bluuebunny/crossref_metadata_2025 huggingface dataset:
Distractor Application and Dry Arthroscopy to Improve Articular Visualization During Scapula Fracture Surgery Via a Posterior Approach
Authors: Saiz Augustine M. , Mayer Ryan , Kellam Patrick J. , Schultz Blake J. , Cunningham Bryce , Warner Stephen J. , Choo Andrew
Published: February 2023

Intra-articular glenoid displacement is an indication for open reduction and internal fixation of scapular fractures. However, direct visualization of the glenoid is limited, and articular reductions are typically performed and assessed using extra-articular cortical reduction reads and fluoroscopic imaging. In this technique, we describe the application of a distractor for direct visualization of the glenoid articular surface. In this way, anatomic reduction of the glenoid articular surface can be assessed and achieved. In addition, we discuss the use of a portable, dry arthroscopy when needed. This technique has resulted in good-to-excellent articular reductions by adjusting extra-articular reads that seemed adequate before intra-articular visualization. This technique is safe, requires minimal extra set-up or instruments, and results in good-to-excellent articular reductions.
Surgeon-Estimated Blood Loss Is Discordant With Calculated Blood Loss in Acetabular and Pelvic Fracture Surgery
Authors: Lindsay Sarah E. , McKibben Natasha , Yang Qian , Zusman Natalie Lacey , Friess Darin M. , Working Zachary Mark
Published: February 2023

Objectives:

To compare blood loss as estimated by surgeon-estimated blood loss (EBL), the Gross formula, and the HB equation in open pelvic and acetabular surgery.

Design:

Retrospective cohort study.

Setting:

Single Level I academic trauma center.

Patients:

We included 710 patients 18–89 years of age who underwent acetabular or pelvic surgery between 2008 and 2018 for the management of fracture.

Intervention:

Surgical treatment for the management of acetabular or pelvic fracture and blood transfusion when deemed clinically appropriate in the perioperative setting.

Main Outcome Measures:

Surgeon EBL and calculated blood loss (using the Gross formula, a Gross formula derivative, and the HB equation with both Moore and Nadler blood volume estimations).

Results:

One hundred ninety-two patients (27%) received intraoperative blood transfusions. Surgeon EBL significantly differed from all formulas except the Gross/Nadler and the modified Gross/Nadler calculations. Gross and HB calculation methods yielded similar results in the overall cohort but yielded significantly different results in the subgroup analysis. Use of a corrective transfusion factor mildly improved correlation of the Gross equation with EBL. At high levels of blood loss, surgeon EBL predictions became more discordant with calculated blood loss values. When assessing only patients who did not receive transfusions, concordance improved.

Conclusion:

Blood loss in pelvic and acetabular surgery is challenging to quantify, and this study demonstrates discordance between formula predictions and surgeon-estimated blood loss. At higher levels of blood loss, this discrepancy worsens. This exploratory study highlights the need for the development of improved methods of quantifying blood loss in orthopaedic trauma surgery.

Level of Evidence:

Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Free Vascularized Fibula Graft for Staged Reconstruction of Infected Humerus Nonunions
Authors: Lefebvre Rachel , Bougioukli Sofia , Marecek Geoffrey , Howard Mark , Cohen Landon , Stevanovic Milan
Published: February 2023

Objective:

To evaluate the union rate and rate of postoperative complications in patients with septic nonunions of the humerus after a two-stage reconstruction using a free vascularized fibula graft.

Design:

Retrospective case series.

Setting:

Academic, tertiary referral center.

Patients/Participants:

Adult patients with staged reconstruction for infected nonunion of the humerus with at least 2 years follow-up after vascularized fibula graft transfer.

Intervention:

First, infected nonunion debridement with antibiotic spacer and external fixator placement. After antimicrobial treatment, free vascularized fibula transfer with internal fixation.

Main Outcome Measurements:

Time to union, pain, affected extremity range of motion, and function.

Results:

10 patients with septic humerus nonunion treated with staged reconstruction using a free vascularized fibula graft, with a mean follow-up of 32.3 months were included. After the two-stage reconstruction using a free fibula, radiographic union was achieved in 6/10 patients, with a mean time to union of 19.9 weeks. The remaining 4 patients required an additional procedure with graft augmentation and/or implant revision. After the revision procedure, union was noted in 3/4 patients, 21 weeks postoperatively. Mean patient visual analog scale pain scores improved from 5.8 preoperatively to 0.9 at final follow-up (P = 0.02). Postoperatively, mean elbow flexion was 110 ± 20 degrees and extension 15 ± 7.5 degrees.

Conclusion:

A two-stage reconstruction using a free fibula graft can be used in patients with septic nonunions of the humerus in the setting of multiple failed prior surgeries and compromised local biology. Additional procedures may be needed in some to achieve final union.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Effects of Technical Errors on the Outcomes of Operatively Managed Femoral Neck Fractures in Adults Less than 50 Years of Age
Authors: Collinge Cory A. , Finlay Andrea , Harris Payton , Rodriguez-Buitrago Andres , de la Fuente Guadalupe , Beltran Michael , Mitchell Phillip , Archdeacon Michael , Tornetta Paul , Mir Hassan R. , Gardner Michael , Sagi H. Claude , LeBus George F. , Cannada Lisa K. , Smyth Brooke ,   and Young Femoral Neck Fracture Working Group
Published: February 2023

Objective:

To evaluate the effect of technical errors (TEs) on the outcomes after repair of femoral neck fractures in young adults.

Design:

Multicenter retrospective clinical study.

