Latarjet procedure restores range of motion at six months postoperatively: a prospective cohort study utilizing motion capture analysis.

BACKGROUND: There is a common concern that range of motion (ROM) is negatively affected by the Latarjet procedure. We hypothesize that the Latarjet procedure results in full recuperation of ROM postoperatively and significantly improved patient reported outcome measures. METHODS: Patient data were prospectively collected from a randomized controlled trial to analyze outcomes after open Latarjet procedure. Inclusion criteria involved a minimum follow-up of six months and unilateral shoulder instability. Study outcome was assessed by postoperative ROM at six months postoperatively and compared to the preoperative ROM of the ipsilateral shoulder as well as the ROM of the unaffected contralateral shoulder. All ROM measurements were performed utilizing a motion capture system to ensure consistent and reliable measurements. RESULTS: The study included a total of 84 patients. ROM was measured in external rotation with the shoulder adducted (ER1), external rotation with the shoulder abducted 90 degrees (ER2), internal rotation with the arm abducted 90 degrees (IR2), and active forward elevation (AE). The average difference in ROM between the operated arm vs. the contralateral healthy arm at six months postoperatively was 3.4 degrees in ER1 (p=0.19), 4.2 degrees in ER2 (p=0.086), 2.2 degrees in IR2 (p=0.36), and 2.4 degrees in AE (p=0.045). Sub-analysis of patients with and without sling use revealed no significant difference in ROM between the operated shoulder and contralateral shoulder at six months in either group, with the exception of ER2 in the sling group. In this latter group, ROM was 71 degrees in the operated arm and 79 degrees in the contralateral arm (p=0.0094). Average preoperative pain score was 25.7 (21.4-30.1, 95%CI) vs. 13.0 postoperatively at six months (9.50-16.5, 95%CI) (p <0.00001). Average preoperative SANE instability was 42.9 (38.4-47.3, 95%CI) vs. 86.2 postoperatively at six months (83.6-88.7, 95%CI) (p <0.00001). Average preoperative Rowe score was 38.5 (34.3-42.7, 95%CI) vs. 84.3 at six postoperative months (81.1-87.4, 95%CI) (p<0.00001). CONCLUSIONS: Latarjet procedure performed for anterior instability utilizing a capsular repair result in complete ROM recovery in ER1, ER2, and IR2 at six months postoperatively, with only a slight discrepancy in active elevation. Sling use after the Latarjet procedure results in no benefit over postoperative recovery without the use of a sling. Sling use negatively affects the ROM in ER2, taking as reference the contralateral arm of the same patient, when compared to patients that did not use a sling postoperatively.

A feasibility cadaver study for placing screws in various pelvic osseous fracture pathways using a robotic arm.

INTRODUCTION: The use of a robotic system for the placement of pedicle screws in spine surgeries is well documented in the literature. However, there is only a single report in the United States describing the use of a robotic system to place two screws in osseous fixation pathways (OFPs) commonly used in the treatment of pelvic and acetabular fractures in a simulated bone model. The purpose of this study was to demonstrate the use of a robotic system to place screws in multiple, clinically relevant OFPs in a cadaveric model and to quantitatively measure accuracy of screw placement relative to the preoperative plan. METHODS: A single cadaveric specimen was obtained for the purpose of this study. All surrounding soft tissues were left intact. Screws were placed in OFPs, namely iliosacral (IS), trans-sacral (TS), Lateral Compression-II (LC-II), antegrade anterior column (AC) and antegrade posterior column (PC) of the right hemipelvis using standard, fluoroscopically assisted percutaneous or mini-open technique. Following the placement of screws into the right hemipelvis using standard techniques, screws were planned and placed in the same OFPs of the contralateral hemipelvis using the commercially available ExcelsiusGPS® robotic system (Globus Medical Inc., Audubon, PA). After robotic-assisted screw placement, a post-procedure CT scan was obtained to evaluate actual screw placement against the pre-procedure plan. A custom-made image analysis program was devised to measure screw tip/tail offset and angular offset on axial and sagittal planes. RESULTS: For different OFPs, the mean tip offset, tail offset and angular offsets were 1.6 ± 0.9 mm (Range 0.0-3.6 mm), 1.4 ± 0.4 mm (Range 0.3-2.5 mm) and 1.1 ± 0.4° (Range 0.5-2.1), respectively. CONCLUSION: In this feasibility study, surgeons were able to place screws into the clinically relevant fracture pathways of the pelvis using ExcelsiusGPS® for robotic-assisted surgery. The measured accuracy was encouraging; however, further investigation is needed to demonstrate that robotic-assisted surgery can be used to successfully place the screws in the bony corridors of the pelvis to treat traumatic pelvic injuries.

