Two-year outcomes of conservatively managed appendicitis during the COVID-19 pandemic-a multicentre cohort study.

PURPOSE: During the COVID-19 pandemic, the new RCSEng guidelines resulted in appendicitis being more commonly managed conservatively to avoid aerosol-generating procedures. This resulted in shorter hospital stays without increased short-term complications. The 2-year outcomes of this change, specifically recurrence and re-admission rates remain unknown. METHODS: We conducted a multicentre, prospective, observational study including all adult patients treated as appendicitis after the implementation of the new surgical guidelines during the COVID-19 pandemic. Outcomes included initial management failure, re-admission rate, appendicitis recurrence, and interval appendicectomy. A historical cohort prior to the COVID-19 pandemic was used for comparison. Patients were followed up for 2-years post index admission. Categorical and continuous variables were compared using Fisher's exact test and Student's T or Mann-Whitney U tests as appropriate. RESULTS: Sixty-three and 79 patients with appendicitis were included from four NHS trusts, before (A) and after (B) the new intercollegiate guidelines respectively. Operative management was used less frequently in cohort B (28/79 vs 52/63; p<0.001). More patients re-presented in cohort B (14/79 vs 3/63; p=0.020), but not when comparing only those managed conservatively (2/11 vs 13/52; p=1.000). A similar trend was observed for appendicitis recurrence although without statistical significance (2/63 vs 9/79; p=0.112); with loss of trend when comparing those managed conservatively-only (2/11 vs 9/52; p=1.000). Among all patients, four (2.8%) were found to have underlying neoplasia of which three were initially managed conservatively (3/63; 4.8%). CONCLUSION: Conservative management of appendicitis has previously been shown to have short-term benefits in expedited hospital discharge without early complications. The present study shows it has a higher readmission and appendicitis recurrence rates. The risks of this alongside missed/delayed management of neoplasia needs to be considered alongside the benefits including avoidance of aerosol-generating general anaesthesia and laparoscopy during the COVID-19 pandemic or similar future health crises. Small case numbers limit analysis.

Suspected appendicitis and COVID-19, a change in investigation and management-a multicentre cohort study.

PURPOSE: The COVID-19 pandemic has reformed global healthcare delivery. On 25 March 2020, Intercollegiate guidelines were published in the UK to promote safe surgical provision during the COVID-19 outbreak advocating non-operative management or avoidance of laparoscopy when surgery is essential. The effects of this on the investigation and management of appendicitis remain unknown. METHODS: We performed a multicentre, prospective, observational study from the start of the new guidelines to the 6th of May 2020. We included all patients referred to surgical teams with suspected appendicitis. A recent historical cohort was identified for comparison. The primary outcome was the impact of the COVID-19 pandemic on the use of non-operative management in appendicitis. Secondary outcomes included imaging, negative appendicectomy rate (NAR), length of stay (LOS) and 30-day complications. RESULTS: A total of 63/164 (38%) patients compared to 79/191 (41%) were diagnosed with appendicitis before and after the guidelines were introduced (p = 0.589). CT scanning increased (71/164 vs 105/191; p = 0.033) while ultrasound scanning decreased (71/164 vs 62/191; p = 0.037). Appendicitis was more likely to be managed non-operatively (11/63 vs 51/79; p < 0.001) and, of those managed surgically, with an open approach (3/52 vs 26/28 p < 0.001). The NAR also reduced (5/52 vs 0/28; p = 0.157). LOS was shorter in non-operatively managed patients (1 day vs 3 days; p < 0.001) without a difference in complications (10/51 vs 4/28; p = 0.760). CONCLUSION: Introduction of the guidelines was associated with changes in practice. Despite these changes, short-term complications did not increase and LOS decreased. Questions remain on the longer-term complication rates in non-operatively managed patients.

A systematic review of the literature assessing the outcomes of stapled haemorrhoidopexy versus open haemorrhoidectomy.

