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The Kennedy Trust for Rheumatology Research (KTRR) has pledged a minimum of £20M over five years to the Kennedy Institute of Rheumatology at the University of Oxford to support pioneering research into chronic inflammatory disease.
Flap reconstruction of pressure ulcers in patients with spinal cord injury: a retrospective cohort study.
STUDY DESIGN: Retrospective case series. OBJECTIVES: To describe our five-year experience of surgical excision and flap reconstruction of pressure ulcers in individuals with spinal cord injury (SCI). SETTING: Tertiary spinal centre in Stoke Mandeville, United Kingdom. METHODS: All spinal injury patients that underwent surgical reconstruction of pressure ulcers at the Stoke Mandeville Hospital National Spinal Injury Centre between 2018 and 2022 inclusive were included. Ulcers underwent 'pseudotumour' excision followed by either immediate or staged flap reconstruction. The primary outcome was complete healing at one year. Secondary outcomes included flap loss, complications, and return to theatre. RESULTS: 52 cases were included across 44 patients. 43 cases (82.7%) underwent immediate debridement and reconstruction. The mean number of procedures was 1.9 (range 1-6). Local flaps were used in 22 (41.5%) cases. There was one (1.9%) free flap (anterolateral thigh), eight (15.4%) pedicled flaps, and 21 (39.6%) flaps based on single perforators. 49 cases completed follow-up; 41 (83.7%) were healed at one year after their initial surgery. Immediate reconstructions were 36.7% more likely to achieve healing at this time point than staged cases (P = .028, Fisher's exact). There was partial or total flap loss in 15 (28.8%) cases. Thirty-nine complications were seen in 24 (46.2%) cases. Twenty-three cases (44.2%) required returns to theatre. CONCLUSIONS: Surgical debridement with flap reconstruction is a safe and reliable treatment approach for pressure ulcers in those with SCI, with a complication rate comparable to existing literature. Immediate flap reconstruction and local flap designs may be associated with a lower risk of complications and higher healing rates.
Outcomes of Flap Reconstruction for Diabetic Foot Ulcers: A Systematic Review and Meta-Analysis of Clinical Studies.
BACKGROUND: People with diabetic foot ulcers (DFUs) are at risk of major amputation, which is associated with a high mortality rate (exceeding 50% at 5 years) and reduced quality of life. The authors hypothesized that flap reconstruction of DFUs improves patient outcomes in comparison with standard treatment modalities, including major amputation. METHODS: MEDLINE, Embase, the Cochrane Library, and gray literature were searched on February 9, 2022. Comparative and single-arm studies reporting outcomes of DFUs treated with local, regional, or free flaps that included function, limb loss, mortality rates, and flap failure rates were included. Risk of bias was assessed, and meta-analysis of proportions was performed. RESULTS: A total of 3878 records were retrieved, of which 45 met the inclusion criteria, including the records of 1681 patients who underwent flap reconstruction of DFUs. Free flaps were most commonly performed ( n = 1257 [72%]). Only one study used a verified functional outcome measure. At 12 months, the mortality rate was 6.35% (95% CI, 3.89% to 10.20%), the limb loss rate was 11.39% (95% CI, 7.02% to 17.96%), and the free flap failure rate was 9.95% (95% CI, 8.19% to 12.05%). All studies were at high risk of bias. A comparative meta-analysis of interventions was not performed because of study method and outcome heterogeneity. CONCLUSIONS: There is short-term evidence that flap reconstruction (including microsurgical transfer) has low mortality, limb loss, and flap failure rates. However, there are limited high-quality comparative studies, and uncertainty remains regarding the outcome of DFU flap reconstruction in comparison to other treatments.
Functional and Immunologic Mapping of Domains of the Reticulocyte-Binding Protein Plasmodium vivax PvRBP2a.
We previously described a novel Plasmodium vivax invasion mechanism into human reticulocytes via the PvRBP2a-CD98 receptor-ligand pair. Using linear epitope mapping, we assessed the PvRBP2a epitopes involved in CD98 binding and recognized by antibodies from patients who were infected. We identified 2 epitope clusters mediating PvRBP2a-CD98 interaction. Cluster B (PvRBP2a431-448, TAALKEKGKLLANLYNKL) was the target of antibody responses in humans infected by P vivax. Peptides from each cluster were able to prevent live parasite invasion of human reticulocytes. These results provide new insights for development of a malaria blood-stage vaccine against P vivax.
What is new in the 5th edition of the World Health Organization classification of mature B and T/NK cell tumors and stromal neoplasms?