Differential chromatin accessibility and transcriptional dynamics define breast cancer subtypes and their lineages.

Breast cancer is a heterogeneous disease, and treatment is guided by biomarker profiles representing distinct molecular subtypes. Breast cancer arises from the breast ductal epithelium, and experimental data suggests breast cancer subtypes have different cells of origin within that lineage. The precise cells of origin for each subtype and the transcriptional networks that characterize these tumor-normal lineages are not established. In this work, we applied bulk, single-cell (sc), and single-nucleus (sn) multi-omic techniques as well as spatial transcriptomics and multiplex imaging on 61 samples from 37 breast cancer patients to show characteristic links in gene expression and chromatin accessibility between breast cancer subtypes and their putative cells of origin. We applied the PAM50 subtyping algorithm in tandem with bulk RNA-seq and snRNA-seq to reliably subtype even low-purity tumor samples and confirm promoter accessibility using snATAC. Trajectory analysis of chromatin accessibility and differentially accessible motifs clearly connected progenitor populations with breast cancer subtypes supporting the cell of origin for basal-like and luminal A and B tumors. Regulatory network analysis of transcription factors underscored the importance of BHLHE40 in luminal breast cancer and luminal mature cells, and KLF5 in basal-like tumors and luminal progenitor cells. Furthermore, we identify key genes defining the basal-like ( PRKCA , SOX6 , RGS6 , KCNQ3 ) and luminal A/B ( FAM155A , LRP1B ) lineages, with expression in both precursor and cancer cells and further upregulation in tumors. Exhausted CTLA4-expressing CD8+ T cells were enriched in basal-like breast cancer, suggesting altered means of immune dysfunction among breast cancer subtypes. We used spatial transcriptomics and multiplex imaging to provide spatial detail for key markers of benign and malignant cell types and immune cell colocation. These findings demonstrate analysis of paired transcription and chromatin accessibility at the single cell level is a powerful tool for investigating breast cancer lineage development and highlight transcriptional networks that define basal and luminal breast cancer lineages.

Epigenetic regulation during cancer transitions across 11 tumour types.

Chromatin accessibility is essential in regulating gene expression and cellular identity, and alterations in accessibility have been implicated in driving cancer initiation, progression and metastasis1-4. Although the genetic contributions to oncogenic transitions have been investigated, epigenetic drivers remain less understood. Here we constructed a pan-cancer epigenetic and transcriptomic atlas using single-nucleus chromatin accessibility data (using single-nucleus assay for transposase-accessible chromatin) from 225 samples and matched single-cell or single-nucleus RNA-sequencing expression data from 206 samples. With over 1 million cells from each platform analysed through the enrichment of accessible chromatin regions, transcription factor motifs and regulons, we identified epigenetic drivers associated with cancer transitions. Some epigenetic drivers appeared in multiple cancers (for example, regulatory regions of ABCC1 and VEGFA; GATA6 and FOX-family motifs), whereas others were cancer specific (for example, regulatory regions of FGF19, ASAP2 and EN1, and the PBX3 motif). Among epigenetically altered pathways, TP53, hypoxia and TNF signalling were linked to cancer initiation, whereas oestrogen response, epithelial-mesenchymal transition and apical junction were tied to metastatic transition. Furthermore, we revealed a marked correlation between enhancer accessibility and gene expression and uncovered cooperation between epigenetic and genetic drivers. This atlas provides a foundation for further investigation of epigenetic dynamics in cancer transitions.

Glenoid-based reference system to differentiate shoulder pathologies on plain radiographs.

