Impact of COVID-19 vaccination on symptoms and immune phenotypes in vaccine-naïve individuals with Long COVID.

Background: Long COVID contributes to the global burden of disease. Proposed root cause hypotheses include the persistence of SARS-CoV-2 viral reservoir, autoimmunity, and reactivation of latent herpesviruses. Patients have reported various changes in Long COVID symptoms after COVID-19 vaccinations, leaving uncertainty about whether vaccine-induced immune responses may alleviate or worsen disease pathology. Methods: In this prospective study, we evaluated changes in symptoms and immune responses after COVID-19 vaccination in 16 vaccine-naïve individuals with Long COVID. Surveys were administered before vaccination and then at 2, 6, and 12 weeks after receiving the first vaccine dose of the primary series. Simultaneously, SARS-CoV-2-reactive TCR enrichment, SARS-CoV-2-specific antibody responses, antibody responses to other viral and self-antigens, and circulating cytokines were quantified before vaccination and at 6 and 12 weeks after vaccination. Results: Self-report at 12 weeks post-vaccination indicated 10 out of 16 participants had improved health, 3 had no change, 1 had worse health, and 2 reported marginal changes. Significant elevation in SARS-CoV-2-specific TCRs and Spike protein-specific IgG were observed 6 and 12 weeks after vaccination. No changes in reactivities were observed against herpes viruses and self-antigens. Within this dataset, higher baseline sIL-6R was associated with symptom improvement, and the two top features associated with non-improvement were high IFN-ß and CNTF, among soluble analytes. Conclusions: Our study showed that in this small sample, vaccination improved the health or resulted in no change to the health of most participants, though few experienced worsening. Vaccination was associated with increased SARS-CoV-2 Spike protein-specific IgG and T cell expansion in most individuals with Long COVID. Symptom improvement was observed in those with baseline elevated sIL-6R, while elevated interferon and neuropeptide levels were associated with a lack of improvement.

Hyperpolarisation of Mitochondrial Membranes Is a Critical Component of the Antifungal Mechanism of the Plant Defensin, Ppdef1.

Plant defensins are a large family of small cationic proteins with diverse functions and mechanisms of action, most of which assert antifungal activity against a broad spectrum of fungi. The partial mechanism of action has been resolved for a small number of members of plant defensins, and studies have revealed that many act by more than one mechanism. The plant defensin Ppdef1 has a unique sequence and long loop 5 with fungicidal activity against a range of human fungal pathogens, but little is known about its mechanism of action. We screened the S. cerevisiae non-essential gene deletion library and identified the involvement of the mitochondria in the mechanism of action of Ppdef1. Further analysis revealed that the hyperpolarisation of the mitochondrial membrane potential (MMP) activates ROS production, vacuolar fusion and cell death and is an important step in the mechanism of action of Ppdef1, and it is likely that a similar mechanism acts in Trichophyton rubrum.

Prevalence of incidental humeral intracondylar fissures in brachycephalic breed dogs in CT studies.

Humeral intracondylar fissures (HIF) have been predominantly reported in spaniel breeds and proposed to be possible risk factors for humeral condyle fractures (HCF). We hypothesized that the prevalence of incidental HIF in French Bulldogs may be greater than that of other brachycephalic breeds. A retrospective, observational, prevalence study was performed using CT examinations of French bulldogs and other brachycephalic breed dogs presenting for an unrelated condition. Two European College of Veterinary Diagnostic and Imaging-certified radiologists reviewed the images of the humeral condyles of these dogs. A classification system was devised to grade the findings. We considered a Score 1 to be normal, Score 2 to have centralised sclerosis, Score 3 to have a partial fissure and Score 4 to have a complete fissure. A total of 228 elbows were reviewed from 122 dogs. Of this population, 145 elbows were from French Bulldogs, 54 were from Pugs, and the remainder were from a mix of other brachycephalic breeds. The prevalence of HIF (score 3 or 4) in elbows of the French bulldog, pug and other breed groups was 6.9% (CI 2.8-11%), 5.6% (CI 0-11.7%), and 3.4% (CI 0-10.15%), respectively. At a dog level, the prevalence of HIF (score 3 or 4 present in at least one elbow) was found to be 11.8% (CI 4.6-19%) in French Bulldogs, 11.1% (CI 0-22.9%) in Pugs, and 5.26% (CI 0-15%) in the other breed group. There was no significant difference between the breed groups. The inter-reviewer reliability for CT scoring of HIF based on Cohen's weighted kappa was low at 0.19.

