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1.
Front Immunol ; 15: 1416820, 2024.
Article in English | MEDLINE | ID: mdl-38947312

ABSTRACT

Background: Traumatic and thermal injuries result in a state of systemic immune suppression, yet the mechanisms that underlie its development are poorly understood. Released from injured muscle and lysed red blood cells, heme is a damage associated molecular pattern with potent immune modulatory properties. Here, we measured plasma concentrations of total heme in over 200 traumatic and thermally-injured patients in order to examine its relationship with clinical outcomes and post-injury immune suppression. Methods: Blood samples were collected from 98 burns (≥15% total body surface area) and 147 traumatically-injured (injury severity score ≥8) patients across the ultra-early (≤1 hour) and acute (4-72 hours) post-injury settings. Pro-inflammatory cytokine production by lipopolysaccharide (LPS) challenged whole blood leukocytes was studied, and plasma concentrations of total heme, and its scavengers haptoglobin, hemopexin and albumin measured, alongside the expression of heme-oxygenase-1 (HO-1) in peripheral blood mononuclear cells (PBMCs). LPS-induced tumour necrosis factor-alpha (TNF-α) production by THP-1 cells and monocytes following in vitro heme treatment was also examined. Results: Burns and traumatic injury resulted in significantly elevated plasma concentrations of heme, which coincided with reduced levels of hemopexin and albumin, and correlated positively with circulating levels of pro and anti-inflammatory cytokines. PBMCs isolated from trauma patients 4-12 and 48-72 hours post-injury exhibited increased HO-1 gene expression. Non-survivors of burn injury and patients who developed sepsis, presented on day 1 with significantly elevated heme levels, with a difference of 6.5 µM in heme concentrations corresponding to a relative 52% increase in the odds of post-burn mortality. On day 1 post-burn, heme levels were negatively associated with ex vivo LPS-induced TNF-α and interleukin-6 production by whole blood leukocytes. THP-1 cells and monocytes pre-treated with heme exhibited significantly reduced TNF-α production following LPS stimulation. This impairment was associated with decreased gene transcription, reduced activation of extracellular signal-regulated kinase 1/2 and an impaired glycolytic response. Conclusions: Major injury results in elevated plasma concentrations of total heme that may contribute to the development of endotoxin tolerance and increase the risk of poor clinical outcomes. Restoration of the heme scavenging system could be a therapeutic approach by which to improve immune function post-injury.


Subject(s)
Burns , Heme , Humans , Heme/metabolism , Burns/blood , Burns/immunology , Male , Adult , Female , Middle Aged , Cytokines/blood , Wounds and Injuries/immunology , Wounds and Injuries/blood , Young Adult , Aged , THP-1 Cells , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/immunology , Biomarkers/blood , Lipopolysaccharides , Heme Oxygenase-1/blood
2.
J Hand Surg Eur Vol ; 49(1): 48-53, 2024 01.
Article in English | MEDLINE | ID: mdl-37656976

ABSTRACT

This study investigates the pattern of hand injuries presenting to a UK regional tertiary centre. All referrals to our Hand Surgery Unit in 2019 were reviewed. Subgroup analyses of sex, deprivation, occupational injuries and assault cases were carried out. Over the study period, 4216 cases were referred. Most were male (70%), with a median age of 36 years and from a deprived area (75.2%). Soft tissue injury was documented in 53.6% and bone injury (fracture/dislocation) in 52.4%. Surgical management was required in 2214 (52.5%) cases. Work-related injuries accounted for 16.7% of cases and were more likely to require surgery. Assault-related injuries accounted for 8% of cases, with a male preponderance. Our findings can help facilitate service provision and guide regional and national prevention policies.Level of evidence: III.


Subject(s)
Hand Injuries , Soft Tissue Injuries , Adult , Female , Humans , Male , Hand Injuries/epidemiology , Hand Injuries/surgery , Referral and Consultation , Retrospective Studies
3.
Br Paramed J ; 8(3): 37-41, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38046792

ABSTRACT

Pavement burns are more common in locations familiarised with high temperatures and a dry climate zone, but have not previously been reported in temperate climates. We present two cases of patients who suffered pavement burns in the United Kingdom during an unprecedentedly hot day in July 2022. The first case involved a 66-year-old male who suffered partial and full thickness burns requiring excision and skin grafting. The second case involved a 58-year-old female with partial thickness burns also requiring excision and skin grafting. Both patients had pre-existing co-morbidities and their pavement burns were precipitated by heat stroke. Pavement burns represent a mechanism of injury that necessitates increased operative management, length of hospital stay and cost per surface area burned when compared to flame or scald burns (Silver et al., 2015). As a result of global warming, we anticipate extreme heat events, and subsequently pavement burns, to increase in incidence in the United Kingdom. There is opportunity for education of the public and health professionals for prevention.

