Clinical and radiological outcomes with an augmented baseplate for superior glenoid wear in reverse shoulder arthroplasty.

Aims: This study aimed to assess the impact of using the metal-augmented glenoid baseplate (AGB) on improving clinical and radiological outcomes, as well as reducing complications, in patients with superior glenoid wear undergoing reverse shoulder arthroplasty (RSA). Methods: From January 2016 to June 2021, out of 235 patients who underwent primary RSA, 24 received a superior-AGB after off-axis reaming (Group A). Subsequently, we conducted propensity score matching in a 1:3 ratio, considering sex, age, follow-up duration, and glenoid wear (superior-inclination and retroversion), and selected 72 well-balanced matched patients who received a standard glenoid baseplate (STB) after eccentric reaming (Group B). Superior-inclination, retroversion, and lateral humeral offset (LHO) were measured to assess preoperative glenoid wear and postoperative correction, as well as to identify any complications. Clinical outcomes were measured at each outpatient visit before and after surgery. Results: There were no significant differences in demographic data and preoperative characteristics between the two groups. Both groups showed significant improvements in patient-reported outcome measures (visual analogue scale for pain, visual analogue scale for function, American Shoulder and Elbow Surgeons, Constant, and Simple Shoulder Test scores) from preoperative to final assessment (p < 0.001). However, AGB showed no additional benefit. Notably, within range of motion, Group B showed significant postoperative decrease in both external rotation and internal rotation, unlike Group A (p = 0.028 and 0.003, respectively). Both groups demonstrated a significant correction of superior-inclination after surgery, while patients in Group B exhibited a significant decrease in LHO postoperatively (p = 0.001). Regarding complications, Group A experienced more acromial stress fractures (3 cases; 12.5%), whereas Group B had a higher occurrence of scapular notching (24 cases; 33.3%) (p = 0.008). Conclusion: Both eccentric reaming with STB and off-axis reaming with AGB are effective methods for addressing superior glenoid wear in RSA, leading to improved clinical outcomes. However, it is important to be aware of the potential risks associated with eccentric reaming, which include excessive bone loss leading to reduced rotation and scapular notching.

Effect of using a small baseplate on the radiological and clinical outcomes of reverse total shoulder arthroplasty in Asian patients.

Aims: The aim of this study was to compare the clinical and radiological outcomes of reverse shoulder arthroplasty (RSA) using small and standard baseplates in Asian patients, and to investigate the impact of a mismatch in the sizes of the glenoid and the baseplate on the outcomes. Methods: This was retrospective analysis of 50 and 33 RSAs using a standard (33.8 mm, ST group) and a small (29.5 mm, SM group) baseplate of the Equinoxe reverse shoulder system, which were undertaken between January 2017 and March 2021. Radiological evaluations included the size of the glenoid, the ß-angle, the inclination of the glenoid component, inferior overhang, scapular notching, the location of the central cage in the baseplate within the vault and the mismatch in size between the glenoid and baseplate. Clinical evaluations included the range of motion (ROM) and functional scores. In subgroup analysis, comparisons were performed between those in whom the vault of the glenoid was perforated (VP group) and those in whom it was not perforated (VNP group). Results: Perforation of the vault of the glenoid (p = 0.018) and size mismatch in height (p < 0.001) and width (p = 0.013) were significantly more frequent in the ST group than in the SM group. There was no significant difference in the clinical scores and ROM in the two groups, two years postoperatively (all p > 0.05). In subgroup analysis, the VP group had significantly less inferior overhang (p = 0.009), more scapular notching (p = 0.018), and more size mismatch in height (p < 0.001) and width (p = 0.025) than the VNP group. Conclusion: In Asian patients with a small glenoid, using a 29.5 mm small baseplate at the time of RSA was more effective in reducing size mismatch between the glenoid and the baseplate, decreasing the incidence of perforation of the glenoid vault, and achieving optimal positioning of the baseplate compared with the use of a 33.8 mm standard baseplate. However, longer follow-up is required to assess the impact of these findings on the clinical outcomes.

