bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updated results from the phase II study: Efficacy and safety of anlotinib plus sintilimab as second-line treatment for patients with advanced biliary tract cancers.
Authors: Jin Shuiling , Zhao Ruihua , Zhou Chuang , Zhong Qian , Zhang Xiaojian , Zong Hong 
Published: February 2023

577 Background: The incidence rate of biliary tract cancer (BTCs) is gradually increasing in china, while chemotherapy and immune checkpoint inhibitors monotherapy demonstrated limited efficacy for BTCs. New effective regimens are urgently needed. In this study, we explore anlotinib plus sintilimab as a chemo-free combination for second-line therapy. Previous results had been reported in 2021 ASCO GI (307 Poster Session). Updated results for longer follow-up and additional enrollment are presented here. Methods: BTC patients (pts) failed after the first-line treatment, aged 18-75 and an ECOG PS of 0-1 were recruited. Eligible pts received anlotinib (12mg, po, d1-14, q3w) and sintilimab (200mg, iv, d1, q3w) until disease progression, unacceptable toxicity or up to 2 years. The primary endpoint was Overall survival (OS). Secondary endpoints included Objective Response Rate, (ORR), Progression-Free Survival (PFS), Disease Control Rate (DCR) and safety. Results: At data cut-off date (Dec 30, 2021), a total of 29 pts were enrolled, of which 20 pts were available for efficacy assessment. The median treatment duration was 5.6 months (IQR: 2.5-10.0), and the median follow-up time was 12.5 months (IQR, 7.1-21.8). The median OS was 12.3 months (95% CI: 10.1-14.5).The median PFS was 6.5 months (95% CI: 4.2-8.8).The ORR was 30% (95% CI: 11.9%-54.3%) and DCR was 95% (95% CI: 75.1%-99.9%). Safety profile exhibited that the regimen was tolerable.The treatment-related adverse events (TRAEs) of any grade occurred in all patients (100%). The most common TRAEs were elevated GGT (75%), followed by hypertension (65%), elevated ALP (65%), elevated D-dimer (65%), elevated ALT (55%), anemia (50%), and elevated AST (50%). Grade 3 TRAEs occurred in 4 (20%) patients, including 2 (10%) hypertension, 1 (5%) elevated GGT, 1 (5%) elevated ALP, 1 (5%) elevated AST and 1 (5%) elevated ALT. No grade 4 or 5 TRAEs were observed. Conclusions: Anlotinib plus sintilimab demonstrated encouraging anti-tumor activity with a tolerable safety profile and deserve to be investigated in randomized trials for patients with advanced BTC. Clinical trial information: 1900022003 .
Unmasking the cloak of comorbidities in OSA-association and their severity – a prospective observational study
Authors: Kamath Sindhu , Naidu B Venkat , Acharya K Vishak , B Unnikrishnan 
Published: February 2023

Background: Obstructive sleep apnoea (OSA) is a common sleep disorder with high prevalence in the community but highly underreported. It is also seen that a significant number of cases with OSA are associated with various comorbidities. The study objective was to estimate and assess the specific type and proportion of various comorbidities seen in association with OSA and association of severity of OSA with comorbidities. Methods: The study was a hospital-based descriptive study of 85 patients with OSA. Descriptive statistics were used to analyse the data and Chi-square test was done to find out the association. Results: The most common comorbidity associated with OSA was obesity (60%). Around half of the patients (49.4%) had severe OSA based on Apnea Hypopnea Index (AHI) scores. Statistically significant association was seen between presence of comorbidities, like diabetes and hypertension, and risk of OSA based on the snoring, tiredness, observed apnea, blood pressure (S.T.O.P) questionnaire. Conclusions: In our study, a significant proportion (73%) of patients with OSA had associated comorbidities at the time of initial diagnosis. This indicates a delayed diagnosis as OSA is diagnosed only after multiple and irreversible comorbidities have developed. A majority (49%) had a severe OSA on initial presentation. This combination of multiple comorbidities and severe OSA at the time on diagnosis is reflective of a huge problem that is peculiar to OSA at large at a community level.
The genome sequence of the marsh skullcap, Scutellaria galericulata L.
Authors: Mian Sahr , Christenhusz Maarten J. M. ,   Royal Botanic Gardens Kew Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective, Howes Melanie-Jayne R. ,   Darwin Tree of Life Consortium
Published: February 2023