The classification of tumors is essential in the diagnosis and clinical management of patients with malignant neoplasms. The World Health Organization (WHO) provides a globally applicable classification scheme of neoplasms and it was updated several times. In this review, we briefly outline the cornerstones of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours on lymphoid neoplasms. As is adopted throughout the 5th edition of the WHO classification of tumors of all organ systems, entities are listed by a hierarchical system. For the first time, tumor-like lesions have been included in the classification, and modifications of nomenclature for some entities, revisions of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities are presented along with mesenchymal lesions specific to the stroma of lymph nodes and the spleen. In addition to specific outlines on constitutional and somatic genetic changes associated with given entities, a separate chapter on germline predisposition syndromes related to hematologic neoplasms has been added.
A Qualitative Study of Patients' Lived Experiences of Free Tissue Transfer for Diabetic Foot Disease.
BACKGROUND: Free tissue transfer (FTT) for reconstruction of diabetic foot disease (DFD) is an emerging field to preserve the lower limb within this patient group. The design of future quantitative research and clinical services in this area must consider the needs, expectations and concerns of patients. This qualitative study explores patient experiences of FTT for reconstruction of DFD. METHODS: Semistructured interviews were conducted to explore patients' lived experiences of FTT for DFD. A purposive sampling strategy identified six patients who underwent FTT for recalcitrant DFD between September 2019 and December 2021 in a single center in the United Kingdom. RESULTS: Three experiential themes emerged. Theme 1: "negative lived experiences of living with DFD" included frustration with the chronic management of nonhealing ulcers and fear regarding limb amputation. Theme 2: "surgery related concerns" included fears of reconstructive failure and subsequent amputation, as well as foot cosmesis and donor-site morbidity. Theme 3: "positive lived experiences following reconstruction" included the positive impact the reconstruction had on their overall life and diabetic control. All patients would repeat the process to obtain their current results. CONCLUSIONS: This qualitative study provides first-hand insight into the lived experience of FTT for DFD, exploring both the negative and positive experiences and reasons for these. We found that FTT for DFD can be positively life-changing for affected individuals.
The 5th edition of the World Health Organization Classification of mature lymphoid and stromal tumors - an overview and update.
The purpose of this review is to give an overview on the conceptual framework and major developments of the upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid tumours (WHO-HAEM5) and to highlight the most significant changes made in WHO-HAEM5 compared with the revised 4th edition (WHO-HAEM4R) of lymphoid and stromal neoplasms. The changes from the revised 4th edition include the reorganization of entities by means of a hierarchical system that is realized throughout the 5th edition of the WHO classification of tumors of all organ systems, a modification of nomenclature for some entities, the refinement of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities. For the first time, tumor-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms are included in the classification.
Deficiency of factor-inhibiting HIF creates a tumor-promoting immune microenvironment.
Hypoxia signaling influences tumor development through both cell-intrinsic and -extrinsic pathways. Inhibiting hypoxia-inducible factor (HIF) function has recently been approved as a cancer treatment strategy. Hence, it is important to understand how regulators of HIF may affect tumor growth under physiological conditions. Here we report that in aging mice factor-inhibiting HIF (FIH), one of the most studied negative regulators of HIF, is a haploinsufficient suppressor of spontaneous B cell lymphomas, particular pulmonary B cell lymphomas. FIH deficiency alters immune composition in aged mice and creates a tumor-supportive immune environment demonstrated in syngeneic mouse tumor models. Mechanistically, FIH-defective myeloid cells acquire tumor-supportive properties in response to signals secreted by cancer cells or produced in the tumor microenvironment with enhanced arginase expression and cytokine-directed migration. Together, these data demonstrate that under physiological conditions, FIH plays a key role in maintaining immune homeostasis and can suppress tumorigenesis through a cell-extrinsic pathway.
Outcomes of Free Flap Reconstruction for Chronic Venous Ulceration in the Lower Limb: A Systematic Review.
BACKGROUND: The mainstay of treatment for venous ulceration is conservative wound management and lifelong compression therapy. For patients with recalcitrant ulcers, free flap reconstruction has been proposed as a treatment option to reconstruct the diseased soft tissues as well as the underlying insufficient venous system. This review systematically evaluates the outcomes of free flap reconstruction for chronic venous ulcers in the lower limb. METHOD: A protocol was developed a priori and registered on the PROSPERO database. A systematic search of literature was performed in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), clinical trials registries, and OpenGrey from inception to April 2020 according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies of patients undergoing free tissue transfer reconstruction for chronic venous ulcers in the lower limb were included. RESULTS: A total of 5 noncomparative cohort studies featuring 56 patients with 62 recalcitrant venous ulcers treated with 64 free flaps who had a mean age of 50 years (range, 17-76 years) were included, and a narrative analysis undertaken. Mean defect size following ulcer debridement was 153.3 cm 2 (range, 24-600 cm 2 ). Defects were reconstructed with muscle (n = 39 [60.9%]), fasciocutaneous (n = 23 [35.9%]), and visceral (n = 2 [3.1%]) free flaps, with latissimus dorsi (n = 16, 25%) and rectus abdominis flaps (n = 16, 25%) being the most frequently used. Mean follow-up ranged from 24 to 125 months. Pooled flap survival rate was 95%. No recurrence within the territory of the flap was reported, but there were 20 instances (35.7%) of new ulcers outside of the flap boundaries. CONCLUSION: There is currently an absence of evidence to support the use of free flap reconstruction for recalcitrant venous ulcers compared with conventional management. Although evidence suggests that it is technically feasible, there is no evidence to suggest it prevents ulceration outside the reconstructed region. Further studies are necessary to evaluate its effectiveness for venous ulcers in the lower limb.
