Effects of antiseptic irrigation solutions on osseointegration in a cementless tibial implantation mouse model.

Despite the success of standard antiseptic irrigation solutions in reducing periprosthetic joint infection (PJI) rates, there is still a need for more effective solutions. Synergistic use of povidone-iodine (PI) and hydrogen peroxide (H2O2) has shown promising results; however, the optimal solution concentration balancing bactericidal activity and osseointegration remains unknown. This study aims to evaluate the impact of these antiseptic irrigation solutions on osseointegration and the bone-implant interface strength in vivo. Forty C57BL/6 mice underwent bilateral tibial implantation surgery and were randomly allocated into three groups receiving 0.3% PI, 10% PI mixed with 3% H2O2, or saline as irrigation solutions intraoperatively. Assessments were performed on postoperative Days 1 and 28, including plain radiographs, microcomputed tomography (microCT) evaluation, histological analysis, immunohistochemistry, and biomechanical pull-out testing. No wound complications were observed. MicroCT scans revealed no differences in peri-implant trabecular bone parameters. Biomechanical pull-out testing showed no differences in the bone-implant interface strength across groups. Histological analysis indicated no differences in bone and bone marrow percentage areas among treatment groups. Immunohistochemical analysis demonstrated no differences among groups in peri-implant osteocalcin, osterix, or endomucin-positive cells. In conclusion, using either antiseptic irrigation solution showed no differences in osseointegration parameters compared to the control group, demonstrating safety and the absence of toxicity. CLINICAL RELEVANCE: Dilute 0.3% povidone-iodine and a 1:1 combination of 10% povidone-iodine mixed with 3% hydrogen peroxide can be safely used during primary and revision total joint arthroplasty without compromising osseointegration or causing wound complications.

The efficacy of antibiotic-eluting material in a two-stage model of periprosthetic joint infection.

Periprosthetic joint infections occur in about 2% of patients who undergo primary total joint arthroplasty, a procedure performed over 1 million times in the United States. The gold standard of treatment is a two-stage revision. This study aimed to establish a two-stage procedure in a preclinical small animal model (rat) to test and compare the efficacy of an antibiotic-eluting material in managing infection. Joint replacement was simulated by transchondylarly implanting a polyethylene (PE) plug into the distal femur and a titanium screw in the proximal tibia. Methicillin-sensitive Staphylococcus aureus (MSSA) 108 CFU/mL was injected into the tibial canal and the joint space before wound closure. The control groups were killed on postoperative day (POD) 18 (n = 12) and on POD 42 (n = 4) to assess both early and later-stage outcomes in the control group. The test group underwent revision surgery on POD 18 for treatment using gentamicin-eluting polyethylene (GPE, n = 4) and was observed until POD 42 to evaluate the efficacy of treatment. Our results showed that the bone loss for the treatment group receiving GPE was significantly less than that of the control (p < 0.05), which was supported by the histology images and an AI-tool assisted infection rate evaluation. Gait metrics duty factor imbalance and hindlimb temporal symmetry were significantly different between the treatment and control groups on Day 42. This animal model was feasible for evaluating treatments for peri-prosthetic joint infections (PJI) with a revision surgery and specifically that revision surgery and local antibiotic treatment largely hindered the peri-prosthetic bone loss. Statement of clinical significance: This revision model of peri-prosthetic infection has the potential of comparatively evaluating prophylaxis and treatment strategies and devices. Antibiotic-eluting UHMWPE is devised as at tool in treating PJI while providing weight bearing and joint space preservation.

A longitudinal rat model for assessing postoperative recovery and bone healing following tibial osteotomy and plate fixation.