We present a genome assembly from an individual Scutellaria galericulata (the marsh skullcap; Streptophyta; Magnoliopsida; Lamiales; Lamiaceae). The genome sequence is 328 megabases in span. Most of the assembly is scaffolded into 15 chromosomal pseudomolecules. The mitochondrial and plastid genomes have also been assembled and have lengths of 326.5 kilobases and 152.6 kilobases respectively.
MEDIUM- TO LONG-TERM OUTCOMES AFTER NON-FIXATION OF THE SMALLER POSTERIOR MALLEOLAR FRAGMENT: A RETROSPECTIVE COHORT STUDY
Authors: Chong S.L. , Khademi M. , Reddy K.M. , Anderson G.H. 
Published: February 2023

Treatment of posterior malleolar (PM) ankle fractures remain controversial. Despite increasing recommendation for small PM fragment fixation, high quality evidence demonstrating improved clinical outcomes over the unfixated PM is limited. We describe the medium-to-long term clinical and radiographical outcomes in younger adult patients with PM ankle fractures managed without PM fragment fixation.A retrospective cohort study of patients aged 18-55 years old admitted under our orthopaedic unit between 1st of April 2009 and 31st of October 2013 with PM ankle fractures was performed. Inclusion criteria were that all patients must mobilise independently pre-trauma, have no pre-existing ankle pathologies, and had satisfactory bimalleolar and syndesmotic stabilisation. Open fractures, talar fractures, calcaneal fractures, pilon fractures, subsequent re-injury and major complications were excluded. All PM fragments were unfixated. Clinical outcomes were evaluated using Foot and Ankle Ability Measure (FAAM) with activities of daily living (ADL) and sports subscale, visual analogue scale (VAS) and patient satisfaction ratings. Osteoarthrosis was assessed using modified Kellgren-Lawrence scale on updated weightbearing ankle radiographs.61 participants were included. Mean follow-up was 10.26 years. Average PM size was 16.19±7.39%. All participants were evaluated for clinical outcomes, demonstrating good functional outcomes (FAAM-ADL 95.48±7.13; FAAM-Sports 86.39±15.52) and patient satisfaction (86.16±14.42%), with minimal pain (VAS 1.13±1.65). Radiographical outcomes were evaluated in 52 participants, showing no-to-minimal osteoarthrosis in 36/52 (69.23%), mild osteoarthrosis in 14/52 (26.92%) and moderate osteoarthrosis in 2/52 (3.85%). Clinical outcomes were not associated with PM fragment size, post-reduction step-off, dislocation, malleoli fractured or syndesmotic injury. PM step-off and dislocation were associated with worse radiographical osteoarthrosis. Other published medium-to-long term studies reported overall good outcomes, with no differences after small fragment fixation.The unfixated smaller posterior malleolus fragment demonstrated overall satisfactory clinical and radiographical outcomes at 10-year follow-up and may be considered a valid treatment strategy.
APPLICATION OF BONE CEMENT DIRECTLY TO THE IMPLANT IN PRIMARY KNEE ARTHROPLASTY: RADIOLOGICAL AND CLINICAL FOLLOW-UP OF TWO DIFFERENT CEMENTING TECHNIQUES
Authors: Holzer L.A. , Finsterwald M. , Sobhi S. , Yates P.J. 
Published: February 2023

This study aimed to analyze the effect of two different techniques of cement application: cement on bone surface (CoB) versus cement on bone surface and implant surface (CoBaI) on the short-term effect of radiolucent lines (RLL) in primary fully cemented total knee arthroplasties (TKA) with patella resurfacing.379 fully cemented TKAs (318 patients) were included in this monocentric study. Preoperative and postoperative at week 4 and 12 month after surgery all patients had a clinical and radiological examination and were administered the Oxford Knee Score (OKS). Cement was applied in two different ways among the two study groups: cement on bone surface (CoB group) or cement on bone surface and implant surface (CoBaI group). The evaluation of the presence of RLL or osteolysis was done as previously described using the updated Knee Society Radiographic Evaluation System.The mean OKS and range of motion improved significantly in both groups at the 4-week and 12-month follow-up, with no significant difference between the groups (CoB vs. CoBaI). RLL were present in 4.7% in the whole study population and were significantly higher in the CoBaI group (10.5%) at the 4-week follow-up. At the 12-month follow-up RLL were seen in 29.8% of the TKAs in the CoBaI group, whereas the incidence was lower in the CoB group (24.0% (n.s.)). There were two revisions in each group. None of these due to aseptic loosening.Our study indicated that the application of bone cement on bone surface only might be more beneficial than onto the bone surface and onto the implant surface as well in respect to the short-term presence of RLL in fully cemented primary TKA.The long-term results will be of interest, especially in respect to aseptic loosening and might guide future directions of bone cement applications in TKA.
DOES SOCIOECONOMIC DEPRIVATION INFLUENCE PATIENT OUTCOMES AFTER PERIACETABULAR OSTEOTOMY?
Authors: Chen W. , Lightfoot N.J. , Boyle M.J. 
Published: February 2023

