Ophthalmic drop waste due to self-imposed use cessation dates.

Self-imposed use cessation dates for multi-use eye drop bottles lead to significant drug waste and increased costs. We quantified the residual medication in eye drop bottles across three clinics in an academic ambulatory setting.

Peripheral Artery Disease among a High-Risk Asian Population with Ischaemic Stroke, Cardiovascular Disease, or Diabetes Mellitus.

Background: Peripheral artery disease (PAD) affects more than 100 million people globally. Most PAD studies have been performed among predominantly White populations-less is known about other ethnicities. The aim of this cross-sectional study was to determine the prevalence and risk factors of PAD in a high-risk Asian population with ischaemic stroke (IS), myocardial infarction, unstable angina (CVD), or diabetes mellitus (DM). Methods: Patients admitted for IS, CVD, or DM were recruited. Data were collected on age, sex, body mass index (BMI), index condition (CVD, IS, DM), history of hypertension, DM, hypercholesterolaemia, cigarette smoking, and claudication. The Edinburgh Claudication Questionnaire was administered, the ankle brachial index (ABI) was determined, and PAD was diagnosed if ABI was ≤0.9. Results: Of the 450 subjects recruited, 150 were placed in each index disease group, the mean age was 61.9 ± 10.32 years, 43.1% were female, and the mean BMI was 23.9 ± 4.3. Hypertension was reported in 59.3%, DM in 63.6%, hypercholesterolaemia in 39.6%, and smoking in 42.9% of patients. The prevalence of PAD was 27.1%, 22.0% in IS, 29.3% in CAD, and 30.0% in DM. PAD was associated with increasing age (adjusted odds ratio (aOR) 1.04/year, 95% confidence interval [CI] 1.01-1.06; p < 0.001), reduced BMI (aOR 0.94, 95% CI 0.89-0.99; p = 0.026), DM (aOR 1.59, 95% CI 1.20-3.18; p = 0.007), and hypercholesterolaemia (aOR 1.82, 95% CI 1.17-2.28; p = 0.007). It was more frequent in non-lacunar versus lacunar acute IS, non-ST segment elevation versus ST-segment elevation acute myocardial infarction, and insulin-treated versus non-insulin-treated DM. Conclusions: Our study showed a high prevalence of PAD among high-risk Asian patients. This was associated with increasing age, DM, and hypercholesterolaemia and inversely associated with BMI. Different rates were found in sub-groups of IS, CVD, and DM. Systematic approaches were used to identify these high-risk individuals and to improve their outcomes.

A critical view on autoantibodies in lupus nephritis: Concrete knowledge based on evidence.

Deposition of autoantibodies in glomeruli is a key factor in the development of lupus nephritis (LN). For a long time, anti-dsDNA and anti-C1q antibodies were thought to be the main cause of the kidney damage. However, recent studies have shown that the list of autoantibidies that have renal tropism and deposit in the kidney in LN is increasing and the link between anti-dsDNA and renal pathology is weak due to potential confounders. Aspecific bindings of dsDNA with cationic antibodies and of anti-dsDNA with several renal antigens such as actinin, laminin, entactin, and annexinA2 raised doubts about the specific target of these antibodies in the kidney. Moreover, the isotype of anti-dsDNA in SLE and LN has never received adequate interest until the recent observation that IgG2 are preponderant over IgG1, IgG3 and IgG4. Based on the above background, recent studies investigated the involvement of anti-dsDNA IgG2 and of other antibodies in LN. It was concluded that circulating anti-dsDNA IgG2 levels do not distinguish between LN versus non-renal SLE, and, in patients with LN, their levels do not change over time. Circulating levels of other antibodies such as anti-ENO1 and anti-H2 IgG2 were, instead, higher in LN vs non-renal SLE at the time of diagnosis and decreased following therapies. Finally, new classes of renal antibodies that potentially modify the anti-inflammatory response in the kidney are emerging as new co-actors in the pathogenetic scenario. They have been defined as 'second wave antibodies' for the link with detoxifying mechanisms limiting the oxidative stress in glomeruli that are classically stimulated in a second phase of inflammation. These findings have important clinical implications that may modify the laboratory approach to LN. Serum levels of anti-ENO1 and anti-H2 IgG2 should be measured in the follow up of patients for designing the length of therapies and identify those patients who respond to treatments. Anti-SOD2 could help to monitor and potentiate the anti-inflammatory response in the kidney.

