Highly Efficient Oral Iguratimod/Polyvinyl Alcohol Nanodrugs Fabricated by High-Gravity Nanoprecipitation Technique for Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis (RA), a systemic autoimmune disease, poses a significant human health threat. Iguratimod (IGUR), a novel disease-modifying antirheumatic drug (DMARD), has attracted great attention for RA treatment. Due to IGUR's hydrophobic nature, there's a pressing need for effective pharmaceutical formulations to enhance bioavailability and therapeutic efficacy. The high-gravity nanoprecipitation technique (HGNPT) emerges as a promising approach for formulating poorly water-soluble drugs. In this study, IGUR nanodrugs (NanoIGUR) are synthesized using HGNPT, with a focus on optimizing various operational parameters. The outcomes revealed that HGNPT enabled the continuous production of NanoIGUR with smaller sizes (ranging from 300 to 1000 nm), more uniform shapes, and reduced crystallinity. In vitro drug release tests demonstrated improved dissolution rates with decreasing particle size and crystallinity. Notably, in vitro and in vivo investigations showcased NanoIGUR's efficacy in inhibiting synovial fibroblast proliferation, migration, and invasion, as well as reducing inflammation in collagen-induced arthritis. This study introduces a promising strategy to enhance and broaden the application of poorly water-soluble drugs.

Starfruit-Shaped Zirconium Metal-Organic Frameworks: From 3D Intermediates to 2D Nanosheet Petals with Enhanced Catalytic Activity.

We present the fabrication of a novel Starfruit-shaped metal-organic framework (SMOF) composed of zirconium and Tetra(4-carboxyphenyl)porphine linkers. The SMOF exhibits a unique morphology with edge-sharing two-dimensional (2D) nanosheet petals. Our investigation unravels a captivating transformation process, wherein three-dimensional (3D) shuttle-shaped MOFs form initially and subsequently evolve into 2D nanosheet-based SMOF structures. The distinct morphology of SMOF showcases superior catalytic activity in detoxifying G-type nerve agent and blister agent simulants, surpassing that of its 3D counterparts. This discovery of the 3D-to-2D transition growth pathway unlocks exciting opportunities for exploring novel strategies in advanced MOF nanostructure development, not only for catalysis but also for various other applications.

Starfruit-Shaped Zirconium Metal-Organic Frameworks: From 3D Intermediates to 2D Nanosheet Petals with Enhanced Catalytic Activity.

Invited for the cover of this issue is the group of Cheng-an Tao, Jianfang Wang and co-workers at the University of Defense Technology. The image depicts a novel starfruit-shaped metal-organic framework composed of zirconium and tetra(4-carboxyphenyl)porphine linkers and characterized by 2D nanosheet petals grown through edge-sharing that showcases superior catalytic activity. Read the full text of the article at 10.1002/chem.202302835.

Correction and removal of expression of concern: Total synthesis of tubulysin U and N14-desacetoxytubulysin H.

Correction and removal of expression of concern for 'Total synthesis of tubulysin U and N14-desacetoxytubulysin H' by Bohua Long et al., Org. Biomol. Chem., 2020, 18, 5349-5353, https://doi.org/10.1039/D0OB01109F.

Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans.

Twelve new alkaloids, scolopenolines A-L (1-7, 9-11, 13, 14), along with six known analogues, were isolated from Scolopendra subspinipes mutilans, identified by analysis of spectroscopic data and quantum chemical and computational methods. Scolopenoline A (1), a unique guanidyl-containing C14 quinoline alkaloid, features a 6/6/5 ring backbone. Scolopenoline B (2) is a novel sulfonyl-containing heterodimer comprising quinoline and tyramine moieties. Scolopenoline G (7) presents a rare C12 quinoline skeleton with a 6/6/5 ring system. Alkaloids 1, 8, 10, and 15-18 display anti-inflammatory activity, while 10 and 16-18 also exhibit anti-renal-fibrosis activity. Drug affinity responsive target stability and RNA-interference assays show that Lamp2 might be a potentially important target protein of 16 for anti-renal-fibrosis activity.

Isolation and target identification of anti-renal fibrosis compounds from Cordyceps militaris.

