Ureteric stenting outside of the operation theatre: challenges and opportunities.

OBJECTIVE: To evaluate the safety, efficacy, tolerability, and cost-effectiveness of bedside or office-based ureteric stent insertion. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) and A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 guidelines, we searched PubMed/the Medical Literature Analysis and Retrieval System Online (MEDLINE), the Excerpta Medica dataBASE (EMBASE), Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and Dimensions for English-language studies from 1978 to April 2023. Inclusion criteria focused on primary ureteric stent placements outside of the operating theatre (OT). RESULTS: A total of 15 studies involving 2072 stents were included. Success rates for correctly positioned stents in bedside or office-based insertions ranged from 60% to 95.8%, with most studies reporting ≥80% success rates. Common failure reasons included impacted stones and difficulty identifying the ureteric orifice. Pain and tolerability were assessed using various methods, with validated tools indicating moderate pain levels, but most patients would undergo the procedure again under local anaesthesia. Complication rates were generally low, with minor complications such as haematuria or postoperative fever being the most common. Procedural costs were significantly lower in non-OT settings, with estimates indicating savings of up to four-fold. CONCLUSION: Bedside or office-based ureteric stent insertion is a viable alternative to OT procedures, offering high success rates, manageable pain levels, low complication rates, and substantial cost savings. This approach is particularly advantageous in settings with limited OT access, highlighting its potential for broader adoption in urological practice. Future research should focus on standardising pain assessment methods and randomised studies.

High-quality identification of volatile organic compounds (VOCs) originating from breath.

INTRODUCTION: Volatile organic compounds (VOCs) can arise from underlying metabolism and are detectable in exhaled breath, therefore offer a promising route to non-invasive diagnostics. Robust, precise, and repeatable breath measurement platforms able to identify VOCs in breath distinguishable from background contaminants are needed for the confident discovery of breath-based biomarkers. OBJECTIVES: To build a reliable breath collection and analysis method that can produce a comprehensive list of known VOCs in the breath of a heterogeneous human population. METHODS: The analysis cohort consisted of 90 pairs of breath and background samples collected from a heterogenous population. Owlstone Medical's Breath Biopsy® OMNI® platform, consisting of sample collection, TD-GC-MS analysis and feature extraction was utilized. VOCs were determined to be "on-breath" if they met at least one of three pre-defined metrics compared to paired background samples. On-breath VOCs were identified via comparison against purified chemical standards, using retention indexing and high-resolution accurate mass spectral matching. RESULTS: 1471 VOCs were present in > 80% of samples (breath and background), and 585 were on-breath by at least one metric. Of these, 148 have been identified covering a broad range of chemical classes. CONCLUSIONS: A robust breath collection and relative-quantitative analysis method has been developed, producing a list of 148 on-breath VOCs, identified using purified chemical standards in a heterogenous population. Providing confirmed VOC identities that are genuinely breath-borne will facilitate future biomarker discovery and subsequent biomarker validation in clinical studies. Additionally, this list of VOCs can be used to facilitate cross-study data comparisons for improved standardization.

Procedural risk factors for deep and organ/space surgical site infection post-coronary artery bypass graft surgery.

In this study, we examined the impact of the number and type of arterial grafts, and surgical dressing type, on deep and organ/space surgical site infection following coronary artery bypass graft procedures. Bilateral internal mammary artery grafts and negative pressure wound therapy were associated with higher odds of infection.

Pharmacological non-hormonal treatment options for male infertility: a systematic review and network meta-analysis.

