Effect of Laparoscopic and Open Pancreaticoduodenectomy for Pancreatic or Periampullary Tumors: Three-year Follow-up of a Randomized Clinical Trial.

OBJECTIVE: This study aimed to estimate whether the potential short-term advantages of laparoscopic pancreaticoduodenectomy (LPD) could allow patients to recover in a more timely manner and achieve better long-term survival than with open pancreaticoduodenectomy (OPD) in patients with pancreatic or periampullary tumors. BACKGROUND: LPD has been demonstrated to be feasible and may have several potential advantages over OPD in terms of shorter hospital stay and accelerated recovery than OPD. METHODS: This noninferiority, open-label, randomized clinical trial was conducted in 14 centers in China. The initial trial included 656 eligible patients with pancreatic or periampullary tumors enrolled from May 18, 2018, to December 19, 2019. The participants were randomized preoperatively in a 1:1 ratio to undergo either LPD (n=328) or OPD (n=328). The 3-year overall survival (OS), quality of life, which was assessed using the 3-level version of the European Quality of Life-5 Dimensions, depression, and other outcomes were evaluated. RESULTS: Data from 656 patients [328 men (69.9%); mean (SD) age: 56.2 (10.7) years] who underwent pancreaticoduodenectomy were analyzed. For malignancies, the 3-year OS rates were 59.1% and 54.3% in the LPD and OPD groups, respectively ( P =0.33, hazard ratio: 1.16, 95% CI: 0.86-1.56). The 3-year OS rates for others were 81.3% and 85.6% in the LPD and OPD groups, respectively ( P =0.40, hazard ratio: 0.70, 95% CI: 0.30-1.63). No significant differences were observed in quality of life, depression and other outcomes between the 2 groups. CONCLUSION: In patients with pancreatic or periampullary tumors, LPD performed by experienced surgeons resulted in a similar 3-year OS compared with OPD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03138213.

The lasso-loop technique is equivalent to the simple suture technique in arthroscopic anterior talofibular ligament repair.

PURPOSE: To compare the clinical outcomes of the lasso-loop and simple suture techniques in arthroscopic anterior talofibular ligament (ATFL) repair for the treatment of chronic lateral ankle instability (CLAI). METHODS: From 2018 to 2020, patients with CLAI who underwent arthroscopic ATFL repair using the lasso-loop or simple suture technique were matched 1:1 (arthroscopic lasso-loop [AL] group, n = 29; simple arthroscopic suture [AS] group, n = 29) based on age, sex, affected side, body mass index, and follow-up duration using propensity score matching and retrospectively evaluated. Karlsson score, visual analogue scale (VAS) score, Tegner score, anterior drawer test (ADT) results, complications, patient-reported satisfaction, and magnetic resonance (MR) re-evaluation findings of ATFL quality were used to describe the outcomes. RESULTS: The patient characteristics or follow-up durations did not significantly differ between the two groups. The Karlsson score, VAS score, and Tegner score improved significantly in both groups after a mean follow-up duration of 29.6 ± 2.8 months. The postoperative clinical scores, ADT results, satisfaction rates, complication rates and MR re-evaluation findings were not significantly different between the two groups at the latest follow-up. CONCLUSION: The lasso-loop technique was equivalent to the simple suture technique in arthroscopic ATFL repair for the treatment of CLAI after a minimum follow-up of 2 years, suggesting that the simple suture technique is sufficient for arthroscopic ATFL repair in most patients without the need to add a lasso loop. LEVEL OF EVIDENCE: Level III.

Autologous Osteoperiosteal Transplantation for the Treatment of Large Cystic Talar Osteochondral Lesions.