Setting:

26 North American Level 1 Trauma Centers.

Patients:

Skeletally mature patients younger than 50 years of age with 492 femoral neck fractures treated between 2005 and 2017.

Intervention:

Operative repair of femoral neck fracture.

Main Outcome Measurements:

The association between TE (malreduction and deviation from optimal technique) and treatment failure (fixation failure, nonunion, malunion, osteonecrosis, malunion, and revision surgery) were examined using logistic regression analysis.

Results:

Overall, a TE was observed in 50% (n = 245/492) of operatively managed femoral neck fractures in young patients. Two or more TEs were observed in 10% of displaced fractures. Treatment failure in displaced fractures occurred in 27% of cases without a TE, 56% of cases with 1 TE, and 86% of cases with 2 or more TEs. TEs were encountered less frequently in treatment of nondisplaced fractures compared with displaced fractures (39% vs. 53%, P < 0.001). Although TE(s) in nondisplaced fractures increased the risk of treatment failure and/or major reconstructive surgery (22% vs. 9%, P < 0.001), they were less frequently associated with treatment failure when compared with displaced fractures with a TE (22% vs. 69% P < 0.001).

Conclusions:

TEs were found in half of all femoral neck fractures in young adults undergoing operative repair. Both the occurrence and number of TEs were associated with an increased risk for failure of treatment. Preoperative planning for thoughtful and well-executed reduction and fixation techniques should lead to improved outcomes for young patients with femoral neck fractures. This study should also highlight the need for educational forums to address this subject.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Gender Diversity, Leadership, Promotion, and Opportunity Among the Members of the Orthopaedic Trauma Association (OTA)
Authors: Murphy Lynn , Miller Anna N. , Vallier Heather A. , Roffey Darren M. , Lefaivre Kelly A.
Published: February 2023

Objectives:

To demonstrate the gender distribution in leadership positions and academic promotion of Orthopaedic Trauma Association (OTA) members.

Methods:

We conducted a cross-sectional examination of the 2020–2021 OTA membership cohort dataset provided by the OTA. Professional and academic information of OTA members at their site of appointment was also abstracted from publicly available online resources. Data included: gender, OTA membership category, OTA leadership position, trauma fellowship completion, trauma practice setting, level of trauma center, percentage of trauma work, year of first practice, academic rank, and university/hospital/institutional leadership role. Statistical analysis included chi-squared, Wilcoxon two-sample, and Fisher exact tests.

Results:

2608 OTA members were identified; 14.1% were women. Female representation was highest in the Trauma Practice Professional category (67.1%) and significantly lower in the Active category (9.1%) (P < 0.0001). No statistically significant gender differences were observed regarding level of trauma center, percentage of trauma work, or trauma practice setting. In the Active, Clinical and Emeritus categories, men achieved a higher level of academic rank than women at their site of employment (P = 0.003), while more men completed trauma fellowships (P = 0.004) and had been in practice for significantly longer (P < 0.0001). Men held more of the highest leadership positions (eg, Board of Directors) (P = 0.0047) and the greatest number of leadership positions (P = 0.017) within the OTA compared with women.

Conclusion:

Gender disparity exists within the upper echelon of leadership and academic representation in orthopaedic trauma. Our findings will help inform strategic policies to address gender diversity within the OTA and the broader orthopaedic trauma subspecialty.
Transtibial Amputation With Fibulectomy and Fibular Collateral Ligament-Biceps Reconstruction: Surgical Technique and Clinical Experience
Authors: Harrington Colin J. , Kaplan Shane A. , Richards John T. , Smith Douglas G. , Souza Jason M. , Potter Benjamin K.
Published: February 2023

Objectives:

To describe our clinical experience and surgical technique of transtibial amputation with fibulectomy and fibular collateral ligament-biceps reconstruction for management of, particularly short, transtibial amputations with proximal fibula prominence, overt instability, or inadequate soft-tissue coverage.

Design:

Retrospective review.

Setting:

Level II trauma center.

Patients:

Twelve consecutive patients who underwent transtibial amputation with fibulectomy and fibular collateral ligament-biceps reconstruction between 2008 and 2021.

Intervention:

We reviewed patient medical records, radiographs, and clinical photographs.

Main Outcome Measurements:

Complications, instability, and pain.

Results:

Eight patients underwent acute transtibial amputation with fibulectomy and reconstruction, whereas 4 patients underwent amputation revision with fibulectomy and reconstruction for chronic pain. All 12 patients were men, with a median age of 39 years (interquartile range, 33–46). All injuries were due to high-energy mechanisms, including improvised explosive device (n = 8), rocket-propelled grenade (n = 2), gunshot wound (n = 1), and motor vehicle accident (n = 1). After a median follow-up of 8.5 years (interquartile range, 3.4–9.3), there was one complication, a postoperative suture abscess. No patients had subjective lateral knee instability after the procedure, and the average pain scores decreased from 4.75 to 1.54 (P = 0.01). All patients returned to regular prosthesis wear and maintained independent functioning with activities of daily living.

Conclusions:

Our experience with fibulectomy and fibular collateral ligament-biceps reconstruction demonstrated no subjective or clinical postoperative instability and may be a useful adjunct for managing transtibial amputations with fibular instability or prominence, pain, or skin breakdown at the fibular head.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
An Acute Fixation Protocol for High-Energy Tibial Plateau Fractures Decreases Time to Fixation and Lowers Operative Costs Without Affecting Wound Complications and Reoperations
Authors: Kim Ye Joon , Scott Tyler , Richard Raveesh D. , Parry Joshua A.
Published: February 2023

Objectives:

To investigate whether an acute fixation protocol for high-energy tibial plateau fractures increases the rate of wound complications.