BACKGROUND: Rodent models are commonly employed to validate preclinical disease models through the evaluation of postoperative behavior and allodynia. Our study investigates the dynamic interplay between pain and functional recovery in the context of traumatic osteotomy and surgical repair. Specifically, we established a rat model of tibial osteotomy, followed by internal fixation using a 5-hole Y-plate with 4 screws, to explore the hypothesis that histological bone healing is closely associated with functional recovery. OBJECTIVE: Our primary objective was to assess the correlation between bone healing and functional outcomes in a rat model of tibial osteotomy and plate fixation. METHODS: Seventeen male Sprague-Dawley rats underwent a metaphyseal transverse osteotomy of the proximal tibia, simulating a fracture-like injury. The resultant bone defect was meticulously repaired by realigning and stabilizing the bone surfaces with the Y-plate. To comprehensively assess recovery and healing, we performed quantitative and qualitative evaluations at 2, 4, 6, and 8 weeks post-surgery. Evaluation methods included micro-CT imaging, X-ray analysis, and histological examination to monitor bone defect healing. Concurrently, we employed video recording and gait analysis to evaluate functional recovery, encompassing parameters such as temporal symmetry, hindlimb duty factor imbalance, phase dispersion, and toe spread. RESULTS: Our findings revealed complete healing of the bone defect at 8 weeks, as confirmed by micro-CT and histological assessments. Specifically, micro-CT data showed a decline in fracture volume over time, indicating progressive healing. Histological examination demonstrated the formation of new trabecular bone and the resolution of inflammation. Importantly, specific gait analysis parameters exhibited longitudinal changes consistent with bone healing. Hindlimb duty factor imbalance, hindlimb temporal symmetry, and phase dispersion correlated strongly with the healing process, emphasizing the direct link between bone healing and functional outcomes. CONCLUSIONS: The establishment of this tibia osteotomy model underscores the association between bone healing and functional outcomes, emphasizing the feasibility of monitoring postoperative recovery using endpoint measurements. Our overarching objective is to employ this model for assessing the local efficacy of drug delivery devices in ameliorating post-surgical pain and enhancing functional recovery.

Medical Therapy and Scleral Windows for Uveal Effusion Syndrome: A Case Series and Literature Review.

INTRODUCTION: Uveal effusion syndrome (UES) is a rare ocular disease causing idiopathic uveal effusion, often with associated ciliochoroidal and retinal detachment. UES diagnosis is challenging because of overlapping features with other ocular inflammatory, neoplastic, iatrogenic, and drug-induced causes of uveal effusion. While several successful surgical treatments have been described, such as full-thickness or partial-thickness sclerectomy, medical therapies may also have a therapeutic role. OBJECTIVE: To provide an updated review of the published literature on the course of the disease, medical and surgical management strategies, as well as newer treatment modalities.

Refractive Outcomes After LASIK for the Treatment of Mixed Astigmatism with the Allegretto WaveLight EX500.

INTRODUCTION: Treatment of mixed astigmatism with laser in situ keratomileusis (LASIK) is complex as the correction requires flattening the cornea in one meridian while steepening the cornea in the other meridian. The bitoric technique has become the most popular approach and has been tested across a variety of platforms. This study is the first to evaluate the results of mixed astigmatism treatment using the Allegretto WaveLight® EX500. METHODS: This study was a single-center, retrospective, noncomparative analysis of 400 eyes that underwent LASIK to correct for mixed astigmatism utilizing the EX500 excimer laser. Data on uncorrected distance visual acuity, corrected distance visual acuity, and spherical equivalent was analyzed at consecutive intervals (1, 3, 6, 9, and 12 months). Refractive measurements were used to perform a vector analysis. RESULTS: Three and 12 months postoperatively, 71% and 74% of eyes had an uncorrected distance visual acuity (UDVA) of 20/20 or better and 99% and 100% of eyes had a UDVA of 20/40 or better, respectively. The postoperative UDVA was within one line of the corrected distance visual acuity (CDVA) in 88% and 93% of eyes at 3 and 12 months, respectively. At 3 months, 78% of eyes achieved refractive astigmatism no greater than 0.50 diopters and at 12 months, 80% achieved this. The mean spherical equivalent refraction was - 0.36 ± 0.57 D at 12 months after surgery. At the 12-month follow-up, the mean refractive cylinder was reduced by 87%, from - 2.79 to - 0.37 diopters. On vector analysis, 99% of eyes had an angle of error within ± 15° from the intended target at 3 and 12 months. CONCLUSION: Treatment of mixed astigmatism using the Allegretto WaveLight® EX500 laser exceeded the industry standards of safety, efficacy, stability, and accuracy.

Constructing ion channels from water-soluble α-helical barrels.

The design of peptides that assemble in membranes to form functional ion channels is challenging. Specifically, hydrophobic interactions must be designed between the peptides and at the peptide-lipid interfaces simultaneously. Here, we take a multi-step approach towards this problem. First, we use rational de novo design to generate water-soluble α-helical barrels with polar interiors, and confirm their structures using high-resolution X-ray crystallography. These α-helical barrels have water-filled lumens like those of transmembrane channels. Next, we modify the sequences to facilitate their insertion into lipid bilayers. Single-channel electrical recordings and fluorescent imaging of the peptides in membranes show monodisperse, cation-selective channels of unitary conductance. Surprisingly, however, an X-ray structure solved from the lipidic cubic phase for one peptide reveals an alternative state with tightly packed helices and a constricted channel. To reconcile these observations, we perform computational analyses to compare the properties of possible different states of the peptide.