OBJECTIVE: The effectiveness of autologous osteoperiosteal transplantation (AOPT) for the treatment of large cystic talar osteochondral lesions (OCLs) should be further evaluated, and the postoperative cartilage coverage is questionable. The purpose of this retrospective observational study was to investigate the clinical outcomes of AOPT for the treatment of large cystic talar OCLs and to report second-look arthroscopic results. METHODS: From June 1, 2017, to June 1, 2021, all talar OCLs at our center were reviewed. Painful cystic lesions treated with AOPT were included in the study. The American Orthopaedic Foot and Ankle Society (AOFAS; 0-100 points) ankle-hindfoot score, Foot Function Index (FFI; 0-100 points), visual analog scale (VAS; 0-10 points) score, and Tegner score (0-10 points) were used to describe pain and functional outcomes. Furthermore, complications, patient-reported satisfaction degrees, imaging results (including computed tomography and magnetic resonance), and second-look arthroscopic evaluation data were also collected for analysis. RESULTS: A total of 29 cases were eligible for the study, and 26 responded to the latest follow-up request, with a mean follow-up duration of 30.2 (range, 12-57) months. The AOFAS score improved from 69.2 ± 10.9 preoperatively to 80.9 ± 10.0 at the latest follow-up (p = 0.000). The FFI score improved from 30.4 ± 18.4 preoperatively to 16.3 ± 14.0 at the latest follow-up (p = 0.000). The VAS pain score improved from 4.0 ± 2.1 preoperatively to 2.5 ± 2.0 at the latest follow-up (p = 0.001). No donor site morbidity was found. The mean postoperative MOCART score was 57.7 ± 9.5. Second-look arthroscopy showed a fibrillated cartilage-like surface at the lesion site in most cases, while two cases exhibited a nearly normal surface. CONCLUSION: The transplantation of osteoperiosteal cylinder autografts taken from the iliac crest for the treatment of large cystic talar OCLs yielded acceptable clinical results. Good integration of the bony part was observed, but cartilage regeneration remained uncertain.

Mesoporous peroxidase nanozyme for synergistic chemodynamic therapy and chemotherapy.

Peroxidase nanozyme, enabling decomposition of hydrogen peroxide (H2O2) into highly toxic hydroxyl radical (•OH), is an emerging technology for tumor treatment. However, limited by the low H2O2 level in the tumor microenvironment, the standalone peroxidase nanozyme-mediated therapy usually fails to achieve desirable therapeutic outcomes. Herein, we presented a mesoporous nanozyme that not only had peroxidase-like activity but also could deliver anticancer drug for synergistic tumor therapy. The nanozyme, that was, iron-doped mesoporous silica nanoparticle (FeMSN), was prepared by a sol-gel method and then a calcination treatment. The introduction of iron endowed FeMSN with peroxidase-like activity that could decompose H2O2 into •OH under acidic condition for chemodynamic therapy of tumors. Meanwhile, the mesoporous structure enabled FeMSN to deliver anticancer drug doxorubicin (DOX) for chemotherapy and enhanced chemodynamic therapy through H2O2 production, ultimately achieving synergistic effect to improve the efficacy of tumor treatment. The in-vitro and in-vivo results demonstrated that DOX-loaded FeMSN exhibited significant cancer cell-killing effect and potently inhibited tumor growth. Collectively, this study represented a paradigm for achieving efficient tumor therapy through design of peroxidase-like nanozyme with drug delivery capability, which might advance the development of nanozyme in tumor chemodynamic therapy.

Multichannel Ca2+ Generator for Synergistic Tumor Therapy via Intracellular Ca2+ Overload and Chemotherapy.

