Major trauma care at a regional trauma centre during the COVID-19 lockdown in England.

INTRODUCTION: The COVID-19 pandemic has changed the presentation of many medical and surgical conditions, including major trauma. We aimed to assess how lockdown changed the presentation, severity and management of major trauma patients at our level 1 trauma centre in England. METHODS: Data were collected retrospectively from the Trauma Audit and Research Network's database between 23 March and 28 April 2020 and compared with the same period in 2019. Collected data included patient demographics, and the mechanism, severity and management of injuries. RESULTS: We experienced a 56.4% reduction in major trauma admissions during the lockdown period when compared with 2019. In 2020, more patients arrived in haemodynamic shock (25.3% vs 12.2%, p=0.02); however, Glasgow Coma Scale and Injury Severity Score were unchanged. A higher proportion of incidents occurred at home (37.2% vs 53.5%, p=0.018), with no difference in trauma secondary to substance abuse or assault. During lockdown, patients had a significantly shorter hospital (17 vs 10 days, p=0.029) and critical care stay (2 vs 1 day, p=0.033). A higher proportion of major trauma patients were assessed by specialty trainees in the emergency department in 2020 (12.8% vs 53.1%, p=0.0001) with a lower proportion assessed by a consultant (69.8% vs 46.7%, p=0.001). CONCLUSIONS: The COVID-19 pandemic and lockdown drastically changed human behaviour, as reflected in the change in presentation of major trauma. Changes in the management of these patients reflect adaptive measures to manage the pressures generated by the worldwide pandemic.

Low body mass index is associated with increased mortality in patients with pelvic and acetabular fractures.

AIMS: Fractures of the pelvis and acetabulum are often the consequence of high energy trauma in young individuals or fragility fractures in osteoporotic bone. They can be life-threatening or life changing injuries. No published data exists comparing body mass index (BMI) and mortality for this patient group. The aim of this study was to identify if low BMI (<18.5) was a predictor of morbidity and mortality for patients with these injuries. PATIENTS AND METHODS: Of the 1033 patients with pelvic or acetabular fractures referred to a single level 1 major trauma centre (MTC) over a 4.5-year period (August 2015 - January 2020); we retrospectively analysed data for all admitted patients. Data was collected on demographics, injury pattern, operative intervention and complications. Comparison was made between patients that were underweight (BMI<18.5) and patients that were not. Both in-hospital and post discharge complications were recorded including pulmonary embolus (PE), deep venous thrombosis (DVT), ileus, infection, loss of reduction and mortality at 6 months. RESULTS: 569 patients admitted to the MTC with a pelvic or acetabular fracture were included in our analysis. Underweight patients had a statistically significant increase in mortality both in-hospital (p = 0.019) and at 6 months post injury (p = 0.039) when compared to other BMI groups. No statistical significance was found between these BMI groups comparing morbidity: DVT (p = 0.712), PE (p = 0.736) nor ileus (p = 0.149). Covariate analysis showed that a low BMI was associated with triple the in-hospital mortality after correction for age and energy of injury (adjusted OR 3.028, 95% CI 1.059-8.659). CONCLUSION: This is the first published study that demonstrates a statistically significant increase in mortality in patients with pelvic or acetabular fractures who are underweight. Surgeons should carefully consider appropriate peri-operative optimisation for these patients. Further investigation into the effects of low BMI and response to trauma is required.

The global burden of trauma during the COVID-19 pandemic: A scoping review.

Purpose; The COVID-19 pandemic has necessitated profound adaptations in the delivery of healthcare to manage a rise in critically unwell patients. In an attempt to slow the spread of the virus nationwide lockdown restrictions were introduced. This review aims to scope the literature on the impact of the pandemic and subsequent lockdown on the presentation and management of trauma globally. Methods; A scoping review was conducted in accordance with PRISMA-ScR guidelines. A systematic search was carried out on the Medline, EMBASE and Cochrane databases to identify papers investigating presentation and management of trauma during the COVID-19 pandemic. All studies based on patients admitted with orthopaedic trauma during the COVID-19 pandemic were included. Exclusion criteria were opinion-based reports, reviews, studies that did not provide quantitative data and papers not in English. Results; 665 studies were screened, with 57 meeting the eligibility criteria. Studies reported on the footfall of trauma in the UK, Europe, Asia, USA, Australia and New Zealand. A total of 29,591 patients during the pandemic were considered. Mean age was 43.7 years (range <1-103); 54.8% were male. Reported reductions in trauma footfall ranged from 20.3% to 84.6%, with a higher proportion of trauma occurring secondary to interpersonal violence, deliberate self-harm and falls from a height. A decrease was seen in road traffic collisions, sports injuries and trauma occurring outdoors. There was no significant change in the proportion of patients managed operatively, and the number of trauma patients reported to be COVID-19 positive was low. Conclusion; Whilst the worldwide COVID-19 pandemic has caused a reduction in the number of trauma patients; the services managing trauma have continued to function despite infrastructural, personnel and pathway changes in health systems. The substantial effect of the COVID-19 pandemic on elective orthopaedics is well described, however the contents of this review evidence minimal change in the delivery of effective trauma care despite resource constraints during this global COVID-19 pandemic.