4.
J Hand Surg Asian Pac Vol ; 27(6): 1035-1037, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36476088

ABSTRACT

Coronavirus disease 2019 (COVID-19) continues to pose significant health challenges, with insights into long-term disease sequelae emerging. The post-viral effects resulting from COVID-19 are being investigated and 'long COVID-19' is now a recognised phenomenon. As part of the spectrum of comorbidities, acute-onset neuropathy is associated with infection. The public health response aimed at limiting morbidity and mortality is rooted in vaccination programmes. With the extensive roll-out of novel vaccinations, there has been careful monitoring of temporally associated health problems. Some of the documented associations include neuropathy and entrapment neuropathies. This case report details a patient presenting with bilateral carpal tunnel syndrome (CTS) post their second dose of AZD1222 (ChAdOx1 nCoV-19) vaccination. Though we do not claim causality, the emerging post-vaccination immune-mediated effects may ultimately be proven to include neuropathy exacerbation. Meticulous recording of such associations is required as it is of great relevance to the hand surgeon managing CTS. Level of Evidence: Level V (Therapeutic).


Subject(s)
COVID-19 Vaccines , COVID-19 , Carpal Tunnel Syndrome , Humans , Carpal Tunnel Syndrome/surgery , ChAdOx1 nCoV-19 , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Median Nerve , Post-Acute COVID-19 Syndrome
5.
BMJ Support Palliat Care ; 12(2): 142-151, 2022 Jun.
Article in English | MEDLINE | ID: mdl-33608254

ABSTRACT

BACKGROUND: Inequalities in access to hospice care is a source of considerable concern; white, middle-class, middle-aged patients with cancer have traditionally been over-represented in hospice populations. OBJECTIVE: To identify from the literature the demographic characteristics of those who access hospice care more often, focusing on: diagnosis, age, gender, marital status, ethnicity, geography and socioeconomic status. DESIGN: Systematic literature review and narrative synthesis. METHOD: Searches of Medline, PsycINFO, CINAHL, Web of Science, Assia and Embase databases from January 1987 to end September 2019 were conducted. Inclusion criteria were peer-reviewed studies of adult patients in the UK, Australia, New Zealand and Canada, receiving inpatient, day, outpatient and community hospice care. Of the 45 937 titles retrieved, 130 met the inclusion criteria. Narrative synthesis of extracted data was conducted. RESULTS: An extensive literature search demonstrates persistent inequalities in hospice care provision: patients without cancer, the oldest old, ethnic minorities and those living in rural or deprived areas are under-represented in hospice populations. The effect of gender and marital status is inconsistent. There is a limited literature concerning hospice service access for the LGBTQ+ community, homeless people and those living with HIV/AIDS, diabetes and cystic fibrosis. CONCLUSION: Barriers of prognostic uncertainty, institutional cultures, particular needs of certain groups and lack of public awareness of hospice services remain substantial challenges to the hospice movement in ensuring equitable access for all.


Subject(s)
Hospice Care , Hospices , Neoplasms , Adult , Aged, 80 and over , Australia , Ethnicity , Humans , Middle Aged
6.
Article in English | MEDLINE | ID: mdl-34489301

ABSTRACT

OBJECTIVE: The aims of this study were to describe community antibiotic prescribing patterns in individuals hospitalised with COVID-19, and to determine the association between experiencing diarrhoea, stratified by preadmission exposure to antibiotics, and mortality risk in this cohort. DESIGN/METHODS: Retrospective study of the index presentations of 1153 adult patients with COVID-19, admitted between 1 March 2020 and 29 June 2020 in a South London NHS Trust. Data on patients' medical history (presence of diarrhoea, antibiotic use in the previous 14 days, comorbidities); demographics (age, ethnicity, and body mass index); and blood test results were extracted. Time to event modelling was used to determine the risk of mortality for patients with diarrhoea and/or exposure to antibiotics. RESULTS: 19.2% of the cohort reported diarrhoea on presentation; these patients tended to be younger, and were less likely to have recent exposure to antibiotics (unadjusted OR 0.64, 95% CI 0.42 to 0.97). 19.1% of the cohort had a course of antibiotics in the 2 weeks preceding admission; this was associated with dementia (unadjusted OR 2.92, 95% CI 1.14 to 7.49). After adjusting for confounders, neither diarrhoea nor recent antibiotic exposure was associated with increased mortality risk. However, the absence of diarrhoea in the presence of recent antibiotic exposure was associated with a 30% increased risk of mortality. CONCLUSION: Community antibiotic use in patients with COVID-19, prior to hospitalisation, is relatively common, and absence of diarrhoea in antibiotic-exposed patients may be associated with increased risk of mortality. However, it is unclear whether this represents a causal physiological relationship or residual confounding.


Subject(s)
COVID-19 , Adult , Anti-Bacterial Agents/adverse effects , Cohort Studies , Diarrhea/chemically induced , Humans , Retrospective Studies , SARS-CoV-2
9.
BMJ Case Rep ; 12(11)2019 Nov 02.
Article in English | MEDLINE | ID: mdl-31678923

ABSTRACT

Glomus tumours are atypical in extracutaneous locations and very rarely located in reproductive organs. We present an unusual case of an incidentally discovered glomus tumour arising from the testis of a 47-year-old man. The testicular occurrence of this tumour type is not only exceptionally rare but also serves to highlight the debate regarding the optimal management of incidentally discovered small testicular lesions.