Ca2+ overload has attracted an increasing attention due to its benefit of precise cancer therapy, but its efficacy is limited by the strong Ca2+ excretion of cancer cells. Moreover, monotherapy of Ca2+ overload usually fails to treat tumors satisfactorily. Herein, we develop a multifunctional nanosystem that could induce Ca2+ overload by multipathway and simultaneously produce chemotherapy for synergistic tumor therapy. The nanosystem (CaMSN@CUR) is prepared by synthesizing a Ca-doped mesoporous silica nanoparticle (CaMSN) followed by loading the anticancer drug curcumin (CUR). CaMSN serves as the basis Ca2+ generator to induce Ca2+ overload directly in the intracellular environment by acid-triggered Ca2+ release, while CUR could not only exhibit chemotherapy but also facilitate Ca2+ release from the endoplasmic reticulum to the cytoplasm and inhibit Ca2+ efflux out of cells to further enhance Ca2+ overload. The in vitro and in vivo results show that CaMSN@CUR could exhibit a remarkable cytotoxicity against 4T1 cells and significantly inhibit tumor growth in 4T1 tumor-bearing mice via the synergy of Ca2+ overload and CUR-mediated chemotherapy. It is expected that the designed CaMSN@CUR has a great potential for effective tumor therapy.

Autocatalytic oncotherapy nanosystem with glucose depletion for the cascade amplification of hypoxia-activated chemotherapy and H2O2-dependent chemodynamic therapy.

Employing hypoxia-activated prodrugs is an appealing oncotherapy strategy, but limited by insufficient tumor hypoxia. Moreover, a standalone prodrug fails to treat tumors satisfactorily due to tumor complexity. Herein, a nanosystem (TPZ@FeMSN-GOX) was established for triple synergetic cancer starvation therapy, hypoxia-activated chemotherapy and chemodynamic therapy (CDT). TPZ@FeMSN-GOX was prepared by synthesizing iron-doped mesoporous silica nanoparticles (FeMSNs) followed by surface conjugation with glucose oxidase (GOX), and then loading with hypoxia-activated prodrug tirapazamine (TPZ). When TPZ@FeMSN-GOX entered the tumor cells, GOX could not only exhaust glucose to starve cancer cells and concomitantly produce H2O2, but also consume O2 to aggravate the hypoxia environment and amplify TPZ-mediated chemotherapy. Meanwhile, the released Fe3+ was reduced to reactive Fe2+ by endogenous glutathione, which ultimately decomposed the produced H2O2 and endogenous H2O2 into highly toxic ˙OH, guaranteeing highly efficient CDT. Together, TPZ@FeMSN-GOX could effectively kill cancer cells and significantly inhibit tumor growth, providing a good paradigm for effective tumor treatment.

Intelligent Nanoplatform with Multi Therapeutic Modalities for Synergistic Cancer Therapy.

Chemodynamic therapy (CDT) has attracted increasing attention in tumor treatment but is limited by insufficient endogenous H2O2. Moreover, it is challenging for monotherapy to achieve a satisfactory outcome due to tumor complexity. Herein, we developed an intelligent nanoplatform that could respond to a tumor microenvironment to induce efficient CDT without complete dependence on H2O2 and concomitantly generate chemotherapy and oncosis therapy (OT). The nanoplatform was constructed by a calcium- and iron-doped mesoporous silica nanoparticle (CFMSN) loaded with dihydroartemisinin (DHA). After entering into cancer cells, the nanoplatform could directly convert the intracellular H2O2 into toxic •OH due to the Fenton-like activity of CFMSN. Meanwhile, the acidic microenvironment and endogenous chelating molecules triggered Ca2+ and Fe3+ release from the nanoplatform, causing particle collapse with accompanying DHA release for chemotherapy. Simultaneously, the released Ca2+ induced intracellular Ca2+-overloading for OT, which was further enhanced by DHA, while the released Fe3+ was reduced to reactive Fe2+ by intracellular glutathione, guaranteeing efficient Fenton reaction-mediated CDT. Moreover, Fe2+ cleaved the peroxy bonds of DHA to generate C-centered radicals to further amplify CDT. Both in vitro and in vivo results confirmed that the nanoplatform exhibited excellent anticancer efficacy via the synergistic effect of multi therapeutic modalities, which is extremely promising for high-efficient cancer therapy.

pH-Responsive size-shrinkable mesoporous silica-based nanocarriers for improving tumor penetration and therapeutic efficacy.