Refractive enhancements for residual refractive error after cataract surgery.

PURPOSE OF REVIEW: Advances in cataract surgery have allowed surgeons to achieve superior refractive outcomes but have also led to higher patient expectations. Despite ever-evolving technology, residual refractive errors still occur. Postcataract refractive enhancements may be required to deliver satisfactory visual outcomes. This review aims to discuss the potential causes of residual refractive errors and the various enhancement modalities to correct them. RECENT FINDINGS: A thorough preoperative workup to detect and address underlying pathologic causes of impaired vision should be performed prior to enhancement or corrective procedures. Corneal-based procedures are the safest and most accurate methods of correcting mild cases of residual refractive error. Hyperopic, high myopic, and high astigmatic errors are best managed with lens-based enhancements. Piggyback intraocular lenses (IOLs) are safer and more effective compared with IOL exchange. Toric IOL rotation and IOL exchange are ideally performed in the early postoperative period. SUMMARY: A multitude of options exist for effective correction of residual refractive errors. The choice on how to best manage these patients depends on many factors such as the cause of refractive error, type of IOL used, ocular comorbidities, and patient preference.

Use of presbyopia-correcting intraocular lenses in patients with prior corneal refractive surgery.

PURPOSE OF REVIEW: Corneal refractive surgery has achieved spectacle-free vision for millions of patients, but this aging population is now developing cataracts. Many of these patients may wish to avoid reliance on glasses after cataract surgery. Presbyopia-correcting intraocular lenses (IOLs) offer a solution, but corneal changes after refractive surgery may compound higher order aberrations and dysphotopic symptoms associated with these IOLs. This review aims to discuss potential factors that could aid in determining suitable postkeratorefractive candidates for presbyopia-correcting IOLs. RECENT FINDINGS: Studies investigating which preoperative measures influence outcomes are lacking. The few studies that have examined presbyopia-correcting IOLs in postkeratorefractive patients report that satisfactory outcomes are possible. However, recommendations for preoperative thresholds appear limited to expert opinion and studies involving virgin corneas. SUMMARY: As the number of presbyopia-correcting IOLs and postkeratorefractive patients grows, continued investigation into relevant preoperative factors and appropriate IOLs is required to make evidence-based decisions. The current literature shows that with rigorous counseling and appropriate patient selection, presbyopia-correcting IOLs can provide postkeratorefractive patients with satisfactory results and spectacle independence. In addition, the development of postoperative modifiable IOLs may prove to be the preferred option.

Integration of geoscience frameworks into digital pathology analysis permits quantification of microarchitectural relationships in histological landscapes.

Although gold-standard histological assessment is subjective it remains central to diagnosis and clinical trial protocols and is crucial for the evaluation of any preclinical disease model. Objectivity and reproducibility are enhanced by quantitative analysis of histological images but current methods require application-specific algorithm training and fail to extract understanding from the histological context of observable features. We reinterpret histopathological images as disease landscapes to describe a generalisable framework defining topographic relationships in tissue using geoscience approaches. The framework requires no user-dependent training to operate on all image datasets in a classifier-agnostic manner but is adaptable and scalable, able to quantify occult abnormalities, derive mechanistic insights, and define a new feature class for machine-learning diagnostic classification. We demonstrate application to inflammatory, fibrotic and neoplastic disease in multiple organs, including the detection and quantification of occult lobular enlargement in the liver secondary to hilar obstruction. We anticipate this approach will provide a robust class of histological data for trial stratification or endpoints, provide quantitative endorsement of experimental models of disease, and could be incorporated within advanced approaches to clinical diagnostic pathology.

Simultaneous (two-surgeon) versus staged bilateral knee arthroplasty: an observational study of intraoperative and post-operative outcomes.

