Core Outcome Set for Necrotizing Enterocolitis Treatment Trials.

BACKGROUND AND OBJECTIVES: Variability in outcome reporting in necrotizing enterocolitis (NEC) treatment trials hinders conducting meta-analyses and implementing novel treatments. We aimed to develop a core outcome set (COS) for NEC treatment trials including outcome measures most relevant to patients and physicians, from NEC diagnosis to adulthood. METHODS: Clinicians and/or researchers from low-middle- and high-income countries were approached based on their scientific contributions to NEC literature, and patients and parents through local organizations. We presented participants with 45 outcomes used in NEC research, identified through a systematic review. To achieve consensus, outcomes were rated on a scale of 1 to 9 in 3 online Delphi rounds, and discussed at a final consensus meeting. RESULTS: Seventy-one participants from 25 countries completed all Delphi rounds, including 15 patients and family representatives. Thirteen outcomes reached consensus in one of the stakeholder groups and were included in the consensus meeting, 6 outcomes reached consensus in both groups. Twenty-seven participants from both high- and low-middle-income countries attended the online consensus meeting, including family representatives and NEC patients. After discussion and a final vote, 5 outcomes reached consensus to be included: mortality, NEC-related mortality, short bowel syndrome, quality of life, and neurodevelopmental impairment. CONCLUSIONS: This NEC COS includes 5 predominantly long-term outcomes agreed upon by clinicians, patients, and family representatives. Use of this international COS will help standardize outcome selection in clinical trials, ensure these are relevant to those most affected by NEC care, and, ultimately, improve the care of infants with NEC.

Quantitative sensory testing in canine musculoskeletal pain: Findings from a systematic review, meta-analysis feasibility assessment, and limitations.

Quantitative sensory testing (QST) allows the study of pain mechanisms, patient phenotyping, and response to therapy. The goals of this study were to conduct a systematic review of the use of QST in dogs with musculoskeletal disease including osteoarthritis (OA), and to assess, by means of a meta-analysis, the ability of QST to differentiate affected dogs from healthy controls. The study protocol was registered; three bibliographic databases were screened. Studies involving QST in healthy dogs and those with musculoskeletal disease were included. Data were extracted using a standardized form. Assessment of quality and risk of bias were performed using the CAMARADES critical assessment tool. Twenty-nine articles met the inclusion criteria [systematic review (n = 11); meta-analysis (n = 28)]. In the systematic review, ten studies performed static QST: mechanical [punctate tactile (n = 6); mechanical pressure (n = 5)]; thermal [cold (n = 3); hot (n = 4)]; electrical (n = 1); and one study performed dynamic QST [conditioned pain modulation (n = 1)]. Most studies were of good scientific quality and showed low to moderate risk of bias. A meta-analysis was not possible due to numerous and severe issues of heterogeneity of data among studies. Methods to reduce risk of bias and use of reporting guidelines are some of the most needed improvements in QST research in dogs. Standardization of QST methodology is urgently needed in future studies to allow for data synthesis and a clear understanding of the sensory phenotype of dogs with and without chronic pain including OA.

Bach1 inhibitor HPP-D mediates γ-globin gene activation in sickle erythroid progenitors.

Sickle cell disease (SCD) is the most common ß-hemoglobinopathy caused by various mutations in the adult ß-globin gene resulting in sickle hemoglobin production, chronic hemolytic anemia, pain, and progressive organ damage. The best therapeutic strategies to manage the clinical symptoms of SCD is the induction of fetal hemoglobin (HbF) using chemical agents. At present, among the Food and Drug Administration-approved drugs to treat SCD, hydroxyurea is the only one proven to induce HbF protein synthesis, however, it is not effective in all people. Therefore, we evaluated the ability of the novel Bach1 inhibitor, HPP-D to induce HbF in KU812 cells and primary sickle erythroid progenitors. HPP-D increased HbF and decreased Bach1 protein levels in both cell types. Furthermore, chromatin immunoprecipitation assay showed reduced Bach1 and increased NRF2 binding to the γ-globin promoter antioxidant response elements. We also observed increased levels of the active histone marks H3K4Me1 and H3K4Me3 supporting an open chromatin configuration. In primary sickle erythroid progenitors, HPP-D increased γ-globin transcription and HbF positive cells and reduced sickled erythroid progenitors under hypoxia conditions. Collectively, our data demonstrate that HPP-D induces γ-globin gene transcription through Bach1 inhibition and enhanced NRF2 binding in the γ-globin promoter antioxidant response elements.

