Association between serum neuron-specific enolase at admission and the risk of delayed neuropsychiatric sequelae in adults with carbon monoxide poisoning: A meta-analysis.

Delayed neuropsychiatric sequelae (DNS) significantly impact the quality of life in patients following acute carbon monoxide poisoning (COP). This systematic review and meta-analysis aimed to assess the relationship between serum neuron-specific enolase (NSE) levels at admission and the risk of DNS in adults after acute COP. Relevant observational studies with longitudinal follow-up were identified through searches in PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure databases. The random-effects model was used to aggregate results, accounting for potential heterogeneity. Nine cohort studies, including 1501 patients, were analyzed, with 254 (16.9%) developing DNS during follow-up. The pooled data indicated that elevated serum NSE in the early phase was linked to a higher risk of subsequent DNS (odds ratio per 1 ng/mL increase in NSE: 1.10, 95% confidence interval: 1.06 to 1.15, P < 0.001). Moderate heterogeneity (I2 = 46%) among the studies was entirely attributed to one study with the longest follow-up duration (22.3 months; I2 = 0% after excluding this study). Subgroup analyses based on country, study design, sample size, age, sex, admission carboxyhemoglobin levels, DNS incidence, follow-up duration, and quality score yielded consistent results (P for subgroup differences all > 0.05). In summary, high serum NSE levels in the early phase of acute COP are associated with an increased risk of developing DNS during follow-up.

Advancing skeletal health and disease research with single-cell RNA sequencing.

Orthopedic conditions have emerged as global health concerns, impacting approximately 1.7 billion individuals worldwide. However, the limited understanding of the underlying pathological processes at the cellular and molecular level has hindered the development of comprehensive treatment options for these disorders. The advent of single-cell RNA sequencing (scRNA-seq) technology has revolutionized biomedical research by enabling detailed examination of cellular and molecular diversity. Nevertheless, investigating mechanisms at the single-cell level in highly mineralized skeletal tissue poses technical challenges. In this comprehensive review, we present a streamlined approach to obtaining high-quality single cells from skeletal tissue and provide an overview of existing scRNA-seq technologies employed in skeletal studies along with practical bioinformatic analysis pipelines. By utilizing these methodologies, crucial insights into the developmental dynamics, maintenance of homeostasis, and pathological processes involved in spine, joint, bone, muscle, and tendon disorders have been uncovered. Specifically focusing on the joint diseases of degenerative disc disease, osteoarthritis, and rheumatoid arthritis using scRNA-seq has provided novel insights and a more nuanced comprehension. These findings have paved the way for discovering novel therapeutic targets that offer potential benefits to patients suffering from diverse skeletal disorders.

In Situ Photoactivated Antibacterial and Antioxidant Composite Materials to Promote Bone Repair.

Trauma and tumor removal usually cause bone defects; in addition, the related postoperative infection also shall be carefully considered clinically. In this study, polylactic acid (PLLA) composite fibers containing Cerium oxide (CeO2) are first prepared by electrospinning technology. Then, the PLLA/CeO2@PDA/Ag composite materials are successfully prepared by reducing silver ion (Ag+) to nano-silver (AgNPs)  coating in situ and binding AgNPs to the materials surface by mussel structure liked polydopamine (PDA). In the materials, Ag+ can be slowly released in simulated body fluids. Based on the photothermal performance of AgNPs, the photothermal conversion efficiency of the materials is 21%, under NIR 808 nm illumination. The effective photothermal conversion can help materials fighting with E. coli and S. aureus in 3 h, with an antibacterial rate of 100%. Additionally, the sustained Ag+ release contributes to the antibacterial in long term. Meanwhile, the materials can mimic the bio-behavior of superoxide dismutase and catalase in decreasing the singlet oxygen level and removing the excess reactive oxygen species. Furthermore, the materials are beneficial for cell proliferation and osteogenic differentiation in vitro. In this study, a promising bone-regenerated material with high photothermal conversion efficiency and antibacterial and anti-oxidation properties, is successfully constructed.