The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms.
The upcoming 5th edition of the World Health Organization (WHO) Classification of Haematolymphoid Tumours is part of an effort to hierarchically catalogue human cancers arising in various organ systems within a single relational database. This paper summarizes the new WHO classification scheme for myeloid and histiocytic/dendritic neoplasms and provides an overview of the principles and rationale underpinning changes from the prior edition. The definition and diagnosis of disease types continues to be based on multiple clinicopathologic parameters, but with refinement of diagnostic criteria and emphasis on therapeutically and/or prognostically actionable biomarkers. While a genetic basis for defining diseases is sought where possible, the classification strives to keep practical worldwide applicability in perspective. The result is an enhanced, contemporary, evidence-based classification of myeloid and histiocytic/dendritic neoplasms, rooted in molecular biology and an organizational structure that permits future scalability as new discoveries continue to inexorably inform future editions.
The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms.
We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.
Prevalence, risk factors and parental perceptions of gastroesophageal reflux disease in Asian infants in Singapore.
INTRODUCTION: Infant gastroesophageal reflux disease (GERD) is a significant cause of concern to parents. This study seeks to describe GERD prevalence in infants, evaluate possible risk factors and assess common beliefs influencing management of GERD among Asian parents. METHODS: Mother-infant dyads in the Singapore PREconception Study of long-Term maternal and child Outcomes (S-PRESTO) cohort were prospectively followed from preconception to 12 months post-delivery. GERD diagnosis was ascertained through the revised Infant Gastroesophageal Reflux Questionnaire (I-GERQ-R) administered at 4 time points during infancy. Data on parental perceptions and lifestyle modifications were also collected. RESULTS: The prevalence of infant GERD peaked at 26.5% at age 6 weeks, decreasing to 1.1% by 12 months. Infants exclusively breastfed at 3 weeks of life had reduced odds of GERD by 1 year (adjusted odds ratio 0.43, 95% confidence interval 0.19-0.97, P=0.04). Elimination of "cold or heaty food" and "gas producing" vegetables, massaging the infant's abdomen and application of medicated oil to the infant's abdomen were quoted as major lifestyle modifications in response to GERD symptoms. CONCLUSION: Prevalence of GERD in infants is highest in the first 3 months of life, and the majority outgrow it by 1 year of age. Infants exclusively breastfed at 3 weeks had reduced odds of GERD. Cultural-based changes such as elimination of "heaty or cold" food influence parental perceptions in GERD, which are unique to the Asian population. Understanding the cultural basis for parental perceptions and health-seeking behaviours is crucial in tailoring patient education appropriately for optimal management of infant GERD.
Seasonal Variation in Hand and Upper Limb Soft Tissue Infections.
Background: Hand and upper limb soft tissue infections result in significant disability and loss of productivity. Many infections have been shown to follow a seasonal variation, however little is known about this is the context of upper limb soft tissue infections. We aimed to evaluate seasonal variation in acute bacterial, hand and upper limb skin and soft-tissue infections, and correlate findings with key environmental variables. Methods: Hand and upper limb soft tissue infection cases from 2006-2016 were retrieved from a single UK center. Cases were reviewed for microbiology culture and sensitivity. Correlation between cases and season, temperature and humidity was assessed. Results: 206 cases were identified for inclusion. Specimens were sent for microbiology in 76.4% of cases. Of these 78.9% were culture positive, 47.6% exhibited antibiotic resistance and 16.9% were multi-resistant. There was a significant difference between season and culture positive cases, with significantly more culture positive cases in the summer vs. winter on post-hoc analysis (p = 0.004). There was a significant positive correlation between higher temperatures and number of culture positive cases (r = 0.75). There was no significant correlation between temperature and antibiotic resistance (r = 0.5) or between humidity and culture positive cases (r = -0.42). Conclusions: This study demonstrates a seasonal variation in hand and upper limb infections, with a significant correlation between infection rates and ambient temperature. Appreciating seasonal variability of these infections could prove beneficial for surgical planning, public health recommendations and antibiotic guidelines. However, further international data is needed to understand potential mechanisms involved.
Performance anxiety among surgeons
In the first of our psychology of surgery series, we look at surgeons’ performance anxiety from a psychological perspective.
Meet Fiona
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Fiona Powrie FRS
Professor of Musculoskeletal Sciences and Director of the Kennedy Institute
Funded by