BACKGROUND: Shoulder radiographs are used for evaluation and the planning of treatment of various pathologies. Making a diagnosis of these pathologies on plain radiographs occurs by recognizing the relationship of the humeral head on the registry of the glenoid. Quantification of these changes in registry does not currently exist. We hypothesize that a geometric relationship of the humeral head and the glenoid exists that is defined on an anteroposterior Grashey view radiograph by the relationship of the best-fit circle of the humeral head relative to the best-fit circle of the glenoid such that relative measurements will define the normal shoulder and the pathologic shoulder. METHODS: One hundred fifty-six shoulders were included: 53 normal shoulders, 51 with primary glenohumeral osteoarthritis (GHOA), and 52 with cuff tear arthropathy (CTA). Humeral head best-fit circle was used to define the circle of the humeral head (cHH). A glenoid best-fit circle (cG) was defined by the following rules: (1) best fit of the glenoid articular surface and (2) was limited by the acromion such that either (a) it reaches maximal interaction with the inferior surface of the acromion or (b) the perimeter of the circle is at the lateralmost point of the acromion. The relationship between cHH and cG is defined by measurement of cHH in horizontal and vertical planes relative to the glenoid circle reference. The horizontal displacement angle (HDA) measures the horizontal position of cHH relative to cG, representing the degree of medialization toward the glenoid. The vertical displacement angle (VDA) measures the vertical position of cHH relative to cG, representing the degree of superiorization toward the acromion. Angles were compared by diagnosis and sex. RESULTS: The mean HDA was 61.0° (95% confidence interval [CI] 60.3°-61.7°) in normal shoulders, 79.9° (95% CI 76.9°-82.9°) in GHOA, and 63.4° (95% CI 61.7°-65.1°) in CTA (P < .001). The mean VDA was 43.1° (95% CI 42.2°-44.0°) in normal shoulders, 40.9° (95% CI 39.9°-42.0°) in GHOA, and 59.7° (95% CI 57.6°-61.7°) in CTA (P < .001). Interobserver reliability was 0.991 (95% CI 0.94-1.0) and intraobserver reliability was 0.998 (95% CI 0.99-1.0). The geometric relationship of cHH to the glenoid circle reference was plotted for each group. CONCLUSION: A geometric relationship exists of the humeral head in reference to the glenoid circle. Together, the HDA and the VDA distinguish between a normal shoulder and those with GHOA or CTA. This suggests that this novel methodology may provide a preoperative planning tool that is easily accessible.

Robotic-assisted percutaneous pelvis fixation: A case report.

Key Clinical Message: It may be possible to extend the use of the robotic arm to pelvic and acetabular surgery leading to safe, repeatable screw placement, and less radiation exposure for patients, surgeons and OR staff. Abstract: In this case, a novel, robotic-assisted technique was used to place a sacroiliac screw in a patient with unstable injuries of the pelvic ring. Intraoperative and postoperative fluoroscopic, radiographic, and CT imaging demonstrated a safely positioned 6.5 mm cannulated screw without unplanned cortical violation or impingement on neurovascular structures. To our knowledge, this is the first such reported case using a robot widely available in the Americas or Europe.

The Integrin Pathway Partially Mediates Stretch-Induced Deficits in Primary Rat Microglia.

Stretch-injured microglia display significantly altered morphology, function and inflammatory-associated gene expression when cultured on a synthetic fibronectin substrate. However, the mechanism by which stretch induces these changes is unknown. Integrins, such as α5ß1, mediate microglial attachment to fibronectin via the RGD binding peptide; following integrin ligation the integrin-associated signaling enzyme, focal adhesion kinase (FAK), autophosphorylates tyrosine residue 397 and mediates multiple downstream cellular processes. We therefore hypothesize that blocking the RGD binding/integrin pathway with a commercially available RGD peptide will mimic the stretch-induced morphological alterations and functional deficits in microglia. Further, we hypothesize that upregulation of stretch-inhibited downstream integrin signaling will reverse these effects. Using primary rat microglia, we tested the effects of RGD binding peptide and a FAK activator on cellular function and structure and response to stretch-injury. Similar to injured cells, RGD peptide administration significantly decreases media nitric oxide (NO) levels and iNOS expression and induced morphological alterations and migratory deficits. While stretch-injury and RGD peptide administration decreased phosphorylation of the tyrosine 397 residue on FAK, 20 nM of ZINC 40099027, an activator specific to the tyrosine 397 residue, rescued the stretch-induced decrease in FAK phosphorylation and ameliorated the injury-induced decrease in media NO levels, iNOS expression and inflammatory associated gene expression. Additionally, treatment alleviated morphological changes observed after stretch-injury and restored normal migratory behavior to control levels. Taken together, these data suggest that the integrin/FAK pathway partially mediates the stretch-injured phenotype in microglia, and may serve as a pathway to modulate microglial responses.

