial differentiation of adipose derived stem cells (ADSCs) in vitro. The BSF patch was constructed by seeding ADSCs on the BSF scaffold. After in vivo transplantation, not only could the BSF patch facilitate the regeneration of urothelium and smooth muscle, but more importantly, stimulate the regeneration of blood vessels. This study demonstrated that the BSF patch exhibited excellent vascularization capability in bladder reconstruction and offered a viable functional bioengineered patch for future clinical studies.

An open-label, prospective trial to evaluate the efficacy and safety of ixazomib in combination with cyclophosphamide and dexamethasone in patients with newly diagnosed POEMS syndrome.

This open-label, prospective trial evaluated the combination of ixazomib, cyclophosphamide and dexamethasone (ICD) in 12 newly diagnosed POEMS syndrome patients. The study is registered with the Chinese Clinical Trials Registry (ChiCTR2000030072). The treatment protocol consisted of 12 cycles of the ICD regimen compromising ixazomib (4 mg on Days 1, 8 and 15), oral cyclophosphamide (300 mg on Days 1, 8 and 15) and dexamethasone (20 mg weekly). A total of 12 patients received a median of 10 (range: 3-23) cycles of the ICD regimen. The haematological response could be evaluated in 10 patients. The overall haematological response rate was 80% (8/10), with 30% (3/10) achieving complete haematological response, and the overall serum VEGF response rate and neurological response were 100% and 83.3% respectively. Two patients experienced grade 3/4 AEs, including diarrhoea (n = 1) and leukopenia (n = 1). The combination of ixazomib, cyclophosphamide and dexamethasone demonstrated both efficacy and safety in newly diagnosed POEMS syndrome, making it a viable treatment option.

Radical Prostatectomy Without Prior Biopsy in Selected Patients Evaluated by 18F-Labeled Prostate-Specific Membrane Antigen-Ligand Positron Emission Tomography/Computed Tomography and Multiparameter Magnetic Resonance Imaging: A Single-Center, Prospective, Single-Arm Trial.

PURPOSE: This study aimed to verify the feasibility and short-term prognosis of prostatectomy without biopsy. MATERIALS AND METHODS: Patients with a rising PSA level ranging from 4 to 30 ng/mL were scheduled for multiparametric (mp) MRI and 18F-labeled prostate-specific membrane antigen (PSMA) positron emission tomography (PET). Forty-seven patients (cT2N0M0) with Prostate Imaging Reporting and Data System ≥ 4 and molecular imaging PSMA score ≥ 2 were enrolled. All candidates underwent robot-assisted laparoscopic radical prostatectomy without biopsy. Prostate cancer detection rate, index tumors localization correspondence rate, positive surgical margin, complications, postoperative hospital stay, and PSA level in a 6-week postoperative follow-up visit were collected. RESULTS: All the patients with positive mpMRI and PSMA PET were diagnosed with clinically significant prostate cancer. A total of 80 lesions were verified as cancer by pathology, of which 63 cancer lesions were clinically significant prostate cancer. Fifty-one lesions were simultaneously found by mpMRI and PSMA PET. A total of 23 lesions were invisible on either image, and all lesions were ≤ International Society of Urological Pathology 2 or ≤ 15 mm. Forty-five (95.7%) index tumors found by mpMRI combined with PSMA PET were consistent with pathology. Nine patients reported positive surgical margin. CONCLUSIONS: Biopsy-free prostatectomy is safe and feasible for patients with evaluation strictly by mpMRI combined with 18F-PSMA PET/CT.

Life disturbance and hospital visit experiences among Chinese patients with benign prostatic hyperplasia: a qualitative study.

BACKGROUND: The impact of lower urinary tract symptoms (LUTS) on the quality of life of patients with benign prostatic hyperplasia (BPH) has been rarely reported. Additionally, the challenges faced by these patients in seeking medical care have often been overlooked. In order to explore the personal struggles caused by LUTS and the difficulties or barriers experienced by Chinese patients with BPH when seeking help, we conducted a qualitative interview study. METHODS: Qualitative interviews were conducted among 46 patients with BPH who were hospitalized in three tertiary hospitals in China from July 2021 to November 2022. Grounded theory was adopted as the methodology for the qualitative study. After obtaining written informed consent from the study participants, semi-structured interviews were conducted according to the question guidelines. The interview process was audio-recorded; subsequently, the recordings were transcribed, coded, and thematically analyzed. RESULTS: The difficulties faced by Chinese patients with BPH were classified into seven main themes: (i) disturbed life, (ii) mental burden, (iii) disease cognition and communication, (iv) delayed treatment, (v) medication status, (vi) hospital visits barriers, and (vii) medical insurance issues. Further, each theme was subdivided into 2-5 sub-themes. CONCLUSIONS: LUTS have a certain effect on the life and spirit of patients with BPH. These patients face different degrees of difficulties in treatment and hospital visits. Therefore, better healthcare systems and additional social support are crucial for improving the current plight of these patients.