Subject(s)
Glomus Tumor/pathology , Testicular Neoplasms/pathology , Diagnosis, Differential , Glomus Tumor/diagnostic imaging , Glomus Tumor/surgery , Humans , Male , Middle Aged , Orchiectomy , Testicular Neoplasms/diagnostic imaging , Testicular Neoplasms/surgery , Ultrasonography
10.
Plast Reconstr Surg Glob Open ; 7(5): e2240, 2019 May.
Article in English | MEDLINE | ID: mdl-31333965

ABSTRACT

Glycemic control represents a modifiable preoperative risk factor in surgery. Traditionally, hemoglobin A1c (HbA1c) and plasma glucose are utilized as measures of glycemic control. However, studies show mixed results regarding the ability of these conventional measures to predict adverse surgical outcomes. This may be explained by the time window captured by HbA1c and serum glucose: long-term and immediate glycemic control, respectively. Fructosamine, glycosylated albumin, and 1,5-anhydroglucitol constitute alternative metrics of glycemic control that are of growing interest but are underutilized in the field of surgery. These nontraditional measures reflect the temporal variations in glycemia over the preceding days to weeks. Therefore, they may more accurately reflect glycemic control within the time window that most significantly affects surgical outcomes. Additionally, these alternative measures are predictive of negative outcomes, even in the nondiabetic population and in patients with chronic renal disease and anemia, for whom HbA1c performs poorly. Adopting these newer metrics of glycemia may enhance the value of preoperative evaluation, such that the effectiveness of any preoperative glycemic control interventions can be assessed, and adverse outcomes associated with hyperglycemia better predicted. The goal of this review is to provide an update on the preoperative management of glycemia and to describe alternative metrics that may improve our ability to predict and control for the negative outcomes associated with poor glycemic control.

11.
Knee Surg Sports Traumatol Arthrosc ; 26(11): 3515-3524, 2018 Nov.
Article in English | MEDLINE | ID: mdl-29679117

ABSTRACT

PURPOSE: The infrapatellar fat pad (IFP) is a common cause of knee pain and loss of knee flexion and extension. However, its anatomy and behavior are not consistently defined. METHODS: Thirty-six unpaired fresh frozen knees (median age 34 years, range 21-68) were dissected, and IFP attachments and volume measured. The rectus femoris was elevated, suprapatellar pouch opened and videos recorded looking inferiorly along the femoral shaft at the IFP as the knee was flexed. The patellar retinacula were incised and the patella reflected distally. The attachment of the ligamentum mucosum (LMuc) to the intercondylar notch was released from the anterior cruciate ligament (ACL), both menisci and to the tibia via meniscotibial ligaments. IFP strands projecting along both sides of the patella were elevated and the IFP dissected from the inferior patellar pole. Magnetic resonance imaging (MRI) of one knee at ten flexion angles was performed and the IFP, patella, tibia and femur segmented. RESULTS: In all specimens the IFP attached to the inferior patellar pole, femoral intercondylar notch (via the LMuc), proximal patellar tendon, intermeniscal ligament, both menisci and the anterior tibia via the meniscotibial ligaments. In 30 specimens the IFP attached to the anterior ACL fibers via the LMuc, and in 29 specimens it attached directly to the central anterior tibia. Proximal IFP extensions were identified alongside the patella in all specimens and visible on MRI [medially (100% of specimens), mean length 56.2 ± 8.9 mm, laterally (83%), mean length 23.9 ± 6.2 mm]. Mean IFP volume was 29.2 ± 6.1 ml. The LMuc, attached near the base of the middle IFP lobe, acting as a 'tether' drawing it superiorly during knee extension. The medial lobe consistently had a pedicle superomedially, positioned between the patella and medial trochlea. MRI scans demonstrated how the space between the anterior tibia and patellar tendon ('the anterior interval') narrowed during knee flexion, displacing the IFP superiorly and posteriorly as it conformed to the trochlear and intercondylar notch surfaces. CONCLUSION: Proximal IFP extensions are a novel description. The IFP is a dynamic structure, displacing significantly during knee motion, which is, therefore, vulnerable to interference from trauma or repetitive overload. Given that this trauma is often surgical, it may be appropriate that surgeons learn to minimize injury to the fat pad at surgery.


Subject(s)
Adipose Tissue/anatomy & histology , Knee Joint/anatomy & histology , Patella/anatomy & histology , Adipose Tissue/diagnostic imaging , Adipose Tissue/physiology , Adult , Aged , Female , Humans , Knee Joint/diagnostic imaging , Knee Joint/physiology , Ligaments, Articular/anatomy & histology , Ligaments, Articular/diagnostic imaging , Ligaments, Articular/physiology , Magnetic Resonance Imaging , Male , Middle Aged , Patella/diagnostic imaging , Patella/physiology , Range of Motion, Articular/physiology , Young Adult
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