Four undescribed compounds including one aromatic glucoside derivative, cordyceglycoside A (1), one new isoleucine derivative inner salt, cordycepisosalt A (2), a rare four-membered lactam, cinerealactam B (3), and one sesquiterpene derivative, cordycepsetp A (4), together with six known compounds were isolated from Cordyceps militaris. The structures including absolute configurations of these new compounds, were unambiguously elucidated by spectroscopic data analysis and single crystal X-ray diffraction. Biological evaluation of compounds 1-4 showed that 3 displays anti-renal fibrotic activities in TGF-ß1 induced NRK-52e cells. Furthermore, DARTS coupled with LC-MS/MS analysis was used to identify candidate target proteins for 3. Subsequently, C1qbp knockdown using siRNA allowed us to validate the target protein of 3.

Expression of concern: Total synthesis of tubulysin U and N14-desacetoxytubulysin H.

Expression of concern for 'Total synthesis of tubulysin U and N14-desacetoxytubulysin H' by Bohua Long et al., Org. Biomol. Chem., 2020, 18, 5349-5353, https://doi.org/10.1039/D0OB01109F.

Asymmetric total synthesis and anti-hepatocellular carcinoma profile of enantiopure euphopilolide and jolkinolide E.

A flexible asymmetric synthesis of both enantiomers of euphopilolide (1) and jolkinolide E (2) [(+)-and (-)-1, (+)-and (-)-2] has been accomplished. This synthesis features an intramolecular oxa-Pauson-Khand reaction (o-PKR) to expeditiously construct the challenging tetracyclic [6.6.6.5] abietane-type diterpene framework, elegantly showcasing the complexity-generating features of o-PKR synthetic methodology leveraging on a judiciously chosen suitable chiral pool scaffold. Furthermore, the anti-hepatocellular carcinoma (HCC) activity of synthetic (-)-euphopilolide (1), (-)-jolkinolide E (2) and their analogues was evaluated. We found that (-)-euphopilolide (1) and (-)-jolkinolide E (2) inhibited the proliferation and induced apoptosis in HCC cells. These findings lay a good foundation for further pharmacology studies of abietane lactone derivatives and provide valuable insight for the development of anti-HCC small molecule drug of natural product origin.

Dimeric oxyberberine CT4-1 targets LINC02331 to induce cytotoxicity and inhibit chemoresistance via suppressing Wnt/ß-catenin signaling in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a type of cancer characterized by high recurrence rates. Overcoming chemoresistance can reduce HCC recurrence and improve patients' prognosis. This work aimed to identify HCC chemoresistance-associated long non-coding RNA (lncRNA) and find an effective drug targeting the identified lncRNA for ameliorating the chemoresistance. In this investigation, bioinformatics analysis based on The Cancer Genome Atlas revealed a new chemoresistance index and suggested LINC02331 as an HCC chemoresistance and patients' prognosis-associated lncRNA that served as an independent prognostic indicator. Moreover, LINC02331 promoted DNA damage repair, DNA replication, and epithelial-mesenchymal transition as well as attenuated cell cycle arrest and apoptosis through regulating Wnt/ß-catenin signaling, thus stimulating HCC resistance to cisplatin cytotoxicity, proliferation, and metastasis. Interestingly, we developed a novel oxidative coupling approach to synthesize a dimeric oxyberberine CT4-1, which exerted superior anti-HCC activities without obvious side effects measured by in vivo mice model and could downregulate LINC02331 mice model and could downregulate LINC02331 to mitigate LINC02331-induced HCC progression by suppressing Wnt/ß-catenin signaling. RNA sequencing analyses verified the involvement of CT4-1-affected differential expression genes in dysregulated pathways and processes, including Wnt, DNA damage repair, cell cycle, DNA replication, apoptosis, and cell adhesion molecules. Furthermore, CT4-1 was demonstrated to be an effective cytotoxic drug in ameliorating HCC patients' prognosis with a prediction model constructed based on RNA-sequencing data from CT4-1-treated cancer cells and public cancer database. In summary, HCC chemoresistance-associated LINC02331 independently predicted poor patients' prognosis and enhanced HCC progression by promoting resistance to cisplatin cytotoxicity, proliferation, and metastasis. Targeting LINC02331 by the dimeric oxyberberine CT4-1 that exhibited synergistic cytotoxicity with cisplatin could alleviate HCC progression and improve patients' prognosis. Our study identified LINC02331 as an alternative target and suggested CT4-1 as an effective cytotoxic drug in HCC treatment.

