A Meta-Analysis of Success Rates of One-Stage Versus Two-Stage Revisions in Knee Prosthetic Joint Infections.

Prosthetic joint infections (PJIs) pose significant challenges following total joint arthroplasties and cause profound complications. They are associated with significant morbidity and mortality. One-stage revision involves the removal of the infected implant and simultaneous re-implantation of a new prosthesis in a single surgical procedure. The two-stage approach is traditionally more common in the United States and follows a deliberate sequence: the infected implant is first removed, followed by a period of antibiotic therapy, and then a second surgery for implant reinsertion. While two-stage revisions were traditionally considered the gold standard, recent advancements have introduced one-stage revisions as a viable alternative. One-stage revision offers the advantage of being a single procedure, significantly reducing the patient's downtime without a functioning knee. Currently, there has not been a comprehensive exploration of the comparative outcomes between two-stage revisions and one-stage revisions. This systematic review and meta-analysis aimed to assess the outcomes of both one- and two-stage revisions for total knee arthroplasties (TKAs), by utilizing comparison studies as the foundation for analysis. Our search encompassed databases such as MEDLINE (Medical Literature Analysis and Retrieval System Online), Embase, and Cochrane to identify articles examining the comparative efficacy and outcomes of one- and two-stage revision procedures between January 2000 and June 2023. We employed keywords relevant to knee PJIs to identify comparative studies reporting on success rates, reinfection rates, microbiological findings, and other pertinent outcomes. Statistical analysis for this investigation was performed using Review Manager 5.4 (The Cochrane Collaboration, 2020) with a standard significance threshold set at a p-value less than .05. This meta-analysis incorporated six comparison articles and 802 patients. Two-stage revisions (547 patients) were associated with greater success rates (i.e., infection eradication) than one-stage revisions (255 patients) (p = .03). The studies did not suggest a difference in the microbiology of the infections. Two-stage revisions are associated with higher success rates than one-stage revisions in the treatment of knee PJIs. Future randomized controlled trials should evaluate the optimization of the management of these complications.

Acute Ankle Diastasis Injuries Treated with Dynamic, Static Fixation or Anatomic Repair: A Meta-Analysis and Systematic Review of Comparison Studies.

BACKGROUND: Acute ankle diastasis injuries are complex and debilitating. These injuries occur when the syndesmotic complex becomes compromised. Treatments of acute syndesmotic injuries include static fixation with screws, dynamic fixation with an elastic device, or anatomic repair of the damaged ligament. However, there is disagreement over which method is most effective. The primary purpose of this study was to compare the 3 treatment methods for acute syndesmotic injuries. METHODS: A systematic literature search was conducted on Embase and PubMed. Studies that compared at least 2 groups with relevant American Orthopaedic Foot & Ankle Society (AOFAS), Visual Analog Scale (VAS), reoperation rate, and complication (implant failure, implant irritation, and infection) data were analyzed. Statistical analysis for this study was performed using Review Manager 5.4, with a standard p-value of ≤0.05 for statistical significance. RESULTS: Twenty-one studies including a total of 1,059 patients (452 dynamic, 529 static, and 78 anatomic) were included for analysis. Dynamic fixation had significantly higher mean AOFAS scores at 3 months postoperation by 5.12 points (95% confidence interval [CI], 0.29-9.96, p = 0.04) as well as at 1 year postoperation by 4.64 points (95% CI, 1.74-7.55, p = 0.002) than static fixation. Anatomic repair had significantly higher AOFAS scores at 6 months postoperation by 3.20 points (95% CI, 1.06-5.34, p = 0.003) and 1 year postoperation by 1.86 points (95% CI, 0.59-3.14, p = 0.004) than static fixation. Dynamic fixation had significantly higher AOFAS scores at 6 months postoperation by 2.81 points (95% CI, 0.76-4.86, p = 0.007), 12 months postoperation by 3.17 points (95% CI, 0.76-5.58, p = 0.01), and at 2 years postoperation by 5.56 points (95% CI, 3.80-7.32, p < 0.001) than anatomic repair. Dynamic fixation also had a lower VAS score average (favorable), only significant at 12 months postoperation, than static fixation by 0.7 points (95% CI -0.99 to -0.40, p < 0.001). Anatomic repair did not have significant difference in VAS scores compared with static fixation. Anatomic repair had significantly lower VAS scores at 12 months postoperation by 0.32 points (95% CI -0.59 to -0.05, p = 0.02) than dynamic fixation. Dynamic fixation had significantly less implant failures (odds ratio [OR], 0.13, 95% CI, 0.05-0.32, p < 0.001) than static fixation. Anatomic repair was not significantly different from static fixation in the complication metrics. Dynamic fixation and anatomic repair were not significantly different in the complication metrics either. Dynamic fixation had a significantly lower reoperation rate than static fixation (OR, 0.23, 95% CI, 0.09-0.54, p < 0.001). Anatomic repair did not have a significantly different reoperation rate compared with static fixation. However, dynamic fixation had a significantly lower reoperation rate than anatomic repair (OR, 4.65, 95% CI, 1.10-19.76, p = 0.04). CONCLUSION: Dynamic fixation seems to demonstrate superior early clinical outcomes. However, these advantages become negligible in the long term when compared with alternative options. Dynamic fixation is associated with a lower risk for complications, specifically seen with the decrease in implant failures. This method also presents a significantly lower reoperation rate compared with the other treatment approaches. Apart from showing improved early clinical outcomes in comparison with static fixation, anatomic repair did not have significant distinctions in other metrics, including complications or reoperation rate. LEVEL OF EVIDENCE: Level III. See Instructions for Authors for a complete description of levels of evidence.