Cost and outcomes of Hospital-based Usual cAre versus Tele-monitor self-directed Rehabilitation (HUATR) in patients with total knee arthroplasty: A randomized, controlled, non-inferiority trial.

OBJECTIVE: To evaluate the clinical efficacy and cost-effectiveness of telemonitored self-directed rehabilitation (TR) compared with hospital-based rehabilitation (HBR) for patients with total knee arthroplasty (TKA). DESIGN: In this randomized, non-inferiority clinical trial, 114 patients with primary TKA who were able to walk independently preoperatively were randomized to receive HBR (n = 58) or TR (n = 56). HBR comprised at least five physical therapy sessions over 10 weeks. TR comprised a therapist-led onboarding session, followed by a 10-week unsupervised home-based exercise program, with asynchronous monitoring of rehabilitation outcomes using a telemonitoring system. The primary outcome was fast-paced gait speed at 12 weeks, with a non-inferiority margin of 0.10 m/s. For economic analysis, quality-adjusted-life-years (QALY) was the primary economic outcome (non-inferiority margin, 0.027 points). RESULTS: In Bayesian analyses, TR had >95% posterior probability of being non-inferior to HBR in gait speed (week-12 adjusted TR-HBR difference, 0.02 m/s; 95%CrI, -0.05 to 0.10 m/s; week-24 difference, 0.01 m/s; 95%CrI, -0.07 to 0.10 m/s) and QALY (0.006 points; 95%CrI, -0.006 to 0.018 points). When evaluated from a societal perspective, TR was associated with lower mean intervention cost (adjusted TR-HBR difference, -S$227; 95%CrI, -112 to -330) after 24 weeks, with 82% probability of being cost-effective compared with HBR at a willingness to pay of S$0/unit of effect for the QALYs. CONCLUSIONS: In patients with uncomplicated TKAs and relatively good preoperative physical function, home-based, self-directed TR was non-inferior to and more cost-effective than HBR over a 24-week follow-up period. TR should be considered for this patient subgroup.

Genome-wide epitope mapping across multiple host species reveals significant diversity in antibody responses to Coxiella burnetii vaccination and infection.

Coxiella burnetii is an important zoonotic bacterial pathogen of global importance, causing the disease Q fever in a wide range of animal hosts. Ruminant livestock, in particular sheep and goats, are considered the main reservoir of human infection. Vaccination is a key control measure, and two commercial vaccines based on formalin-inactivated C. burnetii bacterins are currently available for use in livestock and humans. However, their deployment is limited due to significant reactogenicity in individuals previously sensitized to C. burnetii antigens. Furthermore, these vaccines interfere with available serodiagnostic tests which are also based on C. burnetii bacterin antigens. Defined subunit antigen vaccines offer significant advantages, as they can be engineered to reduce reactogenicity and co-designed with serodiagnostic tests to allow discrimination between vaccinated and infected individuals. This study aimed to investigate the diversity of antibody responses to C. burnetii vaccination and/or infection in cattle, goats, humans, and sheep through genome-wide linear epitope mapping to identify candidate vaccine and diagnostic antigens within the predicted bacterial proteome. Using high-density peptide microarrays, we analyzed the seroreactivity in 156 serum samples from vaccinated and infected individuals to peptides derived from 2,092 open-reading frames in the C. burnetii genome. We found significant diversity in the antibody responses within and between species and across different types of C. burnetii exposure. Through the implementation of three different vaccine candidate selection methods, we identified 493 candidate protein antigens for protein subunit vaccine design or serodiagnostic evaluation, of which 65 have been previously described. This is the first study to investigate multi-species seroreactivity against the entire C. burnetii proteome presented as overlapping linear peptides and provides the basis for the selection of antigen targets for next-generation Q fever vaccines and diagnostic tests.

Natural immunity to malaria preferentially targets the endothelial protein C receptor-binding regions of PfEMP1s.