The Nrf2/HMGB1/NF-κB axis modulates chondrocyte apoptosis and extracellular matrix degradation in osteoarthritis.

Osteoarthritis (OA) is a degenerative or posttraumatic condition of the joints. In OA chondrocytes, Nrf2 functions as a stress response regulator with antioxidant and anti-inflammatory effects. This study aims to investigate the role of Nrf2 and its downstream pathway in the development of osteoarthritis. IL-1ß treatment suppresses Nrf2, aggrecan, and COL2A1 levels and cell viability but promotes apoptosis in chondrocytes. IL-1ß stimulation induces cell apoptosis, upregulates the mRNA expression of inflammatory factors, decreases aggrecan, COL2A1, and Bcl-2 levels but increases ADAMTS-5, ADAMTS-4, MMP13, cleaved caspase 3, and BAX levels, and promotes p65 phosphorylation. Nrf2 overexpression exerts opposite effects on IL-1ß-treated chondrocytes, as demonstrated by the significant attenuation of IL-1ß-induced changes in chondrocytes. By binding to the HMGB1 promoter region, Nrf2 suppresses HMGB1 expression. Similar to Nrf2 overexpression, HMGB1 knockdown also attenuates IL-1ß-induced changes in chondrocytes. Notably, under IL-1ß stimulation, the effects of Nrf2 overexpression or tert-butylhydroquinone (TBHQ, an activator of Nrf2) on apoptosis, inflammatory factor expression, ECM and apoptosis, and NF-κB pathway activity in chondrocytes are remarkably reversed by HMGB1 overexpression or recombinant HMGB1 (rHMGB1). Similarly, rHMGB1 could partially counteract the curative effect of TBHQ on OA damage in mice. In OA cartilage tissue samples, the level of Nrf2 is lower, while the levels of HMGB1, apoptotic, and inflammatory factors are increased compared to normal cartilage tissue samples. In conclusion, for the first time, the Nrf2/HMGB1 axis was found to modulate apoptosis, ECM degradation, inflammation and activation of NF-κB signaling in chondrocytes and OA mice.

Cissus quadrangularis L extract-loaded tricalcium phosphate reinforced natural polymer composite for guided bone regeneration.

Natural medicines plants are significant considerable attention as potential therapeutic agents for bone tissue engineering. Cissus quadrangularis L (CQ). is a potent therapeutic plant known for its own osteogenic properties. In this research work, a phytoconstituents-filled composite was produced by incorporating CQ extract with gelatin (Gel) and pectin (Pec) polymers collective through ß- tricalcium phosphate (ß-TCP) bioceramic via a green template method. The effect of CQ-filled composite morphology and chemical structural properties, in vitro cytotoxicity, cell proliferation, and differentiation was investigated. FTIR spectroscopic results indicated the prepared materials' structural confirmation. The CQ extract was the alcoholic -OH merge with the hydroxyl and -NH groups in the range of 3000 cm-1 to 3500 cm-1. Scanning electron microscopy images showed that the ß-TCP ceramic was perfectly embedded in Gel-Pec polymeric matrix, which is important for bone regeneration. In vitro cell culture results indicated that ß-TCP/Gel-Pec/CQ composite provided 92.0% of a favorable substrate for mesenchymal stem cell viability. The gene expression and RT-PCR studies represent the materials with good osteogenic expression, especially the ß-TCP/Gel-Pec/CQ composite is observed at 168.0% and 188.0% for RUNx2 and OCN, respectively. The result of the physicochemical characterizations and cell viability studies suggest that CQ-loaded ß-TCP/Gel-Pec composite can serve as a potential biomaterial for bone tissue repair and regeneration.