Higher levels of socioeconomic deprivation have been associated with worse health outcomes. The influence of socioeconomic deprivation on patients undergoing periacetabular osteotomy (PAO) has not previously been investigated.A total of 217 patients (171 female, 46 male; median age 23.4 years) who underwent PAO by a single surgeon were identified. Patients were categorised into three groups according to their New Zealand Deprivation (NZDep) Index: minimal deprivation (NZDep Index 1–3, n=89), moderate deprivation (NZDep Index 4-6, n=94), and maximal deprivation (NZDep Index 7-10, n=34). The three groups were compared with respect to baseline variables, surgical details, complications, and pre-operative and two-year post-operative functional scores (including International Hip Outcome Tool (iHOT-12), EQ-5D quality of life score, and University of California Los Angeles (UCLA) activity score). Multivariate regression was undertaken to assess for the effect of NZDep Index on patient outcomes.Patients in the maximal deprivation group were more likely to be Māori (p<0.001) and have surgery in a public rather than a private hospital (p=0.004), while the minimal deprivation group demonstrated a lower BMI (p=0.005). There were otherwise no other significant differences in baseline variables, surgical details, complications, nor pre-operative or two-year post-operative functional scores between the three groups (all p>0.05). Multivariate analysis identified a higher NZDep Index to be independently predictive of a lower pre-operative UCLA activity score (p=0.014) and a higher two-year iHOT-12 score (p<0.001).Our results demonstrate an inequality in access to PAO, with patients exposed to higher levels of socioeconomic deprivation under-represented in our study population. When provided access to PAO, these vulnerable patients achieve significant functional improvement at least as great as patients with less socioeconomic deprivation. Initiatives to improve access to hip preservation care in socioeconomically deprived populations appear warranted.
ANALYSES OF BIOPSIED TISSUES IN AUTOLOGOUS TENOCYTE THERAPY FOR TREATMENT OF TENDINOPATHY
Authors: Damiani M. 
Published: February 2023

Autologous tendon cell injection (ATI) is a promising non-surgical treatment for tendinopathies and tendon tear that address its underlying pathology. The procedure involves harvesting autologous tendon tissue, the isolation of the tendon cells, expansion under quality assured GMP cell laboratory and the injection of the tendon cells via U/S into the degenerative tendon tissue. In clinical practice, the patella (PT) and palmaris longus (PL) tendons are common sites used for tendon tissue biopsy. The objective of this study is to compare the tendon cell quality, identity, purity, doubling time and yield of cells between PT and PL tendons for ATI.Tendon tissue biopsies were harvested from PT via U/S using a 14-gauge needle or resected surgically from the PL tendon. The biopsies were transported to a GMP cell laboratory, where tendon cells were isolated, cultured and expanded for 4 to 6 weeks, and analysed for viability, cell doubling time, cellular characteristics including cell purity, potency and identity (PPI).Tendon samples from 149 patients were analysed (63 PT). Average biopsy weight was 62mg for PT and 119mg for PI (p<0.001). Average cell doubling time (83.9 vs 82.7 hours), cellular yield (16.2 vs 15.2×106), viability (98.7 vs 99.0%) and passage number (3 vs 3) were not significantly different between tendons. Additionally, ddPCR analyses showed no differences of PPI including tendon cell markers of collagen type I, scleraxis and tenomodulin. No post-biopsy complications or contamination were reported for either group. Assessing tendon tissue from palmaris tendon is relatively easier.Tendon tissue biopsy tissue for autologous tendon cell therapy can be obtained from either the PT or PL tendons. Tendon cells isolated from PT and PL were equal in growth characteristics and PPI. There are no differences in the quality of tendon cells isolated from the PT or PL.
APPLICATION OF THE SIMPLE HIP-SPINE CLASSIFICATION TO AN AUSTRALIAN SAMPLE TO DETERMINE LOCAL PATIENT-SPECIFIC CUP ORIENTATION REQUIREMENTS
Authors: Hardwick-Morris M. , Twiggs J. , Miles B. , Jones E. , Bruce W. J. M. , Walter W. L. 
Published: February 2023

