Implementing routine use of self-removed ureteric stents on extraction strings: prospective patient-reported outcome measures and complications.

PURPOSE: Ureteric stents placed after ureteroscopy typically require cystoscopy for removal. Stent extraction strings allow the option of patient self-removal. This facilitates shorter stent dwell time, and cost-savings. Concerns regarding safety and limited evidence regarding patient acceptability are speculated reasons for infrequent clinical use of extraction strings. This study investigates our recent experience using routine self-removal of stents on extraction strings to provide evidence to address these concerns. METHODS: In February 2020, our hospital adopted a policy for self-removal of stents on extraction strings to be routine following ureteroscopy. This was influenced by motivation to improve service capacity for diagnostic flexible cystoscopy, hospital avoidance during the pandemic, perceived improvement for the patient experience, and cost-saving. Prospective clinical and patient-reported outcome data were collected and evaluated. RESULTS: There were 168 patients who had stents on extraction strings. Mean stent dwell time was 5.2 ± 1.8 days. Primary ureteroscopy was performed in 40.5%, and 59.5% had procedures using an access sheath. Self-removal at home was successful for 79% of patients. Stent dislodgement rate was 3.0% (5/168) and retained stents due to string detachment occurred in 1.8% (3/168). Almost all indicated they "would remove the stent on string again" (90%, 128/142) and the majority reported stent removal as "very easy" (61%, 87/142). Cost modelling estimates a total saving of AUD $148,869 per annum for routine use of extraction strings at our hospital. CONCLUSION: Our experience reflects that stent extraction strings may be used routinely with acceptable low complication rates, favourable patient experiences and associated cost savings.

Proton export upregulates aerobic glycolysis.

INTRODUCTION: Aggressive cancers commonly ferment glucose to lactic acid at high rates, even in the presence of oxygen. This is known as aerobic glycolysis, or the "Warburg Effect." It is widely assumed that this is a consequence of the upregulation of glycolytic enzymes. Oncogenic drivers can increase the expression of most proteins in the glycolytic pathway, including the terminal step of exporting H+ equivalents from the cytoplasm. Proton exporters maintain an alkaline cytoplasmic pH, which can enhance all glycolytic enzyme activities, even in the absence of oncogene-related expression changes. Based on this observation, we hypothesized that increased uptake and fermentative metabolism of glucose could be driven by the expulsion of H+ equivalents from the cell. RESULTS: To test this hypothesis, we stably transfected lowly glycolytic MCF-7, U2-OS, and glycolytic HEK293 cells to express proton-exporting systems: either PMA1 (plasma membrane ATPase 1, a yeast H+-ATPase) or CA-IX (carbonic anhydrase 9). The expression of either exporter in vitro enhanced aerobic glycolysis as measured by glucose consumption, lactate production, and extracellular acidification rate. This resulted in an increased intracellular pH, and metabolomic analyses indicated that this was associated with an increased flux of all glycolytic enzymes upstream of pyruvate kinase. These cells also demonstrated increased migratory and invasive phenotypes in vitro, and these were recapitulated in vivo by more aggressive behavior, whereby the acid-producing cells formed higher-grade tumors with higher rates of metastases. Neutralizing tumor acidity with oral buffers reduced the metastatic burden. CONCLUSIONS: Therefore, cancer cells which increase export of H+ equivalents subsequently increase intracellular alkalization, even without oncogenic driver mutations, and this is sufficient to alter cancer metabolism towards an upregulation of aerobic glycolysis, a Warburg phenotype. Overall, we have shown that the traditional understanding of cancer cells favoring glycolysis and the subsequent extracellular acidification is not always linear. Cells which can, independent of metabolism, acidify through proton exporter activity can sufficiently drive their metabolism towards glycolysis providing an important fitness advantage for survival.

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies: incidence using different testing criteria, and case series.