A natural history study to track brain and spinal cord changes in individuals with Friedreich's ataxia: TRACK-FA study protocol.

INTRODUCTION: Drug development for neurodegenerative diseases such as Friedreich's ataxia (FRDA) is limited by a lack of validated, sensitive biomarkers of pharmacodynamic response in affected tissue and disease progression. Studies employing neuroimaging measures to track FRDA have thus far been limited by their small sample sizes and limited follow up. TRACK-FA, a longitudinal, multi-site, and multi-modal neuroimaging natural history study, aims to address these shortcomings by enabling better understanding of underlying pathology and identifying sensitive, clinical trial ready, neuroimaging biomarkers for FRDA. METHODS: 200 individuals with FRDA and 104 control participants will be recruited across seven international study sites. Inclusion criteria for participants with genetically confirmed FRDA involves, age of disease onset ≤ 25 years, Friedreich's Ataxia Rating Scale (FARS) functional staging score of ≤ 5, and a total modified FARS (mFARS) score of ≤ 65 upon enrolment. The control cohort is matched to the FRDA cohort for age, sex, handedness, and years of education. Participants will be evaluated at three study visits over two years. Each visit comprises of a harmonized multimodal Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) scan of the brain and spinal cord; clinical, cognitive, mood and speech assessments and collection of a blood sample. Primary outcome measures, informed by previous neuroimaging studies, include measures of: spinal cord and brain morphometry, spinal cord and brain microstructure (measured using diffusion MRI), brain iron accumulation (using Quantitative Susceptibility Mapping) and spinal cord biochemistry (using MRS). Secondary and exploratory outcome measures include clinical, cognitive assessments and blood biomarkers. DISCUSSION: Prioritising immediate areas of need, TRACK-FA aims to deliver a set of sensitive, clinical trial-ready neuroimaging biomarkers to accelerate drug discovery efforts and better understand disease trajectory. Once validated, these potential pharmacodynamic biomarkers can be used to measure the efficacy of new therapeutics in forestalling disease progression. CLINICAL TRIAL REGISTRATION: ClinicalTrails.gov Identifier: NCT04349514.

Outcomes of dogs undergoing surgery for gastric dilatation volvulus after rapid versus prolonged medical stabilization.

OBJECTIVE: To compare the outcomes of dogs surgically treated for gastric dilatation volvulus (GDV) after rapid versus prolonged medical stabilization. STUDY DESIGN: Prospective cohort study, monoinstitutional. SAMPLE POPULATION: One hundred and sixty-two dogs with GDV. METHODS: Dogs presenting with a GDV were allocated to 1 of 2 groups, immediate or delayed. In the immediate group, dogs were stabilized for 90 min prior to undergoing surgery. In the delayed group, dogs underwent surgery after at least 5 h of stabilization. Medical stabilization included gastric decompression and placement of an indwelling nasogastric tube to prevent further gastric dilatation in all dogs. Short-term outcomes were compared between surgical timings by univariate and multivariate analyses. RESULTS: Dogs (n = 89) in the immediate group underwent surgery a median time of 2.1 h after presentation (range 1.9-2.5 h), whereas those in the delayed surgery group (n = 73) were operated a median time of 9.8 h (range 5.4-13.7 h) after presentation. Survival rates did not differ between dogs undergoing immediate or delayed surgery at discharge (70/89 and 60/73, respectively) or at 1 month postoperatively (68/89 and 55/73, respectively). The degree of gastric torsion was differently distributed between the 2 groups (P = .05). In the immediate group, 19, 52, and 9 dogs had a 0°, 180° and 270° gastric torsion respectively, whereas in the delayed group, 27, 32, and 5 dogs had a 0°, 180° and 270° gastric torsion respectively. Hyperlactatemia 24 h after initiation of fluid therapy was associated with an increased in-hospital mortality risk and at 1 month postoperatively. CONCLUSION: No survival benefit was detected as a result of proceeding to surgery after either a rapid or a prolonged medical stabilization. CLINICAL SIGNIFICANCE: The aggressive stabilization and monitoring protocol described here can be considered as an alternative to stabilize dogs with GDV prior to surgery within 13.7 h of presentation. Further research is required to investigate the potential risks and benefits of prolonged over rapid stabilization and to identify candidates for each approach.

Humeral intracondylar fissures in French bulldogs.