Porous MOF Featuring 2D Intersecting Channels Based on a Pentanuclear Mn5(COO)10CO3 Cluster with Upgrading of Pipeline Natural Gas.

Natural gas plays a crucial role in daily and industrial production, but the impurities contained in natural gas limit its further use. It is very important to develop adsorbents that can separate CH4 from multicomponent mixtures, but there are still many challenges and problems. Herein, a novel porous MOF {[Mn5(pbdia)2(CO3)(H2O)2] ↔ 5H2O ↔ 2DMF}n (pbdia = 2,2'-(5-carboxy-1,3-phenylene)bis(oxy) diterephthalic acid) was successfully synthesized based on a flexible pentacarboxylic acid ligand and a unique pentanuclear Mn5(COO)10CO3 cluster. The MOF reveals a 3D porous structure with 2D intersecting channels, which shows high C3H8, C2H6, and CO2 adsorption capacities and affinities over CH4. Moreover, the ideal adsorption solution theory selectivities of C3H8/CH4, C2H6/CH4, and CO2/CH4 can reach 263.0, 27.0, and 7.7, respectively, suggesting a potential for removing the low content of C3H8, C2H6, and CO2 from pipeline natural gas, which was further confirmed by breakthrough curves and GCMC simulations.

Giant muscle hydatid in lower extremity: a rare case with neurological symptoms as the first manifestation.

BACKGROUND: Human hydatid disease typically occurs in organs such as the liver and kidney. Primary solitary intramuscular hydatid disease, however, is rare. CASE PRESENTATION: We report a case of a giant muscle hydatid in the lower extremity, with neurological symptoms as the first manifestation. The symptoms specifically manifested as intermittent pain in the right lower extremity and numbness in the sole of the right foot. However, there were no obvious abnormalities detected in electromyography and lumbar MRI. Subsequent ultrasonography and calf MRI showed that the patient had cystic lesions in the calf. The patient was initially diagnosed with a muscle hydatid cyst. Treatment involved complete surgical excision of the lesion, and the diagnosis of a hydatid cyst was confirmed through macroscopic and microscopic histopathological examination after the mass was excised. The patient was given oral albendazole, and no recurrence was observed during the 12 months of follow-up. CONCLUSIONS: This case underscores the need to consider hydatid disease when diagnosing soft tissue masses in muscles, particularly in endemic areas. Patients may initially present with atypical symptoms like peripheral nerve issues.

Justifying Ribociclib Dose in Patients with Advanced Breast Cancer with Renal Impairment Based on PK, Safety, and Efficacy Data: An Innovative Approach Integrating Data from a Dedicated Renal Impairment Study and Oncology Clinical Trials.

BACKGROUND AND OBJECTIVE: Renal impairment is common in patients with cancer and can alter the PK and thus the safety and efficacy of drugs. We assessed the impact of renal impairment during treatment with ribociclib, a cyclin-dependent kinase 4/6 inhibitor, and determined dose recommendations for patients with advanced breast cancer with renal impairment. METHODS: A comprehensive assessment integrating pharmacokinetic, safety, and efficacy data from a phase I dedicated renal impairment study in non-cancer subjects and six phase I-III trials in patients with cancer was performed. RESULTS: Ribociclib showed higher pharmacokinetic exposure in subjects with renal impairment than those with normal renal function following a single 400-mg dose in the dedicated renal impairment study. However, in patient trials, both single-dose and steady­state ribociclib exposure was comparable between patients with cancer with mild/moderate renal impairment and those with normal renal function following the recommended starting dose of 600 mg. Model-predicted steady­state exposure in patients with advanced breast cancer was also similar across the renal function groups. Progression-free survival was similar and safety profiles were generally consistent across the renal cohorts (normal/mild/moderate) in patients with advanced breast cancer, with low-grade and manageable adverse events, demonstrating a positive benefit-risk profile. CONCLUSIONS: From the collective evidence and considering a real-world clinical setting, no dose adjustment is recommended for patients with mild/moderate renal impairment, whereas a reduced dose is recommended for patients with severe renal impairment. This report presented a holistic and innovative strategy to determine dose in patients with renal impairment and demonstrated the effectiveness of integrating the data of both a clinical pharmacology study and patient trials to justify doses in patients with renal impairment. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifiers: NCT02431481, NCT01958021, NCT02422615, NCT02278120, NCT01237236, NCT01898845, NCT01872260.