D-SPIN constructs gene regulatory network models from multiplexed scRNA-seq data revealing organizing principles of cellular perturbation response.

Gene regulatory networks within cells modulate the expression of the genome in response to signals and changing environmental conditions. Reconstructions of gene regulatory networks can reveal the information processing and control principles used by cells to maintain homeostasis and execute cell-state transitions. Here, we introduce a computational framework, D-SPIN, that generates quantitative models of gene-regulatory networks from single-cell mRNA-seq data sets collected across thousands of distinct perturbation conditions. D-SPIN models the cell as a collection of interacting gene-expression programs, and constructs a probabilistic model to infer regulatory interactions between gene-expression programs and external perturbations. Using large Perturb-seq and drug-response datasets, we demonstrate that D-SPIN models reveal the organization of cellular pathways, sub-functions of macromolecular complexes, and the logic of cellular regulation of transcription, translation, metabolism, and protein degradation in response to gene knockdown perturbations. D-SPIN can also be applied to dissect drug response mechanisms in heterogeneous cell populations, elucidating how combinations of immunomodulatory drugs can induce novel cell states through additive recruitment of gene expression programs. D-SPIN provides a computational framework for constructing interpretable models of gene-regulatory networks to reveal principles of cellular information processing and physiological control.

Arthroscopic biceps augmentation does not improve clinical outcomes during incomplete repair of large to massive rotator cuff tears.

AIMS: This study compared patients who underwent arthroscopic repair of large to massive rotator cuff tears (LMRCTs) with isolated incomplete repair of the tear and patients with incomplete repair with biceps tendon augmentation. We aimed to evaluate the additional benefit on clinical outcomes and the capacity to lower the re-tear rate. METHODS: We retrospectively reviewed 1,115 patients who underwent arthroscopic rotator cuff repair for full-thickness tears between October 2011 and May 2019. From this series, we identified 77 patients (28 male, 49 female) with a mean age of 64.1 years (50 to 80). Patients were classified into groups A (n = 47 incomplete) and B (n = 30 with biceps augmentation) according to the nature of their reconstruction. Clinical scores were checked preoperatively and at six months, one year, and two years postoperatively. In preoperative MRI, we measured the tear size, the degree of fatty infiltration, and muscle volume ratio of the supraspinatus. In postoperative MRI, the integrity of the repaired rotator cuff tendon was assessed using the Sugaya classification. Tendon thickness at the footprint was evaluated on T2-weighted oblique coronal view. RESULTS: There were no significant differences in the initial preoperative demographic characteristics. In both groups, there were significant improvements in postoperative clinical scores (p < 0.001). However, most clinical outcomes, including range of motion measurements (forward elevation, external rotation, internal rotation, and abduction), showed no differences between the pre- and postoperative values. Comparing the postoperative outcomes of both groups, no further improvement from biceps augmentation was found. Group B, although not reaching statistical significance, had more re-tears than group A (30% vs 15%; p = 0.117). CONCLUSION: In LMRCTs, biceps augmentation provided no significant improvement of an incomplete repair. Therefore, biceps augmentation is not recommended in the treatment of LMRCTs.Cite this article: Bone Joint J 2022;104-B(11):1234-1241.

Comparative analysis of Achilles tendon healing outcomes after open tenotomy versus percutaneous tenotomy: An experimental study in rats.