BACKGROUND: French bulldogs have previously been reported to be at an increased risk of developing humeral condylar fractures (HCF). Humeral intracondylar fissures (HIF) are thought to be a predisposing factor for HCF occurrence in skeletally mature dogs particularly when the fracture occurs during normal activity. We hypothesised that HIF may be a predisposing factor for HCF in French bulldogs. METHODS: A retrospective case series of nine French bulldogs that had sustained HCF and where CT was performed prior to surgery. RESULTS: Five of the fractured humeri had sclerosis adjacent to the fracture site. Six of the contralateral intact humeri were diagnosed with HIF on the basis of a partial (2/6) or complete (4/6) hypoattenuating area extending between the distal articular surface and the supratrochlear foramen in the sagittal plane, with adjacent sclerosis (6/6). CONCLUSIONS: Recognition of sclerosis at the intracondylar fracture surface on CT can prompt suspicion that HIF preceded HCF. A predisposing HIF has potentially great clinical significance for this breed if we draw parallels with breeds such as the springer spaniel for whom HIF and HIF-associated condylar fracture is well documented.

Rate of detecting CIN3+ among patients with ASC-US using digital colposcopy and dynamic spectral imaging.

The present study compared two methods for the detection of severe cervical dysplasia in women with atypical squamous cells of underdetermined significance (ASC-US) cytology; digital colposcopy with adjunctive dynamic spectral imaging (DSI) and conventional colposcopy. IMPROVE-COLPO was a two-arm cross-sectional study of US community-based colposcopy. The active (prospective) arm of this study recruited patients examined by digital colposcopy and adjunctive DSI. Preceding consecutive patients that had been examined with conventional methods were used as historical controls in the retrospective arm of the study after being matched in number to those in the prospective arm by a colposcopist. In the present study, the primary measure was the number of women detected with cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+) following punch biopsy. The study included 1,353 retrospective and 1,226 prospective patients eligible for this analysis who were examined by 146 colposcopists in 42 community-based clinics. The patient baseline characteristics were comparable between the two arms. The average number of biopsies taken per patient was higher among the prospective arm patients (including standard and DSI-assisted biopsies) compared with the retrospective arm control patients (1.21 vs. 0.97 respectively). Biopsy detected 31 patients with CIN3+ [2.29%; 95% confidence interval (CI), 1.56-3.24] in the retrospective arm, and 48 patients with CIN3+ (3.92%; 95% CI, 2.90-5.16) in the prospective arm. The difference in the number of patients detected with CIN3+ in the two arms of the study was 1.62% (95% CI, 0.30-3.04; P=0.022), which corresponds to a 70.9% relative increase in the prospective compared with the retrospective arm. Biopsy appeared less efficient in detecting patients with CIN3+ in the retrospective arm compared with the prospective arm. However, there was no statistically significant difference between the retrospective arm and the prospective arm in terms of: i) Biopsies taken (over the entire population) per patient detected with CIN3+ (42.2 in the retrospective arm vs. 30.8 in the prospective arm; P=0.164) and ii) positive predictive value of using biopsies to identify patients with CIN3+ (2.83 vs. 3.92; P=0.118). Adoption of digital colposcopy with DSI increased the number of biopsies collected from ASC-US patients compared with retrospective controls of standard colposcopy and detected a significantly higher number of patients who were CIN3+. The number of additional biopsies taken in the prospective arm compared with the retrospective arm was too small to explain the increased detection of patients with CIN3+ observed in the prospective arm, suggesting that biopsies in the prospective arm were better at identifying CIN3+.

Circular Permutation of the Native Enzyme-Mediated Cyclization Position in Cyclotides.

Cyclotides are a class of cyclic disulfide-rich peptides found in plants that have been adopted as a molecular scaffold for pharmaceutical applications due to their inherent stability and ability to penetrate cell membranes. For research purposes, they are usually produced and cyclized synthetically, but there are concerns around the cost and environmental impact of large-scale chemical synthesis. One strategy to improve this is to combine a recombinant production system with native enzyme-mediated cyclization. Asparaginyl endopeptidases (AEPs) are enzymes that can act as peptide ligases in certain plants to facilitate cyclotide maturation. One of these ligases, OaAEP1b, originates from the cyclotide-producing plant, Oldenlandia affinis, and can be produced recombinantly for use in vitro as an alternative to chemical cyclization of recombinant substrates. However, not all engineered cyclotides are compatible with AEP-mediated cyclization because new pharmaceutical epitopes often replace the most flexible region of the peptide, where the native cyclization site is located. Here we redesign a popular cyclotide grafting scaffold, MCoTI-II, to incorporate an AEP cyclization site located away from the usual grafting region. We demonstrate the incorporation of a bioactive peptide sequence in the most flexible region of MCoTI-II while maintaining AEP compatibility, where the two were previously mutually exclusive. We anticipate that our AEP-compatible scaffold, based on the most popular cyclotide for pharmaceutical applications, will be useful in designing bioactive cyclotides that are compatible with AEP-mediated cyclization and will therefore open up the possibility of larger scale enzyme-mediated production of recombinant or synthetic cyclotides alike.