Outcome Reporting in Interventional Necrotizing Enterocolitis Studies: A Systematic Review.

BACKGROUND: Despite an increasing necrotizing enterocolitis (NEC) incidence, treatment strategies have failed to make major advancements towards improved NEC outcomes. Heterogeneity in outcome reporting and a lack of treatment efficacy studies potentially hamper these advancements. We aimed to analyze outcome reporting in recent interventional NEC studies. METHODS: We performed a systematic review identifying interventional studies on NEC between 1st of January 2016 and 1st of June 2023 in MEDLINE, Embase, CENTRAL and Cochrane reviews. Systematic reviews, clinical trials and change-in-practice cohort studies reporting any therapeutic intervention for NEC patients (Bell's stage ≥ IIa) were eligible. We excluded studies on NEC diagnostics or prevention and non-English publications. Outcomes were categorized into five core areas and presented descriptively. The review was registered with PROSPERO (CRD42022302712). RESULTS: Out of 1.642 screened records, 65 were eligible for full-text review and 15 were finally included for data extraction. Median number of reported outcomes per article was six (range 1-19). We identified 66 unique outcomes, which were mapped to 53 outcome terms. Thirty-four out of the 53 of the outcome terms (64%) were only reported in a single article. Mortality was the most reported outcome (11/15 articles, 73%). Core area 'Adverse outcomes' contained the most outcome terms (n = 19), whereas 'Life impact' contained the least outcome terms (n = 4) and was represented in 3 articles (20%). CONCLUSIONS: Considerable heterogeneity in outcome reporting and a paucity of outcomes concerning 'Life impact' exist in interventional NEC studies. Development of a NEC core outcome set may improve consistency and patient-relevance in outcome reporting. STUDY TYPE: Systematic Review and Meta-Analyses. LEVEL OF EVIDENCE: III.

Development of an international core outcome set for treatment trials in necrotizing enterocolitis-a study protocol.

AIM: Necrotizing enterocolitis (NEC) is the most lethal disease of the gastrointestinal tract of preterm infants. New and existing management strategies need clinical evaluation. Large heterogeneity exists in the selection, measurement, and reporting of outcome measures in NEC intervention studies. This hampers meta-analyses and the development of evidence-based management guidelines. We aim to develop a Core Outcome Set (COS) for NEC that includes the most relevant outcomes for patients and physicians, from moment of diagnosis into adulthood. This COS is designed for use in NEC treatment trials, in infants with confirmed NEC. METHODS: This study is designed according to COS-STAD (Core Outcome Set-STAndards for Development) recommendations and the COMET (Core Outcome Measures in Effectiveness Trials) Initiative Handbook. We obtained a waiver from the Ethics Review Board and prospectively registered this study with COMET (Study 1920). We will approach 125 clinicians and/or researchers from low-middle and high-income countries based on their scientific output (using SCIVAL, a bibliometric tool). Patients and parents will be approached through local patient organisations. Participants will be separated into three panels, to assess differences in priorities between former patients and parents (1. lay panel), clinicians and researchers involved in the neonatal period (2. neonatal panel) and after the neonatal period (3. post-neonatal panel). They will be presented with outcomes currently used in NEC research, identified through a systematic review, in a Delphi process. Eligible outcome domains are also identified from the patients and parents' perspectives. Using a consensus process, including three online Delphi rounds and a final face-to-face consensus meeting, the COS will be finalised and include outcomes deemed essential to all stakeholders: health care professionals, parents and patients' representatives. The final COS will be reported in accordance with the COS-Standards for reporting (COS-STAR) statement. CONCLUSIONS: Development of an international COS will help to improve homogeneity of outcome measure reporting in NEC, will enable adequate and efficient comparison of treatment strategies, and will help the interpretation and implementation of clinical trial results. This will contribute to high-quality evidence regarding the best treatment strategy for NEC in preterm infants.

Surgery or comfort care for neonates with surgical necrotizing enterocolitis: Lessons learned from behavioral artificial intelligence technology.