BACKGROUND: Male factor infertility affect up to 50% of couples unable to conceive spontaneously. Several non-hormonal pharmacological treatments have been proposed to boost spermatogenesis and increase chances of conception in men with infertility. Still, no clear evidence exists on the most effective treatment strategy. OBJECTIVE: We aimed to compare the effectiveness of non-hormonal pharmacological treatment options for men with infertility using a systematic review and network meta-analysis. METHODS: We searched MEDLINE, EMBASE, and CENTRAL until October 2023 for randomised/quasi-randomised trials that evaluated any non-hormonal pharmacological treatment options for men with idiopathic semen abnormalities or those with hypogonadism. We performed pairwise and network meta-analyses using a random effect model. We assessed risk of bias, heterogeneity, and network inconsistency. We calculated the mean rank and the surface under the cumulative ranking curve (SUCRA) for each intervention the maximum likelihood to achieve each of reported outcomes. We reported primarily on sperm concentration and other important semen and biochemical outcomes using standardised mean difference (SMD) and 95% confidence-intervals(CI). RESULTS: We included 14 randomised trials evaluating four treatments (Clomiphene citrate, Tamoxifen, Aromatase inhibitors, anti-oxidants) and their combinations in 1342 men. The overall quality of included trials was low. Sperm concentration improved with clomiphene compared to anti-oxidants (SMD 2.15, 95%CI 0.78-3.52), aromatase inhibitor (SMD 2.93, 95%CI 1.23-4.62), tamoxifen (SMD - 1.96, 95%CI -3.57; -0.36) but not compared to placebo (SMD - 1.53, 95%CI -3.52- 0.47). Clomiphene had the highest likelihood to achieve the maximum change in sperm concentration (SUCRA 97.4). All treatments showed similar effect for sperm motility, semen volume, and normal sperm morphology. FSH levels showed significant improvement with clomiphene vs.anti-oxidant (SMD 1.48, 95%CI 0.44-2.51) but not compared to placebo. The evidence networks for LH and testosterone suffered from significant inconsistency (p = 0.01) with similar trend of improvement with clomiphene compared to other treatments but not compared to placebo. CONCLUSION: There is insufficient evidence to support the routine use of Clomiphene, tamoxifen, and aromatase inhibitors to optimise semen parameters in men with infertility. Future randomised trials are needed to confirm the efficacy of clomiphene in improving fertility outcomes in men. PROSPERO: CRD42023430179.

Multi-parametric magnetic resonance imaging of the prostate in Victoria, Australia; unintended consequences of changing Medicare Benefits Schedule access.

ObjectiveTo assess whether prostate biopsy rates have altered with the July 2018 change in Australian Medicare Benefits Schedule (MBS) rebates supporting multiparametric magnetic resonance imaging (mpMRI) for diagnosing prostate cancer.MethodsBiopsy data (both trans-rectal and trans-perineal) were obtained from the Victorian Agency for Health Information from July 2016 to June 2022. The data were stratified by financial year, age group and hospital type (public vs private). Comparison was made between rates pre and post the mpMRI MBS code change.ResultsThere was an 11.9% increase in the number of biopsies performed per year compared to the pre-MBS change period. There is a significant decreasing trend (P<0.001-4) in number of biopsies in the 40-49, 50-59 and 60-69-year-old age groups with a significant increasing trend (P<0.001) in the 70-79 and 80-89-year-old age groups. There was a 32.9% reduction in the mean number of biopsies performed per year in public hospitals, compared with an 18.3% increase in private.ConclusionContrary to expectations, and proposed funding, there has been an increase in the number of prostate biopsies since MRI became more easily available. This change will put increased pressure on the health budget and the large increase in biopsies in elderly patients was not anticipated when the changes were proposed. A review of the criteria is suggested.

Advances in the diagnosis of myocarditis in idiopathic inflammatory myopathies: an overview of diagnostic tests.

Cardiac involvement in idiopathic inflammatory myopathies (IIM) purports to worse clinical outcomes, and therefore early identification is important. Research has focused on blood biomarkers and basic investigations such as ECG and echocardiography, which have the advantage of wide availability and low cost but are limited in their sensitivity and specificity. Imaging the myocardium to directly look for inflammation and scarring has therefore been explored, with a number of new methods for doing this gaining wider research interest and clinical availability. Cardiovascular magnetic resonance (CMR) with contemporary multiparametric mapping techniques and late gadolinium enhancement imaging, is an extremely valuable and increasingly used non-invasive imaging modality for the diagnosis of myocarditis. The recently updated CMR-based Lake Louise Criteria for the diagnosis of myocarditis incorporate the newer T1 and T2 mapping techniques, which have greatly improved the diagnostic accuracy for IIM myocarditis.18F-FDG-PET/CT is a well-utilized imaging modality in the diagnosis of malignancies in IIM, and it also has a role for the diagnosis of myocarditis in multiple systemic inflammatory diseases. Endomyocardial biopsy, however, remains the gold standard technique for the diagnosis of myocarditis and is necessary for the diagnosis of specific cases of myocarditis. This article provides an overview of the important tests and imaging modalities that clinicians should consider when faced with an IIM patient with potential myocarditis.

Catheter-associated urinary tract infection (CAUTI) reduction in a neuroscience intensive care unit: A multidisciplinary approach.