BACKGROUND: The advantages of simultaneous bilateral total knee arthroplasty (sim-BTKA) remain controversial. This study investigated the effects of two-surgeon sim-BTKA compared to separate admission staged BTKA regarding intraoperative and post-operative outcomes and health service costs. METHODS: Patients underwent sim-BTKA or staged BTKA between 1 November 2008 and 30 June 2016. Data were extracted from a joint replacement registry and medical records. Median regression and chi-squared tests were used for between-group comparisons. RESULTS: Median hospital total length of stay was 5 days less for sim-BTKA (n = 122) than staged BTKA group (n = 46) (7 versus 12; 95% confidence interval (CI) 3.9, 6.1), and 9 days less for inpatient rehabilitation (17 versus 26; 95% CI 3.7, 14.3). However, 80% of sim-BTKA patients went to inpatient rehabilitation (versus 27% following staged BTKA), so median total length of stay was 9 days less for staged BTKA (13 versus 22; 95% CI -12.8, -5.2). Total anaesthesia time was 135 min less for sim-BTKA (P < 0.001), while staged BTKA required less blood transfusions (P = 0.001). Complication rates were similar, except for superficial infections which were observed twice as often after staged BTKA (30% versus 15%, P = 0.048). Twelve months following sim-BTKA and the first staged total knee arthroplasty, sim-BTKA had better WOMAC pain, stiffness and function scores (P ≤ 0.05). Average inpatient costs (hospital and rehabilitation) were $6388 less for sim-BTKA. CONCLUSION: Sim-BTKA appears to be a comparatively safe alternative to staged BTKA. Sim-BTKA may be superior to staged BTKA due to faster improvements in pain and function and lower healthcare costs. How these results generalize to other health services requires further investigation.

Protocol for a single-centre, parallel-arm, double-blind randomised trial evaluating the effects of tourniquet use in total knee arthroplasty on intra-operative and post-operative outcomes.

BACKGROUND: Tourniquet use during total knee replacement is common, yet uncertainty exists regarding its benefits and harms. The primary aim of the current study is to investigate whether tourniquet use during total knee replacement leads to greater reduction in quadriceps strength than non-tourniquet use at three months post-surgery. Secondary aims include investigating the effects of tourniquet use on: quadriceps strength at day 2 and 5, and 12 months post-surgery; pain and analgesia requirements; self-reported physical function and quality of life; blood loss and replacement; surgeon satisfaction with the intra-operative visual field; operation and anaesthetic time; complications; cement mantle quality; patient satisfaction; and hospital length of stay. METHODS: The study is a single centre, parallel-arm, double-blind (participant and assessor), randomised trial with 1:1 random allocation. Participants will be undergo total knee replacement with or without tourniquet. Linear mixed models will be used for group comparisons of continuous outcomes available at multiple timepoints. Other continuous outcomes that are assessed at baseline and once/twice at follow-up will be analysed using linear regression. Categorical outcomes will be analysed using logistic regression models. DISCUSSION: This study will provide high-quality evidence regarding the effects of tourniquet use during total knee replacement, which can be used to inform surgeon decision-making. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618000425291 . Retrospectively registered 23 March 2018.

Maintaining and breaking symmetry in homomeric coiled-coil assemblies.

In coiled-coil (CC) protein structures α-helices wrap around one another to form rope-like assemblies. Most natural and designed CCs have two-four helices and cyclic (Cn) or dihedral (Dn) symmetry. Increasingly, CCs with five or more helices are being reported. A subset of these higher-order CCs is of interest as they have accessible central channels that can be functionalised; they are α-helical barrels. These extended cavities are surprising given the drive to maximise buried hydrophobic surfaces during protein folding and assembly in water. Here, we show that α-helical barrels can be maintained by the strategic placement of ß-branched aliphatic residues lining the lumen. Otherwise, the structures collapse or adjust to give more-complex multi-helix assemblies without Cn or Dn symmetry. Nonetheless, the structural hallmark of CCs-namely, knobs-into-holes packing of side chains between helices-is maintained leading to classes of CCs hitherto unobserved in nature or accessed by design.

Funnel-Guided Positioning of Multicellular Microtissues to Build Macrotissues.

The field of tissue engineering is developing new additive manufacturing technologies to fabricate 3D living constructs for use as in vitro platforms for the testing of drugs and chemicals, or to restore lost function in vivo. In this article, we describe the funnel-guide (FG), a new additive manufacturing strategy for the noncontact manipulation and positioning of multicellular microtissues and we show that the FG can be used to build macrotissues layer by layer. We used agarose micromolds to self-assemble cells into toroid-shaped and honeycomb-shaped microtissues, and observed that when falling in cell culture medium, the microtissues spontaneously righted themselves to a horizontal orientation. We fabricated a funnel to guide these falling toroids and honeycombs into precise positions and stack them, wherein they fused to form tubular structures. We tested multiple cell types and toroid sizes, and ultimately used the FG to create a stack of 45 toroids that fused into a tube 5 mm long with an inner diameter of 600 µm. The FG is a new principle for the manipulation of microtissues and is a platform for the layer-by-layer positioning of microtissue building blocks to form macrotissues.

Hydra Mesoglea Proteome Identifies Thrombospondin as a Conserved Component Active in Head Organizer Restriction.