Design:

Retrospective comparative study.

Setting:

Urban level 1 trauma center.

Patients/Participants:

One hundred thirty-four patients with high-energy tibial plateau fractures (OTA/AO 41B/C [Schatzker VI/V/VI]) treated with open reduction and internal fixation (ORIF).

Intervention:

Utilization of an acute ORIF (<48 hours) versus delayed ORIF protocol.

Main Outcome Measure:

Primary outcomes: wound complications (wound dehiscence/necrosis, superficial/deep infections) and reoperations. Secondary outcomes: total operative costs and hospital length of stay.

Results:

Overall, 83.9% (26/31) of patients received definitive fixation within 48 hours under the acute ORIF protocol versus 18.4% (19/103) of patients treated under the standard delayed protocol with no observed differences in the rate of wound complications (proportional difference (PD) −4.6%, confidence interval (CI) −17.2% to 11.3%; P = 0.78) or reoperations (PD 2.0%, CI, 13.0% to 12.5%; P = 1.00). The acute ORIF protocol lowered operative costs (median difference (MD) $-2.563.00, CI, 3021.00 to −1661.00; P < 0.001) and hospital length of stay (MD 4.0 days, CI, 6.0–1.0; P = 0.001). On multivariate analysis, wound complications were associated with increasing age (odds ratio (OR) 1.05, CI, 1.01–1.10; P = 0.01) and tobacco use (OR 3.75, CI, 1.19–11.82; P = 0.02).

Conclusion:

An acute ORIF protocol for high-energy tibial plateau fractures decreased time to fixation and lowered operative costs without increasing the risk of wound complications or reoperations.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Art and Pediatric Orthopaedics: “Arm-twisting” by Wyspianski, the Poet, Actor, and Artist
Authors: Alagar Jayalakshmi N. , Rebello Gleeson , Joseph Benjamin
Published: February 2023

Stanislaw Wyspianski, a multifaceted Polish artist painted “A Girl with a Red Hat”, which portrays a young girl with an obviously deformed right upper limb. The pattern of deformities is suggestive of either athetoid hemiplegic cerebral palsy or Erb’s palsy.
Variability in Pain Management Practices for Pediatric Anterior Cruciate Ligament Reconstruction
Authors: Wagner K. John , Beck Jennifer J. , Carsen Sasha , Crepeau Allison E. , Cruz Aristides I. , Ellis Henry B. , Mayer Stephanie W. , Niu Emily , Pennock Andrew T. , Stinson Zachary S. , VandenBerg Curtis , Ellington Matthew D.
Published: February 2023

Background:

The opioid epidemic in the United States is a public health crisis. Pediatric orthopaedic surgeons must balance adequate pain management with minimizing the risk of opioid misuse or dependence. There is limited data available to guide pain management for anterior cruciate ligament reconstruction (ACLR) in the pediatric population. The purpose of this study was to survey current pain management practices for ACLR among pediatric orthopaedic surgeons.

Methods:

A cross-sectional survey study was conducted, in which orthopaedic surgeons were asked about their pain management practices for pediatric ACLR. The voluntary survey was sent to members of the Pediatric Orthopaedic Society of North America. Inclusion criteria required that the surgeon perform anterior cruciate ligament repair or reconstruction on patients under age 18. Responses were anonymous and consisted of surgeon demographics, training, practice, and pain management strategies. Survey data were assessed using descriptive statistics.

Results:

Of 64 included responses, the average age of the survey respondent was 48.9 years, 84.4% were males, and 31.3% practiced in the southern region of the United States. Preoperative analgesia was utilized by 39.1%, 90.6% utilized perioperative blocks, and 89.1% prescribed opioid medication postoperatively. For scheduled non-narcotic medications postoperatively 82.8% routinely advocated and 93.8% recommended cryotherapy postoperatively.

Acetaminophen was the most used preoperative medication (31.3%), the most common perioperative block was an adductor canal block (81.0%), and the most common postoperative analgesic medication was ibuprofen (60.9%). Prior training or experience was more frequently reported than published research as a primary factor influencing pain management protocols.

Conclusions:

Substantial variability exists in pain management practices in pediatric ACLR. There is a need for more evidence-based practice guidelines regarding pain management.

Level of Evidence:

Level V
Does Transitioning to a Brace Improve HRQoL After Casting for Early Onset Scoliosis?
Authors: Henstenburg Jeffrey , Heard Jeremy , Sturm Peter , Blakemore Laurel , Li Ying , Ihnow Stephanie B. ,   Pediatric Spine Study Group, Shah Suken A.
Published: February 2023

Background:

Serial casting is favored for the initial treatment of early onset scoliosis (EOS), but there is concern about significant morbidity and caregiver burden. Studies have examined the utility of bracing as an alternative to casting, but little is known about differences in health-related quality of life (HRQoL) between treatments. We hypothesized that patients with a diagnosis of idiopathic EOS experience an improvement in HRQoL when transitioning from serial casting to bracing as measured by the 24-Item Early Onset Scoliosis Questionnaire (EOSQ).

Methods:

Subjects with idiopathic EOS were retrospectively identified from a multicenter database. EOSQ scores were compared before treatment, after index casting, after transition out of cast to brace, and at the most recent follow-up. Available major curve magnitudes were also compared during these time points. Data were compared using repeated-measures ANOVA with post hoc Bonferroni correction.