Antibody responses to variant surface antigens (VSAs) produced by the malaria parasite Plasmodium falciparum may contribute to age-related natural immunity to severe malaria. One VSA family, P. falciparum erythrocyte membrane protein-1 (PfEMP1), includes a subset of proteins that binds endothelial protein C receptor (EPCR) in human hosts and potentially disrupts the regulation of inflammatory responses, which may lead to the development of severe malaria. We probed peptide microarrays containing segments spanning five PfEMP1 EPCR-binding domain variants with sera from 10 Malian adults and 10 children to determine the differences between adult and pediatric immune responses. We defined serorecognized peptides and amino acid residues as those that elicited a significantly higher antibody response than malaria-naïve controls. We aimed to identify regions consistently serorecognized among adults but not among children across PfEMP1 variants, potentially indicating regions that drive the development of immunity to severe malaria. Adult sera consistently demonstrated broader and more intense serologic responses to constitutive PfEMP1 peptides than pediatric sera, including peptides in EPCR-binding domains. Both adults and children serorecognized a significantly higher proportion of EPCR-binding peptides than peptides that do not directly participate in receptor binding, indicating a preferential development of serologic responses at functional residues. Over the course of a single malaria transmission season, pediatric serological responses increased between the start and the peak of the season, but waned as the transmission season ended. IMPORTANCE Severe malaria and death related to malaria disproportionately affect sub-Saharan children under 5 years of age, commonly manifesting as cerebral malaria and/or severe malarial anemia. In contrast, adults in malaria-endemic regions tend to experience asymptomatic or mild disease. Our findings indicate that natural immunity to malaria targets specific regions within the EPCR-binding domain, particularly peptides containing EPCR-binding residues. Epitopes containing these residues may be promising targets for vaccines or therapeutics directed against severe malaria. Our approach provides insight into the development of natural immunity to a binding target linked to severe malaria by characterizing an "adult-like" response as recognizing a proportion of epitopes within the PfEMP1 protein, particularly regions that mediate EPCR binding. This "adult-like" response likely requires multiple years of malaria exposure, as increases in pediatric serologic response over a single malaria transmission season do not appear significant.

Control of maternal Zika virus infection during pregnancy is associated with lower antibody titers in a macaque model.

Introduction: Zika virus (ZIKV) infection during pregnancy results in a spectrum of birth defects and neurodevelopmental deficits in prenatally exposed infants, with no clear understanding of why some pregnancies are more severely affected. Differential control of maternal ZIKV infection may explain the spectrum of adverse outcomes. Methods: Here, we investigated whether the magnitude and breadth of the maternal ZIKV-specific antibody response is associated with better virologic control using a rhesus macaque model of prenatal ZIKV infection. We inoculated 18 dams with an Asian-lineage ZIKV isolate (PRVABC59) at 30-45 gestational days. Plasma vRNA and infectious virus kinetics were determined over the course of pregnancy, as well as vRNA burden in the maternal-fetal interface (MFI) at delivery. Binding and neutralizing antibody assays were performed to determine the magnitude of the ZIKV-specific IgM and IgG antibody responses throughout pregnancy, along with peptide microarray assays to define the breadth of linear ZIKV epitopes recognized. Results: Dams with better virologic control (n= 9) cleared detectable infectious virus and vRNA from the plasma by 7 days post-infection (DPI) and had a lower vRNA burden in the MFI at delivery. In comparison, dams with worse virologic control (n= 9) still cleared detectable infectious virus from the plasma by 7 DPI but had vRNA that persisted longer, and had higher vRNA burden in the MFI at delivery. The magnitudes of the ZIKV-specific antibody responses were significantly lower in the dams with better virologic control, suggesting that higher antibody titers are not associated with better control of ZIKV infection. Additionally, the breadth of the ZIKV linear epitopes recognized did not differ between the dams with better and worse control of ZIKV infection. Discussion: Thus, the magnitude and breadth of the maternal antibody responses do not seem to impact maternal virologic control. This may be because control of maternal infection is determined in the first 7 DPI, when detectable infectious virus is present and before robust antibody responses are generated. However, the presence of higher ZIKV-specific antibody titers in dams with worse virologic control suggests that these could be used as a biomarker of poor maternal control of infection and should be explored further.

Could Some Patients With Fibromyalgia Potentially Have Hypophosphatasia? A Retrospective Single-Center Study.