Background: Critical decision making in surgical necrotizing enterocolitis (NEC) is highly complex and hard to capture in decision rules due to case-specificity and high mortality risk. In this choice experiment, we aimed to identify the implicit weight of decision factors towards future decision support, and to assess potential differences between specialties or centers. Methods: Thirty-five hypothetical surgical NEC scenarios with different factor levels were evaluated by neonatal care experts of all Dutch neonatal care centers in an online environment, where a recommendation for surgery or comfort care was requested. We conducted choice analysis by constructing a binary logistic regression model according to behavioral artificial intelligence technology (BAIT). Results: Out of 109 invited neonatal care experts, 62 (57%) participated, including 45 neonatologists, 16 pediatric surgeons and one neonatology physician assistant. Cerebral ultrasound (Relative importance = 20%, OR = 4.06, 95% CI = 3.39-4.86) was the most important factor in the decision surgery versus comfort care in surgical NEC, nationwide and for all specialties and centers. Pediatric surgeons more often recommended surgery compared to neonatologists (62% vs. 57%, p = 0.03). For all centers, cerebral ultrasound, congenital comorbidity, hemodynamics and parental preferences were significant decision factors (p < 0.05). Sex (p = 0.14), growth since birth (p = 0.25), and estimated parental capacities (p = 0.06) had no significance in nationwide nor subgroup analyses. Conclusion: We demonstrated how BAIT can analyze the implicit weight of factors in the complex and critical decision for surgery or comfort care for (surgical) NEC. The findings reflect Dutch expertise, but the technique can be expanded internationally. After validation, our choice model/BAIT may function as decision aid.

Safety and Feasibility of Indocyanine Green Fluorescence Angiography in Pediatric Gastrointestinal Surgery: A Systematic Review.

BACKGROUND: Although ICG-FA may be valuable in assessing anastomotic perfusion, reliable data on its use in pediatric gastrointestinal surgery is lacking. This systematic review analyzes whether ICG is useful for intestinal perfusion assessment in pediatric gastrointestinal surgery and safe to use in neonates. METHODS: Systematic searches of PubMed, EMBASE & MEDLINE and CENTRAL were performed (last conducted December 6, 2021). The main inclusion criteria were (1) use of ICG for intestinal perfusion assessment and (2) use of ICG in young infants. Exclusion criteria were lack of an English or Dutch full-text and MINORS quality score <60%. Data was presented in overview tables. The usefulness in pediatric gastrointestinal surgery was assessed by surgical outcome. Safety of ICG in neonates was assessed by complication or adverse event occurrence. RESULTS: Regarding intestinal perfusion assessment, four studies were included, reporting 45 patients (median age 1.5 years). ICG was considered useful for anastomotic blood flow evaluation and intraoperative determination of resection length. Regarding ICG safety in neonates, eight studies were included, reporting 46 infants (median age 24.9 days), of which 18 neonates. All but one studies reported the absence of complications or adverse events. Two studies reported subcutaneous dye retention, which fully disappeared within two weeks. CONCLUSION: Although the number of available studies is small, ICG might be useful for intraoperative intestinal perfusion assessment, perhaps even more than conventional clinical assessment. Furthermore, its safety profile looks promising in neonates. Larger prospective studies are necessary to confirm these assumptions and seem warranted given the safety profile. LEVELS OF EVIDENCE: Since this is a systematic review, a Level of Evidence for clinical studies cannot be determined for this manuscript.

Magnetic resonance imaging during warm ex vivo kidney perfusion.

BACKGROUND: The shortage of donor organs for transplantation remains a worldwide problem. The utilization of suboptimal deceased donors enlarges the pool of potential organs, yet consequently, clinicians face the difficult decision of whether these sub-optimal organs are of sufficient quality for transplantation. Novel technologies could play a pivotal role in making pre-transplant organ assessment more objective and reliable. METHODS: Ex vivo normothermic machine perfusion (NMP) at temperatures around 35-37°C allows organ quality assessment in a near-physiological environment. Advanced magnetic resonance imaging (MRI) techniques convey unique information about an organ's structural and functional integrity. The concept of applying magnetic resonance imaging during renal normothermic machine perfusion is novel in both renal and radiological research and we have developed the first MRI-compatible NMP setup for human-sized kidneys. RESULTS: We were able to obtain a detailed and real-time view of ongoing processes inside renal grafts during ex vivo perfusion. This new technique can visualize structural abnormalities, quantify regional flow distribution, renal metabolism, and local oxygen availability, and track the distribution of ex vivo administered cellular therapy. CONCLUSION: This platform allows for advanced pre-transplant organ assessment, provides a new realistic tool for studies into renal physiology and metabolism, and may facilitate therapeutic tracing of pharmacological and cellular interventions to an isolated kidney.