Liposomal bupivacaine nerve block provides better pain control post-total shoulder arthroplasty than continuous indwelling catheter.

BACKGROUND: Pain control is essential to successful total shoulder arthroplasty (TSA). MATERIALS AND METHODS: This non-blinded, randomized clinical trial compared shoulder pain, narcotic use, interscalene (IS) block application time, and costs in 76 subjects who were randomly assigned to receive either a single injection IS nerve block of 10 cc (133 mg) liposomal bupivacaine mixed with 10 cc of 0.5% bupivacaine (Group 1), or 20 cc of 0.5% ropivacaine direct injection combined with an indwelling IS nerve block catheter delivering 0.2% ropivacaine at a continual 4 cc/h infusion for the initial 3 post-operative days (Group 2). Surgical time, local anesthesia duration, hospital stay length, morphine milligram equivalents (MME) consumed, worst shoulder pain at 24, 48 and 72 h, and complications were recorded. Patient reported function, pain and activity level surveys were completed before, and 6-week post-TSA (P < 0.05). RESULTS: Group 1 had less pain 24-h (0.72 ± 0.8 vs. 3.4 ± 2.9, p < 0.0001) and 48-h (2.5 ± 2.2 vs. 4.8 ± 2.6, p = 0.005) post-TSA. At 24-h post-TSA, MME consumption was similar (Group 1 = 4.5 ± 6.4 vs. Group 2 = 3.7 ± 3.8, p = 0.54), but was lower for Group 1 at 48 h (0.0 ± 0.0 vs. 0.64 ± 0.99, p = 0.001). Group 2 had longer IS block application time (10.00 ± 4.6 min vs. 4.84 ± 2.7 min, p < 0.0001). Only group 2 had a strong relationship between MME consumption over the first 24-h post-TSA and pain 24-h post-TSA (r = 0.76, p < 0.0001), a moderate relationship with pain 48-h post-TSA (r = 0.59, P = 0.001), and a weak relationship with pain 72-h post-TSA (r = 0.44, P = 0.02). Significant relationships for these variables were not observed for Group 1 (r ≤ 0.30, p ≥ 0.23). Group 1 IS block costs were less/patient than Group 2 ($190.17 vs. $357.12 USD). CONCLUSION: A single shot, liposomal bupivacaine interscalene nerve block provided better post-TSA pain control with less narcotic consumption, less time for administration and less healthcare system cost compared to interscalene nerve block using a continuous indwelling catheter. LEVEL OF EVIDENCE: Level I, Prospective, Randomized.

Matrix stiffness enhances cancer-macrophage interactions and M2-like macrophage accumulation in the breast tumor microenvironment.

The role of intratumor heterogeneity is becoming increasingly apparent in part due to expansion in single cell technologies. Clinically, tumor heterogeneity poses several obstacles to effective cancer therapy dealing with biomarker variability and treatment responses. Matrix stiffening is known to occur during tumor progression and contribute to pathogenesis in several cancer hallmarks, including tumor angiogenesis and metastasis. However, the effects of matrix stiffening on intratumor heterogeneity have not been thoroughly studied. In this study, we applied single-cell RNA sequencing to investigate the differences in the transcriptional landscapes between stiff and compliant MMTV-PyMT mouse mammary tumors. We found similar compositions of cancer and stromal subpopulations in compliant and stiff tumors but differential intercellular communication and a significantly higher concentration of tumor-promoting, M2-like macrophages in the stiffer tumor microenvironments. Interestingly, we found that cancer cells seeded on stiffer substrates recruited more macrophages. Furthermore, elevated matrix stiffness increased Colony Stimulating Factor 1 (CSF-1) expression in breast cancer cells and reduction of CSF-1 expression on stiffer substrates reduced macrophage recruitment. Thus, our results demonstrate that tissue phenotypes were conserved between stiff and compliant tumors but matrix stiffening altered cell-cell interactions which may be responsible for shifting the phenotypic balance of macrophages residing in the tumor microenvironment towards a pro-tumor progression M2 phenotype. STATEMENT OF SIGNIFICANCE: Cells within tumors are highly heterogeneous, posing challenges with treatment and recurrence. While increased tissue stiffness can promote several hallmarks of cancer, its effects on tumor heterogeneity are unclear. We used single-cell RNA sequencing to investigate the differences in the transcriptional landscapes between stiff and compliant MMTV-PyMT mouse mammary tumors. We found similar compositions of cancer and stromal subpopulations in compliant and stiff tumors but differential intercellular communication and a significantly higher concentration of tumor-promoting, M2-like macrophages in the stiffer tumor microenvironments. Using a biomaterial-based platform, we found that cancer cells seeded on stiffer substrates recruited more macrophages, supporting our in vivo findings. Together, our results demonstrate a key role of matrix stiffness in affecting cell-cell communication and macrophage recruitment.