Utilizing a multidisciplinary approach to identify catheter-associated urinary tract infection (CAUTI) risks in Neuroscience intensive care patients admitted for aneurysmal subarachnoid hemorrhage, our CAUTI rate decreased from 5.903 per 1,000 catheter days (June 2020-June 2021) to 0.371 per 1,000 catheter days in our postintervention time period (July 2021-March 2023). A review of our clinical treatment guideline to optimize the timing of indwelling urinary catheters and medication management related to bowel regimens has resulted in a sustained CAUTI reduction, particularly in postaneurysmal subarachnoid hemorrhage patients in the Neuroscience intensive care unit.

Antibody predictors of mortality and lung function trends in myositis spectrum interstitial lung disease.

OBJECTIVES: The impact of autoantibody profiles on prognosis of idiopathic inflammatory myositis associated interstitial lung disease (IIM-ILD) and myositis spectrum ILD with Myositis Specific Antibodies (MSA) remains unclear. This retrospective cohort study examines whether serological profiles are associated with mortality and longitudinal lung function change. METHODS: Baseline clinical/demographic characteristics and follow-up lung function of consecutive adult patients with IIM-ILD or Interstitial Pneumonia with Autoimmune Features (IPAF) positive for MSAs were extracted from three hospitals. Univariate and multi-variate Cox-Proportional Hazards analyses were used to compare mortality between autoantibodies. Regression models were used to analyse lung function trends. RESULTS: Of 430 included patients, 81% met IIM criteria, 19% were IPAF-MSA. On univariate analysis, risk factors associated with mortality included higher age, Charlson Co-morbidity Index and CRP; and lower BMI, baseline TLCO% and FEV1%. Compared to anti-MDA5-negativity, anti-MDA5-positivity (MDA5+) was associated with high mortality in the first 3 months (HR 65.2. 95%CI 14.1, 302.0), while no significant difference was seen thereafter (HR 0.55, 95%CI 0.14, 2.28). On multi-variate analysis, combined anti-synthetase antibodies carried a reduced risk of mortality (HR 0.63), although individually, mortality was reduced in anti-Jo1 + (HR 0.61, 95%CI 0.4-0.87) and increased in anti-PL7+ patients (HR 2.07, 95%CI 1.44-2.99). Anti-MDA5+ was associated with slow improvement in %FVC over the first 3 years, while anti-PL7+ was linked with a slow decline from 12 months onwards. CONCLUSIONS: Among autoantibody profiles in myositis spectrum disorders, anti-MDA5+ and anti-PL7+ confer higher mortality risks. Survivors of an early peak of mortality in anti-MDA5+ disease appear to have a favourable prognosis.

International Guideline for Idiopathic Inflammatory Myopathy-Associated Cancer Screening: an International Myositis Assessment and Clinical Studies Group (IMACS) initiative.

Adult-onset idiopathic inflammatory myopathy (IIM) is associated with an increased cancer risk within the 3 years preceding and following IIM onset. Evidence- and consensus-based recommendations for IIM-associated cancer screening can potentially improve outcomes. This International Guideline for IIM-Associated Cancer Screening provides recommendations addressing IIM-associated cancer risk stratification, cancer screening modalities and screening frequency. The international Expert Group formed a total of 18 recommendations via a modified Delphi approach using a series of online surveys. First, the recommendations enable an individual patient's IIM-associated cancer risk to be stratified into standard, moderate or high risk according to the IIM subtype, autoantibody status and clinical features. Second, the recommendations outline a 'basic' screening panel (including chest radiography and preliminary laboratory tests) and an 'enhanced' screening panel (including CT and tumour markers). Third, the recommendations advise on the timing and frequency of screening via basic and enhanced panels, according to risk status. The recommendations also advise consideration of upper or lower gastrointestinal endoscopy, nasoendoscopy and 18F-FDG PET-CT scanning in specific patient populations. These recommendations are aimed at facilitating earlier IIM-associated cancer detection, especially in those who are at a high risk, thus potentially improving outcomes, including survival.

Lightweight macroporous mesh can be used for corporal reconstruction during penile prosthesis surgery.