BACKGROUND: Symptomatic haemorrhoids affect a large number of patients throughout the world. The aim of this systematic review was to compare the surgical outcomes of stapled haemorrhoidopexy (SH) versus open haemorrhoidectomy (OH) over a 20-year period. METHODS: Randomized controlled trials published between January 1998 and January 2019 were extracted from Pubmed using defined search criteria. Study characteristics and outcomes in the form of short-term and long-term complications of the two techniques were analyzed. Any changes in trend of outcomes over time were assessed by comparing article groups 1998-2008 and 2009-2019. RESULTS: Twenty-nine and 9 relevant articles were extracted for the 1998-2008 (period 1) and 2009-2019 (period 2) cohorts, respectively. Over the two time periods, SH was found to be a safe procedure, associated with statistically reduced operative time (in 13/21 studies during period 1 and in 3/8 studies during period 2), statistically less intraoperative bleeding (3/7 studies in period 1 and 1/1 study in period 2) and consistently less early postoperative pain on the visual analogue scale (12/15 studies in period 1 and 4/5 studies in period 2) resulting in shorter hospital stay (12/20 studies in period 1 and 2/2 studies in period 2) at the expense of a higher cost. In the longer term, although chronic pain in SH and OH patents is comparable, patient satisfaction with SH may decline with time and at 2-year follow-up OH appeared to be associated with greater patient satisfaction. CONCLUSIONS: SH appears to be safe with potential advantages, at least in the short term, but the evidence is lacking at the moment to suggest its routine use in clinical practice.

The use of daily electronic prompts to help improve antimicrobial stewardship in a critical care unit.

INTRODUCTION: Antimicrobial resistance (AMR) represents a growing threat to public health, with the potential to reverse many of the gains made in modern medicine. AMR is contributed to by both inappropriate choice of antibiotics and inappropriate antibiotic course durations. OBJECTIVES: The objective of this audit was to determine if the introduction of antimicrobial prescribing electronic prompts in an electronic patient record had a positive impact on antimicrobial stewardship. METHODS: The audit examined the proportion of antibiotic prescriptions within a critical care unit in which both a valid stop date and indication were recorded. The audit was repeated on two occasions: first, after an education programme, and second, after the introduction of an electronic prompt within the patients' electronic patient record. RESULTS: Chi-square analyses indicated that significant improvements in both the recording of indications (χ²(4) = 39.69, P <0.0001) and stop-dates (χ²(4) = 42.10, P <0.0001) occurred across the three audits. CONCLUSION: We conclude that the novel use of daily electronic prompts has a positive impact on antimicrobial stewardship.

Inhibition of MT1-MMP activity using functional antibody fragments selected against its hemopexin domain.

The membrane associated MMP, MT1-MMP, is a critical pericellular protease involved in tumour cell invasion and angiogenesis and is highly up-regulated in numerous human cancers. It therefore represents an exciting new therapeutic cancer-specific target. We have generated recombinant human scFv antibodies against the non-catalytic, hemopexin domain of MT1-MMP that modulate its interactions with collagen. One of these is an effective inhibitor of the invasive capacity of cancer cells and of angiogenesis in model systems. This demonstrates that targeting sites outside the catalytic domain presents a potential novel approach to proteinase inhibition that could have applications in cancer therapeutics.

Myoclonus after cardiac arrest: pitfalls in diagnosis and prognosis.

Accurate prediction of neurological outcome in survivors of cardiac arrest may be difficult. We report the case of a 44-year-old survivor of a hypoxic cardiac arrest who repeatedly developed relentless myoclonic jerks on attempted discontinuation of his propofol infusion. These were initially thought to represent myoclonic status epilepticus before the correct diagnosis of Lance-Adams syndrome was made. Lance-Adams syndrome is a rare disorder seen in survivors of profound hypoxic episodes. It is characterised by intention myoclonus but preserved intellect. Accurate distinction between myoclonic status epilepticus and Lance-Adams syndrome is vital as they have very different prognoses. The different pathophysiology and distinguishing clinical features of these two conditions are highlighted.

The Diamedica Draw-Over Vaporizer: a comparison of a new vaporizer with the Oxford Miniature Vaporizer.