Electrochemical Radical Tandem Difluoroethylation/Cyclization of Unsaturated Amides to Access MeCF2-Featured Indolo/Benzoimidazo [2,1-a]Isoquinolin-6(5H)-ones.

A metal-free electrochemical oxidative difluoroethylation of 2-arylbenzimidazoles was accomplished, which provided an efficient strategy for the synthesis of MeCF2-containing benzo[4,5]imidazo[2,1-a]-isoquinolin-6(5H)-ones. In addition, the method also enabled the efficient construction of various difluoroethylated indolo[2,1-a]isoquinolin-6(5H)-ones. Notably, this electrochemical synthesis protocol proceeded well under mild conditions without metal catalysts or exogenous additives/oxidants added.

Photopromoted Free Radical Silylation of 2-Aryl-2H-indazoles with Silanes.

Photoinduced silylation of silanes with 2-aryl-2H-indazoles was developed under mild conditions, which could efficiently result in diverse 3-silylated 2H-indazoles with good substrate scopes. A series of scaled-up to gram level and radical capture operations were performed in this system. Meanwhile, a bioactive molecule was tolerated well under typical conditions.

Laparoscopic and Robotic-Assisted Extended Pelvic Lymph Node Dissection for Invasive Bladder Cancer: A Review.

Minimally invasive surgical techniques, including laparoscopic and robotic-assisted radical cystectomy (RC), are emerging as the preferred treatment options for invasive bladder cancer. Mounting evidence has demonstrated that laparoscopic and robotic-assisted RC with extended pelvic lymph node dissection (PLND) is a viable alternative for managing invasive bladder cancer. In this review, we summarized recent advances and critically assessed the minimally invasive approaches and risk factors associated with extended PLND in patients undergoing laparoscopic or robotic-assisted RC. The findings indicated that laparoscopic and robotic-assisted PLND, employing either a standard or extended approach, is technically feasible and offers benefits such as minimal invasiveness, superior visualization, reduced blood loss, and expedited recovery. The risk factors involved in the laparoscopic extended PLND are minimal. Clinically, laparoscopic and robotic-assisted extended PLND is significantly advantageous in that it sticks to the principles of open surgery and respects anatomical boundaries. Nevertheless, laparoscopic and robotic-assisted extended PLND is technically challenging and necessitate extended operation time. Furthermore, large-scale, prospective, multicenter trials are warranted to validate the long-term efficacy of laparoscopic and robotic-assisted extended PLND in terms of disease-specific survival.

Transurethral Hem-o-lok Clip Ligation of the Distal Ureter in Retroperitoneal Laparoscopic Radical Nephroureterectomy.

BACKGROUND AND OBJECTIVE: Distal ureter management is an essential part of radical nephroureterectomy (RNU). However, there is no agreement on the optimal surgical treatment for ureter and bladder cuff excision. The classical "pluck" technique following transurethral resection of the intramural ureter increases the risk of extravesical and intravesical tumor cell spillage. We aimed to provide a simple transurethral technique with the Hem-o-lok clip ligation for the management of the distal ureter during retroperitoneal laparoscopic RNU. METHODS: Transurethral resection of the bladder cuff was performed using a bipolar ß electrode mounted on resectoscope. Subsequently, a Super Scope (S-scope) with a 5.6-mm diameter working channel was used with a clip applier to deliver the 5-mm Hem-o-lok clips, which consequently ligated the ureteral stump and avoided urine spillage from the upper tract. Traditional retroperitoneal laparoscopic surgery was used to treat the renal and upper ureter. The resected distal ureter and the Hem-o-lok clip were gently pulled out of the bladder by the "pluck" technique. RESULTS: A total of 14 upper tract urothelial carcinoma patients were analyzed, including 10 men and 4 women. The Hem-o-lok clip ligation took less than 20 s. In each patient, the clip was clearly visible and attached tightly to the ureter, and a clear distal ureter was observed in all patients. Histopathology results showed pT2 in 8 and pT3 in 6 patients. A median follow-up of 15 months revealed no extravesicular or intravesicular recurrences. CONCLUSIONS: Transurethral Hem-o-lok clip ligation technique provides a simple and safe option for distal ureter management in retroperitoneal laparoscopic RNU. This novel approach enables construction of a watertight system of the upper urinary tract, preventing the spread of tumor cells effectively and minimizing local tumor implantation risk.