Comparison of Graft Type and Fixation Method in Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis Based on Randomized Control Studies.

BACKGROUND: The anterior cruciate ligament (ACL) is the most commonly injured ligament in the knee. ACL reconstruction (ACLR) proves the standard for treating this injury. However, graft choice and method of fixation remain a heavily debated topic. This study investigates the following: bone-patellar tendon-bone (BPTB) vs. hamstring tendon (HT) autograft, single-bundle vs. double-bundle hamstring graft, and metal vs. bioabsorbable screws in ACLR. METHODS: A systematic review was performed on PubMed and Google Scholar according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data were collected on patient demographics, complications, and functionality scores including International Knee Documentation Committee (IKDC) and Lysholm scores. A systematic review and meta-analysis were conducted with Review Manager. Outcome measurements were determined using forest plots with significant differences considered p < 0.05. RESULTS: Twenty-five studies were included, accounting for 2,170 patients. No statistically significant difference was appreciated when comparing BPTB to hamstring autografts. Patients who received a double bundle HT autograft exhibited significantly superior outcomes in terms of revision (p = 0.05), failure (p = 0.002), normal pivot shift tests (p = 0.04), and normal IKDC (p = 0.008). When comparing screw types, bioabsorbable screws had a greater Lysholm score (p = 0.01) and lower failure rates for copolymer screws (p = 0.03). CONCLUSION: Overall, the data collected suggested that BPTB and HT autografts display similar postoperative results. However, if an HT autograft is used, the data suggest a double-bundle graft improves both functionality and decreases the possible complications. Finally, bioabsorbable screws prove superior to metal screws when looking at both functionality and failure rates. Further research into the superior graft type is still needed. LEVEL OF EVIDENCE: Level II. See Instructions for Authors for a complete description of levels of evidence.

Adult head and neck rhabdomyosarcoma: radiotherapy- based treatment, outcomes, and predictors of survival.

BACKGROUND: Adult head and neck rhabdomyosarcoma (HNRMS) is an exceptionally rare malignancy, and there is a paucity of data and research dedicated to understanding its characteristics and management in adult populations. This study aimed to assess the outcomes and identify survival predictors in adult HNRMS. METHODS: We retrospectively evaluated 42 adult patients (> 16 years) with HNRMS who received radiotherapy (RT)-based treatment at our institute between 2008 and 2022. We analysed the clinical characteristics and prognosis of these patients, including the locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS), using the Kaplan-Meier method. The chi-square and Fisher's exact tests were used to analyse differences between groups for dichotomous and categorical variables, respectively. Survival rates were calculated using the Kaplan-Meier method. Prognostic variables were assessed through univariate Cox analyses. RESULTS: The median patient age was 28 years (range, 16-82 years). Alveolar RMS was the most common histological type, observed in 21 patients (50.0%), followed by embryonal in 16 patients (38.1%). The anatomic sites of origin were orbital in one (2.4%), parameningeal in 26 (61.9%), and non-orbital/non-parameningeal in 15 (35.7%) patients. Nineteen patients (45.2%) had regional lymph node metastasis, and five patients (11.9%) presented with distant metastatic disease. Distant metastasis (n = 17) was the primary cause of treatment failure. At a median follow-up of 47.0 months, the 5-year LRFS, PFS, and OS rates were 69.0%, 39.7%, and 41.0%, respectively. Univariate analysis revealed that tumour size, lymph node involvement, and the local treatment pattern (surgery and RT vs. RT alone) were significant predictors of survival. CONCLUSIONS: The main failure pattern in patients with HNRMS receiving RT-based treatment was distant metastasis. Tumour size > 5 cm and lymph node involvement were predictors of worse LRFS. Multimodality local treatment, combining surgery and RT, is effective and provides survival benefits.