A Deep Learning Approach for Automated Segmentation of Kidneys and Exophytic Cysts in Individuals with Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: Total kidney volume (TKV) is an important imaging biomarker in autosomal dominant polycystic kidney disease (ADPKD). Manual computation of TKV, particularly with the exclusion of exophytic cysts, is laborious and time consuming. METHODS: We developed a fully automated segmentation method for TKV using a deep learning network to selectively segment kidney regions while excluding exophytic cysts. We used abdominal T2 -weighted magnetic resonance images from 210 individuals with ADPKD who were divided into two groups: one group of 157 to train the network and a second group of 53 to test it. With a 3D U-Net architecture using dataset fingerprints, the network was trained by K-fold cross-validation, in that 80% of 157 cases were for training and the remaining 20% were for validation. We used Dice similarity coefficient, intraclass correlation coefficient, and Bland-Altman analysis to assess the performance of the automated segmentation method compared with the manual method. RESULTS: The automated and manual reference methods exhibited excellent geometric concordance (Dice similarity coefficient: mean±SD, 0.962±0.018) on the test datasets, with kidney volumes ranging from 178.9 to 2776.0 ml (mean±SD, 1058.5±706.8 ml) and exophytic cysts ranging from 113.4 to 2497.6 ml (mean±SD, 549.0±559.1 ml). The intraclass correlation coefficient was 0.9994 (95% confidence interval, 0.9991 to 0.9996; P<0.001) with a minimum bias of -2.424 ml (95% limits of agreement, -49.80 to 44.95). CONCLUSIONS: We developed a fully automated segmentation method to measure TKV that excludes exophytic cysts and has an accuracy similar to that of a human expert. This technique may be useful in clinical studies that require automated computation of TKV to evaluate progression of ADPKD and response to treatment.

Cadmium-Doped and Pincer Ligand-Modified Gold Nanocluster for Catalytic KA2 Reaction.

A gold nanocluster Au17 Cd2 (PNP)2 (SR)12 (PNP=2,6-bis(diphenylphosphinomethyl)pyridine, SR=4-MeOPhS) consisting of an icosahedral Au13 kernel, two Au2 CdS6 staple motifs, and two PNP pincer ligands has been designed, synthesized and well characterized. This cadmium and PNP pincer ligand co-modified gold nanocluster showed high catalytic efficiency in the KA2 reaction, featuring high TON, mild reaction conditions, broad substrate scope as well as catalyst recyclability. Comparison of the catalytic performance between Au17 Cd2 (PNP)2 (SR)12 and the structurally similar single cadmium (or PNP) modified gold nanoclusters demonstrates that the co-existence of the cadmium and PNP on the surface is crucial for the high catalytic activity of the gold nanocluster. This work would be enlightening for developing efficient catalysts for cascade reactions and discovering the catalytic potential of metal nanoclusters in organic transformations.

Is an anteromedial minimally invasive approach for middle and distal third humeral fractures feasible? A cadaveric study and clinical case series.

BACKGROUND: Iatrogenic injury to the radial nerve is a risk in surgical treatment for extraarticular fractures of the middle and distal third of the humerus. We aimed to investigate the safety, feasibility and advantages of minimally invasive percutaneous plate osteosynthesis (MIPPO) via an anteromedial approach in the treatment of middle and middle-distal humeral fractures and to evaluate proximity to neurovascular structures. MATERIALS AND METHODS: In 2016, 13 adult cadaver arms were used to simulate a minimally invasive surgical approach to the anteromedial humerus followed by fixation with a locking compression plate (LCP), and several sets of anatomical data were measured to clarify the possible risk of iatrogenic vascular and nerve injury in this surgical approach. Then, a case series study of 12 patients with humeral fractures who were treated with this surgical approach was conducted between 2017 and 2020. RESULTS: The average humeral length was 29.22 ± 1.62 cm, the average width of the medial epicondyle of the humerus was 1.31 ± 0.17 cm, and the average distance from the vertex of the medial epicondyle to the median nerve was 2.96 ± 1.62 cm. Furthermore, the safe area for distal humeral screw placement was 6.28 ± 0.39 cm, and the average distance from the tip of the distal end of the screw in the medial epicondyle to the ulnar nerve was 1.7 ± 1.25 mm. None of the 12 patients had nerve damage or an incisional infection after the operation. CONCLUSIONS: The new approach was performed as described, and no cases of iatrogenic nerve palsy occurred. This approach can be used as an alternative for the treatment of extraarticular fractures of the middle and distal thirds of the humerus. LEVEL OF EVIDENCE: Level IV, therapeutic study.