The innate immune response, clinical outcomes, and ex vivo HCV antiviral efficacy of a TLR7 agonist (PF-4878691).

Hepatitis C virus (HCV) infection is an issue of global concern, and studies are ongoing to identify new therapies that are both effective and safe. PF-4878691 is a Toll-like receptor 7 (TLR7) agonist modeled so as to dissociate its antiviral activities from its inflammatory activities. In a proof-of-mechanism study in healthy volunteers who received doses of 3, 6, and 9 mg of PF-4878691 twice a week for 2 weeks, PF-4878691 induced biomarkers of the immune and interferon (IFN) responses in a dose-dependent and dose-frequency-related manner. A novel finding was induction of TLR7 expression in vivo in response to PF-4878691, leading to an amplified biomarker response. A nonresponder at the 9-mg dose had a polymorphism in the IFN-α receptor 1 subunit (Val168Leu). Two subjects who had received 9-mg doses experienced serious adverse events (SAEs), characterized by flu-like symptoms, hypotension, and lymphopenia, leading to early termination of the study. TLR7 stimulation results in a pharmacologic response at levels commensurate with predicted antiviral efficacy, but these doses are associated with SAEs, raising concerns about the therapeutic window of this class of compounds for the treatment of HCV infection.

Splenic injury following colonoscopy--an underdiagnosed, but soon to increase, phenomenon?

INTRODUCTION: We present a case of splenic rupture in a 71-year-old woman admitted 6 days following a diagnostic colonoscopy. She underwent an open splenectomy and made a delayed, but complete, recovery. We proceeded to perform a retrospective review of all relevant literature to assess the frequency of similar post-colonoscopy complications. MATERIALS AND METHODS: Using relevant keywords, we identified 63 further PubMed reports of splenic injury associated with colonoscopy that were reported in English. FINDINGS: We have described only the fourth report of splenic injury secondary to colonoscopy from a UK centre. Literature review reveals a mean age of 63 years and a female preponderance for this complication. Most patients present on the day of their colonoscopy with abdominal pain, anaemia, elevated white cell count and Kehr's sign. CT is the investigation of choice and splenectomy the definitive management of choice. Most patients make a routine recovery, with mortality rates of approximately 8%. There is likely to be an under-reporting of this complication from UK-based centres, with the majority of reports originating from Europe and US. This points to a possible under-diagnosis or under-recognition of this potentially fatal complication. The incidence of such post-colonoscopic complications may increase with the forthcoming introduction of the National Bowel Cancer Screening Programme.

Strategies to prevent N-acetyltransferase-mediated metabolism in a series of piperazine-containing pyrazalopyrimidine compounds.

1. (1-Methyl-5-piperazine-1-yl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)-(5-methyl-pyridin-2-yl)-amine (UK-469,413) was identified as a lead compound in a new medicinal chemistry programme. UK-469,413 had good physicochemical properties and was slowly metabolized by cytochromes P450 in rat and human liver microsomes. 2. In the rat in vivo the compound was rapidly cleared. Subsequent studies showed that UK-469,413 was rapidly acetylated in rat liver cytosol to an N-acetylpiperazine metabolite that was the major circulating metabolite in rat plasma in vivo. 3. Analogues of UK-469,413 containing the unsubstituted piperazine moiety were rapidly acetylated in rat liver cytosol and had high plasma clearance in the rat in vivo. These compounds were also acetylated in human liver cytosol and the N-acetyl metabolite was a major metabolite formed in incubations with cryopreserved human hepatocytes. 4. Using specific inhibitors, correlation analysis and expressed human N-acetyltransferase (NAT) enzymes the compounds were shown to be substrates of the polymorphically expressed NAT-2 isozyme. 5. Further experiments showed that it was possible to make small structural changes to the piperazine group that retained potency but prevented metabolism by NAT.