Impact of Anti-HER2 Therapy Alone and With Weekly Paclitaxel on the Ovarian Reserve of Young Women With HER2-Positive Breast Cancer.

BACKGROUND: The potential gonadotoxicity of anti-HER2 agents remains largely unknown, and limited, conflicting evidence exists for taxanes. Antimüllerian hormone (AMH) is an established biomarker of ovarian reserve that may aid in quantifying anticancer treatment-induced gonadotoxicity. PATIENTS AND METHODS: The present biomarker analysis of the randomized phase III neoadjuvant NeoALTTO trial included premenopausal women aged ≤45 years at diagnosis of HER2-positive early breast cancer with available frozen serum samples at baseline (ie, before anticancer treatments), at week 2 (ie, the "biological window" of anti-HER2 therapy alone), and/or at the time of surgery (ie, after completing paclitaxel + anti-HER2 therapy, before starting adjuvant chemotherapy). RESULTS: The present analysis included 130 patients with a median age of 38 years (interquartile ratio [IQR], age 33-42 years). AMH values at the 3 time points differed significantly (P<.001). At baseline, median AMH levels were 1.29 ng/mL (IQR, 0.56-2.62 ng/mL). At week 2, a small but significant reduction in AMH levels was observed (median, 1.10 ng/mL; IQR, 0.45-2.09 ng/mL; P<.001). At surgery, a larger significant decline in AMH levels was observed (median, 0.01 ng/mL; IQR, 0.01-0.03 ng/mL; P<.001). Although the type of anti-HER2 treatment (trastuzumab and/or lapatinib) did not seem to impact the results, age and pretreatment ovarian reserve had a major influence on treatment-induced gonadotoxicity risk. CONCLUSIONS: This NeoALTTO biomarker analysis showed that anti-HER2 therapies alone had limited gonadotoxicity but that the addition of weekly paclitaxel resulted in marked AMH decline with possible negative implications for subsequent ovarian function and fertility.

Subaxial Cervical Pedicular Screw Insertion via the Nonanatomic Axis: Technical Notes and Preliminary Clinical Report.

STUDY DESIGN: Retrospective study. OBJECTIVE: To report the technical details of subaxial cervical pedicular screw insertion via the nonanatomic axis (nAA-CPS) and evaluate its clinical safety and accuracy. METHODS: The nAA-CPS technique was performed in 21 patients. Preoperative and intraoperative management-related details are described, and a manipulation protocol is presented. Clinical outcomes were used to assess the safety and accuracy of screws was evaluated using postoperative computed tomography (CT) according to the pedicle perforation grading system, and the nonanatomic pedicle transverse angle (nPTA) and nonanatomic pedicle axis length (nPAL) were assessed based on pre- and postoperative CT images. RESULTS: According to "one constant entry point (EP) and two perpendicular trajectory angles" protocol, nAA-CPS was performed without much interference from the muscles. No intraoperative or postoperative neurovascular complications related to the technique were observed. Of the 112 inserted screws, 78 (69.64%) were assessed as grade 0, 24 (21.43%) as grade 1, 4 (3.57%) as grade 2 and 6 (5.36%) as grade 3. The overall rate of correct position (grades 0 and 1) was 91.07% (102/112), and the rate of malposition was 8.93% (10/112), including five screws implanted medially and the other five laterally. The nPTA was highly consistent on pre- and postoperative CT (P < .05), while postoperative nPAL was significantly shorter than preoperative nPAL (P > .05). CONCLUSIONS: Clinically, the accuracy and safety of nAA-CPS was similar to the traditional CPS technique. The protocol, derived from previous radiological studies and workshops, greatly helped standardize clinical manipulation; thus, nAA-CPS is a promising alternative to the traditional CPS.