Does Preoperative Opioid Consumption Influence Patient Satisfaction following Total Knee Arthroplasty?

Chronic opioid use prior to total knee arthroplasty (TKA) has been implicated in adverse outcomes. The purpose of this study was to evaluate clinical outcome measures and patient satisfaction in patients with a history of preoperative chronic opioid use undergoing primary TKA. A retrospective cohort study was performed on 296 consecutive patients undergoing primary TKA. Seventy-four (25%) patients were identified with chronic preoperative opioid use (study group; 22 males, 52 females). A 3:1 matched cohort ratio of control versus study group was utilized resulting in a control group consisting of 222 patients (97 males, 125 females) without chronic opioid use prior to surgery. There was no statistically significant difference in age, BMI, or follow-up. Average follow-up was 23.4 months in the control group and 23.6 months in the study group (p = 0.87). Clinical data including patient satisfaction (Likert score), Knee Society (KS) Knee scores, KS Function scores, Forgotten Joint Score (FJS), length of stay (LOS), and complications were evaluated. Patient satisfaction at the most recent visit was 92.8% in the control group versus 83.8% in the chronic opioid group (p = 0.0016). Differences in patient-reported outcomes measures comparing the control and study cohorts included KS Function Score of 83.23 versus 75.31 (p = 0.0034). The FJS of 63.7 versus 58 (p = 0.1883) and the KS Knee Score of 89.5 versus 88.1 (p = 0.4075) were not significant. Postoperative opioid usage for the control versus the study group was 62/222 (27.9%) versus 56/74 (75.7%) at 4 to 8 weeks (p <0.0001), and 4/222 (1.80%) versus 27/74 (36.5%) at 12 months (p <0.0001). Overall complication occurrence was 18.9% in the study group versus 11.3% in the control group (p = 0.11). Patients with history of chronic preoperative opioid use had significantly lower patient satisfaction and KS Function scores and increased postoperative opioid usage at 12 months compared with patients without a history of opioid use prior to TKA.

Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemo-resistant pancreatic cancer.

Pancreatic ductal adenocarcinoma is a lethal disease with limited treatment options and poor survival. We studied 83 spatial samples from 31 patients (11 treatment-naïve and 20 treated) using single-cell/nucleus RNA sequencing, bulk-proteogenomics, spatial transcriptomics and cellular imaging. Subpopulations of tumor cells exhibited signatures of proliferation, KRAS signaling, cell stress and epithelial-to-mesenchymal transition. Mapping mutations and copy number events distinguished tumor populations from normal and transitional cells, including acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia. Pathology-assisted deconvolution of spatial transcriptomic data identified tumor and transitional subpopulations with distinct histological features. We showed coordinated expression of TIGIT in exhausted and regulatory T cells and Nectin in tumor cells. Chemo-resistant samples contain a threefold enrichment of inflammatory cancer-associated fibroblasts that upregulate metallothioneins. Our study reveals a deeper understanding of the intricate substructure of pancreatic ductal adenocarcinoma tumors that could help improve therapy for patients with this disease.

Pollock: fishing for cell states.