Poor tumor penetration is a major obstacle to nanomedicine for achieving effective anticancer therapy. Tumor microenvironment-induced nanomedicine size shrinkage is a promising strategy to overcome the drug penetration barrier across the dense tumor matrix. Herein, we design a size-shrinkable nanocarrier that uses acid as a means of triggering a change in particle size for co-achievement of efficient tumor accumulation followed by deep tumor penetration and rapid clearance from the body. This nanocarrier is constructed from a pH-sensitive lipid layer shell and an ultrasmall amino-functionalized mesoporous silica nanoparticle core capable of loading drugs. After intravenous injection into mice bearing the 4T1 tumor, the nanocarrier with an initial hydrodynamic size of about 33 nm could effectively accumulate at the tumor site through the enhanced permeability and retention effect. Subsequently, in the acidic tumor microenvironment, the lipid layer comprising 9 alkyl-spiropyran (SP-C9) undergoes a volume shrinkage due to the conversion of hydrophobic SP-C9 to amphiphilic 9 alkyl-merocyanine (MC-C9), thus leading to a significant decrease in the entire particle size (hydrodynamic size ∼17 nm) for enhanced intratumoral penetration. Moreover, we find that this size-shrinkable nanocarrier could be rapidly excreted out of the body based on the ICP analysis, significantly reducing biosafety issues. Benefiting from the effective tumor accumulation and penetration of the nanocarrier, the released doxorubicin shows potent antitumor efficacy. This demonstrates the high potential of the designed nanocarrier in solid tumor treatment.

Laparoscopic versus open pancreatoduodenectomy for pancreatic or periampullary tumours: a multicentre, open-label, randomised controlled trial.

BACKGROUND: The benefit and safety of laparoscopic pancreatoduodenectomy (LPD) for the treatment of pancreatic or periampullary tumours remain controversial. Studies have shown that the learning curve plays an important role in LPD, yet there are no randomised studies on LPD after the surgeons have surmounted the learning curve. The aim of this trial was to compare the outcomes of open pancreatoduodenectomy (OPD) with those of LPD, when performed by experienced surgeons. METHODS: In this multicentre, open-label, randomised controlled trial done in 14 Chinese medical centres, we recruited patients aged 18-75 years with a benign, premalignant, or malignant indication for pancreatoduodenectomy. Eligible patients were randomly assigned (1:1) to undergo either LPD or OPD. Randomisation was centralised via a computer-generated system that used a block size of four. The patients and surgeons were unmasked to study group, whereas the data collectors, outcome assessors, and data analysts were masked. LPD and OPD were performed by experienced surgeons who had already done at least 104 LPD operations. The primary outcome was the postoperative length of stay. The criteria for discharge were based on functional recovery, and analyses were done on a modified intention-to-treat basis (ie, including patients who had a pancreatoduodenectomy regardless of whether the operation was the one they were assigned to). This trial is registered with Clinicaltrials.gov, number NCT03138213. FINDINGS: Between May 18, 2018, and Dec 19, 2019, we assessed 762 patients for eligibility, of whom 656 were randomly assigned to either the LPD group (n=328) or the OPD group (n=328). 31 patients in each group were excluded and 80 patients crossed over (33 from LPD to OPD, 47 from OPD to LPD). In the modified intention-to-treat analysis (297 patients in the LPD group and 297 patients in the OPD group), the postoperative length of stay was significantly shorter for patients in the LPD group than for patients in the OPD group (median 15·0 days [95% CI 14·0-16·0] vs 16·0 days [15·0-17·0]; p=0·02). 90-day mortality was similar in both groups (five [2%] of 297 patients in the LPD group vs six [2%] of 297 in the OPD group, risk ratio [RR] 0·83 [95% CI 0·26-2·70]; p=0·76). The incidence rate of serious postoperative morbidities (Clavien-Dindo grade of at least 3) was not significantly different in the two groups (85 [29%] of 297 patients in the LPD group vs 69 [23%] of 297 patients in OPD group, RR 1·23 [95% CI 0·94-1·62]; p=0·13). The comprehensive complication index score was not significantly different between the two groups (median score 8·7 [IQR 0·0-26·2] vs 0·0 [0·0-20·9]; p=0·06). INTERPRETATION: In highly experienced hands, LPD is a safe and feasible procedure. It was associated with a shorter length of stay and similar short-term morbidity and mortality rates to OPD. Nonetheless, the clinical benefit of LPD compared with OPD was marginal despite extensive procedural expertise. Future research should focus on identifying the populations that will benefit from LPD. FUNDING: National Natural Science Foundation of China and Tongji Hospital, Huazhong University of Science and Technology, China.