Results:

Sixty-six subjects met the inclusion criteria. Thirty-seven (56%) subjects were male and the average age at the time of index treatment was 1.9 (0.37-6.4) years. The average follow-up was 3.2 (0.90-6.8) years. In 57 subjects, the major curve magnitude improved from a mean of 33 (CI 28-37) degrees before treatment initiation to 27 (CI 23-30) degrees after casting and to 24 (CI 20-29) degrees at the most recent follow-up. The HRQoL subdomain showed a significant decrease in HRQoL during casting treatment 75.7 (CI 72.9-78.5) from pre-index treatment 84.9 (CI 81.4-88.5), during brace treatment 84.8 (CI 81.8-88.0) and at most recent follow-up 87.0 (CI 83.6-90.3) (P<0.001). The parental impact subdomain improved from the beginning to the end of treatment (77.7 to 87.7, P=0.001) (n=64). Satisfaction improved from casting to bracing (73.4 to 86.7, P<0.001) (n=63) and to the most recent follow-up (73.4 to 87.9, P<0.001).

Conclusion:

Patients treated with casting for EOS experience reversible declines in HRQoL. After patients transition from casting to bracing, EOSQ scores recover to pretreatment baseline levels and are maintained at follow-up. This information must be balanced with the effectiveness of treatment for EOS with either method and customized for each patient.

Level of Evidence:

Level III—retrospective comparative study.
Previous Emergency Department Admission Is Associated With Increased 90-Day Readmission Following Cervical Spine Surgery
Authors: Amakiri Uchechukwu O. , Dominy Calista , Kumar Anish , Arvind Varun , Pitaro Nicholas L. , Kim Jun S. , Cho Samuel K.
Published: February 2023

Study Design:

This was a retrospective case-control study.

Objective:

The objective of this study was to evaluate whether prior emergency department admission was associated with an increased risk for 90-day readmission following elective cervical spinal fusion.

Summary of Background Data:

The incidence of cervical spine fusion reoperations has increased, necessitating the improvement of patient outcomes following surgery. Currently, there are no studies assessing the impact of emergency department visits before surgery on the risk of 90-day readmission following elective cervical spine surgery. This study aimed to fill this gap and identify a novel risk factor for readmission following elective cervical fusion.

Methods:

The 2016–2018 Nationwide Readmissions Database was queried for patients aged 18 years and older who underwent an elective cervical fusion. Prior emergency admissions were defined using the variable HCUP_ED in the Nationwide Readmissions Database database. Univariate analysis of patient demographic details, comorbidities, discharge disposition, and perioperative complication was evaluated using a χ2 test followed by multivariate logistic regression.

Results:

In all, 2766 patients fit the inclusion criteria, and 18.62% of patients were readmitted within 90 days. Intraoperative complications, gastrointestinal complications, valvular, uncomplicated hypertension, peripheral vascular disorders, chronic obstructive pulmonary disease, cancer, and experiencing less than 3 Charlson comorbidities were identified as independent predictors of 90-day readmission. Patients with greater than 3 Charlson comorbidities (OR=0.04, 95% CI 0.01–0.12, P<0.001) and neurological complications (OR=0.29, 95% CI 0.10–0.86, P=0.026) had decreased odds for 90-day readmission. Importantly, previous emergency department visits within the calendar year before surgery were a new independent predictor of 90-day readmission (OR=9.74, 95% CI 6.86–13.83, P<0.001).

Conclusions:

A positive association exists between emergency department admission history and 90-day readmission following elective cervical fusion. Screening cervical fusion patients for this history and optimizing outcomes in those patients may reduce 90-day readmission rates.
Comparison of Endoscopic and Minimally Invasive Transforaminal Lumbar Interbody Fusion for Lumbar Degenerative Diseases
Authors: Xiao Shanwen , Zhou Shufang , Pan Shixin , Ning Jinpei , Gan Xiutian , Guan Yanhua
Published: February 2023

Study Design:

Systematic review and meta-analysis.

Objective:

To compare the results of endoscopic transforaminal lumbar interbody fusion (Endo-TLIF) and minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for patients with lumbar degenerative diseases.

Summary of Background Data:

The MIS-TLIF has been widely used in lumbar degenerative diseases and achieved favorable clinical effects. The main disadvantage is the limited working space and visualization, especially in the deeper operational field, for preparing fusion bed. In recent years, with the development of surgical techniques, optical technology, and special instruments, Endo-TLIF has gradually been applied.

Materials and Methods:

A systematic review and meta-analysis of cohort studies between Endo-TLIF and MIS-TLIF in the lumbar degenerative diseases. The following outcome measures were extracted: visual analog scale (VAS), Oswestry Disability Index, fusion rate, disk height, segmental lordosis, operative time, length of hospital stay and complications. Data analysis was performed by RevMan 5.3.

Results:

Eight studies comprising 687 patients were included in this meta-analysis. The pooled result revealed there was no significant differences in the VAS of leg, Oswestry Disability Index, fusion rate, disk height, segmental lordosis, and complication rate between the 2 groups (P>0.05). However, the VAS of back in the Endo-TLIF group was significantly less than those in the MIS-TLIF group within 2 weeks after surgery [weighted mean difference (WMD)=−1.33 (−1.98, −0.68), P<0.0001] and at 3 months postoperatively [WMD=−0.72(−0.85, −0.59), P<0.00001]. The Endo-TLIF group also seemed to fewer VAS of back at the last follow-up (≥12 mo) [WMD=−0.12 (−0.25, −0.00), P=0.05]. Compared with the MIS-TLIF group, the Endo-TLIF group was associated with longer operation time [WMD=26.74 (2.14, 51.34), P=0.03], but shorter length of hospital stay [WMD=−1.98(−2.91, −1.05), P<0.0001].