Harnessing the Therapeutic Potential of the Nrf2/Bach1 Signaling Pathway in Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative movement disorder characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Although a complex interplay of multiple environmental and genetic factors has been implicated, the etiology of neuronal death in PD remains unresolved. Various mechanisms of neuronal degeneration in PD have been proposed, including oxidative stress, mitochondrial dysfunction, neuroinflammation, α-synuclein proteostasis, disruption of calcium homeostasis, and other cell death pathways. While many drugs individually targeting these pathways have shown promise in preclinical PD models, this promise has not yet translated into neuroprotective therapies in human PD. This has consequently spurred efforts to identify alternative targets with multipronged therapeutic approaches. A promising therapeutic target that could modulate multiple etiological pathways involves drug-induced activation of a coordinated genetic program regulated by the transcription factor, nuclear factor E2-related factor 2 (Nrf2). Nrf2 regulates the transcription of over 250 genes, creating a multifaceted network that integrates cellular activities by expressing cytoprotective genes, promoting the resolution of inflammation, restoring redox and protein homeostasis, stimulating energy metabolism, and facilitating repair. However, FDA-approved electrophilic Nrf2 activators cause irreversible alkylation of cysteine residues in various cellular proteins resulting in side effects. We propose that the transcriptional repressor of BTB and CNC homology 1 (Bach1), which antagonizes Nrf2, could serve as a promising complementary target for the activation of both Nrf2-dependent and Nrf2-independent neuroprotective pathways. This review presents the current knowledge on the Nrf2/Bach1 signaling pathway, its role in various cellular processes, and the benefits of simultaneously inhibiting Bach1 and stabilizing Nrf2 using non-electrophilic small molecules as a novel therapeutic approach for PD.

Bach1 derepression is neuroprotective in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder characterized by the loss of nigrostriatal dopaminergic neurons. Mounting evidence suggests that Nrf2 is a promising target for neuroprotective interventions in PD. However, electrophilic chemical properties of the canonical Nrf2-based drugs cause irreversible alkylation of cysteine residues on cellular proteins resulting in side effects. Bach1 is a known transcriptional repressor of the Nrf2 pathway. We report that Bach1 levels are up-regulated in PD postmortem brains and preclinical models. Bach1 knockout (KO) mice were protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity and associated oxidative damage and neuroinflammation. Functional genomic analysis demonstrated that the neuroprotective effects in Bach1 KO mice was due to up-regulation of Bach1-targeted pathways that are associated with both Nrf2-dependent antioxidant response element (ARE) and Nrf2-independent non-ARE genes. Using a proprietary translational technology platform, a drug library screen identified a substituted benzimidazole as a Bach1 inhibitor that was validated as a nonelectrophile. Oral administration of the Bach1 inhibitor attenuated MPTP neurotoxicity in pre- and posttreatment paradigms. Bach1 inhibitor-induced neuroprotection was associated with the up-regulation of Bach1-targeted pathways in concurrence with the results from Bach1 KO mice. Our results suggest that genetic deletion as well as pharmacologic inhibition of Bach1 by a nonelectrophilic inhibitor is a promising therapeutic approach for PD.

Magnetic resonance imaging assessment of renal flow distribution patterns during ex vivo normothermic machine perfusion in porcine and human kidneys.

