The Sheen Paajanen grOin Recommended Treatment 'SPoRT' score for groin pain.

INTRODUCTION: Evaluating groin pain still evades many clinicians at times as they have difficulty determining the cause of pain when no true hernia exists. This study's aim was to evaluate a simple and novel scoring system which is reproducible, to help determine whether conservative measures or surgery is recommended for the management of groin pain attributable to inguinal disruption. MATERIAL & METHODS: A retrospective analysis of all patients from 2018 to 2020 that underwent surgery or conservative management for inguinal disruption with at least a 1-year follow-up were evaluated. The scoring system is based on MRI and ultrasound imaging as well as clinical findings, with scores given from - 2 to + 2 based on the defined findings listed. A maximum total of four points scored for each assessment was used. Sensitivity and specificity analysis was conducted for each potential score cut off point. RESULTS: A total of 172 patients were evaluated with 33 patients (19%) undergoing conservative management and 139 patients (81%) undergoing surgery. The median SPoRT score for the surgery group was 2.0 (1.0, 3.0), and - 1.0 (- 3.0, 0.0) in the physiotherapy group which was a significant difference (p < 0.001). An optimal cut off of ≤ 0 for physio and ≥ 1 for surgery was established, yielding a sensitivity of 90.9% (95% CI 75.7%-98.1%), a specificity of 89.2% (95% CI 82.8%-93.8%) and an area under the curve (AUC) of 0.936 (95% CI 0.874-0.997). DISCUSSION: SPoRT score of ≤ 0 can recommend a patient should undergo conservative measures or physiotherapy as a mainstay of treatment with a score of ≥ 1 recommending surgery. Further validation of the score is necessary.

The reorganisation of emergency general surgery services during the COVID-19 pandemic in the UK: outcomes of delayed presentation, socio-economic deprivation and Black, Asian and Minority Ethnic patients.

INTRODUCTION: The COVID-19 pandemic is a global public health emergency. Lockdown restrictions and the reconfiguration of healthcare systems to accommodate an increase in critical care capacity have had an impact on 'non-COVID' specialties. This study characterises the utilisation of emergency general surgery (EGS) services during the UK lockdown period at a university teaching hospital with a catchment population that represents one of the most deprived and ethnically diverse areas in the UK. METHODS: EGS admissions during the UK lockdown period (March to May 2020) were compared with the same period in 2019. Patient demographics were recorded together with clinical presentation, hospital stay and treatment outcomes, and readmission data. RESULTS: The study included 645 patients, comprising 223 in the COVID-19 period and 422 in the non-COVID-19 period. There was no difference in age, sex, comorbidity or socio-economic status. A lower proportion of patients of Black, Asian and Minority Ethnicity (BAME) were admitted during the pandemic (20.6% vs 35.4%, p < 0.05). The duration of symptoms prior to presentation was longer, and admission clinical parameters and serum inflammatory markers. More patients presented with an acute kidney injury (9.9% vs 4.7%, p = 0.012). There was no difference in perioperative outcomes or 30-day mortality, but more patients were readmitted following conservative management (10.6% vs 4.7%, p = 0.023). CONCLUSIONS: The reorganisation of EGS to a senior-led model has been successful in terms of outcomes and access to treatment despite a more unwell population. There was a significantly lower proportion of BAME admissions suggesting additional barriers to healthcare access under pandemic lockdown conditions.

Angiostatin formation involves disulfide bond reduction and proteolysis in kringle 5 of plasmin.

Plasmin is processed in the conditioned medium of HT1080 fibrosarcoma cells producing fragments with the domain structures of the angiogenesis inhibitor, angiostatin, and microplasmin. Angiostatin consists of kringle domains 1-4 and part of kringle 5, while microplasmin consists of the remainder of kringle 5 and the serine proteinase domain. Our findings indicate that formation of angiostatin/microplasmin involves reduction of plasmin by a plasmin reductase followed by proteolysis of the reduced enzyme. We present evidence that the Cys461-Cys540 and Cys511-Cys535 disulfide bonds in kringle 5 of plasmin were reduced by plasmin reductase. Plasmin reductase activity was secreted by HT1080 and Chinese hamster ovary cells and the human mammary carcinoma cell lines MCF-7, MDA231, and BT20 but not by the monocyte/macrophage cell line THP-1. Neither primary foreskin fibroblasts, blood monocyte/macrophages, nor macrovascular or microvascular endothelial cells secreted detectable plasmin reductase. In contrast, cultured bovine and rat vascular smooth muscle cells secreted small but reproducible levels of plasmin reductase. Reduction of the kringle 5 disulfide bonds triggered cleavage at either Arg529-Lys530 or two other positions C-terminal of Cys461 in kringle 5 by a serine proteinase. Plasmin autoproteolysis could account for the cleavage, although another proteinase was mostly responsible in HT1080 conditioned medium. Three serine proteinases with apparent Mr of 70, 50, and 39 were purified from HT1080 conditioned medium, one or more of which could contribute to proteolysis of reduced plasmin.