Conclusions:

Compared with minimally invasive TLIF, endoscopic TLIF achieved comparable improvement of symptoms and intervertebral fusion, longer operation time, and smaller surgical trauma. Endoscopic TLIF, which requires a demanding learning curve, maybe a feasible and effective technique for the patients with symptomatic lumbar degenerative diseases.
Femoral Reconstruction Using Long Tibial Autograft After Resection of Giant Aneurysmal Bone Cyst
Authors: Alisi Mohammed S. , Abu Hassan Freih , Alswerki Mohammad N. , Abdulelah Ahmed A. , Alshrouf Mohammad A.
Published: February 2023

Introduction:

Management of giant aneurysmal bone cyst in skeletally immature patients is challenging. The huge size can be destructive and can lead to significant deformity, disability, and limb-length discrepancy. Hence, reconstruction is warranted as a treatment option.

Materials and Methods:

Here, we present a case of giant aneurysmal bone cyst in the distal femur of a 9 year old obese child. After complete resection, we reconstructed the large distal femur defect by a 15 cm long-tibia autograft of the same limb. Fixation was done using hybrid (monoplanar and circular) external fixation. Detailed surgical techniques and several clinical and technical challenges have been discussed.

Results:

After 13 years of follow-up, the distal femur is well formed with preservation of the articular surface, and the site of the tibia autograft is completely regenerated.

Conclusion:

The tibia can be used as an autograft for the reconstruction of large-sized defects in skeletally immature patients.
A systematic review and meta-analysis on overall survival, failure-free survival and safety outcomes in patients with metastatic hormone-sensitive prostate cancer treated with new anti-androgens.
Authors: Ramos-Esquivel Allan , Garita-Rojas Esteban , Masis-Marroquín Adriana
Published: February 2023

Objective

Androgen-deprivation therapy (ADT) combined with new antiandrogens have shown to improve the outcomes of patients with hormone-sensitive metastatic prostate cancer. This systematic review and meta-analysis aim to compare the efficacy and toxicity of these agents in this specific scenario.

Methods

Randomized clinical trials (RCT) were identified after systematic searching of databases. A random-effect model was used to determine the pooled hazard ratio (HR) for overall survival (OS) and failure-free survival according to the inverse-variance method. The Mantel-Haenszel method was used to calculate the pooled odds ratio (OR) for treatment-related adverse events (AEs) grade 3 or higher. Heterogeneity was determined using the Tau2 and I
2 statistics.

Results

Seven trials were included in this meta-analysis (n = 7544). The addition of ADT plus new-generation anti-androgens, specifically: abiraterone, apalutamide, darolutamide or enzalutamide was associated with improved OS (pooled HR, 0.66; 95% CI, 0.61–0.71; P < 0.00001) with no significant heterogeneity detected among trials. (Tau2 = 0; I
2 = 0%; P = 0.88). Failure-free survival was significantly longer in the combination-therapy group than in the control group (pooled HR, 0.43; 95% CI, 0.39–0.47; P < 0.00001) This effect was consistent among trials (Tau2 = 0; I
2 = 27%; P = 0.22). The overall OR of AEs grade 3 or higher was significantly increased with the use of the combination therapy (pooled OR, 1.40; 95% CI, 1.13–1.74; P = 0.002), with significant heterogeneity among trials (Tau2 = 0.07; I
2 = 82%; P < 0.0001).

Conclusion:

The addition of either abiraterone, apalutamide, darolutamide or enzalutamide to ADT improves OS and failure-free survival in hormone-sensitive metastatic prostate cancer, albeit an increase in AEs.
Time above threshold plasma concentrations as pharmacokinetic parameter in the comparison of oral and intravenous docetaxel treatment of breast cancer tumors
Authors: van Eijk Maarten , Beijnen Jos H. , Huitema Alwin D.R.
Published: February 2023

Background

Prolonging the time which plasma concentrations of antimitotic drugs, such as the taxanes, exceed cytotoxic threshold levels may be beneficial for their efficacy. Orally administered docetaxel offers an undemanding approach to optimize such time above threshold plasma concentrations (tC>threshold).

Methods

A nonsystematic literature screen was performed to identify studies reporting in-vitro half-maximal inhibitory concentration (IC50) values for docetaxel. Pharmacokinetics of intravenously (i.v.) docetaxel (75 mg/m2) and orally administered docetaxel (ModraDoc006) co-administered with ritonavir (r) given twice daily (30 + 20 mg concomitant with 100 mg ritonavir bis in die) were simulated using previously developed population models. TC>threshold was calculated for a range of relevant thresholds in terms of in-vitro cytotoxicity and plasma concentrations achieved after i.v. and oral administration of docetaxel. A published tumor growth inhibition model for i.v. docetaxel was adapted to predict the effect of attainment of time above threshold levels on tumor dynamics.

Results

Identified studies reported a wide range of in vitro IC50 values [median 0.04 µmol/L, interquartile range (IQR): 0.0046–0.62]. At cytotoxic thresholds <0.078 µmol/L oral docetaxel shows up to ~7.5-fold longer tC>threshold within each 3-week cycle for a median patient compared to i.v.. Simulations of tumor dynamics showed the increased relative potential of oral docetaxel for inhibition of tumor growth at thresholds of 0.075, 0.05 and 0.005 µmol/L.