In 2021, Vigdorchik et al. published a large multicentre study validating their simple Hip-Spine Classification for determining patient-specific acetabular component positioning in total hip arthroplasty (THA). The purpose of our study was to apply this Hip-Spine Classification to a sample of Australian patients undergoing THA surgery to determine the local acetabular component positioning requirements. Additionally, we propose a modified algorithm for adjusting cup anteversion requirements.790 patients who underwent THA surgery between January 2021 and June 2022 were assessed for anterior pelvic plane tilt (APPt) and sacral slope (SS) in standing and relaxed seated positions and categorized according to their spinal stiffness and flatback deformity. Spinal stiffness was measured using pelvic mobility (PM); the ΔSS between standing and relaxed seated. Flatback deformity was defined by APPt <−13° in standing. As in Vigdorchik et al., PM of <10° was considered a stiff spine. For our algorithm, PM of <20° indicated the need for increased cup anteversion. Using this approach, patient-specific cup anteversion is increased by 1° for every degree the patient's PM is <20°.According to the Vigdorchik simple Hip-Spine classification groups, we found: 73% Group 1A, 19% Group 1B, 5% Group 2A, and 3% Group 2B. Therefore, under this classification, 27% of Australian THA patients would have an elevated risk of dislocation due to spinal deformity and/or stiffness. Under our modified definition, 52% patients would require increased cup anteversion to address spinal stiffness.The Hip-Spine Classification is a simple algorithm that has been shown to indicate to surgeons when adjustments to acetabular cup anteversion are required to account for spinal stiffness or flatback deformity. We investigated this algorithm in an Australian population of patients undergoing THA and propose a modified approach: increasing cup anteversion by 1° for every degree the patient's PM is <20°.
ARE THE CAUSES OF ILIOPSOAS-RELATED GROIN PAIN IN TOTAL HIP ARTHROPLASTY AND HIP RESURFACING ARTHROPLASTY EQUIVALENT? A CASE-CONTROLLED INVESTIGATION USING A VALIDATED SIMULATION
Authors: Hardwick-Morris M. , Twiggs J. , Miles B. , Walter W. L. 
Published: February 2023

Iliopsoas tendonitis occurs in up to 30% of patients after hip resurfacing arthroplasty (HRA) and is a common reason for revision. The primary purpose of this study was to validate our novel computational model for quantifying iliopsoas impingement in HRA patients using a case-controlled investigation. Secondary purpose was to compare these results with previously measured THA patients.We conducted a retrospective search in an experienced surgeon's database for HRA patients with iliopsoas tendonitis, confirmed via the active hip flexion test in supine, and control patients without iliopsoas tendonitis, resulting in two cohorts of 12 patients. The CT scans were segmented, landmarked, and used to simulate the iliopsoas impingement in supine and standing pelvic positions. Three discrete impingement values were output for each pelvic position, and the mean and maximum of these values were reported. Cup prominence was measured using a novel, nearest-neighbour algorithm.The mean cup prominence for the symptomatic cohort was 10.7mm and 5.1mm for the asymptomatic cohort (p << 0.01). The average standing mean impingement for the symptomatic cohort was 0.1mm and 0.0mm for the asymptomatic cohort (p << 0.01). The average standing maximum impingement for the symptomatic cohort was 0.2mm and 0.0mm for the asymptomatic cohort (p << 0.01). Impingement significantly predicted the probability of pain in logistic regression models and the simulation had a sensitivity of 92%, specificity of 91%, and an AUC ROC curve of 0.95.Using a case-controlled investigation, we demonstrated that our novel simulation could detect iliopsoas impingement and differentiate between the symptomatic and asymptomatic cohorts. Interestingly, the HRA patients demonstrated less impingement than the THA patients, despite greater cup prominence. In conclusion, this tool has the potential to be used preoperatively, to guide decisions about optimal cup placement, and postoperatively, to assist in the diagnosis of iliopsoas tendonitis.
ROBOTIC-ARM ASSISTED UNICOMPARTMENTAL KNEE ARTHROPLASTY HAS A LEARNING CURVE OF 11 CASES AND INCREASED OPERATIVE TIME
Authors: Tay M.L. , Carter M. , Bolam S.M. , Zeng N. , Young S.W. 
Published: February 2023