Motivation: The use of single-cell methods is expanding at an ever-increasing rate. While there are established algorithms that address cell classification, they are limited in terms of cross platform compatibility, reliance on the availability of a reference dataset and classification interpretability. Here, we introduce Pollock, a suite of algorithms for cell type identification that is compatible with popular single-cell methods and analysis platforms, provides a set of pretrained human cancer reference models, and reports interpretability scores that identify the genes that drive cell type classifications. Results: Pollock performs comparably to existing classification methods, while offering easily deployable pretrained classification models across a wide variety of tissue and data types. Additionally, it demonstrates utility in immune pan-cancer analysis. Availability and implementation: Source code and documentation are available at https://github.com/ding-lab/pollock. Pretrained models and datasets are available for download at https://zenodo.org/record/5895221. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

Pluripotent stem cells related to embryonic disc exhibit common self-renewal requirements in diverse livestock species.

Despite four decades of effort, robust propagation of pluripotent stem cells from livestock animals remains challenging. The requirements for self-renewal are unclear and the relationship of cultured stem cells to pluripotent cells resident in the embryo uncertain. Here, we avoided using feeder cells or serum factors to provide a defined culture microenvironment. We show that the combination of activin A, fibroblast growth factor and the Wnt inhibitor XAV939 (AFX) supports establishment and continuous expansion of pluripotent stem cell lines from porcine, ovine and bovine embryos. Germ layer differentiation was evident in teratomas and readily induced in vitro. Global transcriptome analyses highlighted commonality in transcription factor expression across the three species, while global comparison with porcine embryo stages showed proximity to bilaminar disc epiblast. Clonal genetic manipulation and gene targeting were exemplified in porcine stem cells. We further demonstrated that genetically modified AFX stem cells gave rise to cloned porcine foetuses by nuclear transfer. In summary, for major livestock mammals, pluripotent stem cells related to the formative embryonic disc are reliably established using a common and defined signalling environment. This article has an associated 'The people behind the papers' interview.

Differential pre-malignant programs and microenvironment chart distinct paths to malignancy in human colorectal polyps.

Colorectal cancers (CRCs) arise from precursor polyps whose cellular origins, molecular heterogeneity, and immunogenic potential may reveal diagnostic and therapeutic insights when analyzed at high resolution. We present a single-cell transcriptomic and imaging atlas of the two most common human colorectal polyps, conventional adenomas and serrated polyps, and their resulting CRC counterparts. Integrative analysis of 128 datasets from 62 participants reveals adenomas arise from WNT-driven expansion of stem cells, while serrated polyps derive from differentiated cells through gastric metaplasia. Metaplasia-associated damage is coupled to a cytotoxic immune microenvironment preceding hypermutation, driven partly by antigen-presentation differences associated with tumor cell-differentiation status. Microsatellite unstable CRCs contain distinct non-metaplastic regions where tumor cells acquire stem cell properties and cytotoxic immune cells are depleted. Our multi-omic atlas provides insights into malignant progression of colorectal polyps and their microenvironment, serving as a framework for precision surveillance and prevention of CRC.

Tanning Attitudes and Behaviors in Adolescents and Young Adults.

Skin cancer rates have been steadily increasing over the last 20 years despite persistent efforts to educate the public on skin cancer prevention and sun safety. Adolescents and young adults are an especially important demographic to reach, as increased UV exposure during these years leads to greatly increased risks of developing skin cancer. Our survey aims to investigate the attitudes and behaviors regarding sun protection and tanning among adolescents and young adults (age range, 13-27 years).

Patient satisfaction following total knee arthroplasty using restricted kinematic alignment.