A systematic review of posterior pilon variant fractures.

Posterior pilon variant ankle fractures (PPVF) are a unique subtype of posterior malleolar fractures which have been a source of controversy and confusion in recent years. There has not been a thorough literature review previously written on the topic. Database searches of PubMed and Embase were conducted from inception until June 2023. The key words included "pilon variant," "posterior pilon variant," and "posterior pilon" fractures. Outcomes were evaluated by union time, rates of delayed union, nonunion, malunion, and complication. A total of 15 articles relevant to surgical repair of pilon variant fractures were included in the literature review. The unique mechanism of injury has been reported to involve both rotational and axial forces, leading to involvement of the posterior and medial aspects of the distal tibia. Pilon variant fractures can be suspected by several characteristics on radiographs and have a high confirmation rate via CT images. Multiple systems have been proposed to classify this fracture pattern, but there is no consensus on the ideal classification system. Surgically, direct fixation has shown better short-term clinical outcomes versus indirect fixation or no fixation. PPVF have a distinct fracture pattern involving the posterior and medial columns of the distal tibial plafond, and results from a mechanism intermediate to rotational and axial forces. These fractures are more severe than tri-malleolar fractures due to increased rates of articular impaction and incongruity. Future classification systems should focus on joint surface area and the tibial pilon column involved to avoid confusion with less severe posterior malleolar fractures.

A Comprehensive Analysis of Transcriptomics and Metabolomics Revealed Key Pathways Involved in Saccharum spontaneum Defense against Sporisorium scitamineum.

Sugarcane smut, caused by Sporisorium scitamineum, poses a severe threat to sugarcane production. The genetic basis of sugarcane resistance to S. scitamineum remains elusive. A comparative transcriptomic and metabolomic study was conducted on two wild Saccharum species of S. spontaneum with contrast smut resistance. Following infection, the resistant line exhibited greater down-regulation of genes and metabolites compared to the susceptible line, indicating distinct biological processes. Lignan and lignin biosynthesis and SA signal transduction were activated in the resistant line, while flavonoid biosynthesis and auxin signal transduction were enhanced in the susceptible line. TGA2.2 and ARF14 were identified as playing positive and negative roles, respectively, in plant defense. Exogenous auxin application significantly increased the susceptibility of S. spontaneum to S. scitaminum. This study established the significant switching of defense signaling pathways in contrast-resistant S. spontaneum following S. scitamineum infection, offering a hypothetical model and candidate genes for further research into sugarcane smut disease.

A systematic review of the operative techniques for treating cubitus varus deformity in children.

A systematic review of the operative techniques for treating cubitus varus deformity in children was performed using research databases including PubMed and Embase. Outcome measurements included mean angular correction of the humerus-elbow-wrist angle, complications, revisions and outcome scores. A total of 45 papers and 911 patients were included. Lateral closing wedge osteotomy (LCWO) (427 patients) was the most common procedure and 5.56% of these patients experienced lateral condylar prominence. This technique had the highest revision rate at 3%. The step-cut osteotomy (111 patients) yielded zero postoperative infections or loss of motion. Distraction osteogenesis (92 patients) was the least common technique. Superficial pin tract infections occurred in 18% of patients and 88.04% of patients reported excellent results, the highest of any technique in this study. The infection rate of dome osteotomy (151 patients) was 9.45% and 4.72% of patients experienced loss of motion. 3D osteotomy (130 patients) had no infections, 87.78% of patients reported excellent outcomes, and 2.22% of patients reported poor outcomes, the lowest of all techniques. For unidimensional correction, LCWO provides a technically simple procedure and reasonable outcomes. Step-cut osteotomy has less lateral condylar prominence but is more complicated than LCWO. Distraction osteogenesis is a minimally invasive alternative to LCWO and step-cut osteotomy, but it has more superficial infections and can be bothersome to patients. For a multidimensional correction, 3D osteotomy is superior to dome osteotomy due to its lower infection rate and higher rate of functionally excellent outcomes.