OBJECTIVES: To estimate the incidence of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies utilising different testing criteria, and review the clinical details of a series of patients with associated autoimmune myopathy. METHODS: The incidence of anti-HMGCR antibodies in 2019 from 3 groups, South West London, Berkshire/Surrey and Southampton, were compared in the adult population. Anti-HMGCR antibodies were measured by commercial chemiluminescent and immunodot assays. The case notes of patients with anti-HMGCR antibodies were reviewed for the case series. RESULTS: The estimated incidence of anti-HMGCR antibodies in the first 2 groups was 1.94 per million adults per year, and in the third group 10.3 per million adults per year. In the first 2 groups the test criteria restricted analysis to specific clinician request for anti-HMGCR. In the third group test criteria included cases with less specific clinical features or a cytoplasmic indirect immunofluorescence anti-nuclear antibody pattern. The latter strategy had a positive predictive value of 66.1% for anti-HMGCR associated myopathy. A case series of 27 patients with anti-HMGCR antibodies revealed 19 with myopathy, oesophageal involvement in 26% and median peak CK 8000 IU/L. Response to treatment, including intravenous immunoglobulin, was good with CK normalising after median 5.5 months. In 8 cases there was no evidence of autoimmune muscle disease, 7 not statin exposed. CONCLUSIONS: Varying criteria result in a 5-fold difference in estimated incidence of anti-HMGCR antibodies, revealing positive cases without evidence of myopathy. Patients with anti-HMGCR myopathy respond well to immune suppression, supporting wider testing for these antibodies amongst patients with myopathy.

Rituximab and intravenous immunoglobulin treatment in PM/Scl antibody-associated disease: case-based review.

Autoantibodies to the 75-kDa and 100-kDa subunits of the PM/Scl nucleolar protein complex are associated with an overlap syndrome, manifesting with clinical features of systemic sclerosis and idiopathic inflammatory myopathy. We describe the diverse clinical features in a series of 4 cases with anti-PM/Scl-75 and/or anti-PM/Scl-100 antibodies, including severe proximal muscle weakness, oesophageal dysfunction, respiratory weakness requiring mechanical ventilation, Raynaud's, calcinosis cutis, sclerodactyly and critical digital ischaemia. Despite the severity of striated and oesophageal muscle weakness, all patients responded very well to immune suppression, and calcinosis cutis in one case regressed substantially. We highlight the efficacy of Rituximab and intravenous immunoglobulin therapy (IVIg) in these cases, enabling return to normal muscle function within six months. Rituximab was preferentially chosen for cases with hyper-gammaglobulinemia and multiple autoantibodies in addition to anti-PM/Scl, and IVIg was utilised for cases where a rapid onset of effect was required, such as severe ventilator-dependent respiratory muscle weakness and oesophageal dysfunction.

Systematic Review of Medpor Versus Autologous Ear Reconstruction.

ABSTRACT: Ear reconstruction is 1 of the most technically challenging sub-specialties of craniofacial and reconstructive plastic surgery. The reconstructive ear must not only fulfil the requirement of being aesthetically pleasing but must also have good vascularity with a low complication rate. Several ear reconstructive techniques have been developed such as the autologous ear reconstruction technique using costal cartilage and ear reconstruction with high-density porous polyethylene or Medpor (Porex Surgical, Inc, College Park, GA). Autologous ear reconstructive techniques have advantages of durability and low infection rates however are associated with poorer aesthetic outcomes such as poor projection of the ear. Medpor has advantages of a more consistent three-dimensional definition without the need to harvest costochondral cartilage and create a donor site. However, due to its alloplastic material properties, Medpor has historically been reported as having a higher rate of extrusion and infection. This is the first systematic review to compare the outcomes of both techniques. The 6 studies that were reviewed were analyzed against 3 evaluative criteria: aesthetic outcome, complication rate, and convenience of intervention. This is so a comprehensive, evidence-based decision can be made by the surgeon and patient when ear reconstruction is required. The results showed heterogeneity in data and a lack of detailed descriptions of the assessment for aesthetic outcomes and convenience, hence were inconclusive. The results however showed that there were more complications with Medpor framework with 15% of total cases resulting in either extrusion or infection compared to 2% of autologous ear reconstruction framework.

Ankle arthritis - an important signpost in rheumatologic practice.