Subaxial Cervical Pedicular Screw Insertion via the Nonanatomic Axis: Identification of Entry Point and Trajectory Based on a Radiographic Study and Workshop.

STUDY DESIGN: A radiological study and workshop. OBJECTIVE: To propose a novel technique for subaxial cervical pedicle screw (CPS) insertion via the nonanatomic axis (nAA) and identify a new entry point (EP) and trajectory based on a radiological study. METHODS: The new EP was determined to be the center of the upper half of the lateral mass, and the nAA was defined as the line connecting the EP and center of the pedicle. CT images of 493 subaxial cervical pedicles from 51 adults were utilized. The pedicle axis length (PAL/nPAL), pedicle transverse angle (PTA/nPTA), sagittal and transverse pedicle screw depth ratio (S-DO, T-DO), and sagittal and transverse angles (S-angle, T-angle) were measured in the anatomical axis (AA) and nAA. nAA-CPS insertions were conducted on dry specimens, and the positions of the screws were graded. RESULTS: The nPTA (22.35° ± 1.57°), nPAL (23.75 ± 2.07 mm), T-DO (45.61% ± 3.10%), and S-DO (70.46% ± 4.44%) of the nAA-CPS were significantly different from the PTA (41.86° ± 2.77°), PAL (31.98 ± 2.40 mm), T-DO and S-DO of the AA-CPS (both 100% in ideal conditions), respectively (P < .05). The T-angle and S-angle were 92.78° ± 3.07° and 92.18° ± 3.78°, respectively. A constant EP and consistent trajectory of the nAA-CPS identified by 2 perpendicular angles were summarized and utilized as the manipulation protocols of the workshop, and a perfect position was achieved in 80.00% (24/30) of screws. CONCLUSION: The nAA-CPS is a novel alternative to the classic CPS technique. A constant entry point and 2 perpendicular angles in the sagittal and transverse planes for identifying the trajectory of the nAA-CPS should be taken into account in the establishment of a manipulation protocol.

Efficacy and Safety of Ceritinib 450 mg/day with Food and 750 mg/day in Fasted State in Treatment-Naïve Patients with ALK+ Non-Small Cell Lung Cancer: Results from the ASCEND-8 Asian Subgroup Analysis.

PURPOSE: Previous report from the ASCEND-8 trial showed consistent efficacy with less gastrointestinal (GI) toxicity in patients with anaplastic lymphoma kinase-rearranged (ALK+) advanced/metastatic non-small cell lung cancer (NSCLC) treated with ceritinib 450-mg with food compared with 750-mg fasted. In this subgroup analysis, we report outcomes in Asian patients of the ASCEND-8 trial. MATERIALS AND METHODS: Key efficacy endpoints were blinded independent review committee (BIRC)-assessed overall response rate (ORR) and duration of response (DOR) evaluated per Response Evaluation Criteria in Solid Tumors v1.1. Other efficacy endpoints were investigator-assessed ORR and DOR; BIRC- and investigator-assessed progression-free survival (PFS) and disease control rate; overall survival (OS). Safety was evaluated by frequency and severity of adverse events. RESULTS: At final data cutoff (6 March 2020), 198 treatment-naïve patients were included in efficacy analysis, of which 74 (37%) comprised the Asian subset; 450-mg fed (n=29), 600-mg fed (n=19), and 750-mg fasted (n=26). Baseline characteristics were mostly comparable across study arms. At baseline, more patients in 450-mg fed arm (44.8%) had brain metastases than in 750-mg fasted arm (26.9%). Per BIRC, patients in the 450-mg fed arm had a numerically higher ORR, 24-month DOR rate and 24-month PFS rate than the 750-mg fasted arm. The 36-month OS rate was 93.1% in 450-mg fed arm and 70.9% in 750-mg fasted arm. Any-grade GI toxicity occurred in 82.8% and 96.2% of patients in the 450-mg fed and 750-mg fasted arms, respectively. CONCLUSION: Asian patients with ALK+ advanced/metastatic NSCLC treated with ceritinib 450-mg fed showed numerically higher efficacy and lower GI toxicity than 750-mg fasted patients.