High-flow nasal cannula versus conventional oxygen therapy in acute COPD exacerbation with mild hypercapnia: a multicenter randomized controlled trial.

BACKGROUND: High-flow nasal cannula (HFNC) can improve ventilatory function in patients with acute COPD exacerbation. However, its effect on clinical outcomes remains uncertain. METHODS: This randomized controlled trial was conducted from July 2017 to December 2020 in 16 tertiary hospitals in China. Patients with acute COPD exacerbation with mild hypercapnia (pH ≥ 7.35 and arterial partial pressure of carbon dioxide > 45 mmHg) were randomly assigned to either HFNC or conventional oxygen therapy. The primary outcome was the proportion of patients who met the criteria for intubation during hospitalization. Secondary outcomes included treatment failure (intolerance and need for non-invasive or invasive ventilation), length of hospital stay, hospital cost, mortality, and readmission at day 90. RESULTS: Among 337 randomized patients (median age, 70.0 years; 280 men [83.1%]; median pH 7.399; arterial partial pressure of carbon dioxide 51 mmHg), 330 completed the trial. 4/158 patients on HFNC and 1/172 patient on conventional oxygen therapy met the criteria for intubation (P = 0.198). Patients progressed to NPPV in both groups were comparable (15 [9.5%] in the HFNC group vs. 22 [12.8%] in the conventional oxygen therapy group; P = 0.343). Compared with conventional oxygen therapy, HFNC yielded a significantly longer median length of hospital stay (9.0 [interquartile range, 7.0-13.0] vs. 8.0 [interquartile range, 7.0-11.0] days) and a higher median hospital cost (approximately $2298 [interquartile range, $1613-$3782] vs. $2005 [interquartile range, $1439-$2968]). There were no significant differences in other secondary outcomes between groups. CONCLUSIONS: In this multi-center randomized controlled study, HFNC compared to conventional oxygen therapy did not reduce need for intubation among acute COPD exacerbation patients with mild hypercapnia. The future studies should focus on patients with acute COPD exacerbation with respiratory acidosis (pH < 7.35). However, because the primary outcome rate was well below expected, the study was underpowered to show a meaningful difference between the two treatment groups. TRIAL REGISTRATION: NCT03003559 . Registered on December 28, 2016.

Novel isatin-based hybrids as potential anti-rheumatoid arthritis drug candidates: Synthesis and biological evaluation.

Rheumatoid arthritis (RA) is an autoimmune disease accompanied with serious symptoms, such as joint destruction and chronic synovitis. Though many anti-RA drugs could improve the outcome of RA patients to a certain extent, about 40% inefficient rate, severe side effects, and high costs have become urgent problems. Therefore, exploring new alternative drugs for RA therapy is still an urgent need so far. Isatin is an important structural motif found in numerous biologically active compounds and therapeutic agents. Herein, we aim to synthesize several novel isatin analogues for RA therapy and further explore the mechanism of the most potential anti-RA drug candidate in suppressing the pathological progress of RA in vitro and in vivo. We found that the most therapeutic potential compound, a novel small molecule isatin-honokiol hybrid named CT5-2 inhibited the viability of RA-fibroblast-like synoviocytes (FLSs), an effector cell of synovial hyperplasia in the RA synovial tissue with IC50 ranging from 8.54 to 10.66 µM. In addition, CT5-2 reduced the DNA replication and triggered cell cycle arrest and apoptosis of RA-FLSs. Moreover, differential analyses of RNA-sequencing and the mechanistic studies demonstrated that CDCA7 is a key gene correlated with RA progression, and CT5-2 could inhibit the c-Myc/CDCA7/p65 pathway to regulate CDK1, Bcl-2, and vimentin in RA-FLSs. Furthermore, CT5-2 relieved collagen-induced arthritis (CIA) and reduced the level of CDCA7, CDK1, Bcl-2, and vimentin of synovial tissue in CIA mice. Taken together, the novel small molecule isatin-honokiol hybrid CT5-2 exhibits a potential anti-RA drug candidate that inhibits proliferation and triggers cell cycle arrest and apoptosis of RA-FLSs by regulating the c-Myc/CDCA7/p65 pathway. Our study lays a good foundation for further clinical research and structuralmodification of CT5-2.