Source of the study: University of Auckland, Auckland, New ZealandUnicompartmental knee arthroplasty (UKA) has benefits for patients with appropriate indications. However, UKA has a higher risk of revision, particularly for low-usage surgeons. The introduction of robotic-arm assisted systems may allow for improved outcomes but is also associated with a learning curve. We aimed to characterise the learning curve of a robotic-arm assisted system (MAKO) for UKA in terms of operative time, limb alignment, component sizing, and patient outcomes.Operative times, pre- and post-surgical limb alignments, and component sizing were prospectively recorded for consecutive cases of primary medial UKA between 2017 and 2021 (n=152, 5 surgeons). Patient outcomes were captured with the Oxford Knee Score (OKS), EuroQol-5D (EQ-5D), Forgotten Joint Score (FJS-12) and re-operation events up to two years post-UKA. A Cumulative Summation (CUSUM) method was used to estimate learning curves and to distinguish between learning and proficiency phases.Introduction of the system had a learning curve of 11 cases. There was increased operative time of 13 minutes between learning and proficiency phases (learning 98 mins vs. proficiency 85 mins; p<0.001), associated with navigation registration and bone preparation/cutting. A learning curve was also found with polyethylene insert sizing (p=0.03). No difference in patient outcomes between the two phases were detected for patient-reported outcome measures, implant survival (both phases 98%; NS) or re-operation (learning 100% vs. proficiency: 96%; NS). Implant survival and re-operation rates did not differ between low and high usage surgeons (cut-off of 12 UKAs per year).Introduction of the robotic-arm assisted system for UKA led to increased operative times for navigation registration and bone preparation, but no differences were detected in terms of component placement or patient outcomes regardless of usage. The short learning curve regardless of UKA usage indicated that robotic-arm assisted UKA may be particularly useful for low-usage surgeons.
POROUS METAL WEDGE AUGMENTS TO ADDRESS GLENOID RETROVERSION IN PRIMARY ANATOMICAL TOTAL SHOULDER ARTHROPLASTY: AN UPDATE
Authors: Sandow M.J. , Cheng Z.X. 
Published: February 2023

This paper presents an ongoing review of the use of a wedge-shaped porous metal augments in the shoulder to address glenoid retroversion as part of anatomical total shoulder arthroplasty (aTSA).Seventy-five shoulders in 66 patients (23 women and 43 men, aged 42 to 85 years) with Walch grade B2 or C glenoids underwent porous metal glenoid augment (PMGA) insertion as part of aTSA. Patients received either a 15º or 30º PMGA wedge (secured by screws to the native glenoid) to correct excessive glenoid retroversion before a standard glenoid component was implanted using bone cement. Neither patient-specific guides nor navigation were used. Patients were prospectively assessed using shoulder functional assessments (Oxford Shoulder Score [OSS], American Shoulder and Elbow Standardized Shoulder Assessment Form [ASES], visual analogue scale [VAS] pain scores and forward elevation [FE]) preoperatively, at three, six, and 12 months, and yearly thereafter, with similar radiological surveillance.Forty-nine consecutive series shoulders had a follow-up of greater than 24 months, with a median follow-up of 48 months (range: 24–87 months). Median outcome scores improved for OSS (21 to 44), ASES (24 to 92), VAS (7 to 0), and FE (90º to 140º). Four patients died, but no others were lost to follow-up. Apart from one infection at 18 months postoperatively and one minor peg perforation, there were no complications, hardware failures, implant displacements, significant lucency or posterior re-subluxations. Radiographs showed good incorporation of the wedge augment with correction of glenoid retroversion from median 22º (13º to 46º) to 4º. All but four glenoids were corrected to within the target range (less than 10º retroversion).The porous metal wedge-shaped augments effectively addressed posterior glenoid deficiency as part of aTSA for rotator cuff intact osteoarthritis, producing satisfactory clinical outcomes with no signs of impending future failure.