The Charlson comorbidity score: a superior comorbidity assessment tool for the prostate cancer multidisciplinary meeting.

INTRODUCTION: Multidisciplinary team (MDT) meetings use precise prognostic factors to select treatment options for patients with prostate cancer. Comorbidity is judged subjectively. Recent publications favour the Charlson comorbidity score (CS) for the use in the management of prostate cancer. We assess the feasibility of using the CS by our MDT in planning the treatment of patients with prostate cancer. PATIENTS AND METHODS: Patients from the histopathology database aged less than 75 years and with a diagnosis of localized prostate cancer between 1993 and 1995 were included in a notes audit. A second group consisted of patients recommended for curative treatment for localized prostate cancer by the local MDT in 2004. Data on comorbidity, prostatic malignancy and survival up to 10 years was collected. The prognostic accuracy of the CS was assessed for those patients offered radical treatment between 1993 and 1995. RESULTS: Of 1043 patients initially assessed, 37 patients with localized prostate cancer were identified. Using Cox regression, we found the CS to be a statistically significant predictor of survival, following radical treatment for localized prostate cancer (P=0.005). Current practice in 2004 (56 patients) shows a mean (range) Charlson probability of 10-year survival for radical prostatectomy of 0.823 (0.592-0.923) and for radical radiotherapy of 0.653 (0.07-0.936). CONCLUSIONS: Our results support the findings of recent research. We also found the CS easy to calculate and therefore feasible to use in our MDT setting. We propose the introduction of the Charlson score by prostate cancer MDTs to assess age and comorbidity.

Blueberry muffin rash as a presentation of alveolar cell rhabdomyosarcoma in a neonate.

Soft tissue sarcomas of childhood continue to present problems with pathologic diagnosis, staging and treatment. Rhabdomyosarcoma, the most common soft tissue sarcoma, represents 4-8% of all malignant solid tumours in children. We report a case of congenital alveolar rhabdomyosarcoma who presented with "blueberry muffin"-like rash. A full-term female infant was noted at birth to have multiple skin lesions resembling blueberry muffin rash and an abdominal mass in the left iliac fossa, which appeared to be fixed to the posterior abdominal wall. There was no enlargement of liver and spleen, but her para-aortic lymph nodes were enlarged. Biopsy from the mass confirmed the diagnosis of alveolar cell rhabdomyosarcoma. Molecular investigation for the t (2:13) translocation was negative. The infant received chemotherapy but died within 1 mo of diagnosis.

Gastric evacuation for acute ethanol intoxication in a three year old.

A three year old girl presented in a deeply comatose state. She had drunk ethanol four hours previously and her blood ethanol concentration on arrival was 79.8 mmol/litre (3.69 g/litre). Because of her young age, high blood ethanol concentration, time since ingestion, and severe neurological depression on presentation, nasogastric aspiration of the stomach contents was performed and 4.2 g of ethanol were removed. She made an uneventful recovery.

HIV-1 gp160 envelope protein modulates proliferation and apoptosis in mesangial cells.

Mesangial cell (MC) hyperplasia and accumulation of extracellular matrix are the predominant features of HIV-associated nephropathy (HIVAN). Since mice transgenic for HIV-1 genes show renal lesions mimicking HIVAN, we studied the effect of HIV-1 gp160 protein on cultured murine MC (MMC) proliferation and apoptosis. HIV-1 gp160 protein stimulated (p < 0.001) MMC proliferation when compared with control MMCs. This effect of gp160 protein peaked at a concentration of 0.01 microg/ml. MMCs treated with a higher concentration of gp160 protein (0.1 microg/ml) or for a prolonged period of time (72 h) showed apoptosis rather than cell proliferation. These studies were further confirmed by DNA fragmentation and end labeling assays. gp160 also enhanced apoptosis in human MCs. Tumor necrosis factor (TNF)-alpha enhanced (p < 0.001) MMC apoptosis, and anti-TNF-alpha antibodies inhibited gp160-induced MMC apoptosis. In addition, gp160 protein attenuated MMC expression of Bcl-2 mRNA expression. These results suggest that gp160-induced apoptosis may be affected in part by the release of TNF-alpha and associated with attenuated mRNA expression of Bcl-2 by MMCs.

Percutaneous transvenous mitral commissurotomy using Inoue balloon catheter: a left femoral vein approach.

Percutaneous transvenous mitral commissurotomy by the Inoue technique is usually recommended from right femoral vein approach only. We report an unusual patient in whom the left femoral vein approach was used successfully. We believe that the left femoral vein approach can be reserved as a last resort in certain cases.