Outcomes of patients with small and node-negative HER2-positive early breast cancer treated with adjuvant chemotherapy and anti-HER2 therapy-a sub-analysis of the ALTTO study.

BACKGROUND: Patients with small node-negative HER2-positive breast cancer are commonly treated with paclitaxel and 1 year of adjuvant trastuzumab. We performed a sub-analysis of the ALTTO trial to explore the long-term outcomes of patients with small node-negative tumours. METHODS: The ALTTO trial randomised 8381 patients with early HER2-positive BC treated with adjuvant chemotherapy (anthracycline/taxane- or taxane/carboplatin-based), to trastuzumab (T), lapatinib (L), their sequence (T → L) or their combination (L + T). Patients with tumours ≤3 cm and node-negative were included in this sub-analysis. RESULTS: A total of 2821 patients were analysed (median follow-up of 7 years). The median age was 52 years, and most patients had tumours ≤2 cm (64.3%). The 7-year disease-free survival (DFS) was 88.1% (95% CI: 86.7-89.3%). DFS was similar for arms T, T + L and T⟶L and significantly lower for arm L (stratified log-rank P = 0.031). The 7-year overall survival rate was 95.9% (95% CI: [95.0-96.6%) and the 7-year time-to-distant recurrence was 93.4% (95% CI: 92.3-94.4%). CONCLUSION: With most patients treated with anthracycline-based regimens, ALTTO shows that patients with small tumours treated with trastuzumab and concomitant chemotherapy have excellent long-term outcomes, similar to those of the APT trial. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT00490139.

A new attempt to treat coronal plane fractures of the elbow joint with salvage via an anterior approach.

BACKGROUND: Existing approaches for treating elbow fractures include lateral, medial, anterior and posterior approaches, though the anterior approach is often not chosen by surgeons to avoid damage to important nerves and blood vessels. However, the anterior approach has unique advantages. The purpose of this study was to report outcomes of 38 patients with coronal plane elbow fractures treated through the anterior approach. METHODS: We retrospectively analyzed 38 cases of coronal plane elbow fracture treated through an anterior approach at our institution between March 2015 and July 2019. The length of the surgical incision, operation time, and postoperative complications were recorded. The range of flexion, extension, and rotation of the affected elbow and the healthy elbow were collected at follow-up. Functional outcomes were evaluated using the Mayo Elbow Function Score (MEPS). RESULTS: All 38 patients were followed up for a mean of 21.26 months (range 12-36 months). Intraoperatively, the mean surgical incision length was 8 ± 2 cm and the mean operative time was 123 ± 59 min. At the final follow-up, solid osseous union was confirmed for all coronal plane elbow fractures. The mean elbow flexion arc was 129 ± 7°, and the extension arc was 9 ± 6°. The mean pronation arc was 83 ± 3°, and the supination arc was 80 ± 3°. The mean MEPS was 90 ± 8 points, with 18 excellent cases and 20 cases of excellent and good results, respectively. In 31 cases, there was no significant difference in elbow extension, flexion, or pronation between the single-fracture and healthy elbows (P > 0.05), though the arc of supination was slightly worse than that of the healthy elbow (P < 0.05). VAS pain scores before the operation, at three months after the operation, and during follow-up were compared, and pain was significantly reduced after treatment (P < 0.05). Two patients experienced transient postoperative median nerve paralysis, from which they recovered within three months. One patient had mild heterotopic ossification and was not treated because it did not affect the function of the elbow joint. All patients returned to work and were satisfied with the treatment. CONCLUSION: The anterior approach has the benefits of simplicity, safety, minimal invasiveness, excellent exposure, and satisfactory prognosis for coronal plane elbow fracture.