BACKGROUND: Options to reinforce or reconstruct the corpora cavernosa during penile prosthesis surgery are limited. Synthetic grafts may confer a higher infection risk. Lightweight macroporous mesh is a promising alternative due to better integration and tissue ingrowth. AIM: The study sought to report the first experience of using lightweight mesh to reinforce or reconstruct the corpora. METHODS: The medical records of all patients undergoing insertion or revision of penile prosthesis between May 2016 and May 2021 were reviewed retrospectively. Patient characteristics, management, and outcomes were extracted in which mesh was used for corporal reconstruction. Poliglecaprone-25/polypropylene mesh (UltraPro) was used in all cases. The surgical technique and alternatives were summarized. OUTCOMES: The outcomes were infection rate, postoperative complications by Clavien-Dindo classification, and patient-reported outcomes. RESULTS: Mesh was required during penile prosthesis surgery in 21 men (median age 56 [range, 18-74] years). Reasons for reconstruction were severe corporal fibrosis (n = 6), impending erosion (n = 6), crossover/perforation (n = 6), congenital corporal agenesis (n = 2), and excision of Peyronie's plaque. All but 2 patients (with corporal agenesis) presented for revision penile prosthesis surgery with a median number of previous revision attempts of 2 (range, 1-5). Two (10%) patients required explant after a mean follow-up of 23 ± 8.7 months. One man developed infection of the device 2 years after surgery, translating to an infection rate of 5% despite a high prevalence of diabetes (25%) in this cohort. Another required explantation due to debilitating chronic pain after 3 months. Further revision surgery for stiction syndrome was required in a third patient. Finally, another man was not satisfied with the position of the pump within the scrotum or the axial rigidity of the device, despite a second opinion suggesting no issues with the device. All men were sexually active following surgery. CLINICAL IMPLICATIONS: A lightweight mesh can be considered to reinforce or reconstruct the corpora cavernosa in complex cases in which there are no alternative techniques available. STRENGTHS AND LIMITATIONS: This is the first study using a lightweight macroporous mesh for revision penile prosthesis surgery. This was a well-characterized cohort of patients. A larger cohort with 5-year follow-up would be preferable. CONCLUSION: These early results suggest that a lightweight macroporous mesh may be an acceptable synthetic graft for corporal reconstruction. Poliglecaprone-25/polypropylene mesh may be ideal because it is partially absorbable, easy to handle, and not bulky.

UBE2L3 regulates TLR7-induced B cell autoreactivity in Systemic Lupus Erythematosus.

Both TLR7 and NF-κB hyperactivity are known to contribute to pathogenesis in Systemic Lupus Erythematosus (SLE), driving a pro-interferon response, autoreactive B cell expansion and autoantibody production. UBE2L3 is an SLE susceptibility gene which drives plasmablast/plasma cell expansion in SLE, but its role in TLR7 signalling has not been elucidated. We aimed to investigate the role of UBE2L3 in TLR7-mediated NF-κB activation, and the effect of UBE2L3 inhibition by Dimethyl Fumarate (DMF) on SLE B cell differentiation in vitro. Our data demonstrate that UBE2L3 is critical for activation of NF-κB downstream of TLR7 stimulation, via interaction with LUBAC. DMF, which directly inhibits UBE2L3, significantly inhibited TLR7-induced NF-κB activation, differentiation of memory B cells and plasmablasts, and autoantibody secretion in SLE. DMF also downregulated interferon signature genes and plasma cell transcriptional programmes. These results demonstrate that UBE2L3 inhibition could potentially be used as a therapy in SLE through repurposing of DMF, thus preventing TLR7-driven autoreactive B cell maturation.

A Systematic Review and Metaanalysis of Predictors of Mortality in Idiopathic Inflammatory Myopathy-Associated Interstitial Lung Disease.