OBJECTIVE: Hypophosphatasia (HPP) is a rare disease characterized by incomplete or defective bone mineralization due to a mutation in the alkaline phosphatase (ALP) gene causing low levels of ALP. Disease presentation is heterogeneous and can present as a chronic pain syndrome like fibromyalgia (FM). Our objective was to determine if there are any potential patients with HPP in the group of patients who were diagnosed with FM. Antiresorptive therapy use can trigger atypical femur fractures in patients with HPP. METHODS: We performed a retrospective chart review of all patients 18 years or older at a single academic center who were diagnosed with FM and had either a low or a normal ALP level. The following characteristics were reviewed: biological sex; age; history of fractures; diagnosis of osteoporosis, osteopenia, osteoarthritis, and chondrocalcinosis; genetic testing; vitamin B6 level testing; and medications. RESULTS: Six hundred eleven patients with FM were identified. Two hundred had at least one low ALP level, and 57 had at least three consecutively low measurements of ALP, 44% of which had a history of fractures. No patients had vitamin B6 levels checked. None of the patients had previous genetic testing for HPP or underwent testing for zinc or magnesium levels. CONCLUSION: The percentage of patients with FM who were found to have consistently low ALP levels was 9.3%. None had vitamin B6 level or genetic testing, suggesting that the diagnosis was not suspected. It is important to diagnose HPP given the availability of enzyme replacement therapy to prevent complications from HPP such as fractures. Our data support screening for this condition as a part of the initial workup of FM.

Physiological Effects of Handling in Moderate to Late Preterm Infants Receiving Neonatal Intensive Care.

BACKGROUND: Of all preterm births, approximately 82% are moderate to late preterm. Moderate to late preterm infants are often treated like full-term infants despite their physiological and metabolic immaturity, increasing their risk for mortality and morbidity. PURPOSE: To describe the relationship between routine caregiving methods and physiological markers of stress and hypoxemia in infants born between 32 and 36 6/7 weeks' gestation. METHODS: This descriptive study used a prospective observational design to examine the relationship between routine caregiving patterns (single procedure vs clustered care) and physiological markers of stress and hypoxemia such as regional oxygen saturation, quantified as renal and cerebral regional oxygen saturation (StO 2 ), systemic oxygen saturation (Sp o2 ), and heart rate (HR) in moderate to late preterm infants. Renal and cerebral StO 2 was measured using near-infrared spectroscopy during a 6-hour study period. Sp o2 and HR were measured using pulse oximetry. RESULTS: A total of 231 procedures were captured in 37 participants. We found greater alterations in cerebral StO 2 , renal StO 2 , Sp o2 , and HR when routine procedures were performed consecutively in clusters than when procedures were performed singly or separately. IMPLICATIONS FOR PRACTICE AND RESEARCH: Our results suggest that the oxygen saturation and HR of moderate to late preterm infants were significantly altered when exposed to routine procedures that were performed consecutively, in clusters, compared with when exposed to procedures that were performed singly or separately. Adequately powered randomized controlled trials are needed to determine the type of caregiving patterns that will optimize the health outcomes of this vulnerable population.

Clinical Interpretability of Quadriceps Strength and Gait Speed Performance in Total Knee Arthroplasty: A Longitudinal Study.

OBJECTIVE: After a total knee arthroplasty, physical assessments of quadriceps strength and gait speed performance are often undertaken during rehabilitation. Our study aimed to improve their clinical interpretability by examining trajectory curves across levels of self-reported walking and stair climbing function. DESIGN: A sample of 2624 patients with primary total knee arthroplasty participated in this retrospective longitudinal study. Monthly, for 4 mos after surgery, quadriceps strength and gait speed were quantified. At the month-6 time point, self-reported walking and stair climbing function was measured. RESULTS: All physical measures improved nonlinearly over time. In mixed-effects models, greater quadriceps strength and gait speed over time were associated with higher month-6 self-reported walking and stair climbing function ( P < 0.001). Steeper gains in quadriceps strength and gait speed were associated with higher levels of walking and stair-climbing function (interaction P < 0.001). Among female patients who had great difficulty with stair ascent and ambulation, quadriceps strength trajectory curves plateaued after 8 wks after total knee arthroplasty. CONCLUSIONS: By stratifying trajectory curves across clinically interpretable functional levels, our findings potentially provide patients and clinicians a means to better interpret the continuous-scaled quadriceps strength and gait speed values. This information may be valuable when engaging patients in shared decision making and expectation setting. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME. CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Understand how self-reported walking and stair climbing abilities improved from baseline before total knee arthroplasty (total knee arthroplasty) to 6 mos postoperatively; (2) Describe the time course of the 2 performance-based measures of quadriceps strength and walking speed after a total knee arthroplasty; and (3) Relate the trajectories of post-total knee arthroplasty quadriceps strength and walking speed measurements across distinct levels of self-reported walking and stair climbing function. LEVEL: Advanced. ACCREDITATION: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) ™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