Ankle arthritis is a useful clinical signpost to differential diagnosis in rheumatic disease. Biomechanical features and differences in cartilage physiology compared with the knee may confer protection of the ankle joint from factors predisposing to certain arthritides. The prevalence of ankle OA is low, and usually secondary to trauma. Primary OA of the ankle should be investigated for underlying causes, especially haemochromatosis. New presentations of inflammatory mono/oligo arthritis involving the ankle are more likely due to undifferentiated arthritis or spondyloarthritis than RA, and gout over CPPD. The ankle is often involved in bacterial and viral causes of septic arthritis, especially bacterial, chikungunya and HIV infection, but rarely tuberculosis. Periarticular hind foot swelling can be confused with ankle arthritis, exemplified by Lofgren's syndrome and hypertrophic osteoarthropathy where swelling is due to subcutaneous oedema and osteitis respectively, and the ankle joint is rarely involved.

Secukinumab as a potential trigger of inflammatory bowel disease in ankylosing spondylitis or psoriatic arthritis patients.

OBJECTIVE: Real-world secukinumab gastrointestinal-related adverse events (GIRAE) data during treatment for AS and PsA are lacking. We aimed to obtain this through baseline evaluation of pre-existing IBD rates and predictors of GIRAE. METHODS: Patient electronic and paper records commencing secukinumab from 10 UK hospitals between 2016 and 2019 were reviewed. GIRAE after initiation were defined as: definite [objective evidence of IBD (biopsy proven), clear temporal association, resolution of symptoms on drug withdrawal, no alternative explanation felt more likely], probable (as per definite, but without biopsy confirmation) or possible (gastrointestinal symptoms not fulfilling definite or probable criteria). RESULTS: Data for all 306 patients started on secukinumab were analysed: 124 (40.5%) AS and 182 (59.5%) PsA. Twenty-four of 306 (7.8%) experienced GIRAE after starting secukinumab. Amongst patients who developed GIRAE, four (1.3%) had definite, seven (2.3%) probable and 13 (4.2%) possible IBD. All definite cases were patients with AS and stopped secukinumab; two had pre-existing IBD and two (0.7%) were de novo cases of which one required surgical intervention. Seven patients (2.3%) had pre-existing diagnoses of IBD prior to initiation, of which five patients experienced GIRAE. CONCLUSION: Absolute rates of new IBD in patients starting secukinumab are low. The majority of patients developing new GIRAE did not develop objective evidence of IBD or stop therapy. For patients with pre-existing IBD and AS the risk of GIRAE is much higher, and prescribing alternatives should be considered.

Quadrant Excision of Benign Lesions: A Prospective Outcome Study of Pediatric Patients.

ABSTRACT: Serial excision is a commonly used technique for the excision of large lesions. The procedure in children is challenging due to different skin quality and unpredictable scar patterns compared to adults. Quadrant excision is a modification of serial excision. The authors report quadrant excisions in 3 pediatric cases with facial congenital melanocytic naevi in aesthetically challenging areas. Based on our results we recommend the use of this technique in similar cases.

A Single Surgeon's Experience of Starting a New Ear Reconstruction Service in the UK.

ABSTRACT: Autologous ear reconstruction is known as one of the most difficult types of reconstruction to perform in plastic surgery. Very rarely is a trainee exposed to the level of complexity and variety of cases they will treat as a sole care provider in a tertiary care setting. This is because the learning curve is steep and those few surgeons that already perform ear reconstruction are limited in what technical experience they can offer trainees due to the plethora of factors competing against the surgeon. These include patient expectations, level of experience, length of anesthetic and accountability for results and complications. For this reason, once a plastic surgeon is nominated to provide autologous ear reconstruction, they face the daunting prospect of not only performing what is a very complex surgery with a very steep learning curve but also the judgment of their patients and colleagues. This paper charts the endeavors of the senior author to provide a service over the last 5 years. It will hopefully provide insight and context on setting up a service, dealing with complications, patient and peer expectations, and finally acknowledgment from both alike as experience is gained and excellence is reached.

Objective Scoring of Information Websites for Vascular Anomalies.

ABSTRACT: One of the challenging aspects of caring for patients with vascular anomalies has been the use of inconsistent terminologies which has resulted in inconsistencies with treatment, miscommunication between clinicians, and subsequently patient misinformation and confusion. In this study, we objectively assessed the quality of online information on vascular anomalies. Our results emphasize the crucial role of vascular anomaly services in the communication and provision of patient information.