Acceptance criteria of deceased donor organs have gradually been extended toward suboptimal quality, posing an urgent need for more objective pre-transplant organ assessment. Ex vivo normothermic machine perfusion (NMP) combined with magnetic resonance imaging (MRI) could assist clinicians in deciding whether a donor kidney is suitable for transplantation. Aim of this study was to characterize the regional distribution of perfusate flow during NMP, to better understand how ex vivo kidney assessment protocols should eventually be designed. Nine porcine and 4 human discarded kidneys underwent 3 h of NMP in an MRI-compatible perfusion setup. Arterial spin labeling scans were performed every 15 min, resulting in perfusion-weighted images that visualize intrarenal flow distribution. At the start of NMP, all kidneys were mainly centrally perfused and it took time for the outer cortex to reach its physiological dominant perfusion state. Calculated corticomedullary ratios based on the perfusion maps reached a physiological range comparable to in vivo observations, but only after 1 to 2 h after the start of NMP. Before that, the functionally important renal cortex appeared severely underperfused. Our findings suggest that early functional NMP quality assessment markers may not reflect actual physiology and should therefore be interpreted with caution.

Bach1 Inhibition Suppresses Osteoclastogenesis via Reduction of the Signaling via Reactive Oxygen Species by Reinforced Antioxidation.

Bone destructive diseases such as periodontitis are common worldwide and are caused by excessive osteoclast formation and activation. Receptor activator of nuclear factor-κB ligand (RANKL) is essential factor for osteoclastogenesis. This triggers reactive oxygen species (ROS), which has a key role in intracellular signaling as well exerting cytotoxicity. Cells have protective mechanisms against ROS, such as nuclear factor E2-related factor 2 (Nrf2), which controls the expression of many antioxidant enzyme genes. Conversely, BTB and CNC homology 1 (Bach1), a competitor for Nrf2, transcriptionally represses the expression of anti-oxidant enzymes. Previously, we demonstrated that RANKL induces Bach1 nuclear import and attenuates the expression of Nrf2-mediated antioxidant enzymes, thereby augmenting intracellular ROS signaling and osteoclastogenesis. However, it remains unknown if Bach1 inhibitors attenuate osteoclastogenesis. In this study, we hypothesized that Bach1 inhibition would exert an anti-osteoclastogenic effects via diminishing of intracellular ROS signaling through augmented antioxidation. We used RAW 264.7 cells as osteoclast progenitor cells. Using flow cytometry, we found that Bach1 inhibitors attenuated RANKL-mediated ROS generation, which resulted in the inhibition of osteoclastogenesis. Local injection of a Bach1 inhibitor into the calvaria of male BALB/c mice blocked bone destruction induced by lipopolysaccharide. In conclusion, we demonstrate that Bach1 inhibitor attenuates RANKL-mediated osteoclastogenesis and bone destruction in mice by inducing the expression of Nrf2-regulated antioxidant enzymes that consequently decrease intracellular ROS levels. Bach1 inhibitors have potential in inhibiting bone destructive diseases such as periodontitis, rheumatoid arthritis and osteoporosis.

Quantitative sensory testing in feline osteoarthritic pain - a systematic review and meta-analysis.

Quantitative sensory testing (QST) is a psychophysical test used to quantify somatosensory sensation under normal or pathological conditions including osteoarthritis (OA). OBJECTIVE: This study aimed to conduct a systematic review and meta-analysis of studies using QST in healthy and osteoarthritic cats, registered at Systematic Review Research Facility (#26-06-2017). DESIGN: Hierarchical models with random intercepts for each individual study extracted through the systematic review were fit to subject-level data; QST measures were contrasted between healthy and osteoarthritic cats. Four bibliographic databases were searched; quality and risk of bias assessment were performed using pre-established criteria. RESULTS: Six articles were included; most were of high quality and low risk of bias. Punctate tactile threshold (n = 70) and mechanical temporal summation (n = 35) were eligible for analysis. Cats with OA have lower punctate tactile threshold [mean difference (95%HDI): -44 (-60; -26) grams] and facilitated temporal summation of pain [hazard ratio (95%HDI): 5.32 (2.19; 14) times] when compared with healthy cats. The effect of sex and body weight on sensory sensitivity remained inconclusive throughout all analyses. Due to the correlation between age and OA status, it remains difficult to assess the effect of OA on sensory sensitivity, independently of age. CONCLUSIONS: Clear and transparent reporting using guidelines are warranted. Similar to people, centralized sensitization is a feature of OA in cats. Future studies should try to elucidate the age effect on feline OA. Research with natural OA in cats is promising with potential to benefit feline health and welfare, and improve translatability to clinical research.

Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases.

The transcription factor NF-E2 p45-related factor 2 (NRF2; encoded by NFE2L2) and its principal negative regulator, the E3 ligase adaptor Kelch-like ECH-associated protein 1 (KEAP1), are critical in the maintenance of redox, metabolic and protein homeostasis, as well as the regulation of inflammation. Thus, NRF2 activation provides cytoprotection against numerous pathologies including chronic diseases of the lung and liver; autoimmune, neurodegenerative and metabolic disorders; and cancer initiation. One NRF2 activator has received clinical approval and several electrophilic modifiers of the cysteine-based sensor KEAP1 and inhibitors of its interaction with NRF2 are now in clinical development. However, challenges regarding target specificity, pharmacodynamic properties, efficacy and safety remain.

Do surgical helmet systems affect intraoperative wound contamination? A randomised controlled trial.

BACKGROUND: Deep infection following arthroplasty remains a devastating complication. Some registry data suggests that modern positive-pressure surgical helmet systems (SHS) are associated with a paradoxical increase in infection rates, and as such their role in arthroplasty remains unclear. The aim of this study was to investigate whether SHS increase wound contamination in total knee arthroplasty (TKA) and if this contamination can be reduced by placing tape around the gown/glove interface. METHODS: Seventy-five patients were randomised into three groups: scrubbed theatre staff wore standard surgical gowns (SG), SHS without tape at the gown/glove interface, or SHS with tape. All TKA operations were carried out by the same surgeon. Wound contamination was assessed using a wound culture technique. Blinded laboratory analysis was performed. RESULTS: There were 5/50 culture positive cases when a SHS was used compared to 0/25 when a SG was used; but this difference was not statistically significant (p = 0.16). There were 4/24 culture positive cases when SHS with tape was used compared to 1/26 when SHS without tape was used; but this difference was not statistical significant p = 0.18. CONCLUSION: We found no difference in wound contamination between SG and SHS. Addition of tape at the gown/glove interface did not alter the contamination rate. The choice of surgical gown should take into account cost, comfort and personal protection; as this study found no evidence that wound contamination rates will be altered.

Impact of fine mesh sieve primary treatment on nitrogen removal in moving bed biofilm reactors.

The purpose of this project was to investigate the effect of selective particle removal during primary treatment on nitrogen removal in moving bed biofilm reactors (MBBRs). Two small MBBR pilot plants were operated in parallel, where one train treated 2 mm screened municipal wastewater and the other train treated wastewater that had passed through a Salsnes Filter SF1000 rotating belt sieve (RBS) with a 33 µs sieve cloth. The SF1000 was operated without a filter mat on the belt. The tests confirmed that, for the wastewater characteristics at the test plant, Salsnes Filter primary treatment with a 33 µs RBS and no filter mat produced a primary effluent that was close to optimum. Removal of organic matter with the 33 µs sieve had no negative effect on the denitrification process. Nitrification rates improved by 10-15% in the train with 33 µs RBS primary treatment. Mass balance calculations showed that without RBS primary treatment, the oxygen demand in the biological system was 36% higher. Other studies have shown that the sludge produced by RBS primary treatment is beneficial for biogas production and will also significantly improve sludge dewatering of the combined primary and biological sludge.

Do 'Surgical Helmet Systems' or 'Body Exhaust Suits' Affect Contamination and Deep Infection Rates in Arthroplasty? A Systematic Review.

This systematic review examined whether negative-pressure Charnley-type body exhaust suits (BES) or modern positive-pressure surgical helmet systems (SHS) reduce deep infection rates and/or contamination in arthroplasty. For deep infection, four studies (3990 patients) gave adjusted relative risk for deep infection of 0.11 (P = 0.09) against SHS. Five of 7 (71%) studies found less air contamination and 2 of 4 studies (50%) less wound contamination with BES. One of 4 (25%) found less air contamination with SHS and 0 of 1 (0%) less wound contamination. In contrast to BES, modern SHS designs were not shown to reduce contamination or deep infection during arthroplasty.

Leukocyte esterase analysis in the diagnosis of joint infection: can we make a diagnosis using a simple urine dipstick?