The association between bronchopulmonary dysplasia grade and risks of adverse neurodevelopmental outcomes among preterm infants born at less than 30 weeks of gestation.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a multifactorial disease with neurodevelopmental implications. This study aims to quantify the risks of adverse neurodevelopmental outcomes for each BPD grade among preterm infants born at less than 30 weeks' gestation. METHODS: We retrospectively studied infants who received care in our institution until at least 36 weeks postmenstrual age and had a formal neurodevelopmental assessment in our infant follow-up clinic using the Bayley Scales for Infant and Toddler Development (BSID). We assessed the association between BPD grade and adverse neurodevelopmental outcomes using descriptive statistics and regression models. RESULTS: Two hundred and fifty infants, including 89 (35.6%), 87 (34.8%), 65 (20.6%), and 9 (3.6%) with No BPD, Grade 1, Grade 2, and Grade 3 BPD, were included in the study. Small for gestational age, late pulmonary hypertension, dexamethasone administration, and adverse neurodevelopmental outcomes were more common as BPD grade increased. In a logistic regression analysis, Grades 2 and 3, but not Grade 1, BPD were associated with increased odds of a composite adverse neurodevelopmental outcome by 2.7 and 7.2 folds, respectively. A BSID domain-specific analysis showed that higher grades were associated with lower scores in the cognitive, gross motor, and fine motor domains. CONCLUSIONS: Grades 2 and 3 BPD, but not Grade 1, correlate with risks of adverse neurodevelopmental outcomes at a grade-dependent manner in our single-center cohort retrospective study. Further validation using a multi-center large cohort is warranted.

Insect biorefinery: A circular economy concept for biowaste conversion to value-added products.

With rapid growing world population and increasing demand for natural resources, the production of sufficient food, feed for protein and fat sources and sustainable energy presents a food insecurity challenge globally. Insect biorefinery is a concept of using insect as a tool to convert biomass waste into energy and other beneficial products with concomitant remediation of the organic components. The exploitation of insects and its bioproducts have becoming more popular in recent years. This review article presents a summary of the current trend of insect-based industry and the potential organic wastes for insect bioconversion and biorefinery. Numerous biotechnological products obtained from insect biorefinery such as biofertilizer, animal feeds, edible foods, biopolymer, bioenzymes and biodiesel are discussed in the subsequent sections. Insect biorefinery serves as a promising sustainable approach for waste management while producing valuable bioproducts feasible to achieve circular bioeconomy.

Assessing Immune Factors in Maternal Milk and Paired Infant Plasma Antibody Binding to Human Rhinoviruses.

Before they can produce their own antibodies, newborns are protected from infections by transplacental transfer of maternal IgG antibodies and after birth through breast milk IgA antibodies. Rhinovirus (RV) infections are extremely common in early childhood, and while RV infections often result in only mild upper respiratory illnesses, they can also cause severe lower respiratory illnesses such as bronchiolitis and pneumonia. We used high-density peptide arrays to profile infant and maternal antibody reactivity to capsid and full proteome sequences of three human RVs - A16, B52, and C11. Numerous plasma IgG and breast milk IgA RV epitopes were identified that localized to regions of the RV capsid surface and interior, and also to several non-structural proteins. While most epitopes were bound by both IgG and IgA, there were several instances where isotype-specific and RV-specific binding were observed. We also profiled 62 unique RV-C dominant protein loop sequences characteristic of this species' capsid VP1 protein. Many of these RV-C sites were highly bound by IgG from one-year-old infants, indicating recent or ongoing active infections, or alternatively, a level of cross-reactivity among homologous RV-C sites.