Multi-omics investigation of the resistance mechanisms of pomalidomide in multiple myeloma.

Background: Despite significant therapeutic advances over the last decade, multiple myeloma remains an incurable disease. Pomalidomide is the third Immunomodulatory drug that is commonly used to treat patients with relapsed/refractory multiple myeloma. However, approximately half of the patients exhibit resistance to pomalidomide treatment. While previous studies have identified Cereblon as a primary target of Immunomodulatory drugs' anti-myeloma activity, it is crucial to explore additional mechanisms that are currently less understood. Methods: To comprehensively investigate the mechanisms of drug resistance, we conducted integrated proteomic and metabonomic analyses of 12 plasma samples from multiple myeloma patients who had varying responses to pomalidomide. Differentially expressed proteins and metabolites were screened, and were further analyzed using pathway analysis and functional correlation analysis. Also, we estimated the cellular proportions based on ssGSEA algorithm. To investigate the potential role of glycine in modulating the response of MM cells to pomalidomide, cell viability and apoptosis were analyzed. Results: Our findings revealed a consistent decrease in the levels of complement components in the pomalidomide-resistant group. Additionally, there were significant differences in the proportion of T follicular helper cell and B cells in the resistant group. Furthermore, glycine levels were significantly decreased in pomalidomide-resistant patients, and exogenous glycine administration increased the sensitivity of MM cell lines to pomalidomide. Conclusion: These results demonstrate distinct molecular changes in the plasma of resistant patients that could be used as potential biomarkers for identifying resistance mechanisms for pomalidomide in multiple myeloma and developing immune-related therapeutic strategies.

[Integrated Analysis on Source-exposure Risk of Heavy Metals in Farmland Soil Based on PMF Model: A Case Study in the E-waste Dismantling Area in Zhejiang Province].

In order to explore the characteristics and sources of heavy metals in farmland soil and their risks to human health and to provide an important scientific basis for farmland pollution control, 133 surface soils (0-20 cm) were collected from typical agricultural production areas in Zhejiang Province, and the contents of soil Cd, Pb, Cr, Cu, Zn, Ni, As, and Hg were determined. Various methods were applied to evaluate the degree of heavy metal pollution in farmland and its ecological risks in the study area. The method of combining Kriging interpolation and positive definite matrix factor analysis (PMF) was applied to analyze the pollution sources and quantify the contribution of each pollution source. Combined with the health risk assessment model, the risk to human health of each pollution source was evaluated from the perspective of source exposure. The results showed that the average ω(Cd), ω(Pb), ω(Cr), ω(Cu), ω(Zn), ω(Ni), ω(As), and ω(Hg) were 0.76, 65.22, 92.02, 103.92, 198.49, 36.65, 5.97, and 0.20 mg·kg-1, respectively. The average contents of Cd and Cu were higher than the risk screening values of soil contamination of agricultural land, and 85.71% and 96.24% of soil was contaminated by heavy metals. The average contents of Pb, Cr, Zn, and Ni exceeded the soil background values of the Wenhuang Plain in Zhejiang Province, and the As and Hg contents were within the limit values. The potential soil ecological risks were mainly light-moderate, accounting for 90.98%, and both high and higher risk accounted for 4.51%; Cd was the main potential ecological risk element. The main sources of heavy metal pollution in the study area were the sources of the electronic waste dismantling process (26.82%), the mixed sources of coal combustion and traffic emissions (34.50%), mixed sources of natural parent materials and agricultural inputs (25.59%), and e-waste pickling runoff and solid waste leaching sources (13.09%). The health risk of heavy metal exposure to children was significantly greater than that in adults. Mixed sources of natural parent materials and agricultural inputs contributed the most to human health risks, and Cr was the element with the greatest contribution to human health risks.

Chitin nanocrystal-assisted 3D bioprinting of gelatin methacrylate scaffolds.