Thrombospondins (TSPs) are multidomain glycoproteins with complex matricellular functions in tissue homeostasis and remodeling. We describe a novel role of TSP as a Wnt signaling target in the basal eumetazoan Hydra. Proteome analysis identified Hydra magnipapillata TSP (HmTSP) as a major component of the cnidarian mesoglea. In general, the domain organization of cnidarian TSPs is related to the pentameric TSPs of bilaterians, and in phylogenetic analyses cnidarian TSPs formed a separate clade of high sequence diversity. HmTSP expression in polyps was restricted to the hypostomal tip and tentacle bases that harbor Wnt-regulated organizer tissues. In the hypostome, HmTSP- and Wnt3-expressing cells were identical or in close vicinity to each other, and regions of ectopic tentacle formation induced by pharmacological ß-Catenin activation (Alsterpaullone) corresponded to foci of HmTSP expression. Chromatin immunoprecipitation (ChIP) confirmed binding of Hydra TCF to conserved elements in the HmTSP promotor region. Accordingly, ß-Catenin knockdown by siRNAs reduced normal HmTSP expression at the head organizer. In contrast, knockdown of HmTSP expression led to increased numbers of ectopic organizers in Alsterpaullone-treated animals, indicating a negative regulatory function. Our data suggest an unexpected role for HmTSP as a feedback inhibitor of Wnt signaling during Hydra body axis patterning and maintenance.

Presentation, diagnostic assessment and surgical outcomes in primary hyperparathyroidism: a single centre's experience.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is a common reason for referral to endocrinology but the evidence base guiding assessment is limited. We evaluated the clinical presentation, assessment and subsequent management in PHPT. DESIGN: Retrospective cohort study. PATIENTS: PHPT assessed between 2006 - 2014 (n = 611) in a university hospital. MEASUREMENTS: Symptoms, clinical features, biochemistry, neck radiology and surgical outcomes. RESULTS: Fatigue (23.8%), polyuria (15.6%) and polydipsia (14.9%) were associated with PHPT biochemistry. Bone fracture was present in 16.4% but was not associated with biochemistry. A history of nephrolithiasis (10.0%) was associated only with younger age (P = 0.006) and male gender (P = 0.037). Thiazide diuretic discontinuation was not associated with any subsequent change in calcium (P = 0.514). Urine calcium creatinine clearance ratio (CCCR) was <0.01 in 18.2% of patients with confirmed PHPT. Older age (P < 0.001) and lower PTH (P = 0.043) were associated with failure to locate an adenoma on ultrasound (44.0% of scans). When an adenoma was identified on ultrasound the lateralization was correct in 94.5%. Non-curative surgery occurred in 8.2% and was greater in those requiring more than one neck imaging modality (OR 2.42, P = 0.035). CONCLUSIONS: Clinical features associated with PHPT are not strongly related to biochemistry. Thiazide cessation does not appear to attenuate hypercalcaemia. PHPT remains the likeliest diagnosis in the presence of low CCCR. Ultrasound is highly discriminant when an adenoma is identified but surgical failure is more likely when more than one imaging modality is required.

Identifying complications requiring re-operation following primary hip or knee arthroplasty: a consecutive series of 98 patients.

BACKGROUND: The number of hip and knee arthroplasties completed is expected to double over the next decade. In public hospitals, regular post-arthroplasty orthopaedic review has commonly occurred for the duration of a patient's life, which requires substantial outpatient resources. However, there is limited evidence regarding the utility of these reviews for identifying complications. The current study investigated when and where complications requiring re-operation were identified following primary hip or knee arthroplasty. METHODS: The medical records of all patients requiring re-operation for complications following primary hip arthroplasty (n = 48, 2004 to 2015) or knee primary arthroplasty (n = 50, 1998 to 2015) at a large regional health service were evaluated. Data were extracted by one of four investigators using a standardised electronic data extraction tool. Variables of interest included the health setting where the complication was initially identified, how long following the original operation the complication was identified and whether the complication was symptomatic. RESULTS: Routine post-arthroplasty orthopaedic appointments identified 15 (15.3%) complications requiring re-operation; all were identified in the first-year post-surgery. For each complication identified in the first-year post-surgery, approximately 1000 orthopaedic outpatient appointments were required. After the first year, all complications were identified in Emergency Departments (n = 30, 30.6%), General Practice (n = 24, 24.5%) or non-routine orthopaedic outpatient appointments (n = 19, 19.4%). All patients with complications reported symptoms. CONCLUSIONS: Routine post-arthroplasty review appointments were an inefficient mechanism for identifying complications requiring re-operation more than one year following surgery. Public health services should consider assessing and redesigning post-arthroplasty review services to reduce the burden on patients and the demand for outpatient appointments.