Interaction of platelet-derived growth factor with thrombospondin 1.

Key factors that mediate vascular smooth muscle cell proliferation and migration are platelet-derived growth factor (PDGF) and thrombospondin 1 (TSP1). We now report that PDGFBB bound tightly and specifically to TSP1, that this interaction was markedly dependent on the disulphide bond arrangement in TSP1, and that binding of PDGFBB to TSP1 did not preclude PDGFBB from binding to its receptor on rat aortic vascular smooth-muscle cells. At physiologic ionic strength and pH, PDGFBB bound to Ca2+-depleted TSP1 with a dissociation constant of 11 +/- 2 nM and to Ca2+-replete TSP1 with a dissociation constant of 32 +/- 5 nM. Binding was specific, as both soluble TSP1 and unlabelled PDGFBB competed for binding of iodinated PDGFBB to immobilized TSP1, whereas other platelet alpha-granule proteins did not compete. The tertiary structure of TSP1 is regulated by intramolecular disulphide interchange; we found that catalysis of disulphide interchange in TSP1 by protein disulphide isomerase ablated the binding of PDGFBB. The interaction of PDGFBB with TSP1 was weakened by increasing salt concentration and essentially ablated at 0.65 ionic strength; it was inhibited by heparin with a half-maximal effect at 20 i.u./ml, implying that the binding was mediated largely by ionic interactions. An anti TSP1 monoclonal antibody decreased the binding of iodinated PDGFBB to PDGF receptor on rat aortic vascular smooth-muscle cells by 37 +/- 2%, whereas platelet TSP1 non-competitively inhibited binding of iodinated PDGFBB. Uncomplexed PDGFBB bound to PDGF receptor with an affinity 5 +/- 2 times that of PDGFBB-TSP1 complexes. These results suggest that TSP1 might assist in the targeting of PDGF to its receptor on vascular smooth-muscle cells.

Generation of angiostatin by reduction and proteolysis of plasmin. Catalysis by a plasmin reductase secreted by cultured cells.

Extracellular manipulation of protein disulfide bonds has been implied in diverse biological processes, including penetration of viruses and endotoxin into cells and activation of certain cytokine receptors. We now demonstrate reduction of one or more disulfide bonds in the serine proteinase, plasmin, by a reductase secreted by Chinese hamster ovary or HT1080 cells. Reduction of plasmin disulfide bond(s) triggered proteolysis of the enzyme, generating fragments with the domain structure of the angiogenesis inhibitor, angiostatin. Two of the known reductases secreted by cultured cells are protein disulfide isomerase and thioredoxin, and incubation of plasmin with these purified reductases resulted in angiostatin fragments comparable with those generated from plasmin in cell culture. Thioredoxin-derived angiostatin inhibited proliferation of human dermal microvascular endothelial cells with half-maximal effect at approximately 0.2 microg/ml. Angiostatin made by cells and by purified reductases contained free sulfhydryl group(s), and S-carbamidomethylation of these thiol group(s) ablated biological activity. Neither protein disulfide isomerase nor thioredoxin were the reductases used by cultured cells, because immunodepletion of conditioned medium of these proteins did not affect angiostatin generating activity. The plasmin reductase secreted by HT1080 cells required a small cofactor for activity, and physiologically relevant concentrations of reduced glutathione fulfilled this role. These results have consequences for plasmin activity and angiogenesis, particularly in the context of tumor growth and metastasis. Moreover, this is the first demonstration of extracellular reduction of a protein disulfide bond, which has general implications for cell biology.

The course of the right recurrent laryngeal nerve within the vagus nerve of the rat.

The course of the right recurrent laryngeal nerve (RLN) within the vagus nerve was examined under the light microscope, using horseradish peroxidase. In the higher cervical vagus, i.e. from the base of the skull to the level of the carotid bifurcation, the recurrent laryngeal nerve fibres formed on average 5-6 small separate bundles (15-40 microns in diameter); in the middle cervical vagus, on average from the level of 8-14 mm caudally from the bifurcation, there were fewer bundles with a diameter range of 10-50 microns; in the lower cervical vagus, indicated as being from 14-26 mm caudally from the middle cervical vagus, the bundles merged into a single larger bundle (50-70 microns).