The association between foot posture, single leg balance and running biomechanics of the foot.

OBJECTIVES: A mal-aligned foot posture (high-arched and flat feet) and poor single leg balance ability have been separately associated with foot injuries during running. Therefore, clinicians assess these routinely. However, the extent to which foot posture and single-leg balance ability affect actual foot biomechanics during running is not known. This study aims to investigate the association of foot posture, single-leg balance ability, and foot biomechanics during running. METHOD: This is a cross sectional study of sixty-nine participants who had their foot postures and single-leg balance ability assessed. The Foot Posture Index and Balance Error Scoring System were used. Their foot kinetics was measured as they ran on an instrumented treadmill and foot kinematics was processed using a 3D motion capture system. Multiple-regression was used to analyse the variance of foot biomechanics explained by foot posture and single-leg balance ability. RESULTS: Foot posture and single-leg balance ability were found to account significantly for the variance in rearfoot eversion (24%) and forefoot dorsiflexion (7%). Two regression equations were derived, where rearfoot eversion and forefoot dorsiflexion during running may be predicted. CONCLUSION: Foot posture and single-leg balance ability can predict rearfoot eversion and forefoot dorsiflexion only during running. Based on the regression equations, individuals with the same foot posture but different single-leg balance ability may exhibit different foot kinematics. However, the angular differences are small. The equations may be useful for clinicians working in places where running gait analysis equipment are not readily accessible. Further studies with larger sample sizes are required to validate these equations. In addition, further studies are necessary to investigate the effect of these two variables under different running conditions e.g. with footwear and with orthoses.

Data analytics in a clinical setting: Applications to understanding breathing patterns and their relevance to neonatal disease.

In this review, we focus on the use of contemporary linear and non-linear data analytics as well as machine learning/artificial intelligence algorithms to inform treatment of pediatric patients. We specifically focus on methods used to quantify changes in breathing that can lead to increased risk for apnea of prematurity, retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC) and provide a list of potentially useful algorithms that comprise a suite of software tools to enhance prediction of outcome. Next, we provide a brief overview of machine learning/artificial intelligence methods and applications within the sphere of perinatal care. Finally, we provide an overview of the infrastructure needed to use these tools in a clinical setting for real-time data acquisition, data synchrony, data storage and access, and bedside data visualization to assist in clinical decision making and support the medical informatics mission. Our goal is to provide an overview and inspire other investigators to adopt these tools for their own research and optimization of perinatal patient care.

Machine learning for prediction of bronchopulmonary dysplasia-free survival among very preterm infants.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is one of the most common and serious sequelae of prematurity. Prompt diagnosis using prediction tools is crucial for early intervention and prevention of further adverse effects. This study aims to develop a BPD-free survival prediction tool based on the concept of the developmental origin of BPD with machine learning. METHODS: Datasets comprising perinatal factors and early postnatal respiratory support were used for initial model development, followed by combining the two models into a final ensemble model using logistic regression. Simulation of clinical scenarios was performed. RESULTS: Data from 689 infants were included in the study. We randomly selected data from 80% of infants for model development and used the remaining 20% for validation. The performance of the final model was assessed by receiver operating characteristics which showed 0.921 (95% CI: 0.899-0.943) and 0.899 (95% CI: 0.848-0.949) for the training and the validation datasets, respectively. Simulation data suggests that extubating to CPAP is superior to NIPPV in BPD-free survival. Additionally, successful extubation may be defined as no reintubation for 9 days following initial extubation. CONCLUSIONS: Machine learning-based BPD prediction based on perinatal features and respiratory data may have clinical applicability to promote early targeted intervention in high-risk infants.

Discovery of anti-Formin-like 1 protein (FMNL1) antibodies in membranous nephropathy and other glomerular diseases.