AIMS: Alternative alignment concepts, including kinematic and restricted kinematic, have been introduced to help improve clinical outcomes following total knee arthroplasty (TKA). The purpose of this study was to evaluate the clinical results, along with patient satisfaction, following TKA using the concept of restricted kinematic alignment. METHODS: A total of 121 consecutive TKAs performed between 11 February 2018 to 11 June 2019 with preoperative varus deformity were reviewed at minimum one-year follow-up. Three knees were excluded due to severe preoperative varus deformity greater than 15°, and a further three due to requiring revision surgery, leaving 109 patients and 115 knees to undergo primary TKA using the concept of restricted kinematic alignment with advanced technology. Patients were stratified into three groups based on the preoperative limb varus deformity: Group A with 1° to 5° varus (43 knees); Group B between 6° and 10° varus (56 knees); and Group C with varus greater than 10° (16 knees). This study group was compared with a matched cohort of 115 TKAs and 115 patients using a neutral mechanical alignment target with manual instruments performed from 24 October 2016 to 14 January 2019. RESULTS: Mean overall patient satisfaction for the entire cohort was 4.7 (SE 0.1) on a 5-point Likert scale, with 93% being either very satisfied or satisfied compared with a Likert of 4.3 and patient satisfaction of 81% in the mechanical alignment group (p < 0.001 and p < 0.006 respectively). At mean follow-up of 17 months (11 to 27), the mean overall Likert, Knee Injury and Osteoarthritis Outcome Score for Joint Replacement, Western Ontario and McMaster Universities Osteoarthritis Index, Forgotten Joint Score, and Knee Society Knee and Function Scores were significantly better in the kinematic group than in the neutral mechanical alignment group. The most common complication in both groups was contracture requiring manipulation under anaesthesia, involving seven knees (6.1%) in the kinematic group and nine knees (7.8%) in the mechanical alignment group. CONCLUSION: With the advent of advanced technology, and the ability to obtain accurate bone cuts, the target limb alignment, and soft-tissue balance within millimetres, using a restricted kinematic alignment concept demonstrated excellent patient satisfaction following primary TKA. Longer-term analysis is required as to the durability of this method. Cite this article: Bone Joint J 2021;103-B(6 Supple A):59-66.

Cancer-Related Mutations Are Not Enriched in Naive Human Pluripotent Stem Cells.

Previous analysis of RNA sequencing (RNA-seq) data from human naive pluripotent stem cells reported multiple point "mutations" in cancer-related genes and implicated selective culture conditions. We observed, however, that those mutations were only present in co-cultures with mouse feeder cells. Inspection of reads containing the polymorphisms revealed complete identity to the mouse reference genome. After we filtered reads to remove sequences of mouse origin, the actual incidence of oncogenic polymorphisms arising in naive pluripotent stem cells is close to zero.

Chance health locus of control beliefs in Hindu Nepali patients following anterior cruciate ligament reconstruction relates to perceived sports knee function and symptoms.

PURPOSE: In western society an internal health locus of control (perception that health outcomes are due to one's own behavior) is related to perceived sports knee function following anterior cruciate ligament reconstruction. This prospective cohort study was performed to determine if similar health beliefs exist among athletically active Hindu patients from Nepal following primary anterior cruciate ligament reconstruction. MATERIALS AND METHODS: Twenty-five consecutive patients (21 men, 4 women) of 26.7 ± 7.7 years of age participated in this study at 4.2 ± 2 months post-surgery. All subjects had undergone primary anterior cruciate ligament reconstruction using a bone-patellar tendon-bone autograft, with anteromedial portal use for femoral tunnel drilling and interference screw fixation. Subjects completed the Knee Outcome Survey - Sports Activities Scale symptoms and functional limitations during sports subscales and Form C of the Multidimensional Health Locus of Control scales. Descriptive and correlational statistical analysis was performed. An alpha level of p < 0.05 was selected to indicate statistical significance. RESULTS: Knee Outcome Survey - Sports Activity Scale symptoms scores were 71.3 ± 18 (range = 43-97) and functional limitations scores were 42.4 ± 34 (range = 10-95). Multidimensional Health Locus of Control subscale scores were Internal (27.8 ± 4.6), Chance (21.5 ± 6.3), Doctors (16.1 ± 1.9) and other people (14 ± 3.5). Significant relationships were not observed between symptoms or functional limitations subscale scores and Multidimensional Health Locus of Control internal, doctors or powerful others subscale scores. However, strong (r = 0.72) and moderately strong (r = 0.48) relationships were observed between the Multidimensional Health Locus of Control chance subscale score and Knee Outcome Survey - Sports Activities Scale functional limitations and symptoms subscales, respectively. CONCLUSION: Following primary anterior cruciate ligament reconstruction, Hindu patients from Nepal displayed strong relationships between perceived knee function and symptoms and the Multidimensional Health Locus of Control chance subscale. Identification and targeting the beliefs of patients may be clinically important to facilitating positive treatment progression and behavioral changes during post-surgical rehabilitation programs. Further studies are needed to determine how medical and rehabilitation clinicians who provide care to patients from eastern, collectivist cultures can optimize healthcare strategies for patients with sociocultural or religious/spirituality influences that possess strong chance or luck beliefs.Implications for RehabilitationFollowing primary anterior cruciate ligament reconstruction, Hindu patients from Nepal displayed strong relationships between perceived knee function and chance health locus of control beliefs.Identification and targeting the health locus of control beliefs of patients may be clinically important to facilitating positive treatment progression and behavioral changes during post-surgical rehabilitation programs.Medical and rehabilitation professionals need to become more aware of how a patient's religious or spiritual beliefs may conflict with healthcare instructions, or, alternatively, could be better harnessed to facilitate improved program adherence.