Genome-wide DNase I-hypersensitive site assay reveals distinct genomic distributions and functional features of open chromatin in autopolyploid sugarcane.

The characterization of cis-regulatory DNA elements (CREs) is essential for deciphering the regulation of gene expression in eukaryotes. Although there have been endeavors to identify CREs in plants, the properties of CREs in polyploid genomes are still largely unknown. Here, we conducted the genome-wide identification of DNase I-hypersensitive sites (DHSs) in leaf and stem tissues of the auto-octoploid species Saccharum officinarum. We revealed that DHSs showed highly similar distributions in the genomes of these two S. officinarum tissues. Notably, we observed that approximately 74% of DHSs were located in distal intergenic regions, suggesting considerable differences in the abundance of distal CREs between S. officinarum and other plants. Leaf- and stem-dependent transcriptional regulatory networks were also developed by mining the binding motifs of transcription factors (TFs) from tissue-specific DHSs. Four TEOSINTE BRANCHED 1, CYCLOIDEA, and PCF1 (TCP) TFs (TCP2, TCP4, TCP7, and TCP14) and two ethylene-responsive factors (ERFs) (ERF109 and ERF03) showed strong causal connections with short binding distances from each other, pointing to their possible roles in the regulatory networks of leaf and stem development. Through functional validation in transiently transgenic protoplasts, we isolate a set of tissue-specific promoters. Overall, the DHS maps presented here offer a global view of the potential transcriptional regulatory elements in polyploid sugarcane and can be expected to serve as a valuable resource for both transcriptional network elucidation and genome editing in sugarcane breeding.

Comparison of outcomes of different Graf grades of developmental dysplasia of the hip in infants treated with Tubingen splint versus Pavlik harness - A systematic review.

This systematic review was designed to compare the outcomes of the two braces against each other classified by the Graf method. The databases sources included PubMed, Embase, and Google Scholar. The keywords included "DDH Tubingen versus Pavlik" and Tubingen and Pavlik separately. Included papers provided specific data regarding success and failure rate, avascular necrosis (AVN), duration, and age of intervention. The excluded studies discussed surgeries, diagnosis and mechanism, and ones that weren't in English. Total of 20 papers were included, resulting in 1243 Tubingen and 420 Pavlik samples. It was seen that the Tubingen splint had a statistically significant greater success rate and lower failure rate for Graf 2, D, and 3 hips, while both braces were not very successful for Graf 4 at success rates less than 60 %. Tubingen also had a lower incidence of AVN. Both braces shared similar ages of intervention, duration, and time per day. Both braces are very comparable to each other, each having better success rates for lower Graf grades, which points to the importance of bracing earlier to improve the success rates. The Tubingen splint had a higher success rate, lower failure rate, and lower AVN rate compared to the Pavlik harness. This points to the Tubingen splint potentially being the preferred option for bracing in infants.

Comparison of Risk Factors Between Syndesmotic Screws With and Without Breakage.

Background Screw fixation continues to be a commonly used treatment for syndesmotic disruption; however, screw breakage remains a complication post-fixation. Despite this complication, investigation on the variability of surgical placement in conjunction with syndesmotic screw characteristics affecting breakage has not been fully elucidated. The purpose of this study is to compare patients with syndesmotic screw breakage versus those with intact screws based on surgically controlled variables. Methods A total of 176 patients and 260 syndesmotic screws were included in the study, 88 patients each with and without broken syndesmotic screws. A retrospective analysis of patients who underwent syndesmotic screw fixation was performed. Patients with syndesmotic screw breakage were compared to those with intact screws. Screw width and length, the number of screws used, fracture type, and the number of cortices for fixation were all collected. Further analysis included radiographic measurement of syndesmotic screw angle and height of placement above the tibial plafond. Results Decreased screw width, increased number of screws used, and younger age were all associated with increased rates of screw breakage (p < .001, p = .019, p = 0.020). No statistical difference was appreciated between groups based on screw length, number of cortices used, or angle relative to the tibial plafond (p = .2432, p = .4699, p = .9233). Conclusion Higher placement of syndesmotic screws above the tibiotalar joint, specifically greater than 20 mm above the tibial plafond, increases the screw breakage rate. Decreased screw width, increasing numbers of screws used, and younger age were all also associated with increased rates of screw breakage. No difference was appreciated based on the screw angle relative to the tibial plafond.