Herpes Simplex Virus Keratitis.

Herpes simplex virus (HSV) is a highly prevalent infection in the United States. One complication of HSV is HSV keratitis, an ocular HSV infection thought to be the leading cause of corneal blindness in the United States. Home care clinicians with knowledge of the signs and symptoms of HSV and HSV keratitis can aid in early detection and treatment of this potentially serious infection. This article discusses signs and symptoms of HSV keratitis, preventive measures, and treatment.

A suite of kinetically superior AEP ligases can cyclise an intrinsically disordered protein.

Asparaginyl endopeptidases (AEPs) are a class of enzymes commonly associated with proteolysis in the maturation of seed storage proteins. However, a subset of AEPs work preferentially as peptide ligases, coupling release of a leaving group to formation of a new peptide bond. These "ligase-type" AEPs require only short recognition motifs to ligate a range of targets, making them useful tools in peptide and protein engineering for cyclisation of peptides or ligation of separate peptides into larger products. Here we report the recombinant expression, ligase activity and cyclisation kinetics of three new AEPs from the cyclotide producing plant Oldenlandia affinis with superior kinetics to the prototypical recombinant AEP ligase OaAEP1b. These AEPs work preferentially as ligases at both acidic and neutral pH and we term them "canonical AEP ligases" to distinguish them from other AEPs where activity preferences shift according to pH. We show that these ligases intrinsically favour ligation over hydrolysis, are highly efficient at cyclising two unrelated peptides and are compatible with organic co-solvents. Finally, we demonstrate the broad scope of recombinant AEPs in biotechnology by the backbone cyclisation of an intrinsically disordered protein, the 25 kDa malarial vaccine candidate Plasmodium falciparum merozoite surface protein 2 (MSP2).

Rapid and Scalable Plant-Based Production of a Potent Plasmin Inhibitor Peptide.

The backbone cyclic and disulfide bridged sunflower trypsin inhibitor-1 (SFTI-1) peptide is a proven effective scaffold for a range of peptide therapeutics. For production at laboratory scale, solid phase peptide synthesis techniques are widely used, but these synthetic approaches are costly and environmentally taxing at large scale. Here, we developed a plant-based approach for the recombinant production of SFTI-1-based peptide drugs. We show that transient expression in Nicotiana benthamiana allows for rapid peptide production, provided that asparaginyl endopeptidase enzymes with peptide-ligase functionality are co-expressed with the substrate peptide gene. Without co-expression, no target cyclic peptides are detected, reflecting rapid in planta degradation of non-cyclized substrate. We test this recombinant production system by expressing a SFTI-1-based therapeutic candidate that displays potent and selective inhibition of human plasmin. By using an innovative multi-unit peptide expression cassette, we show that in planta yields reach ~60 µg/g dry weight at 6 days post leaf infiltration. Using nuclear magnetic resonance structural analysis and functional in vitro assays, we demonstrate the equivalence of plant and synthetically derived plasmin inhibitor peptide. The methods and insights gained in this study provide opportunities for the large scale, cost effective production of SFTI-1-based therapeutics.

In Vitro and In Planta Cyclization of Target Peptides Using an Asparaginyl Endopeptidase from Oldenlandia affinis.

Cyclization of the peptide backbone by connecting the N- and C-terminus can endow target peptides with favorable properties, such as increased stability or potential oral bioavailability. However, there are few tools available for carrying out this modification. Asparaginyl endopeptidases (AEPs) are a class of enzymes that typically work as proteases, but a subset is highly efficient at cyclization of the peptide backbone. In this chapter we describe how to utilize a cyclizing AEP (OaAEP1b) to produce backbone-cyclized peptides both in planta and in vitro. Using the in planta method, OaAEP1b and the target precursor peptide are coexpressed in the leaves of the model plant Nicotiana benthamiana, and cyclization of the target peptide occurs in planta. Using the in vitro method, purified recombinant OaAEP1b produced in bacteria is used to cyclize the target precursor peptide in vitro.