The Diamedica Draw-Over Vaporizer (DDV) has been developed as an alternative to the Oxford Miniature Vaporizer (OMV). Both can function as draw-over or plenum vaporizers. The performances of these two vaporizers were compared under conditions simulating intermittent positive pressure ventilation (IPPV) and continuous flow (CF). Series 1 experiments were conducted with the vaporizers in water baths at 20, 25 and 30 degrees C. Vaporizers were tested at dial settings of 1-4% over a range of minute volumes (1.75-6 l.min(-1)) and flow rates (3-8 l.min(-1)). Series 2 experiments compared output of the vaporizers over time at ambient temperatures of 20, 25 and 30 degrees C. A minute volume of 6 l.min(-1) (IPPV) and a gas flow of 8 l.min(-1) (CF) were used with a vaporizer setting of 2%. Vapour concentrations were recorded at 5-min intervals. In series 1 IPPV experiments, the DDV vaporizer was more accurate, producing significantly fewer vapour concentrations 0.5% more than or less than setting (p = 0.013). The OMV tended to produce more favourable results under continuous flow (p = 0.42). In series 2 experiments, the accuracy of both vaporizers was similar but consistency of output over time was better for the DDV and consistency of output according to differences in ambient temperature was better for the DDV. The OMV produced more vapour concentrations that were markedly higher than dial setting, particularly at high ambient temperatures. The DDV is a suitable alternative to the OMV with some distinct advantages. These include a larger reservoir, tendency towards greater accuracy during IPPV and improved consistency of output.

Absence of p300 induces cellular phenotypic changes characteristic of epithelial to mesenchyme transition.

p300 is a transcriptional cofactor and prototype histone acetyltransferase involved in regulating multiple cellular processes. We generated p300 deficient (p300-) cells from the colon carcinoma cell line HCT116 by gene targeting. Comparison of epithelial and mesenchymal proteins in p300- with parental HCT116 cells showed that a number of genes involved in cell and extracellular matrix interactions, typical of 'epithelial to mesenchyme transition' were differentially regulated at both the RNA and protein level. p300- cells were found to have aggressive 'cancer' phenotypes, with loss of cell-cell adhesion, defects in cell-matrix adhesion and increased migration through collagen and matrigel. Although migration was shown to be metalloproteinase mediated, these cells actually showed a downregulation or no change in the level of key metalloproteinases, indicating that changes in cellular adhesion properties can be critical for cellular mobility.

Comparison of articaine and bupivacaine/lidocaine for sub-Tenon's anaesthesia in cataract extraction.

BACKGROUND: Articaine is the most widely used local anaesthetic for dental anaesthesia in Germany, Italy and The Netherlands and has recently been introduced and licensed for dental use in the UK. We have previously shown articaine to be superior to a standard mixture of bupivacaine 0.5%/lidocaine 2% for peribulbar anaesthesia. Sub-Tenon's anaesthesia arguably provides a safer method of anaesthetic delivery for cataract surgery. A blunt cannula is used in this technique, thus greatly reducing the risk of globe perforation, intrathecal injection and sight-threatening periocular haemorrhage. METHODS: We compared articaine and bupivacaine/lidocaine for sub-Tenon's anaesthesia in cataract surgery. RESULTS: Sub-Tenon's anaesthesia using articaine 2% resulted in a more rapid onset of motor block compared with a bupivacaine/lidocaine (P=0.0076). Ocular movement scores were significantly lower from 2 min after injection until the end of surgery (P=0.031 ANOVA). CONCLUSION: Articaine 2% is safe and effective for sub-Tenon's anaesthesia and is a suitable alternative to the traditional bupivacaine 0.5%/lidocaine 2% mixture.

Mesenteric ischemia: an unusual presentation of traumatic intrahepatic arterioportal fistula.

Traumatic hepatic arterioportal fistulae (APF) are described infrequently as sequelae of hepatic trauma. These anomalies are usually associated with blunt hepatic trauma or iatrogenic injury. The majority of APF present within weeks to months of injury with gastrointestinal hemorrhage, hemobilia, abdominal pain, and diarrhea. When presenting remotely APFs are associated with portal hypertension, heart failure, gastrointestinal hemorrhage, ascites, and splenomegaly. We report an unusual case of mesenteric ischemia due to an APF that resulted from a penetrating liver injury 20 years before presentation. Successful treatment of the APF was achieved by intravascular catheter occlusion resulting in resolution of symptoms.

Characterization of the role of the "MT-loop": an eight-amino acid insertion specific to progelatinase A (MMP2) activating membrane-type matrix metalloproteinases.