Phase 1 clinical trial to assess safety and efficacy of NY-ESO-1-specific TCR T cells in HLA-A∗02:01 patients with advanced soft tissue sarcoma.

New York esophageal squamous cell carcinoma-1 (NY-ESO-1)-specific T cell receptor (TCR) T cell therapy is effective in tumors with NY-ESO-1 expression, but a safe and effective TCR-T cell therapeutic protocol remains to be improved. Here, we report a phase 1 investigational new drug clinical trial with TCR affinity-enhanced specific T cell therapy (TAEST16001) for targeting NY-ESO-1. Enrolled patients receive TAEST16001 cell infusion after dose-reduced lymphodepletion with cyclophosphamide (15 mg/kg/day × 3 days) combined with fludarabine (20 mg/m2/day × 3 days), and the TCR-T cells are maintained with low doses of interleukin-2 injection post-adoptive transfer. Analysis of 12 patients treated with the regimen demonstrates no treatment-related serious adverse events. The overall response rate is 41.7%. The median progression-free survival is 7.2 months, and the median duration of response is 13.1 months. The protocol of TAEST16001 cells delivers a safe and highly effective treatment for patients with advanced soft tissue sarcoma (ClinicalTrials.gov: NCT04318964).

Design of phenothiazine-based cationic amphiphilic derivatives incorporating arginine residues: Potential membrane-active broad-spectrum antimicrobials combating pathogenic bacteria in vitro and in vivo.

Multidrug-resistant bacteria infections pose an increasingly serious threat to human health, and the development of antimicrobials is far from meeting the clinical demand. It is urgent to discover and develop novel antibiotics to combat bacterial resistance. Currently, the development of membrane active antimicrobial agents is an attractive strategy to cope with antimicrobial resistance issues. In this study, the synthesis and biological evaluation of cationic amphiphilic phenothiazine-based derivatives were reported. Among them, the most promising compound 30 bearing a n-heptyl group and two arginine residues displayed potent bactericidal activity against both Gram-positive (MICs = 1.56 µg/mL) and Gram-negative bacteria (MICs = 3.125-6.25 µg/mL). Compound 30 showed low hemolysis activity (HC50 = 281.4 ± 1.6 µg/mL) and low cytotoxicity (CC50 ＞ 50 µg/mL) toward mammalian cells, as well as excellent salt resistance. Compound 30 rapidly killed bacteria by acting on the bacterial cell membrane and appeared less prone to resistance. Importantly, compound 30 showed potent in vivo efficacy in a murine model of bacterial keratitis. Hence, the results suggested compound 30 has a promising prospect as a broad-spectrum antibacterial agent for the treatment of drug-resistant bacterial infections.

Evaluation of Humeral Shaft Fracture Outcomes by Treatment Method: A Systematic Review and Meta-analysis Based on Comparison Studies.

BACKGROUND: The purpose of this systematic review and meta-analysis was to evaluate various outcomes of humeral shaft fractures treated with different treatment methods, which included functional bracing, open reduction and internal fixation, intramedullary nailing, and locked compression plate. METHODS: A systematic review was performed using research databases including PubMed, EMBASE, and Google Scholar. Keywords relating to treatment of humeral shaft fractures were used, and comparison studies that reported patient characteristics and outcomes, including nonunion, malunion, function scores, and complications, were included. One hundred fourteen records were screened, with 18 studies ultimately included in the meta-analysis. Treatment groups were consolidated into brace or surgery and then further categorized into subgroups based on surgical technique used. Postoperative events, complications, and functional scores were compared among the treatment groups. Statistical analysis for this study was conducted using Review Manager 5.3, with a standard p-value of ≤0.05 for statistical significance. RESULTS: Eighteen studies were included in this review with a total of 706 patients. Z-tests showed that risks of revision, nonunion, and malunion were higher in the brace treatment group compared with the surgical treatment group (p < 0.0001, <0.0001, 0.004, respectively). Risk of infection was expectedly higher in the surgical group compared with the brace group (p = 0.04). Radial nerve injury rates were also higher in the unspecified surgical group compared with the brace group (p = 0.01). In the surgical group, the mean Constant shoulder score was also significantly higher than that in the brace group (p = 0.004). When comparing the nail and plate groups, Z-tests revealed higher risks of delayed unions and other complications in the nail group (p = 0.04 and 0.001, respectively) but higher risk of infection in the plate group (p = 0.05). CONCLUSION: The conservative treatment of humeral shaft fractures with functional braces may be associated with a lower incidence of infection and nerve injury when compared with operative treatment methods. However, nonoperative treatment may also come with higher risks of revision, nonunion, and malunion than the many available surgical modalities. Operative management with either intramedullary nail or plate has shown to be a reliable method of management with reasonable outcomes for humeral shaft fractures. While the nail group had higher risk of delayed unions and other complications, the plate group had higher risk of infections. Both nail and plate surgical treatments have shown to result in high union rates and should be considered by the surgeon on a case-by-case basis when treating humeral shaft fractures. LEVEL OF EVIDENCE: Level I. See Instructions for Authors for a complete description of levels of evidence.