Optimizing preoperative requirements for outpatient cataract surgery at the Royal Alexandra Hospital.

OBJECTIVE: To evaluate preoperative testing for cataract surgery, implement stakeholder-driven change, and increase the number of patients who arrived for surgery with complete preoperative requirements, for the purpose of delivering safe, high-quality, and cost-effective care for patients. DESIGN: Quality improvement. PARTICIPANTS: Cataract surgery patients, health care staff in Ophthalmology Day Surgery, an Ophthalmology improvement team, the Clinical Section Heads of Ophthalmology and Anaesthesia, Quality Consultants, and members of the Quality Council participated in this study. METHODS: A lean quality improvement approach was used to define and build understanding of the problem. Between July and November 2016, a chart-based reporting system captured all patients who arrived for cataract surgery with expired or incomplete preoperative requirements. A cost analysis was completed, and evidence was reviewed to ensure alignment with best practice preoperative recommendations. RESULTS: On average, 25% (619/2451 over a 17-week period) of patients per day arrived at the Ophthalmology Day Surgery for cataract surgery with incomplete and/or expired physical history forms and ECGs. An improvement team worked to implement a radical improvement idea and relied on an existing questionnaire to ensure patient safety preoperatively. CONCLUSIONS: Based on the literature, best practice guidelines, and a cost analysis, it was decided that patients undergoing routine cataract surgery in Edmonton Zone Hospitals under regional anaesthesia would no longer require physician history and physicals and ECGs. Elimination of the preoperative requirements for all but select high-risk patients meant that 100% of patients who arrived for cataract surgery would not have outstanding presurgery requirements.

Advocating for Early-Career Nurse Innovators: Modeling the Institute of Medicine Report.

The Future of Nursing: Leading Change, Advancing Health was published by the of Medicine (IOM) of the National Academies in 2011. The Missouri Nurses Foundation and Missouri nurses modeled a sustainable project, the Early Career Nurse Innovator Project, exemplifying the intent of that report. The Missouri Nurses Foundation Executive Board comprises experienced nurses, nurse educators, nurses in other leadership roles, retired nurses, public members of the board, and administrative support staff. This article describes a project that was developed, implemented, and evaluated to recognize and encourage early-career nurses who have designed and led innovations to improve and promote the health of Missourians. Five of these early-career nurses were the recipients of monetary awards to encourage future innovations; the second recognition cycle is in the planning phase. Through the work of the Missouri Nurses Foundation, the scholarship of bedside nurses was recognized.

Etiology of teacher knowledge and instructional skills for literacy at the upper elementary grades.

The purpose of this research was to study the etiology of teacher knowledge about and factors that influence implementation of evidence-based reading and writing interventions at the upper elementary grade levels. Five data sources are used in this study: first, we used teacher surveys about their pre-service preparation on reading comprehension and literacy practices gathered during a recent cluster randomized control trial on a reading comprehension intervention conducted with 280 fourth and fifth-grade teachers and their classroom students. We also conducted focus group interviews with 43% of the teachers and observed 90% of the teachers once during the implementation years. For writing, we used data collected from 32 teachers during a 3-year design project for a teacher-led computer-supported writing intervention. We also collected data from groups of school administrators using structured interviews during both studies. Finally, we conducted an artifact review of school curricula and posted professional development (PD) plans. Our results show that in both reading comprehension and writing, all teachers reported not receiving sound evidence-based pre-service preparation and they were not currently employing any evidence-based approaches. Most teachers reported using the basal reading series with very little variation from the lesson scope and sequence. Teachers and administrators frequently reported that skills were being taught in isolation (e.g., skill of the week is summarizing) and that writing was neglected. The interviews showed very interesting patterns of curricula decision-making by school administrators and these findings were further confirmed through the artifact reviews. Based on these results, we recommend that any review of teacher practices focus also on administrator decision-making and school level factors that are driving what happens in the classrooms. The review showed that the teachers themselves do not feel empowered to learn and deliver evidence-based literacy practices and feel constrained by the system.

Gottesfeld-Hohler Memorial Foundation Zika Virus Think Tank Summary.

At a think tank bringing together experts on fetal neuroimaging, obstetric infectious diseases, and public health, we discussed trends in all of these areas for Zika virus. There is a wide variety of imaging findings in affected fetuses, influenced by timing of infection and probably host factors. The resources for diagnosis and interventions also vary by location with the hardest hit areas often having the fewest resources. We identified potential areas for both research and clinical collaboration as the Zika virus epidemic continues to evolve.