OBJECTIVE: Idiopathic inflammatory myopathy (IIM)-associated interstitial lung disease (ILD) can range from rapidly progressive disease with high mortality to indolent disease with minimal morbidity. This systematic review and metaanalysis describe immunological, clinical, and radiographical predictors of mortality in IIM-ILD. METHODS: MEDLINE and Embase database searches were completed on October 18, 2021, to identify articles providing survival data according to baseline characteristics in patients with concurrent IIM and ILD. Prognostic factors common to more than 5 papers were included in the metaanalysis using a random-effects model to report odds ratios (ORs) for binary variables and Hedges g for continuous variables. Risk of bias was assessed using the Newcastle-Ottawa Scale score and the Egger test for publication bias. RESULTS: From 4433 articles, 62 papers were suitable for inclusion; among these studies, 38 different variables were considered. The OR for risk of death regarding the presence of anti-melanoma differentiation-associated protein 5 (MDA5) antibodies was 6.20 (95% CI 3.58-10.71), and anti-tRNA synthetase antibodies were found to be protective (OR 0.24, 95% CI 0.14-0.41). Neither antinuclear antibodies, anti-52-kDa Ro antigen antibodies, nor SSA significantly altered mortality, nor was MDA5 titer predictive. Examples of prognostic factors that are significantly associated with mortality in this study include the following: age; male sex; acute/subacute onset; clinically amyopathic dermatomyositis; dyspnea; ulceration; fever; raised C-reactive protein, ferritin, lactate dehydrogenase, alveolar to arterial O2 (A-aO2) gradient, ground-glass opacity on high-resolution computed tomography (HRCT), and overall HRCT score; and reduced albumin, lymphocytes, ratio of partial pressure of oxygen in the arterial blood to fraction of inspired oxygen (PF ratio), percentage predicted transfer factor for carbon monoxide, and percentage predicted forced vital capacity. Baseline surfactant protein-D and Krebs von den Lungen-6 levels were not predictors of mortality. CONCLUSION: Many mortality risk factors were identified, though heterogeneity was high, with a low quality of evidence and a risk of publication bias. Studies regarding anti-MDA5 antibody-positive disease and and those from East Asia predominate, which could mask risk factors relevant to other IIM subgroups or populations.

Lhx2 is a progenitor-intrinsic modulator of Sonic Hedgehog signaling during early retinal neurogenesis.

An important question in organogenesis is how tissue-specific transcription factors interact with signaling pathways. In some cases, transcription factors define the context for how signaling pathways elicit tissue- or cell-specific responses, and in others, they influence signaling through transcriptional regulation of signaling components or accessory factors. We previously showed that during optic vesicle patterning, the Lim-homeodomain transcription factor Lhx2 has a contextual role by linking the Sonic Hedgehog (Shh) pathway to downstream targets without regulating the pathway itself. Here, we show that during early retinal neurogenesis in mice, Lhx2 is a multilevel regulator of Shh signaling. Specifically, Lhx2 acts cell autonomously to control the expression of pathway genes required for efficient activation and maintenance of signaling in retinal progenitor cells. The Shh co-receptors Cdon and Gas1 are candidate direct targets of Lhx2 that mediate pathway activation, whereas Lhx2 directly or indirectly promotes the expression of other pathway components important for activation and sustained signaling. We also provide genetic evidence suggesting that Lhx2 has a contextual role by linking the Shh pathway to downstream targets. Through these interactions, Lhx2 establishes the competence for Shh signaling in retinal progenitors and the context for the pathway to promote early retinal neurogenesis. The temporally distinct interactions between Lhx2 and the Shh pathway in retinal development illustrate how transcription factors and signaling pathways adapt to meet stage-dependent requirements of tissue formation.

Validation of methods to identify people with idiopathic inflammatory myopathies using hospital episode statistics.

Objective: Hospital episode statistics (HES) are routinely recorded at every hospital admission within the National Health Service (NHS) in England. This study validates diagnostic ICD-10 codes within HES as a method of identifying cases of idiopathic inflammatory myopathies (IIMs). Methods: All inpatient admissions at one NHS Trust between 2010 and 2020 with relevant diagnostic ICD-10 codes were extracted from HES. Hospital databases were used to identify all outpatients with IIM, and electronic care records were reviewed to confirm coding accuracy. Total hospital admissions were calculated from NHS Digital reports. The sensitivity and specificity of each code and code combinations were calculated to develop an optimal algorithm. The optimal algorithm was tested in a sample of admissions at another NHS Trust. Results: Of the 672 individuals identified by HES, 510 were confirmed to have IIM. Overall, the positive predictive value (PPV) was 76% and sensitivity 89%. Combination algorithms achieved PPVs between 89 and 94%. HES can also predict the presence of IIM-associated interstitial lung disease (ILD) with a PPV of 79% and sensitivity of 71%. The optimal algorithm excluded children (except JDM code M33.0), combined M33.0, M33.1, M33.9, M36.0, G72.4, M60.8 and M33.2, and included M60.9 only if it occurred alongside an ILD code (J84.1, J84.9 or J99.1). This produced a PPV of 88.9% and sensitivity of 84.2%. Retesting this algorithm at another NHS Trust confirmed a high PPV (94.4%). Conclusion: IIM ICD-10 code combinations in HES have high PPVs and sensitivities. Algorithms tested in this study could be applied across all NHS Trusts to enable robust and cost-effective whole-population research into the epidemiology of IIM.