Butein Inhibits the Glycation of α-Crystallin: An Approach in Prevention of Retinopathy.

The aggregation of lens proteins induced by glycation is one of the key drivers of diabetic retinopathy and development of diabetic cataracts. Moreover, glycation also causes numerous alterations not only to the tertiary structure of lens proteins but also to serum proteins. There are also evidences of covalent crosslinking among lens crystallins resulting in development of cataract. In this article, the inhibitory potential of butein was tested against the glucose induced glycation and the aggregation α-crystallin (α-cry). The results showed that there was inhibition of advanced glycation products (78.28%) and early glycation products (86.30%) following the treatment of butein. Additionally, the presence of butein caused a significant improvement in the tested biochemical markers of glycation. The treatment with butein reduced the free lysine modification to 23.67%. The secondary and tertiary structural distortions of α-cry were also protected. The mechanism of inhibition further investigated at the molecular level using biophysical and computational techniques. The interaction data showed the butein exhibited strong affinity towards the α-cry. The binding event was entropically driven and energetically favourable. The Gibb's free energy of the interaction was found to be -5.99 to -7.17 kcal mol-1. The binding site of butein in α-cry was deciphered by molecular docking and the dynamics was studied using molecular dynamics (MD) simulations. The simulation data showed that butein formed stable complex with α-cry under physiological conditions. Most of the tested parameters from molecular simulations, such as secondary structure, was found to be stable. The data clearly show the potential of butein in inhibiting the glycation induced aggregation of α-cry and hence can be developed as useful inhibitor in the management of diabetic cataract and retinopathy.

Haplotype variations of sucrose phosphate synthase B gene among sugarcane accessions with different sucrose content.

BACKGROUND: Sucrose phosphate synthase B (SPSB) gene encoding an important rate-limiting enzyme for sucrose synthesis in sugarcane is mainly expressed on leaves, where its alleles control sucrose synthesis. In this study, genetic variation of SPSB gene represented by different haplotypes in sugarcane was investigated in hybrid clones with high and low sugar content and various accessory species. RESULTS: A total of 39 haplotypes of SPSB gene with 2, 824 bp in size were identified from 18 sugarcane accessions. These haplotypes mainly distributed on Chr3B, Chr3C, and Chr3D according to the AP85-441 reference genome. Single nucleotide polymorphisms (SNPs) and insertion/deletion (InDels) were very dense (42 bp/sequence variation) including 44 transitional and 23 transversional SNPs among the 39 haplotypes. The sequence diversity related Hd, Eta, and Pi values were all lower in clones of high sucrose content (HS) than those in clones of low sucrose content (LS). The evolutionary network analysis showed that about half SPSB haplotypes (19 out of 39) were clustered into one group, including 6 (HAP4, HAP6, HAP7, HAP9, HAP17 and HAP20) haplotypes under positive selection in comparison to HAP26 identified in Badila (S. officinarum), an ancestry noble cane species and under purification selection (except HAP19 under neutral selection) in comparison to HAP18 identified from India1 (S. spontaneum), an ancestry species with low sugar content but high stress tolerance. The average number of haplotypes under positive selection in HS clones was twice as that in LS. Most of the SNPs and InDels sequence variation sites were positively correlated with sucrose and fiber content and negatively correlated with reducing sugar. CONCLUSIONS: A total of 39 haplotypes of SPSB gene were identified in this study. Haplotypes potentially associated with high sucrose synthesis efficiency were identified. The mutations of SPSB haplotypes in HS were favorable and tended to be selected and fixed. The results of this study are informative and beneficial to the molecular assisted breeding of sucrose synthesis in sugarcane in the future.