Imaging topological and correlated insulating states in twisted monolayer-bilayer graphene.

Flat bands in Van der Waals heterostructure provide an ideal platform for unveiling emergent quantum electronic phases. One celebrated example is twisted monolayer-bilayer graphene, in which the effects of electronic correlation have been observed. Here, we report the observation via scanning tunnelling microscopy and spectroscopy of correlated insulating states in twisted monolayer-bilayer graphene, leading to the formation of an electron crystal phase. At integer fillings, the strong Coulomb interaction redistributes flat-band electrons within one moiré unit cell, producing an insulating state with vanishing density of states at the Fermi level. Moreover, our approach enables the direct visualization of an ordered lattice of topological torus-shaped states, generated by the interaction between the electron crystal and the non-trivial band topology of twisted monolayer-bilayer graphene. Our results illustrate an efficient strategy for entwining topological physics with strong electron correlation in twisted van der Waals structures.

PREDICT underestimates survival of patients with HER2-positive early-stage breast cancer.

The prognostic performance of PREDICT in patients with HER2-positive early breast cancer (EBC) treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies is unclear. Therefore, we investigated its prognostic performance using data extracted from ALTTO, a phase III trial evaluating adjuvant lapatinib ± trastuzumab vs. trastuzumab alone in patients with HER2-positive EBC. Our analysis included 2794 patients. After a median follow-up of 6.0 years (IQR, 5.8-6.7), 182 deaths were observed. Overall, PREDICT underestimated 5-year OS by 6.7% (95% CI, 5.8-7.6): observed 5-year OS was 94.7% vs. predicted 88.0%. The underestimation was consistent across all subgroups, including those according to the type of anti HER2-therapy. The highest absolute differences were observed for patients with hormone receptor negative-disease, nodal involvement, and large tumor size (13.0%, 15.8%, and 15.3%, respectively). AUC under the ROC curve was 73.7% (95% CI 69.7-77.8) in the overall population, ranging between 61.7% and 77.7% across the analyzed subgroups. In conclusion, our analysis showed that PREDICT highly underestimated OS in HER2-positive EBC. Hence, it should be used with caution to give prognostic estimation to HER2-positive EBC patients treated in the modern era with effective chemotherapy and anti-HER2 targeted therapies.

Nine-year-long complex humeral nonunion salvaged by distraction osteogenesis technique: a case report and review of the literature.

BACKGROUND: Humeral nonunion with significant bone loss or shortening is uncommon and poses a complex clinical problem. We present a case of humeral nonunion with a large segmental bone defect treated with the distraction osteogenesis technique and remedy the radial nerve palsy produced during distraction osteogenesis by forearm tendon transfers. The reconstruction of upper limb function was achieved with satisfactory results. This case provides a referenceable alternative method for repairing large segmental bone defects due to complex nonunion of the upper extremity, as well as a remedy in the unfortunate event of radial nerve palsy, providing a reference and lessons learned for the treatment of similar cases and the management of possible complications. CASE PRESENTATION: A 31-year-old male patient experienced 9 years of hypertrophic nonunion due to an unreliable internal fixation. The radiographs showed the absence of bone bridging between the two fragments, loosening of the screws, and extensive osteolysis around the internal screws. The patient was treated with distraction osteogenesis. At the end of the distraction period, the patient unfortunately developed right radial nerve paresis, which was salvaged by forearm tendon transplantation, and finally reconstructed hand function and achieved bone union of the humerus. CONCLUSION: Distraction osteogenesis, although not a panacea for all humeral nonunions with significant segmental bone loss, does offer a viable salvage procedure in this unusual and often complex clinical problem. When irreversible radial nerve palsy occurs during distraction, forearm tendon transfers can have a good clinical effect.

Tumor Cellularity and Infiltrating Lymphocytes as a Survival Surrogate in HER2-Positive Breast Cancer.