PURPOSE: Analysis of joint fluid remains a key factor in the diagnosis of periprosthetic infection. Recent reports have shown that neutrophils in infected joint fluid release esterase, an enzyme that is a reliable marker for infection. Testing for leukocyte esterase is routinely done in the analysis of urine for the presence of urinary tract infection, by a simple "dipstick" method. We report our experience with this technique in the evaluation of patients suspected of having septic arthritis or periprosthetic joint infection (PJI) by comparing results of leukocyte esterase positivity with confirmed joint infection as defined by the American Academy of Orthopaedic Surgeons (AAOS). MATERIALS AND METHODS: We retrospectively reviewed leukocyte esterase test results performed on synovial fluid aspirated from 57 patients with prosthetic (52) and native (5) joints. Patients either presented with unexplained painful arthroplasties, routine testing of PROSTALAC (PROSthesis with Antibiotic-Loaded Acrylic Cement) orthopedic implants, or clinical suspicion of periprosthetic infection or septic arthritis. Synovial fluid was percutaneously aspirated using a standard technique. The patient age range was 31-91 years with a mean age of 69.1 years, consisting of 30 women (52.6 %) and 27 men (47.4 %). The "gold standard" for the presence or absence of infection at our institution and in the study group was based on the most recent recommendations of the AAOS. Positive culture remained the "gold standard" for native joint infection. RESULTS: Of the total 57 joints aspirated and included in the study, 20 (35.1 %) were read as positive (2+) on the leukocyte test strip and 37 (64.9 %) were read as negative (negative, trace, or 1+). PJI was diagnosed in 19 patients and native joint septic arthritis was identified in one patient. Sensitivities were excellent at 100 % with no false negatives in the entire cohort. There was one false positive in the periprosthetic group yielding a specificity, positive predictive value and negative predictive value of 97, 95, and 100 %, respectively. The results for the native joints showed markedly less specificity and positive predictive value at 50 and 33 %; however, its negative predictive value remained at 100 %. CONCLUSIONS: Our test results confirm that the leukocyte esterase test can accurately detect PJI and that it can be used as a part of the traditional PJI workup. In the assessment of native joints, its high negative predictive value suggests that it is a valuable tool in excluding native joint septic arthritis.

Who wants to be a surgeon? Patterns of medical student career choice.

AIM: NZ needs a surgical workforce with the capacity to meet the increasing health demands of an aging population. This study determined longitudinal patterns of medical student interest in a surgical career and factors influencing that choice. METHOD: We studied medical students entering the Auckland medical programme from 2006-2008 who completed an entry and exit questionnaire on career intentions. Four notional groups were created, depending on the level of interest at entry and at exit. Demographic factors for each category were compared. Analysis of influencing factors was also undertaken. RESULTS: Of 488 students, 310 (64%) completed both an entry and exit questionnaire. Over 50% of students had a strong interest in a surgical career at entry, dropping to 26% at exit. The 'Never Evers' (No interest at entry /No interest at exit) made up 39%,'Divergers' (Strong/No) 35%, 'Die Hards' (Strong/Strong) 18%, and 'Convertibles' (No/Strong) 8%. Less interest in a surgical career was seen among female (P=0.001) and older students (P=0.017). Influencing factors differentiating the 'Die Hards' from the 'Divergers' were work hours and flexibility (less influence among 'Die Hards'), with procedural nature and consultants/mentors (higher). CONCLUSION: There is a significant reduction in interest in a surgical career over the course of the undergraduate programme, especially among female and older students. Yet the level appears sufficient for available training places. Consultant role models are an important career influence. Lack of flexibility in work and training programmes continue to provide challenges in creating a diverse surgical workforce.

PET/CT and MRI of chondroid lipoma of the deltoid muscle.

Chondroid lipoma is an uncommon benign tumor of mesenchymal origin characterized by the presence of adipose tissue and chondroid matrix. Its imaging features have been reported with radiography, ultrasonography, CT, and MRI. Because this lesion may be mistaken histologically for myxoid liposarcoma and myxoid chondrosarcoma, it is of value, through this presentation, to raise the awareness of this benign tumor, which may demonstrate prominent 18F-FDG avidity on PET/CT imaging. The authors present a case of a 52-year-old male patient with a 6-month history of painless chondroid lipoma of the left shoulder.