99mTc-Rituximab sentinel lymph node mapping and biopsy, the effective technique avoids axillary dissection and predicts prognosis in 533 cutaneous melanoma.

OBJECTIVE: To evaluate the efficiency of a novel lymph node radiotracer 99mTc-rituximab in sentinel lymph node (SLN) lymphoscintigraphy and SLN biopsy (SLNB), and the influence of SLNB results on the prognosis of cutaneous malignant melanoma (CMM) patients. METHODS: A retrospective study was performed on 533 patients with CMM who underwent lymphoscintigraphy and SLNB. All patients received a preoperative peritumoral injection of 11.1-18.5 MBq of 99mTc-rituximab 0.5 to 1 h before lymphoscintigraphy and SLNB. RESULTS: The detection rate of lymphoscintigraphy and SLNB was both 99.81% (532/533), and the average number of detected SLNs was 2.1 (range 1 to 8) and 2.7 (range 1 to 11) per patient, respectively. 12.1% SLNs and 22.2% patients were found metastatic, with an average of 1.5 (range 1 to 5) metastatic SLNs per patient. The SLN metastatic rates were different in patients with different Breslow thickness, Clark levels, ulceration, mitotic counts, and HMB45 expression (p < 0.05). Ninety patients were proceeded with the regional lymph node dissection (RLND) after SLNB, and the sensitivity, specificity and accuracy of SLNB in metastatic diagnosis is 97.4, 100 and 96.7%, respectively. And SLNs with metastases was an independent prognostic factor for OS and PFS by multivariate prognostic analyses (HR was 5.9 and 4.3, p < 0.001). For patients with metastatic SLNs, the non-SLNs with metastasis and non-SLNs without metastasis in RLND, and observation groups showed different mean PFS as 14.9, 24.8 and 25.5 months (p = 0.018), but no statistically significant difference existed in the OS. CONCLUSION: The novel radiotracer 99mTc-rituximab could identify SLNs specifically in SLN lymphoscintigraphy and SLNB in CMM patients, and the pathology obtained from SLNB rather than from RLND better indicated the staging and long-term prognosis.

A narrative review of the pharmaceutical management of osteoporosis.

Background and Objective: Osteoporosis is a skeletal disorder classified by the loss of bone density in older adults leading to compromised bone strength and an increased risk of fracture. It can be divided into categories based on its etiology: senile, post-menopausal, and secondary osteoporosis. Specific prevention measures and treatments exist for targeting bone loss. Here we review and summarize the literature regarding the presentation of osteoporosis and discuss pharmaceutical therapies. Methods: PubMed and Google Scholar were searched for articles published in English between 1980 and 2021. Search terms combined "senile osteoporosis", "osteoporosis treatment", "osteoporosis", "bisphosphonates", "denosumab", types of hormone therapy, and other relevant keywords used in various combinations. Key Content and Findings: Osteoporosis affects millions but often goes undiagnosed until a pathologic fracture. Dual-energy X-ray absorptiometry (DEXA) scans evaluate bone mineral density (BMD) and are a diagnostic tool for osteoporosis. Adults over the age of 65, post-menopausal women, and those with risk factors such as previous fractures are recommended to receive DEXA scans every one to two years. Bisphosphonates, denosumab, and hormonal therapies are among the most common pharmacologic treatments for osteoporosis. Conclusions: Daily, orally administered bisphosphonates are the first-line therapy for osteoporosis given their efficacy in decreasing fracture risk and favorable safety profile. Denosumab is an alternative that is administered subcutaneously every six months and may be given as initial therapy to select patients. Hormonal therapies are used if patients cannot tolerate bisphosphonates or denosumab or are refractory to these medications. Preventative measures for osteoporosis include tailored exercise and sufficient intake of calcium and vitamin D via diet or supplementation.

Management of Syndesmosis Injury: A Narrative Review.