Conclusion

ModraDoc006/r is superior to i.v. docetaxel 75 mg/m2 in terms of median time above cytotoxic threshold levels <0.078 µmol/L. This may indicate superior cytotoxicity and inhibition of tumor growth compared to i.v. administration for relatively docetaxel-sensitive tumors.
A new inhibitor of human peptide deformylase suppresses cell proliferation and induces cell apoptosis and autophagy in cancers
Authors: Guo Yanzhi , Han Yuqiao , Li Ziyan , Ji Jiali , Zhu Tong , Du Yijie , Dong Suzhen
Published: February 2023

Human peptide deformylase (hsPDF) has been found overexpressed in many cancer cells and its inhibitors exhibit antitumor activity. Studies were performed to validate that hsPDF is a good antitumor target. The inhibitory effect of PDF64 on hsPDF enzymatic activity was measured and confirmed by computation analysis. Antiproliferation activity was determined and in-vivo antitumor activity were analyzed in HCT116 and HL60 nude mice xenografts. Mitochondrial membrane potential (MMP), cell apoptosis, and autophagic cell death were analyzed by flow cytometry. ATP level was quantified using an ATP assay kit. Protein expression and kinase phosphorylation were determined by western blotting. A new hsPDF inhibitor PDF64 was identified. It showed evident antiproliferation activity in 10 cancer cells and significantly suppressed tumor growth in HCT116 and HL60 xenografts. It induced an obvious decrease in MMP and caused apparent cell apoptosis and autophagy in HCT116 and Jurkat cells. PDF64 treatment also led to an evident decrease in cellular ATP levels in these cells. Moreover, PDF64 downregulated c-Myc expression and had some effects on extracellular regulated protein kinases (ERK) and protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) pathways. PDF64 exhibited good antitumor effects both in vivo and in vitro. It caused cell apoptosis and autophagic death in HCT116 and Jurkat cells. The effects may be mediated by inhibiting c-Myc expression and ERK or PI3K-Akt-mTOR pathway. Therefore, PDF64 may be a promising reagent for antitumor drug development, which further supports that hsPDF is a good antitumor drug target.
Zoledronic acid-associated osteonecro sis of the jaw in patients with EGFR-sensitive mutant lung cancer: two case reports
Authors: Aosiman Aliya , Nuermaimaiti Gulinuer , Yuan Meng , Liu Junyuan , Aerxiding Patiguli
Published: February 2023

Bone metastasis from lung cancer predicts a decrease in the quality of life and a shortening of survival for patients. While controlling the primary disease, active prevention and treatment of skeletal-related events (SREs) are crucial. The use of bisphosphonates as a basic drug for bone metastases from lung cancer has been increasing; also, the corresponding adverse effects have emerged. The case is here reported of two cases of osteonecrosis of the jaw associated with zoledronic acid treatment were reported in patients with epidermal growth factor receptor -sensitive mutation non-small-cell lung cancer(NSCLC) and discussed the clinical features, early recognition and interventions.
Panaxadiol targeting IL2 inducible T cell kinase promotes T cell immunity in radiotherapy
Authors: Li Jiuwei , Wang Lu , Yu Xiaodan , Guan Yong , Wang Xue
Published: February 2023

Ginseng, as a traditional Chinese medicine, has a good protective effect against radiotherapy, but its mechanism in radiotherapy still needs to be further explored. The active ingredients of Ginseng were analyzed according to pharmacodynamics in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, and the target genes of active ingredients were screened by UniProt, PubChem and Swiss target prediction database. The differentially expressed genes of GSE6871 and GSE20162 were analyzed from the GEO database. Further, cluster analysis and enrichment analysis were carried out through protein–protein interaction network to determine hub gene. Next, build the drug-disease target network, conduct molecular docking simulation, and determine the key ingredients and targets of Ginseng on radiotherapy. We screened 16 active ingredients of Ginseng and 747 target genes from the TCMSP database. Eighty-two common differentially expressed genes were obtained by the GEO database. After topological analysis, we finally determined CD28, FYN, IL2 inducible T cell kinase (ITK), MYC and CD247 as hub genes. After integrating the drug-disease target network and molecular docking, we found that Panaxadiol, as an active ingredient of Ginseng, can target ITK to participate in T cell signal receptor pathway and act on radiotherapy. Panaxadiol can act on the key target ITK of radiotherapy, participate in T cell signal receptor pathway, and then affect the proliferation, differentiation and immune response of radiotherapy T cells, so as to reduce the side effects of radiotherapy.
Identifying predictive biomarkers of apatinib in third-line treatment of advanced colorectal cancer through comprehensive genomic profiling
Authors: Yang Dongyang , Xu Fei , Lai Xiaorong , Li Ying , Hou Ting , Wu Lihong , Ma Dong , Li Zijun
Published: February 2023

Apatinib is a selective inhibitor of vascular endothelial growth factor receptor-2. Despite encouraging anticancer activity in different cancer types, some patients may not benefit from apatinib treatment. Herein, we characterized genomic profiles in colorectal cancer (CRC) patients to explore predictive biomarkers of apatinib at molecular level. We retrospectively recruited 19 CRC patients receiving apatinib as third-line treatment. Tissue samples before apatinib treatment were collected and subjected to genomic profiling using a targeted sequencing panel covering 520 cancer-related genes. After apatinib treatment, the patients achieved an objective response rate of 21% (4/19) and disease control rate of 57.9% (11/19). The median progression-free survival (PFS) and overall survival were 5 and 8.7 months, respectively. Genetic alterations were frequently identified in TP53 (95%), APC (53%), KRAS (53%) and PIK3CA (26%). Higher tumor mutation burden levels were significantly observed in patients harboring alterations in ERBB and RAS signaling pathways. Patients harboring FLT1 amplifications (n = 3) showed significantly worse PFS than wild-type patients. Our study described molecular profiles in CRC patients receiving apatinib treatment and identified FLT1 amplification as a potential predictive biomarker for poor efficacy of apatinib. Further studies are warranted to validate the use of FLT1 amplification during apatinib treatment.
Circ_0058063 regulates the development of esophageal cancer through miR-377-3p/HOXA1 axis
Authors: Chen Lisha , Luo Cheng , Xu Yongcheng , Hu Jianjun , Chen Huixin
Published: February 2023

Background

Esophageal cancer is one of the deadliest cancers. Circular RNA (CircRNA) can be used as a tumor marker. Therefore, this provides an important idea for our research.