Hyperbaric oxygen therapy for spinal cord injury: A protocol for systematic review and meta-analysis.

BACKGROUND: Hyperbaric oxygen (HBO) therapy can prevent further spinal cord injury (SCI) caused by spinal cord ischemia-reperfusion injury to the maximum extent, which has been reported increasingly in recent years. However its security and effectiveness still lack of high-quality medical evidence. In this study, we will perform a systematic review of previously published randomized controlled trials (RCTs) to evaluate the efficacy and safety of HBO therapy for SCI. METHODS: All potential RCTs on HBO therapy for SCI will be searched from the following electronic databases: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, Wanfang database and Chinese Biomedical Literature Database. We will search all electronic databases from their initiation to the September 30, 2020 in spite of language and publication date. Two contributors will independently select studies from all searched literatures, extract data from included trials, and evaluate study quality for all eligible RCTs using Cochrane risk of bias tool, respectively. Any confusion will be resolved by consulting contributor and a consensus will be reached. We will utilize RevMan 5.3 software to pool the data and to conduct the data analysis. RESULTS: The quality of the assessments will be assessed through Grading of Recommendations Assessment, Development, and Evaluation. Data will be disseminated through publications in peer-reviewed journals. CONCLUSION: This study will provide evidence to evaluate the efficacy and safety of HBO therapy for SCI at evidence-based medicine level. TRIAL REGISTRATION NUMBER: INPLASY 2020100084.

Extracorporeal shockwave therapy combined with multiple drilling and intramedullary drug injection for treating early-stage Femur Head Necrosis: Protocol for a randomized controlled trial.

BACKGROUND: Early diagnosis and treatment of the osteonecrosis of the femoral head (ONFH), a refractory disease, is imperative to prevent femoral head collapse; however, the existing solutions remain controversial. This study assessed the safety and efficacy of extracorporeal shock wave therapy (ESWT) combined with multiple drilling and intramedullary drug injection, a novel cocktail therapy, as a randomized controlled trial (RCT) model to postulate an alternative therapy for patients with early-stage ONFH. METHODS: Femoral head necrosis patients aged 20 to 60 years with stage ARCO I-II were recruited. One hundred twenty eligible participants were randomized into four groups in a 1:1:1:1 ratio: extracorporeal shock wave therapy combined with multiple drilling and intramedullary drug injection (group EMI), extracorporeal shock wave therapy (group E), multiple drilling combined with intramedullary drug injection (group MI), and multiple drilling ("positive" control group; group M). The primary outcomes included effective rate, subchondral collapse rate of the femoral head, lesion size, and grade of bone marrow edema. Secondary outcomes included the Harris Hip Score and the visual analog scale. All outcomes were measured at the screening visit (baseline) and at the planned time intervals during treatment and follow-up, and the efficacy was statistically analyzed according to the intention-to-treat sub-populations and per-protocol sub-populations. OBJECTIVES: To examine the clinical efficacy of ESWT combined with multiple drilling and intramedullary drug injection to provide a safe and more effective method for treating early-stage ONFH. TRIAL REGISTRATION NUMBER: ChiCTR1900020888; Pre-results.

Comparison of the perioperative parameters between computer navigation and fluoroscopy guidance for pedicle screw placement: A protocol for a systematic review and meta-analysis.