In early-stage HER2-positive breast cancer, biomarkers that guide deescalation and/or escalation of systemic therapy are needed. CelTIL score is a novel, combined biomarker based on stromal tumor-infiltrating lymphocytes and tumor cellularity and is determined in tumor biopsies at week 2 of anti-HER2 therapy only. We evaluated the prognostic value of CelTIL in 196 patients with early-stage HER2-positive disease treated with standard trastuzumab-based chemotherapy in the NeoALTTO phase III trial. Using a prespecified CelTIL cutoff, a better 5-year event-free survival and overall survival was observed between CelTIL-high and CelTIL-low score with a 76.4% (95% confidence interval [CI] = 68.0% to 85.0%) vs 59.7% (95% CI = 50.0% to 72.0%) (hazard ratio = 0.40, 95% CI = 0.17 to 0.94) and 86.4% (95% CI = 80.0% to 94.0%) vs 73.5% (95% CI = 64.0% to 84.0%) (hazard ratio = 0.43, 95% CI = 0.20 to 0.92), respectively. Statistical significance was maintained after adjusting for baseline tumor-infiltrating lymphocytes, hormone receptor status, pretreatment tumor size and nodal status, type of surgery, treatment arm, and pathological complete response. Further studies to support CelTIL as an early readout biomarker to help deescalate or escalate systemic therapy in HER2-positive breast cancer seem warranted.

What if the future of HER2-positive breast cancer patients was written in miRNAs? An exploratory analysis from NeoALTTO study.

BACKGROUND: Neoadjuvant therapy with dual HER2 blockade improved pathological complete response (pCR) rate in HER2-positive breast cancer patients. Nevertheless, it would be desirable to identify patients exquisitely responsive to single agent trastuzumab to minimize or avoid overtreatment. Herein, we evaluated the predictive and prognostic value of basal primary tumor miRNA expression profile within the trastuzumab arm of NeoALTTO study (ClinicalTrials.gov Identifier: NCT00553358). METHODS: RNA samples from baseline biopsies were randomized into training (n = 45) and testing (n = 47) sets. After normalization, miRNAs associated with Event-free survival (EFS) and pCR were identified by univariate analysis. Multivariate models were implemented to generate specific signatures which were first confirmed, and then analyzed together with other clinical and pathological variables. RESULTS: We identified a prognostic signature including hsa-miR-153-3p (HR 1.831, 95% CI: 1.34-2.50) and hsa-miR-219a-5p (HR 0.629, 95% CI: 0.50-0.78). For two additional miRNAs (miR-215-5p and miR-30c-2-3p), we found a statistically significant interaction term with pCR (p.interaction: 0.017 and 0.038, respectively). Besides, a two-miRNA signature was predictive of pCR (hsa-miR-31-3p, OR 0.70, 95% CI: 0.53-0.92, and hsa-miR-382-3p, OR: 1.39, 95% CI: 1.01-1.91). Notably, the performance of this predictive miRNA signature resembled that of the genomic classifiers PAM50 and TRAR, and did not improve when the extended models were fitted. CONCLUSION: Analyses of primary tumor tissue miRNAs hold the potential of a parsimonious tool to identify patients with differential clinical outcomes after trastuzumab based neoadjuvant therapy.

Outcomes in Thoracolumbar and Lumbar Traumatic Fractures: Does Restoration of Unfused Segmental Mobility Correlated to Implant Removal Time?