Methods

Real-time quantitative PCR (RT-qPCR) was used to analyze the expression of circ_0058063, miR-377-3p and homeobox protein Hox-A1 (HOXA1), western blot was used to analyze the protein levels of HOXA1 and cyclinD1, B cell leukemia/lymphoma 2 associated X (Bax). Cell Counting Kit-8 (CCK-8) assay, colony formation assay and wound healing assay were used to analyze cell proliferation and migration; apoptosis was analyzed by flow cytometry. Dual-luciferase reporter assays were performed to analyze the luciferase activities. Transwell assay was used to analyze the cell invasion. A glycolysis metabolism assay was used to analyze cell glycolysis ability. Xenograft models were used to validate the effect of circ_0009035 in the growth of esophageal cancer in vivo.

Results

Circ_0009035 and HOXA1 were upregulated, while miR-377 was downregulated in esophageal cancer.. Circ_0058063 targeted miR-377-3p, and HOX4 was a target of miR-377-3p. Knockdown of circ_0058063 inhibited migration, invasion and proliferation and promoted apoptosis of esophageal cancer cells. MiR-377-3p inhibition or HOXA1 overexpression could restore the effect of si-circ_0058063 on esophageal cancer cells. Knockdown of circ_0058063 repressed the growth of esophageal cancer tumors in vivo.

Conclusions

Our study found that circ_0058063 could regulate the expression of HOXA1 by targeting miR-377-3p, thereby affecting the progress of esophageal cancer.
Neutrophil-to-lymphocyte ratio predicts therapy outcomes of transarterial chemoembolization combined with tyrosine kinase inhibitors plus programmed cell death ligand 1 antibody for unresectable hepatocellular carcinoma
Authors: Zheng Xin , Qian Kun
Published: February 2023

The objective is to assess the predictive value of preoperative biochemical markers, expressed as neutrophil-to-lymphocyte ratio (NLR), in patients with unresectable hepatocellular carcinoma (uHCC) receiving a combination of tailored tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) plus transarterial chemoembolization (TACE). A total of 95 patients with uHCC treated with TACE + TKIs + ICIs in our hospital between March 2018 and October 2021 were included in this retrospective study. The prognosis of the patients was analyzed based on NLRs. Overall survival (OS), progression-free survival (PFS), and adverse events (AEs) were evaluated. Univariate and multivariate analyses were used to determine factors affecting survival. Patients with a low pretreatment NLR (NLR ≤ 2.22) had significantly longer OS (25.8 months vs. 16.4 months; P = 0.000) and PFS (14.0 months vs. 11.1 months; P = 0.002). In multivariate analysis, two independent factors affecting PFS were identified: hepatitis B virus infection and NLR. Three independent factors affected OS: tumor size, Eastern Cooperative Oncology Group performance, and NLR. All AEs were tolerable, whereas NLR could be suspected as an indicator of immunotherapy-related AEs. A lower pretreatment NLR (≤2.22) might indicate a better prognosis for patients with uHCC treated with TACE + TKIs + ICIs. NLR could provide better guidance for clinicians when evaluating the prognosis of patients with uHCC treated with TACE + TKIs + ICIs and making clinical treatment decisions.
The incidence and risk factors for acute kidney injury in patients treated with immune checkpoint inhibitors
Authors: Guven Deniz Can , Ozbek Deniz Aral , Sahin Taha Koray , Kavgaci Gozde , Aksun Melek Seren , Erul Enes , Yildirim Hasan Cagri , Chalabiyev Elvin , Cebroyilov Cebrayil , Yildirim Tolga , Dizdar Omer , Aksoy Sercan , Yalcin Suayib , Kilickap Saadettin , Erman Mustafa , Arici Mustafa
Published: February 2023

Introduction

Recent observational studies reported acute kidney injury (AKI) events in over 10% of the patients treated with immune checkpoint inhibitors (ICIs). However, these studies included patients treated in high-resource settings and earlier lines. Therefore, we aimed to assess the AKI rates and predisposing factors in ICI-treated patients from a limited resource setting.

Methods

We evaluated 252 patients with advanced cancer for this retrospective cohort study. AKI events were defined by Kidney Disease Improving Global Outcomes criteria.

Results

The median age was 59 years. The melanoma (18.3%), non-small cell lung cancer (14.7%) and renal cell carcinoma (22.6%) patients comprised over half of the cohort. During the follow-up, 45 patients (17.9%) had at least one AKI episode. In multivariable analyses, patients with chronic kidney disease (CKD) [odds ratio (OR), 3.385; 95% confidence interval (CI), 1.510–7.588; P = 0.003], hypoalbuminemia (OR, 2.848; 95% CI, 1.225–6.621; P = 0.015) or renin-angiotensin-aldosterone system (RAAS) inhibitor use (OR, 2.236; 95% CI, 1.017–4.919; P = 0.045) had increased AKI risk. There was a trend towards increased AKI risk in patients with diabetes (OR, 2.042; 95% CI, 0.923–4.518; P = 0.78) and regular proton pump inhibitors use (OR, 2.024; 95% CI, 0.947–4.327; P = 0.069).