Co-expression of a cyclizing asparaginyl endopeptidase enables efficient production of cyclic peptides in planta.

Cyclotides are ultra-stable, backbone-cyclized plant defence peptides that have attracted considerable interest in the pharmaceutical industry. This is due to their range of native bioactivities as well as their ability to stabilize other bioactive peptides within their framework. However, a hindrance to their widespread application is the lack of scalable, cost-effective production strategies. Plant-based production is an attractive, benign option since all biosynthetic steps are performed in planta. Nonetheless, cyclization in non-cyclotide-producing plants is poor. Here, we show that cyclic peptides can be produced efficiently in Nicotiana benthamiana, one of the leading plant-based protein production platforms, by co-expressing cyclotide precursors with asparaginyl endopeptidases that catalyse peptide backbone cyclization. This approach was successful in a range of other plants (tobacco, bush bean, lettuce, and canola), either transiently or stably expressed, and was applicable to both native and engineered cyclic peptides. We also describe the use of the transgenic system to rapidly identify new asparaginyl endopeptidase cyclases and interrogate their substrate sequence requirements. Our results pave the way for exploiting cyclotides for pest protection in transgenic crops as well as large-scale production of cyclic peptide pharmaceuticals in plants.

Pregnancy-Related Deaths, Florida, 1999-2012: Opportunities to Improve Maternal Outcomes.

Objectives To examine pregnancy-related deaths (PRDs) in Florida, to identify quality improvement (QI) opportunities, and to recommend strategies aimed at reducing maternal mortality. Methods The Florida Pregnancy-Associated Mortality Review (PAMR) Committee reviewed PRDs occurring between 1999 and 2012. The PAMR Committee determined causes of PRDs, identified contributing factors, and generated recommendations for prevention and quality improvement. Information from the PAMR data registry, and live births from Florida vital statistic data were used to calculate pregnancy-related mortality ratios (PRMR) and PRD univariate risk ratios (RR) with 95% confidence intervals (CI). Results Between 1999 and 2012, the PRMR fluctuated between 14.7 and 26.2 PRDs per 100,000 live births. The five leading causes of PRD were hypertensive disorders (15.5%), hemorrhage (15.2%), infection (12.7%), cardiomyopathy (11.1%), and thrombotic embolism (10.2%), which accounted for 65% of PRDs. Principal contributing factors were morbid obesity (RR = 7.0, 95% CI 4.9-10.0) and late/no prenatal care (RR = 4.2, 95% CI 3.1-5.6). The PRMR for black women was three-fold higher (RR = 3.3, 95% CI 2.7-4.0) than white women. Among the five leading causes of PRDs, 42.5% had at least one clinical care or health care system QI opportunity. Two-third of these were associated with clinical quality of care, which included standards of care, coordination, collaboration, and communication. The QI opportunities varied by PRD cause, but not by race/ethnicity. Conclusion Gaps in clinical care or health care systems were assessed as the primary factors in over 40% of PRDs leading the PAMR Committee to generate QI recommendations for clinical care and health care systems.

Management of feline tibial diaphyseal fractures using orthogonal plates performed via minimally invasive plate osteosynthesis.

Objectives The objective was to assess the medium- and long-term outcomes (radiographic and owner questionnaire) of feline tibial diaphyseal fractures with orthogonal plate fixation via a minimally invasive plate osteosynthesis (MIPO) approach. Methods Medical records and radiographs of cats that had tibial diaphyseal fractures stabilised with orthogonal plates were obtained (2012-2016). Immediate postoperative radiographs were reviewed to assess the construct configuration and follow-up radiographs (where available) were used to assess bone healing and implant-related complications. An owner-completed questionnaire (feline musculoskeletal pain index [FMPI]) was used at a minimum of 6 months following surgery to assess the cats' ability to perform normal activities. Results Eight feline tibial diaphyseal fractures met the inclusion criteria. One major complication was observed, most likely due to an operative technical error. There were no further complications following revision surgery. Six of the eight cases that had radiographic follow-up either had clinical bone union or showed evidence of bone healing. All cases were classified as successful according to FMPI. Conclusions and relevance Orthogonal plating of feline tibial diaphyseal fractures via an MIPO approach resulted in successful outcomes and a lower complication rate compared with previously reported techniques.