Evidence has shown that podocyte-directed autoantibodies can cause membranous nephropathy (MN). In the present work we investigated sera of MN patients using a high-density peptide array covering the whole coding sequences of the human genome encompassing 7,499,126 tiled peptides. A panel of 21 proteins reactive to MN sera were identified. We focused our attention on Formin-like 1 (FMNL1), a protein expressed by macrophages in MN patients tissues. High levels of anti-FMNL1 IgG4 were demonstrated in sera of MN patients with an orthogonal methodology (ELISA) contemporary demonstrating FMNL1 positive cells in kidney co-staining with CD68 in glomeruli. High levels of circulating anti-FMNL1 IgG4 were associated with lack of remission of proteinuria, potentially indicating that autoantibodies directed against cells other than podocytes, involved in tissue repair, might play a role in MN disease progression. High serum levels of anti-FMNL1 IgGs were also observed in other non-autoimmune glomerolonephrites, i.e. idiopathic and genetic FSGS, IgAGN. These findings are suggestive of a broader role of those autoantibodies in other glomerular disease conditions.

Sit-to-Stand Weight-Bearing Symmetry Performance in Total Knee Arthroplasty: Recovery Curves, Correlates, and Predictive Validity With Gait Speed.

OBJECTIVE: After total knee arthroplasty, the ability to weight bear symmetrically during the sit-to-stand task provides important information regarding altered movement patterns. Despite this, comprehensive recovery curves and validity data for sit-to-stand weight-bearing symmetry are lacking in the total knee arthroplasty population. Our study aimed to (1) develop recovery curves with reference ranges, (2) identify the correlates of standard and constrained sit-to-stand weight-bearing symmetry, and (3) evaluate their predictive validity with gait speed. DESIGN: We performed a retrospective longitudinal study of 706 patients with primary unilateral total knee arthroplasty. Monthly, for 4 mos after surgery, sit-to-stand weight-bearing symmetry, knee pain, knee range of motion, quadriceps strength, and gait speed were quantified. RESULTS: Standard and constrained sit-to-stand weight-bearing symmetry measures improved nonlinearly over time. Standard sit-to-stand weight-bearing symmetry was most strongly associated with bilateral quadriceps strength, whereas constrained sit-to-stand weight-bearing symmetry was most strongly associated with ipsilateral quadriceps strength. Knee range of motion and contralateral knee pain were additional correlates. Both standard sit-to-stand and constrained sit-to-stand weight-bearing symmetry were independently and nonlinearly associated with gait speed in multivariable models. CONCLUSIONS: Our study provided recovery curves and validity data to support routine clinical measurement of sit-to-stand weight-bearing symmetry in total knee arthroplasty. Our results also indicate that constrained sit-to-stand may promote greater use of the operated limb than standard sit-to-stand.

Assessment of Coronary Artery Obstruction Risk During Transcatheter Aortic Valve Replacement Utilising 3D-Printing.

BACKGROUND: Current imaging techniques may inadequately rule out coronary artery obstruction (CAO), a potentially fatal complication during transcatheter aortic valve replacement (TAVR). Advancements in three-dimensional (3D)-printing allow the development of models capable of replicating cardiac anatomy and predicting CAO. We sought to simulate TAVR utilising 3D-printed cardiac models to improve CAO risk assessment and procedural safety. METHODS: Thirteen (13) patients with aortic stenosis at high-risk of CAO during TAVR were selected for 3D-printed modelling. The relevant anatomy for TAVR was precisely reconstructed with Materialise Heart Print-Flex (Materialse, Leuven, Belgium) technology. An appropriately sized valve prosthesis was deployed in each 3D-model and coronary ostia assessed for obstruction. RESULTS: Model-derived results were compared to clinical outcomes in 13 cases. One high-risk case underwent TAVR resulting in left main obstruction and subsequent stenting. This outcome was accurately predicted by the 3D-model simulation. Two (2) high-risk TAVR cases were abandoned following transient CAO during balloon aortic valvuloplasty (BAV). The 3D-model simulations correlated with these findings, demonstrating CAO either by a calcium nodule or the native valve leaflet. In another two cases, BAV was uncertain, however the 3D-simulation demonstrated patency and successful TAVR was undertaken. In remaining cases, no obstruction was demonstrated in-vitro, and all underwent uncomplicated TAVR. CONCLUSIONS: In this proof-of-concept study, 3D-model TAVR simulation correlates well to clinical outcomes. 3D-models of patients at high-risk of CAO may be utilised in pre-procedural planning to accurately predict this complication. As lower-risk surgical cohorts are considered for TAVR, 3D-models may minimise complications leading to safer patient outcomes.