There is growing interest in conservative treatment of Achilles tendon rupture. However, the majority of experimental studies of Achilles tendon have been performed by open tenotomy. More appropriate model of conservative treatment of Achilles tendon rupture is required. We performed an experimental study to evaluate whether outcomes differ between open tenotomy and percutaneous tenotomy of the Achilles tendon in rats. The Achilles tendons of 48 rats were transected. The animals were divided into two groups according to surgical technique: open tenotomy or microscopy-assisted percutaneous tenotomy. After 1, 2, and 4 weeks, functional, biomechanical, and histological analyses were performed. Western blot was performed for quantitative molecular analysis at 1 week. The Achilles functional index was superior in the percutaneous tenotomy group, compared with the open tenotomy group, at 1 week. The cross-sectional area was significantly larger in the percutaneous tenotomy group than in the open tenotomy group at 4 weeks. Relative to the native tendons, load to failure and stiffness yielded comparable results at 2 weeks in the percutaneous tenotomy group and at 4 weeks in the open tenotomy group. The histological score was significantly better in the percutaneous tenotomy group than in the open tenotomy group at 1 week. At 1 week, interleukin-1ß expression in the open tenotomy group was higher than in the percutaneous tenotomy group. In summary, Achilles tendon healing was substantially affected by the tenotomy method. We presume that our percutaneous tenotomy method might constitute a useful experimental animal model for conservative treatment of Achilles tendon rupture.

Dissecting heterogeneous cell populations across drug and disease conditions with PopAlign.

Single-cell measurement techniques can now probe gene expression in heterogeneous cell populations from the human body across a range of environmental and physiological conditions. However, new mathematical and computational methods are required to represent and analyze gene-expression changes that occur in complex mixtures of single cells as they respond to signals, drugs, or disease states. Here, we introduce a mathematical modeling platform, PopAlign, that automatically identifies subpopulations of cells within a heterogeneous mixture and tracks gene-expression and cell-abundance changes across subpopulations by constructing and comparing probabilistic models. Probabilistic models provide a low-error, compressed representation of single-cell data that enables efficient large-scale computations. We apply PopAlign to analyze the impact of 40 different immunomodulatory compounds on a heterogeneous population of donor-derived human immune cells as well as patient-specific disease signatures in multiple myeloma. PopAlign scales to comparisons involving tens to hundreds of samples, enabling large-scale studies of natural and engineered cell populations as they respond to drugs, signals, or physiological change.

Bimodal function of chromatin remodeler Hmga1 in neural crest induction and Wnt-dependent emigration.

During gastrulation, neural crest cells are specified at the neural plate border, as characterized by Pax7 expression. Using single-cell RNA sequencing coupled with high-resolution in situ hybridization to identify novel transcriptional regulators, we show that chromatin remodeler Hmga1 is highly expressed prior to specification and maintained in migrating chick neural crest cells. Temporally controlled CRISPR-Cas9-mediated knockouts uncovered two distinct functions of Hmga1 in neural crest development. At the neural plate border, Hmga1 regulates Pax7-dependent neural crest lineage specification. At premigratory stages, a second role manifests where Hmga1 loss reduces cranial crest emigration from the dorsal neural tube independent of Pax7. Interestingly, this is rescued by stabilized ß-catenin, thus implicating Hmga1 as a canonical Wnt activator. Together, our results show that Hmga1 functions in a bimodal manner during neural crest development to regulate specification at the neural plate border, and subsequent emigration from the neural tube via canonical Wnt signaling.

The neural plate is a structure that serves as the basis for the brain and central nervous system during the development of animals with a backbone. In particular, the tissues at the border of the neural plate become the neural crest, a group of highly mobile cells that can specialize to form nerves and parts of the face. The exact molecular mechanisms that allow the crest to emerge are still unknown. The protein Hmga1 alters how genes are packaged and organized inside cells, which in turn influences how genes are switched on and off. Here, Gandhi et al. studied how Hmga1 helps to shape the neural crest in developing chicken embryos. To do so, they harnessed a genetic tool called CRISPR-Cas9, and deleted the gene that encodes Hmga1 at specific developmental stages. This manipulation highlighted two periods where Hmga1 is active. First, Hmga1 helped to define neural crest cells at the neural plate border by activating a gene called pax7. Then, at a later stage, Hmga1 allowed these cells to move to other parts of the body by triggering the Wnt communication system. Failure for the neural crest to develop properly causes birth defects and cancers such as melanoma and childhood neuroblastoma, highlighting the need to better understand how this structure is formed. In addition, a better grasp of the roles of Hmga1 in healthy development could help to appreciate how it participates in a range of adult cancers.