Primary results of the randomized trial of metformin administration in polycystic kidney disease (TAME PKD).

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by growth of kidney cysts and glomerular filtration rate (GFR) decline. Metformin was found to impact cystogenesis in preclinical models of polycystic disease, is generally considered safe and may be a promising candidate for clinical investigation in ADPKD. In this phase 2 two-year trial, we randomly assigned 97 patients, 18-60 years of age, with ADPKD and estimated GFR over 50 ml/min/1.73 m2, in a 1:1 ratio to receive metformin or placebo twice daily. Primary outcomes were medication safety and tolerability. Secondary outcomes included estimated GFR decline, and total kidney volume growth. Thirty-eight metformin and 39 placebo participants still received study product at 24-months. Twenty-one participants in the metformin arm reduced drug dose due to inability to tolerate, compared with 14 in the placebo arm (not significant). Proportions of participants experiencing serious adverse events was similar between the groups. The Gastrointestinal Symptoms Rating Scale score was low at baseline and did not significantly change over time. The annual change for estimated GFR was -1.71 with metformin and -3.07 ml/min/1.73m2 per year with placebo (mean difference 1.37 {-0.70, 3.44} ml/min/1.73m2), while mean annual percent change in height-adjusted total kidney volume was 3.87% in metformin and 2.16% per year in placebo, (mean difference 1.68% {-2.11, 5.62}). Thus, metformin in adults with ADPKD was found to be safe and tolerable while slightly reducing estimated GFR decline but not to a significant degree. Hence, evaluation of efficacy requires a larger trial, with sufficient power to detect differences in endpoints.

Beam complexity and monitor unit efficiency comparison in two different volumetric modulated arc therapy delivery systems using automated planning.

BACKGROUND: To investigate the beam complexity and monitor unit (MU) efficiency issues for two different volumetric modulated arc therapy (VMAT) delivery technologies for patients with left-sided breast cancer (BC) and nasopharyngeal carcinoma (NPC). METHODS: Twelve left-sided BC and seven NPC cases were enrolled in this study. Each delivered treatment plan was optimized in the Pinnacle3 treatment planning system with the Auto-Planning module for the Trilogy and Synergy systems. Similar planning dose objectives and beam configurations were used for each site in the two different delivery systems to produce clinically acceptable plans. The beam complexity was evaluated in terms of the segment area (SA), segment width (SW), leaf sequence variability (LSV), aperture area variability (AAV), and modulation complexity score (MCS) based on the multileaf collimator sequence and MU. Plan delivery and a gamma evaluation were performed using a helical diode array. RESULTS: With similar plan quality, the average SAs for the Trilogy plans were smaller than those for the Synergy plans: 55.5 ± 21.3 cm2 vs. 66.3 ± 17.9 cm2 (p < 0.05) for the NPC cases and 100.7 ± 49.2 cm2 vs. 108.5 ± 42.7 cm2 (p < 0.05) for the BC cases, respectively. The SW was statistically significant for the two delivery systems (NPC: 6.87 ± 1.95 cm vs. 6.72 ± 2.71 cm, p < 0.05; BC: 8.84 ± 2.56 cm vs. 8.09 ± 2.63 cm, p < 0.05). The LSV was significantly smaller for Trilogy (NPC: 0.84 ± 0.033 vs. 0.86 ± 0.033, p < 0.05; BC: 0.89 ± 0.026 vs. 0.90 ± 0.26, p < 0.05). The mean AAV was significantly larger for Trilogy than for Synergy (NPC: 0.18 ± 0.064 vs. 0.14 ± 0.037, p < 0.05; BC: 0.46 ± 0.15 vs. 0.33 ± 0.13, p < 0.05). The MCS values for Trilogy were higher than those for Synergy: 0.14 ± 0.016 vs. 0.12 ± 0.017 (p < 0.05) for the NPC cases and 0.42 ± 0.106 vs. 0.30 ± 0.087 (p < 0.05) for the BC cases. Compared with the Synergy plans, the average MUs for the Trilogy plans were larger: 828.6 ± 74.1 MU and 782.9 ± 85.2 MU (p > 0.05) for the NPC cases and 444.8 ± 61.3 MU and 393.8 ± 75.3 MU (p > 0.05) for the BC cases. The gamma index agreement scores were never below 91% using 3 mm/3% (global) distance to agreement and dose difference criteria and a 10% lower dose exclusion threshold. CONCLUSIONS: The Pinnacle3 Auto-Planning system can optimize BC and NPC plans to achieve the same plan quality using both the Trilogy and Synergy systems. We found that these two systems resulted in different SAs, SWs, LSVs, AAVs and MCSs. As a result, we suggested that the beam complexity should be considered in the development of further methodologies while optimizing VMAT autoplanning.