Improved Patient Satisfaction following Robotic-Assisted Total Knee Arthroplasty.

Approximately 20% of the patients are dissatisfied with their total knee arthroplasty (TKA). Computer technology has been introduced for TKA to provide real time intraoperative information on limb alignment and exact flexion/extension gap measurements. The purpose of this study was to determine if patient satisfaction could be improved with the use of robotic-assisted (RA) technology following primary TKA. A total of 120 consecutive patients undergoing RA-TKA with real time intraoperative alignment and gap balancing information were compared with a prospective cohort of 103 consecutive patients undergoing TKA with manual jig-based instruments during the same time period. There were no differences between groups with age, gender, baseline Knee Society Score (KSS) knee and function scores, follow-up, and ASA scores. TKAs were performed using same technique, implant design, anesthesia, and postoperative treatment protocols. Patient satisfaction survey using KSS and Likert scoring system were obtained at 1-year follow-up. Likert scoring system demonstrated 94% of the patients in the RA group were either very satisfied or satisfied versus 82% in the manual instruments TKA group (p = 0.005). RA-TKA group had better average scores of all five satisfaction questions although not significant. RA-TKA group had a better average overall satisfaction score of 7.1 versus 6.6 in the manual instrument group, p = 0.03. KSS function scores were significantly better at 6 weeks and 1 year postoperatively (p = 0.02, 0.005), and KSS knee scores were significantly better at 1 year postoperatively (p = 0.046). There are multiple reasons for patient dissatisfaction following primary TKA. Using intraoperative computer technology with RA surgery for patients undergoing a primary TKA, a significant improvement in patient satisfaction was demonstrated compared with TKA using conventional manual jig-based instruments. RA surgery provides several advantages in TKA including real time information in millimeters to help obtain balanced gaps, accurate bone cuts, reduced soft tissue injury, and achieve the target alignment which may lead to improved patient satisfaction.

Decreased Opioid Consumption and Length of Stay Using an IPACK and Adductor Canal Nerve Block following Total Knee Arthroplasty.

Peripheral nerve blocks such as a femoral + sciatic block have demonstrated significant pain relief following TKA. However, these nerve blocks have residual motor deficits which prevent immediate postoperative ambulation. The purpose of this study was to compare outcomes in patients undergoing primary TKA with femoral and sciatic (Fem + Sci) motor nerve blocks versus an adductor canal and the interspace between the popliteal artery and the capsule of the posterior knee and adductor canal block (IPACK + ACB) sensory nerve blocks. A total of 100 consecutive patients were reviewed, 50 received Fem + Sci nerve blocks and 50 received IPACK + ACB blocks preoperatively. There were no differences in the two groups with respect to surgical technique, implant type, postoperative pain, and physical therapy protocols. Differences in opioid requirements, length of stay (LOS), distance walked, and common knee scoring systems were analyzed. Among them, 62% IPACK + ACB patients were discharged on postoperative day 1 compared with 14% in the Fem + Sci group (p < 0.0001). The IPACK + ACB patients had a shorter LOS (mean 1.48 days vs. 2.02 days, p < 0.001), ambulated further on postoperative day 0 (mean 21.4 feet vs. 5.3 feet, p < 0.001), and required less narcotics the day after surgery (mean, 15.7 vs. 24.0 morphine equivalents p < 0.0001) and at 2 weeks (mean, 6.2 vs. 9.3 morphine equivalents, p = 0.025). The use of this combination IPACK and ACB demonstrated improved early ambulation with a decrease in opioid use and length of stay compared with a femoral and sciatic motor nerve block in patients undergoing primary TKA.