Vitamin D Status as a Predictor of Postoperative Hypocalcemia after Thyroidectomy.

OBJECTIVE: To determine whether perioperative vitamin D levels are predictive of postoperative hypocalcemia in patients receiving thyroidectomy. STUDY DESIGN: Single center retrospective study. SUBJECTS AND METHODS: This study included all patients receiving total or completion thyroidectomy between January 2007 and March 2017 at a single tertiary care hospital. 25-Hydroxyvitamin D (25[OH]D) levels were measured within 42 days prior to surgery or 1 day postoperatively. Hypocalcemia was defined as an adjusted serum calcium <8.0 mg/dL (based on albumin levels) or symptomatic hypocalcemia. Univariate analysis was performed with a 2-sample t test and chi-square test, while multivariate analysis was performed with logistic regression analysis to determine whether perioperative 25(OH)D level is a predictor of postoperative hypocalcemia. RESULTS: A total of 517 subjects were included in the study, 15.7% (n = 81) of whom experienced postoperative hypocalcemia with a mean ± SD serum calcium level of 7.6 ± 0.5 mg/dL as compared with 8.9 ± 0.5 mg/dL in the normocalcemic population (P < .01). The mean 25(OH)D level for patients with hypocalcemia was 24.4 ± 12.0 ng/mL as compared with 27.5 ± 12.2 ng/mL in patients with normocalcemia (P = .038). Subjects who were hypocalcemic experienced a significantly longer hospital stay (2.9 ± 2.5 vs 1.4 ± 1.1 days, P < .01). After adjusting for preoperative calcium, age, and performance of a neck dissection, subjects with a 25(OH)D level <30 ng/mL were significantly associated with postoperative hypocalcemia (odds ratio, 1.9; P = .041; 95% CI, 1.0-3.3). CONCLUSION: Using a single-center retrospective study design, we demonstrated that 25(OH)D level is a significant predictor of postoperative hypocalcemia after thyroidectomy.

Parkinson disease-related cortical and striatal cognitive patterns in dual time F-18 FP CIT: evidence for neural correlates between the caudate and the frontal lobe.

BACKGROUND: Using dual time F-18 FP-CIT, we evaluated cortical perfusion, striatal binding and neuropsychological performance simultaneously in Parkinson disease (PD) with and without mild cognitive impairment (MCI), to investigate neural correlates between caudate and frontal cortex. METHODS: According to the neuropsychological scores, subjects were classified into 26 healthy controls (HC), 38 PD-MCI (executive) (PE), 24 PD-MCI (non-executive) (PN) and 21 PD (motor) (PM). Scans were acquired at 10 minutes and 2 hours. Group differences of early perfusion and delayed binding were compared using SPM and volume of interest method. The relationships between neuropsychological variables and the striatal binding were investigated with correlation and regression analysis. RESULTS: Compared with PM, PE showed decreased prefrontal perfusion and binding of both caudates (right: P=0.0010, left: P=0.014), but not of both putamens. Compared with PN, PE showed decreased binding of both caudates (right: P=0.001, left: P=0.005), but not in both putamens. Binding of both caudates correlated with the Stroop z-score, but not of both putamens. Executive score was a contributing factor to binding of the caudate, and not the putamen. CONCLUSIONS: PE showed decreased prefrontal perfusion and caudate binding, supporting neural correlates between the caudate and the prefrontal cortex. Dopaminergic binding of the caudate, but not of the putamen, was related to executive scores. Caudate hypofunction was specific to executive domain. This is the first study that elucidated the clinical use of dual time F-18 FP-CIT for integrative evaluation of cognitive and motor function in PD.