The syndesmosis is an important fibrous joint that plays a crucial role in normal ankle weight-bearing and movements. Syndesmosis injuries include disruption of one or more of the ligaments comprising the distal tibiofibular syndesmosis and are commonly associated with ankle fractures. The treatment of grade 1 syndesmosis injury should be conservative, such as immobilization for one to three weeks followed by gradual return to activity. For the treatment of grade 2 syndesmosis injury, if it was stable enough, the patients still could be managed with conservative therapies. But majority of them strongly favor surgical treatment. For the treatment of grade 3 syndesmosis injury, it should treat with surgical reconstruction. If syndesmosis injury is associated with ankle fractures, surgical reduction, fixation, and reconstruction are usually required. Common surgical treatment methods include syndesmosis screws, composed of either metallic or bioabsorbable material; fibula intramedullary nails; and dynamic button-suture fixation, TightRope or ZipTight. Each method has advantages and disadvantages which must be considered while determining which treatment will provide the best outcomes depending on the patient's needs. Continued exploration of new materials, devices, and methods for surgical fixation is necessary for advancement in this field.

Membrane-Active Nonivamide Derivatives as Effective Broad-Spectrum Antimicrobials: Rational Design, Synthesis, and Biological Evaluation.

Antibiotic resistance is emerging as a "global public health concern". To address the growing epidemic of multidrug-resistant pathogens, the development of novel antimicrobials is urgently needed. In this study, by biomimicking cationic antibacterial peptides, we designed and synthesized a series of new membrane-active nonivamide and capsaicin derivatives as peptidomimetic antimicrobials. Through modulating charge/hydrophobicity balance and rationalizing structure-activity relationships of these peptidomimetics, compound 51 was identified as the lead compound. Compound 51 exhibited potent antibacterial activity against both Gram-positive bacteria (MICs = 0.39-0.78 µg/mL) and Gram-negative bacteria (MICs = 1.56-6.25 µg/mL), with low hemolytic activity and low cytotoxicity. Compound 51 displayed a faster bactericidal action through a membrane-disruptive mechanism and avoided bacterial resistance development. Furthermore, compound 51 significantly reduced the microbial burden in a murine model of keratitis infected by Staphylococcus aureus or Pseudomonas aeruginosa. Hence, this design strategy can provide a promising and effective solution to overcome antibiotic resistance.

Clinical features and therapeutic outcomes of alveolar soft part sarcoma in children: A single-center, retrospective study.

Background: Alveolar soft part sarcoma (ASPS) is a rare sarcoma that has been shown to be highly effective to antiangiogenic agents and immune checkpoint inhibitors, but most reported studies about ASPS were concentrated on adult population. In this study, we aimed to describe the clinical features and therapeutic outcomes of ASPS in children. Methods: We retrospectively reviewed the records of patients with ASPS in our institution since Jan 2015. All patients included in this study were pathologically confirmed ASPS and aged under 12 years at the time of initial diagnosis. Demographic characteristics, tumor sizes, primary tumor sites, metastasis, treatments used, therapeutic responses and survivals were evaluated. Results: We identified a total of 56 patients to be initially diagnosed as ASPS since Jan 2015. A predisposition of high occurrence in head and neck (32.1%) was observed (versus 41.1% in limbs and 21.4% in trunk). 26 (46.4%) patients developed metastasis at the time of diagnosis or during follow-up. Tumors in tongue, pharynx and larynx had the least likelihood to metastasize (7.7%, P<0.05). Observation was recommended for 15 stage IV patients with only pulmonary metastasis. 7 (46.7%) patients remained stable until last follow up. The 1-year PFS rate was 83.3% and median progression-free survival time (PFS) was 29.4 months. 15 patients with progressive disease received mono or combined therapy. 11 patients received PD-1 monotherapy. 2 patients achieved partial response and 5 stable disease. The overall response rate was 18.2%. The median PFS of this group was 22.0 months, and the 1-year PFS rate was 70.0%. 4 patients received a combination therapy of PD-1 inhibitors plus tyrosine kinase inhibitors. All of them remained stable. No disease-related death occurred during follow-up. Conclusions: ASPS exhibits a higher occurrence in head and neck in children. ASPS originating from glossopharyngeal region tends to have a lower metastasis rate. ASPS displays a more indolent growth pattern in children, which makes observation a preferable choice for children with sole pulmonary metastasis. Pediatric ASPS appears to be less effective to targeted therapy and immunotherapy than adults. The treatment of progressive ASPS in children remains challenging.