In recent years, there has been an increasing focus on the application of hydrogels in tissue engineering. The integration of 3D bioprinting technology has expanded the potential applications of hydrogels. However, few commercially available hydrogels used for 3D biological printing exhibit both excellent biocompatibility and mechanical properties. Gelatin methacrylate (GelMA) has good biocompatibility and is widely used in 3D bioprinting. However, its low mechanical properties limit its use as a standalone bioink for 3D bioprinting. In this work, we designed a biomaterial ink composed of GelMA and chitin nanocrystal (ChiNC). We explored fundamental printing properties of composite bioinks, including rheological properties, porosity, equilibrium swelling rate, mechanical properties, biocompatibility, effects on the secretion of angiogenic factors and fidelity of 3D bioprinting. The results showed that adding 1% (w/v) ChiNC to 10% (w/v) GelMA improved the mechanical properties and printability of the GelMA hydrogels, promoted cell adhesion, proliferation and vascularization and enabled the printing of complex 3D scaffolds. This strategy of incorporating ChiNC to enhance the performance of GelMA biomaterials could potentially be applied to other biomaterials, thereby expanding the range of materials available for use. Furthermore, in combination with 3D bioprinting technology, this approach could be leveraged to bioprint scaffolds with complex structures, further broadening the potential applications in tissue engineering.

Derivation and validation of a novel score for early prediction of severe CRS after CAR-T therapy in haematological malignancy patients: A multi-centre study.

Chimeric antigen receptor T (CAR-T) cell therapy is highly effective in inducing complete remission in haematological malignancies. Severe cytokine release syndrome (CRS) is the most significant and life-threatening adverse effect of this therapy. This multi-centre study was conducted at six hospitals in China. The training cohort included 87 patients with multiple myeloma (MM), an external validation cohort of 59 patients with MM and another external validation cohort of 68 patients with acute lymphoblastic leukaemia (ALL) or non-Hodgkin lymphoma (NHL). The levels of 45 cytokines on days 1-2 after CAR-T cell infusion and clinical characteristics of patients were used to develop the nomogram. A nomogram was developed, including CX3CL1, GZMB, IL4, IL6 and PDGFAA. Based on the training cohort, the nomogram had a bias-corrected AUC of 0.876 (95% CI = 0.871-0.882) for predicting severe CRS. The AUC was stable in both external validation cohorts (MM, AUC = 0.907, 95% CI = 0.899-0.916; ALL/NHL, AUC = 0.908, 95% CI = 0.903-0.913). The calibration plots (apparent and bias-corrected) overlapped with the ideal line in all cohorts. We developed a nomogram that can predict which patients are likely to develop severe CRS before they become critically ill, improving our understanding of CRS biology, and may guide future cytokine-directed therapies.

Bortezomib, Melphalan, and Prednisone With or Without Daratumumab in Transplant-ineligible Asian Patients With Newly Diagnosed Multiple Myeloma: The Phase 3 OCTANS Study.

INTRODUCTION: In the global phase 3 ALCYONE trial, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) improved outcomes versus VMP in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. Here, we report the primary analysis of the phase 3 OCTANS trial of D-VMP versus VMP in transplant-ineligible Asian NDMM patients. PATIENTS AND METHODS: In total, 220 patients were randomized (2:1) to receive 9 cycles of VMP (bortezomib 1.3 mg/m2 subcutaneously twice weekly in Cycle 1 and weekly in Cycles 2 to 9; melphalan 9 mg/m2 orally; and prednisone 60 mg/m2 orally on Days 1 to 4 of each cycle) ± daratumumab 16 mg/kg intravenously weekly in Cycle 1, every 3 weeks in Cycles 2 to 9, and every 4 weeks thereafter until disease progression. RESULTS: After a median follow-up of 12.3 months, very good partial response or better rates (primary endpoint) were 74.0% versus 43.2% with D-VMP versus VMP (odds ratio, 3.57; 95% confidence interval [CI], 1.99-6.43; P < .0001). Median progression-free survival (PFS) with D-VMP versus VMP was not reached versus 18.2 months (hazard ratio, .43; 95% CI, .24-.77; P = .0033); 12-month PFS rates were 84.2% versus 64.6%. The most frequent grade 3/4 treatment-emergent adverse events with D-VMP/VMP were thrombocytopenia (46.5%/45.1%), neutropenia (39.6%/50.7%), and leukopenia (31.3%/36.6%). CONCLUSION: D-VMP demonstrated a favorable benefit/risk profile in transplant-ineligible Asian NDMM patients. This trial was registered at www. CLINICALTRIALS: gov as #NCT03217812.

Prognostic nomogram for multiple myeloma early relapse after autologous stem cell transplant in the novel agent era.