In vivo intraocular pressure monitoring during microincision vitrectomy with and without active control of infusion pressure.

PURPOSE: To evaluate intraocular pressure (IOP) fluctuation during vitrectomy, we directly monitored IOP in vivo using 2 vitrectomy machines with or without constant infusion pressure monitoring and control. METHODS: Among 61 eyes of 61 consecutive patients, 32 were assigned to the Accurus system (group 1) and 29 were assigned to the Constellation system (group 2) in this prospective case series. The IOP fluctuations were evaluated during routine vitrectomy procedures. RESULTS: The initial IOP before vitrectomy was 20.3 ± 2.4 mm Hg in group 1 using a conventional vented gas forced infusion system and 20.0 ± 0.0 mm Hg in group 2 using active IOP control at 20 mm Hg (p = 0.532). However, the average IOP change during core vitrectomy was -8.6 ± 4.3 mm Hg in group 1 and -0.8 ± 1.1 in group 2 (p<00.001). Maximum IOP was significantly decreased in group 1 (-17.0 ± 2.6 mm Hg) compared with that in group 2 (-4.1 ± 2.2 mm Hg) (p<00.001). Partial ocular collapse was observed during vitrectomy only in group 1 (78.1%). Peak IOP significantly increased during scleral compression and gas and fluid injection but was not significantly different between the groups (all p≥0.147). The IOP fluctuation range was 50-70 mm Hg in both groups. CONCLUSIONS: The IOP fluctuated significantly during routine vitrectomy using both systems. Hypotony and partial ocular collapse were more frequently observed during vitrectomy with the Accurus system than with the Constellation system. Both systems were vulnerable to IOP surge during indentation and intravitreal injection.

Practices and predictors of 2009 H1N1 vaccination in cancer patients: a nationwide survey in Korea.

BACKGROUND: Because patients with cancer are considered to be at high-risk for influenza infection and related complications, annual vaccination is recommended. The emergence of the novel H1N1 influenza virus in 2009 complicated the medical care of patients with cancer. The present study examined H1N1 vaccination practices among patients with cancer during the pandemic season and investigated factors related to the vaccination. METHODS: A national multicenter cross-sectional survey of patient-doctor dyads was performed; A total of 97 oncologists (response rates of invited participants, 87.4%) and 495 patients (response rates of recruited participants, 86.5%) were included. Patients with cancer provided information concerning vaccination practices and reasons for/against it. Oncologists answered questions about their recommendations and knowledge of H1N1 vaccination. Mixed logistic regression was used to identify patient-level and physician-level predictors of H1N1 vaccination. RESULTS: Only 34.1% of the patients had received H1N1 vaccination, and 53.5% had not considered the need for vaccination. The H1N1 vaccine was proactively recommended by physicians in only a small fraction of patients (8.3%). Increasing age, higher educational status, longer time since the cancer diagnosis, comorbidities, and greater knowledge of H1N1 vaccination among oncologists were significant predictors of patients being vaccinated. CONCLUSIONS: The present results showed low levels of utilization and poor interaction between patients and physicians with regard to the need for vaccination. In addition, the oncologist's level of knowledge affected the adoption of preventive services. Intervention strategies are needed to maximize the rapid adoption of preventive methods to confront future pandemic threats in the cancer patient population.

In situ intestinal permeability and in vivo absorption characteristics of olmesartan medoxomil in self-microemulsifying drug delivery system.