BACKGROUND: Computer navigation technology is gradually applied to the placement of pedicle screws, but its security and effectiveness still lack of high-quality evidence-based medical evidence. In this study, we will perform a systematic review of previously published randomized controlled trials to investigate the accuracy and effectiveness of computer navigation vsersus fluoroscopy guidance for pedicle screw placement. METHODS: All study protocols adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. PubMed (MEDLINE), The excerpta medica database, Web of Science (science and social science citation index), The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology Register), China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database, WanFang, Chinese Biomedical Literature Database will be searched for relevant articles up to 18 April, 2020. We will include randomized controlled trials of computer navigation and fluoroscopy guidance for pedicle screw placement. The Cochrane Handbook (v6) will be used for assessment of study bias and reliability, and a meta-analysis will be performed using STATA 16.0. The main outcome will be the proportion of accurate implanted screws. Additional outcomes including: overall complication rate, radiation dosage, length of surgery, length of stay, estimated blood loss. RESULTS: The quality of the assessments will be assessed through Grading of Recommendations Assessment, Development, and Evaluation. Data will be disseminated through publications in peer-reviewed journals. CONCLUSION: We will evaluate the accuracy and other perioperative parameters between computer navigation and fluoroscopy guidance for pedicle screw placement. TRIAL REGISTRATION NUMBER: PROSPERO 2020 CRD42020172087.

Elevated homocysteine levels contribute to larger hematoma volume in patients with intracerebral hemorrhage.

BACKGROUND: We investigate whether plasma homocysteine (HCY) levels are associated with hematoma volume and outcome in patients with intracerebral hemorrhage (ICH). METHODS: A total of 69 patients admitted within 24 hours after ICH onset was divided into 2 groups based on admission plasma HCY levels (low homocysteinemia [LHCY] group, plasma HCY concentrations ≤14.62 µmol/L, versus high homocysteinemia [HHCY] group, >14.62 µmol/L). RESULTS: Mean hematoma volumes for 2 groups (LHCY and HHCY) were 13.18 and 23.09 mL (P = .012), respectively, in patients with thalamoganglionic ICH, but hematoma volumes between 2 groups had no significant difference among patients with lobar or infratentorial ICH. On multivariate linear regression analysis, elevated HCY levels significantly correlated with larger hematoma volume in patients with thalamoganglionic ICH (B = .604, P = .004) after adjustment for confounding factors. Poor outcomes (6-month modified Rankin Scale scores ≥3) were not significantly different between 2 groups (low homocysteinemia group, 31.4%, versus high homocysteinemia group, 41.2%, P = .400). CONCLUSIONS: Elevated plasma HCY levels were associated with larger hematoma volume only in patients with thalamoganglionic ICH. HCY levels might not be predictors of the 6-month clinical outcome in patients with ICH.

Fundamental modal properties of SRR metamaterials and metamaterial based waveguiding structures.

A rigorous full wave analysis of bianisotropic split ring resonator (SRR) metamaterials is presented for different electromagnetic field polarization and propagation directions. An alternative physical explanation is gained by revealing the fact that imaginary wave number leads to the SRR resonance. Metamaterial based parallel plate waveguide and rectangular waveguide are then examined to explore the resonance response to transverse magnetic and transverse electric waves. It is shown that different dispersion properties, such as non-cutoff frequency mode propagation and enhanced bandwidth of single mode operation, become into existence under certain circumstances. In addition, salient dispersion properties are imparted to non-radiative dielectric waveguides and H waveguides by uniaxial bianisotropic SRR metamaterials. Both longitudinal-section magnetic and longitudinal-section electric modes are capable of propagating very slowly due to metamaterial bianisotropic effects. Particularly, the abnormal falling behavior of some higher-order modes, eventually leading to the leakage, may appear when metamaterials are double negative. Fortunately, for other modes, leakage can be reduced due to the magnetoelectric coupling. When the metamaterials are of single negative parameters, leakage elimination can be achieved.