Progelatinase A (proGLA) activation is thought to be initiated almost exclusively by the type I transmembrane members of the membrane type matrix metalloproteinase family (MT-MMP): MT1, -2, -3, and -5-MMP (MMP14, -15, -16, and -24). One difference between these enzymes and the other MMP family members is the insertion of eight amino acids between strands betaII and III in the catalytic domain. In MT1-MMP, the best characterized of these enzymes to date, these residues consist of (163)PYAYIREG(170). To investigate the role of this region of MT1-MMP on its catalytic activities, we have made a variety of mutations and deletions in both soluble and membrane-bound forms of the enzyme. Characterization of the activity of the soluble forms toward peptides and fibrinogen revealed that neither mutation nor deletion of residues 163-170 significantly impaired catalytic function, suggesting these residues have little influence on conformation of the active site cleft. Equally none of the mutants showed significant differences in K(I)(app) for the N-terminal inhibitory domain of TIMP2, again indicating that mutation or deletion of resides 163-170 has no major effect on the overall topology of the active site of MT1-MMP. However, characterization of the kinetics of activation of proGLA with and without its gelatin binding region by the mutants generated have shown that efficient activation of proGLA is, at least in part, through an interaction with residues 163-170 of MT1-MMP. The expression, localization, and processing from the 63- to the 60/45-kDa forms of wild-type and key mutant forms of MT1-MMP were also examined by transient transfection in Chinese hamster ovary cells, but no differences were observed. Processing and activation of proGLA was also examined in transiently transfected cells. All the mutants examined were able process proGLA but, as found with the soluble forms, were kinetically impaired when compared with wild-type MT1-MMP.

Origin of the left pulmonary artery from the aorta: embryologic considerations.

We observed a case of anomalous origin of the left pulmonary artery from the aorta in which the media of the abnormal vessel and the main pulmonary artery were fused, but without communication. This is the fifth isolated case of repair without the use of cardiopulmonary bypass reported in the literature. This pathology should be included in the aortic arch anomalies as a partial or complete failure of development of the left sixth arch.

Catalytic activities of membrane-type 6 matrix metalloproteinase (MMP25).

This study describes the biochemical characterisation of the catalytic domain of membrane-type 6 matrix metalloproteinase (MT6-MMP, MMP25, leukolysin). Its activity towards synthetic peptide substrates, components of the extracellular matrix and inhibitors of MMPs was studied and compared with MT1-MMP, MT4-MMP and stromelysin-1. We have found that MT6-MMP is closer in function to stromelysin-1 than MT1 and MT4-MMP in terms of substrate and inhibitor specificity, being able to cleave type-IV collagen, gelatin, fibronectin and fibrin. However, it differs from stromelysin-1 and MT1-MMP in its inability to cleave laminin-I, and unlike stromelysin-1 cannot activate progelatinase B. Our findings suggest that MT6-MMP could play a role in cellular migration and invasion of the extracellular matrix and basement membranes and its activity may be tightly regulated by all members of the TIMP family.

Membrane type 4 matrix metalloproteinase (MMP17) has tumor necrosis factor-alpha convertase activity but does not activate pro-MMP2.

Membrane type 4 matrix metalloproteinase (MT4-MMP) shows the least sequence homology to the other MT-MMPs, suggesting a distinct function for this protein. We have isolated a complete cDNA corresponding to the mouse homologue which includes the signal peptide and a complete pro-domain, features that were lacking from the human form originally isolated. Mouse MT4-MMP (mMT4-MMP) expressed in COS-7 cells is located at the cell surface but does not show ability to activate pro-MMP2. The pro-catalytic domain was expressed in Escherichia coli as insoluble inclusions and active enzyme recovered after refolding. Activity of the isolated catalytic domain against synthetic peptides commonly used for MMP enzyme assays could be inhibited by TIMP1, -2, and -3. The recombinant mMT4-MMP catalytic domain was also unable to activate pro-MMP2 and was very poor at hydrolyzing components of the extracellular matrix with the exception of fibrinogen and fibrin. mMT4-MMP was able to hydrolyze efficiently a peptide consisting of the pro-tumor necrosis factor alpha (TNFalpha) cleavage site, a glutathione S-transferase-pro-TNFalpha fusion protein, and was found to shed pro-TNFalpha when co-transfected in COS-7 cells. MT4-MMP was detected by Western blot in monocyte/macrophage cell lines which in combination with its fibrinolytic and TNFalpha-converting activity suggests a role in inflammation.