BACKGROUND: The present study intended to establish a predictive nomogram for early relapse (ER) (<12 months) after autologous stem cell transplantation (ASCT) in the novel drug era for multiple myeloma (MM). PATIENTS AND METHODS: The nomogram was designed and constructed to a retrospective clinical data of newly diagnosed MM patients received novel agent induction therapy and subsequent ASCT at three centers in China from July 2007 to December 2018. The retrospective study was conducted among 294 patients in the training cohort and 126 in the validation cohort. The nomogram's predictive accuracy was evaluated by the concordance index, calibration curve and decision clinical curve. RESULTS: The study cohort included 420 newly diagnosed MM patients, and 100 (23.8%) were identified as having ER, including 74 in the training cohort and 26 in the validation cohort. According to the result of multivariate regression in the training cohort, the prognostic variables included in the nomogram were high-risk cytogenetics, LDH > UNL, and response less than very good partial response (VGPR) after ASCT. The calibration curve showed good fitness between the nomogram predictions and the actual observations and the nomogram was further validated by a clinical decision curve. The nomogram's C-index achieved 0.75 (95% CI, 0.70-0.80), which was higher than that of the Revised International Staging System (R-ISS) (0.62), ISS (0.59), and Durie-Salmon (DS) staging system (0.52). The discrimination ability of the nomogram in the validation cohort was superior to that of the other staging systems (C-index: 0.73 vs. R-ISS (0.54), ISS (0.55), and DS staging system (0.53)). DCA showed the prediction nomogram adds much more clinical utility. Different scores of the nomogram draw a distinction of OS. CONCLUSION: The present nomogram could serve as a feasible and accurate prediction of ER in novel drug induction transplantation-eligible MM patients, which could help modify the post-ASCT strategy for patients at high risk of ER.

Injectable, stretchable, toughened, bioadhesive composite hydrogel for bladder injury repair.

The bladder is exposed to constant internal and external mechanical forces due to its deformation and the dynamic environment in which it is placed, which can hamper its repair after an injury. Traditional hydrogel materials have limitations regarding their use in the bladder owing to their poor mechanical and tissue adhesion properties. In this study, a composite hydrogel composed of methacrylate gelatine, methacrylated silk fibroin, and Pluronic F127 diacrylate was developed, which combines the characteristics of natural and synthetic polymers. The mechanical properties of the novel hydrogel, such as stretchability, viscoelasticity, and toughness, were improved by virtue of a particular molecular design strategy whereby covalent and non-covalent bond interactions create a cross-linking effect. In addition, the composite hydrogel has important usability properties; it can be injected in liquid format and rapidly transformed into a gel via photo-initiated crosslinking. This was demonstrated on an isolated porcine bladder where the hydrogel closed arbitrarily-shaped tissue defects within 90 s of its application, verifying its effective bioadhesive and sealing properties. This composite hydrogel has great potential for application in bladder injury repair as a tissue-engineering scaffold.

The Oral PI3Kδ Inhibitor Linperlisib for the Treatment of Relapsed and/or Refractory Follicular Lymphoma: A Phase II, Single-Arm, Open-Label Clinical Trial.

PURPOSE: To investigate the efficacy and safety of the novel orally active PI3Kδ inhibitor in relapsed and/or refractory patients with follicular lymphoma (FL) who had received at least two prior systemic treatments. PATIENTS AND METHODS: Histologically confirmed relapsed and/or refractory patients with FL with disease progression after receiving second-line or greater systemic therapy were enrolled. Linperlisib was administered at 80 mg every day, orally in a 28-day cycle until disease progression or intolerable toxicity occurred. The primary outcome for the study was the objective response rate (ORR), with secondary outcomes including the duration of response (DOR), progression-free survival (PFS), overall survival (OS), disease control rate, and drug safety profile. RESULTS: Of 114 screened relapsed and/or refractory patients with FL, 84 were enrolled in the full analysis set (FAS). The ORR of the 84 FAS patients was 79.8% [95% confidence interval (CI), 69.6-87.8, 67 patients], with 13 patients (15.5%) achieving a complete response and 54 patients (64.3%) with a partial response. The median DOR was 12.3 months (95% CI, 9.3-15.9). The median PFS was 13.4 months (95% CI, 11.1-16.7). The 12-month OS rate was 91.4% (95% CI, 82.7-95.8) and a median OS not reached by 42 months. The most frequent (>3%) treatment-related adverse events Grade ≥3 were infectious pneumonia (19.0%), neutropenia (15.5%), decreased lymphocyte count (4.8%), decreased leukocyte count (4.8%), increased lipase (3.6%), decreased platelet count (3.6%), hypertriglyceridemia (3.6%), and interstitial lung disease (3.6%). CONCLUSIONS: Linperlisib demonstrated compelling clinical activity and manageable tolerability for relapsed and/or refractory patients with FL who had received at least two prior systemic therapies.