To characterize the intestinal absorption behavior of olmesartan medoxomil (OLM) and to evaluate the absorption-improving potential of a self-microemulsifying drug delivery system (SMEDDS), we performed in situ single-pass intestinal perfusion (SPIP) and in vivo pharmacokinetic studies in rats. The SPIP study revealed that OLM is absorbed throughout whole intestinal regions, favoring proximal segments, at drug levels of 10-90 µM. The greatest value for effective permeability coefficient (P(eff)) was 11.4 × 10(-6) cm/s in the duodenum (90 µM); the lowest value was 2.9 × 10(-6) cm/s in the ileum (10 µM). A SMEDDS formulation consisting of Capryol 90, Labrasol, and Transcutol, which has a droplet size of 200 nm and self-dispersion time of 21 s, doubled upper intestinal permeability of OLM. The SMEDDS also improved oral bioavailability of OLM in vivo: a 2.7-fold increase in the area under the curve (AUC) with elevated maximum plasma concentration (C(max)) and shortened peak time (T(max)) compared to an OLM suspension. A strong correlation (r(2) = 0.955) was also found between the in situ jejunal P(eff) and the in vivo AUC values. Our study illustrates that the SMEDDS formulation holds great potential as an alternative to increased oral absorption of OLM.

Large-scale co-evolution analysis of protein structural interlogues using the global protein structural interactome map (PSIMAP).

MOTIVATION: Interacting pairs of proteins should co-evolve to maintain functional and structural complementarity. Consequently, such a pair of protein families shows similarity between their phylogenetic trees. Although the tendency of co-evolution has been known for various ligand-receptor pairs, it has not been studied systematically in the widest possible scope. We investigated the degree of co-evolution for more than 900 family pairs in a global protein structural interactome map (PSIMAP--a map of all the structural domain-domain interactions in the PDB). RESULTS: There was significant correlation in 45% of the total SCOPs Family level pairs, rising to 78% in 454 reliable family interactions. Expectedly, the intra-molecular interactions between protein families showed stronger co-evolution than inter-molecular interactions. However, both types of interaction have a fundamentally similar pattern of co-evolution except for cases where different interfaces are involved. These results validate the use of co-evolution analysis with predictive methods such as PSIMAP to improve the accuracy of prediction based on "homologous interaction". The tendency of co-evolution enabled a nearly 5-fold enrichment in the identification of true interactions among the potential interlogues in PSIMAP. The estimated sensitivity was 79.2%, and the specificity was 78.6%. AVAILABILITY: The results of co-evolution analysis are available online at http://www.biointeraction.org

Visualization and analysis of protein interactions.

SUMMARY: We have developed a new program called InterViewer for drawing large-scale protein interaction networks in three-dimensional space. Unique features of InterViewer include (1) it is much faster than other recent implementations of drawing algorithms; (2) it can be used not only for visualizing protein interactions but also for analyzing them interactively; and (3) it provides an integrated framework for querying protein interaction databases and directly visualizes the query results. AVAILABILITY: http://wilab.inha.ac.kr/protein/

Brain-derived neurotrophic factor can act as a pronecrotic factor through transcriptional and translational activation of NADPH oxidase.

Several lines of evidence suggest that neurotrophins (NTs) potentiate or cause neuronal injury under various pathological conditions. Since NTs enhance survival and differentiation of cultured neurons in serum or defined media containing antioxidants, we set out experiments to delineate the patterns and underlying mechanisms of brain-derived neurotrophic factor (BDNF)-induced neuronal injury in mixed cortical cell cultures containing glia and neurons in serum-free media without antioxidants, where the three major routes of neuronal cell death, oxidative stress, excitotoxicity, and apoptosis, have been extensively studied. Rat cortical cell cultures, after prolonged exposure to NTs, underwent widespread neuronal necrosis. BDNF-induced neuronal necrosis was accompanied by reactive oxygen species (ROS) production and was dependent on the macromolecular synthesis. cDNA microarray analysis revealed that BDNF increased the expression of cytochrome b558, the plasma membrane-spanning subunit of NADPH oxidase. The expression and activation of NADPH oxidase were increased after exposure to BDNF. The selective inhibitors of NADPH oxidase prevented BDNF-induced ROS production and neuronal death without blocking antiapoptosis action of BDNF. The present study suggests that BDNF-induced expression and activation of NADPH oxidase cause oxidative neuronal necrosis and that the neurotrophic effects of NTs can be maximized under blockade of the pronecrotic action.