Expanded Imaging Classification of Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND: The Mayo Clinic imaging classification of autosomal dominant polycystic kidney disease (ADPKD) uses height-adjusted total kidney volume (htTKV) and age to identify patients at highest risk for disease progression. However, this classification applies only to patients with typical diffuse cystic disease (class 1). Because htTKV poorly predicts eGFR decline for the 5%-10% of patients with atypical morphology (class 2), imaging-based risk modeling remains unresolved. METHODS: Of 558 adults with ADPKD in the HALT-A study, we identified 25 patients of class 2A with prominent exophytic cysts (class 2Ae) and 43 patients of class 1 with prominent exophytic cysts; we recalculated their htTKVs to exclude exophytic cysts. Using original and recalculated htTKVs in association with imaging classification in logistic and mixed linear models, we compared predictions for developing CKD stage 3 and for eGFR trajectory. RESULTS: Using recalculated htTKVs increased specificity for developing CKD stage 3 in all participants from 82.6% to 84.2% after adjustment for baseline age, eGFR, BMI, sex, and race. The predicted proportion of class 2Ae patients developing CKD stage 3 using a cutoff of 0.5 for predicting case status was better calibrated to the observed value of 13.0% with recalculated htTKVs (45.5%) versus original htTKVs (63.6%). Using recalculated htTKVs reduced the mean paired difference between predicted and observed eGFR from 17.6 (using original htTKVs) to 4.0 ml/min per 1.73 m2 for class 2Ae, and from -1.7 (using original htTKVs) to 0.1 ml/min per 1.73 m2 for class 1. CONCLUSIONS: Use of a recalculated htTKV measure that excludes prominent exophytic cysts facilitates inclusion of class 2 patients and reclassification of class 1 patients in the Mayo classification model.

Treatment of humeral shaft fractures: a new minimally-invasive plate osteosynthesis versus open reduction and internal fixation: a case control study.

BACKGROUND: To evaluate the feasibility and safety of a new minimally-invasive surgical approach-anteromedial minimally-invasive plate osteosynthesis (MIPO)-in the treatment of middle and distal humeral shaft fractures. METHODS: Fourteen patients with humeral shaft fracture treated with anteromedial MIPO from November 2016 to March 2020 (MIPO Group) were selected as the study subjects. Open reduction and internal fixation (ORIF) were used to treat 14 patients with humeral shaft fractures as the control group (ORIF group). The two groups were fixed with a locking compression plate (LCP) or LCP + multi-directional locking screw system (MDLS). The incision length, intraoperative blood loss, intraoperative fluoroscopy time, operation time, length of hospital stay, fracture healing time, QuickDASH score and Constant score were observed and compared between the two groups. RESULTS: Fourteen patients were enrolled in each group. The incision length (7.79 ± 2.39 cm), intraoperative blood loss (96.07 ± 14.96 mL), operative time (110.57 ± 21.90 min), hospital stay (6.29 ± 1.49 days) and fracture healing time (14.94 ± 0.99 weeks) in the MIPO group were all lower than those in the ORIF group, and the difference was statistically significant for each parameter (P < 0.05). The intraoperative fluoroscopy time (20.07 ± 3.22) in the MIPO group was significantly higher than that in the ORIF group (P < 0.05). There were no significant differences in age (P = 0.078), QuickDASH score (P = 0.074) or Constant score (P = 0.293) between the two groups and no postoperative complications occurred in any of the patients. CONCLUSION: The anteromedial approach MIPO technique has the advantages of less trauma, less bleeding, low risk of nerve injury and high rate of fracture healing. It is one of the most effective methods for the treatment of middle and middle-distal humeral shaft fractures.