Conclusion

In this study, we observed AKI development under ICIs in almost one in five patients with cancer. The increased AKI rates in CKD, hypoalbuminemia or RAAS inhibitor use pointed out a need for better onco-nephrology collaboration and efforts to improve the nutritional status of ICI-treated patients.
CircSETDB1 contributes to paclitaxel resistance of ovarian cancer cells by sponging miR-508-3p and regulating ABCC1 expression
Authors: Huang Chunyan , Qin Li , Chen Sailan , Huang Qin
Published: February 2023

Ovarian cancer is a gynecological tumor with a poor prognosis. The chemotherapy failure and recurrence induced by paclitaxel (Ptx) resistance are the main reason for the failure of ovarian cancer treatment. In this study, we aimed to explore the role of circular RNA (circRNA) in the regulation of Ptx resistance in ovarian cancer. Quantitative reverse transcription PCR was performed to detect the expression of circRNA SET domain bifurcated histone lysine methyltransferase 1 (circSETDB1), microRNA (miR)-508-3p and ATP-binding cassette subfamily C member 1 (ABCC1) mRNA. The effects of circSETDB1 on Ptx resistance were explored by cell counting kit-8, 5-ethynyl-2′-deoxyuridine, and flow cytometry experiments in vitro. The protein level was assessed by western blot. Dual-luciferase reporter and RNA pull-down assays were carried out to confirm the interactions among circSETDB1, miR-508-3p, and ABCC1. Xenograft tumor experiment was performed to investigate the effect of circSETDB1 on Ptx resistance in vivo. CircSETDB1 was highly expressed in Ptx-resistant ovarian cancer. CircSETDB1 knockdown inhibited cell proliferation viability, half maximal inhibitory concentration value of Ptx, cell cycle progression, and induced cell apoptosis in Ptx-resistant ovarian cancer cells. miR-508-3p was a target of circSETDB1, and inhibition of miR-508-3p overturned the effects of circSETDB1 knockdown on the Ptx resistance of ovarian cancer cells. miR-508-5p could bind to ABCC1. Overexpression of ABCC1 reversed the effects of circSETDB1 knockdown on the Ptx resistance of ovarian cancer cells. CircSETDB1 knockdown also enhanced Ptx sensitivity in vivo. In conclusion, circSETDB1 regulated Ptx resistance of ovarian cancer by targeting miR-508-3p/ABCC1 axis.
Complete response in patient with liver metastasis of HER2-positive breast cancer following therapy with margetuximab: a case report
Authors: Chang Haiyan , Hu Ting , Hu Jie , Ding Teng , Wang Qiong , Cheng Jing
Published: February 2023

Metastatic human epidermal growth factor receptor 2 (HER2) positive breast cancer has a poor prognosis and few effective targeted therapies. However, several anti-HER2 agents are emerging in conjunction with chemotherapy, which may lead to increased rates of pathological complete response in patients with HER2-positive metastatic breast cancer. Among them, margetuximab demonstrated a significant improvement in progression-free survival compared with trastuzumab, when combined with chemotherapy in pretreated patients. Here we present a case of a 67-year-old female patient who was diagnosed with HER2-positive, histological grade III and invasive ductal carcinoma of the left breast in September 2018. She received postoperative adjuvant therapy with EC-TH plus radiotherapy, followed by therapy with HER2-targeted trastuzumab for 1 year (till December 2019). In May 2020, routine reexamination showed a supraclavicular lymph node and bone metastasis. Patient was then treated with pyrotinib, capecitabine and bisphosphonate for a period of 3 months. In December 2020, liver MRI revealed multiple liver metastases. The patient received eight cycles of second-line therapy (vinorelbine plus margetuximab) from January 2021. Since the ninth cycle, the patient was continued with only margetuximab. In March 2021, MRI showed a 70% decrease in the liver metastasis lesions. By June 2021, liver lesions were totally disappeared. During therapy, patient experienced only grade-1 anemia. This case demonstrates that margetuximab plus chemotherapy is safe and might bring clinical benefits for patients with HER2-positive breast cancer with liver metastasis. Further studies evaluating the efficacy and safety of margetuximab in Chinese HER2-positive breast cancer patients are needed.
Significant response to margetuximab in Chinese HER2-positive metastatic breast cancer patient who progressed after second-line targeted therapy
Authors: Li Jiaping , Lu Qianyi , Zhou Hanxing , Xu Fei , Huang Jiajia , Hong Ruoxi , Wang Shusen
Published: February 2023

Activation of the antibody-dependent cellular cytotoxicity is one of the key mechanisms of anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody treatment. Margetuximab is a fragment C (Fc)-modified chimeric anti-HER2 immunoglobulin G1 monoclonal antibody that shares epitope specificity with trastuzumab. In this case, we reported that margetuximab plus chemotherapy was effective as later-line therapy in a postmenopausal Chinese woman with metastatic diseases, who was diagnosed with estrogen receptor -, progesterone receptor (PR)-, HER2+ invasive ductal carcinoma. This patient used paclitaxel-albumin plus trastuzumab and pertuzumab as the first-line therapy with progression-free survival (PFS) of 14 months, and pyrotinib in combined with vinorelbine as the second-line therapy with a PFS of 17 months. Then she received margetuximab plus capecitabine as the third-line treatment, the metastatic lesions in the liver were obviously shrunk, indicating clinical partial response and the PFS was 7 months. This case revealed that margetuximab plus chemotherapy may be an appropriate option for the patients who progressed after treating with anti-HER2 monoclonal antibodies and pyrotinib.