BACKGROUND: Posterior fixation without fusion can treat thoracolumbar and lumbar traumatic fractures effectively in certain cases. However, whether patients benefit from implant removal and the correlation between the range of motion (ROM) of the involved segments and the removal time have not been determined. METHODS: From 2018 to 2020, we retrospectively reviewed data of patients with AO spine type A or B thoracolumbar or lumbar traumatic fractures who underwent implant removal. A total of 17 patients (group A), 21 patients (group B), and 12 patients (group C) underwent implant removal after the index surgery within 12 months, between 12 and 24 months, and over 24 months, respectively. Clinical and radiological outcomes, including visual analog scale for back pain, patient satisfaction, Oswestry disability index, and EuroQol 5 dimensions questionnaire, for quality of life and segmental ROM were analyzed. RESULTS: The average follow-up time was 9.1 ± 5.7 months after implant removal. There were no significant differences in visual analog scale and patient satisfaction among the 3 groups at the same observation time point. Among the 3 groups, patients in group A gained the lowest Oswestry disability index and highest EuroQol 5 dimensions questionnaire scores after removal and at the final follow-up. The best ROM was obtained in group A followed by groups B and C (11.5° ± 6.2°, 5.5° ± 1.6°, and 2.4° ± 0.6°, respectively). CONCLUSIONS: Immobilization of the involved segments over 24 months may lead to loss of ROM. Regained segmental ROM is correlated negatively with implant removal time, and removal within 12 months promises a better ROM and quality of life.

Modified lumbar foraminoplasty using a power-aided reciprocating burr for percutaneous transforaminal endoscopic lumbar discectomy: A technical note and clinical report.

Background: One of the main difficulties in a transforaminal endoscopic lumbar discectomy (TELD), and simultaneously the most critical step, is performing an effective and safe foraminoplasty, which is especially difficult for beginners. To make it safer and faster for beginners to perform, we have used a specially designed power-aided reciprocating burr for TELD and reported the technical details. Methods: From Jan. 2019 to Nov. 2022, 432 patients with single-level, symptomatic L4/5 or L5/S1 disc herniation were treated with TELD using a novel power-aided reciprocating burr. The surgical procedure is described in detail. Magnetic resonance imaging (MRI) was performed the following day and 3 months after the operation. The learning curves of surgeons with different seniority levels are displayed. The Visual Analogue Scale (VAS) score and the Oswestry Disability Index (ODI) were used to measure low back pain, leg pain, and lumbar function. All patients were followed up for at least 1 year. Results: All patients underwent endoscopic surgery successfully. Among the 432 patients, radicular outer membrane damage was observed in 6 cases, and 1 case had hernia of the nerve tract. Except for this patient with aggravation of postoperative numbness, the postoperative neurological symptoms of all patients were significantly improved. The mean VAS scores for low back pain and leg pain and ODI scores were significantly decreased 6 w post-operatively and were maintained until 12 months post-operatively compared to preoperative scores (P < 0.05). All three doctors involved in the study had substantial experience in traditional open spinal surgery. The more operations all three surgeons completed, the more time spent on intervertebral foraminoplasty decreased (P < 0.05). Among them, doctors without experience in TELD surgery became proficient in this technique after accumulating experience in 13 cases. There was no significant difference in foraminoplasty time among these three surgeons during the same growing period (P > 0.05). Conclusions: Current clinical data demonstrated the safety and efficacy of modified TELD using a power-aided reciprocating burr for treating lumbar disc herniation (LDH) and showed that this technique significantly reduces the learning curve for beginners when performing foraminoplasty.

Application of Supercritical CO2 Foaming Technology for Waste Double-Base Propellants.

This paper used a supercritical CO2 batch foaming process to treat a waste SP double-base propellant, which is a type of double-base propellants containing 58.6% nitrocellulose, 40.0% nitroglycerin, 0.8% centralite, and 0.5% vaseline, to solve a problem of poor stability of industrial explosives directly prepared by the propellant. Experiments show that this process can produce dense pores inside the SP double-base propellant. With the increase of the pressure of supercritical CO2, the number of pores inside the foamed SP double-base propellant increased, and these pores served as hotspots in the detonation reaction. An increased number of hotspots improved the detonation stability of the perfusion explosive. During the explosion, the energy of the perfusion explosive with the foamed SP double-base propellant was released more completely, so the shock wave energy and bubble energy of the explosive gradually increased with the increase of pressure. Therefore, the supercritical CO2 foaming process can promote the treatment technology of waste double-base propellants and can optimize the detonation performance of perfusion explosives by increasing the pressure of supercritical CO2.