The novel application of the Lightning Process to treat Long COVID in primary care - Case report.

As a result of the COVID-19 pandemic, Long COVID (LC) is now prevalent in many countries. Little evidence exists regarding how this chronic condition should be treated, but guidelines suggest for most people it can be managed symptomatically in primary care. The Lightning Process is a trademarked positive psychology focused self-management programme which has shown to be effective in reducing fatigue and accompanying symptoms in other chronic conditions including Chronic Fatigue Syndrome/Myalgic Encephalomyelitis. Here we outline its novel application to two patients with LC who both reported improvements in fatigue and a range of physical and emotional symptoms post-treatment and at 3 months follow-up.

The Royal College of Surgeons of England Damage Control Orthopaedic Trauma Skills course (DCOTS): resuscitative knowledge and confidence in surgical skills are reliably maintained at six months post course.

INTRODUCTION: Since 2012, the Damage Control Orthopaedic Trauma Skills course (DCOTS) has trained more than 250 surgeons in the principles and practice of damage control orthopaedics and early appropriate care. This Royal College of Surgeons of England (RCS England) course takes place at the RCS England Partner cadaver laboratory at Brighton and Sussex Medical School. Trauma is a leading cause of morbidity and mortality in the UK, and the course has tried to pass on the lessons of war and conflict from its military faculty and hard-won lessons of "developed world" trauma from its experienced civilian faculty. METHODS: Participating surgeons were invited to score their self-reported confidence before attending the DCOTS course, immediately afterwards and again 6 months later. A modified four-point Likert scale was used, with responses from 1 = No Confidence to 4 = Very Confident. Damage control resuscitation principles with damage control surgery showed the greatest retained increase at 6 months - 100% - which is extremely satisfying. RESULTS: Self-reported confidence in pelvic external fixation was initially 93% dropping to 85%, which is also considered good to excellent. For pelvic packing, confidence was 90% at the end of the course, up from 19% precourse. This dropped to 62%, which was still considered good but low for the high standards of the course. This may relate to UK trainees' lack of familiarity with the concept. CONCLUSIONS: Three of the main skills taught on the DCOTS are effectively retained at 6 months post course.

Broström Repair With and Without Augmentation: Comparison of Outcomes at Median Follow-up of 5 Years.

BACKGROUND: An augmented Broström repair with nonabsorbable suture tape has demonstrated strength and stiffness more similar to the native anterior talofibular ligament (ATFL) compared to Broström repair alone at the time of repair in cadaveric models for the treatment of lateral ankle instability. The study purpose was to compare minimum 2-year patient-reported outcomes (PROs) following treatment of ATFL injuries with Broström repair with vs without suture tape augmentation. METHODS: Between 2009 and 2018, patients >18 years old who underwent primary surgical treatment for an ATFL injury with either a Broström repair alone (BR Cohort) or Broström repair with suture tape augmentation (BR-ST Cohort) were identified. Demographic data and PROs, including Foot and Ankle Ability Measure (FAAM) with activities of daily living (ADL) and sport subscales, 12-Item Short Form Health Survey (SF-12), Tegner Activity Scale, and patient satisfaction with surgical outcome, were compared between groups, and proportional odds ordinal logistic regression was used. RESULTS: Ninety-one of 102 eligible patients were available for follow-up at median 5 years. The BR cohort had 50 of 53 patients (94%) completed follow-up at a median of 7 years. The BR-ST cohort had 41 of 49 (84%) complete follow-up at a median of 5 years. There was no significant difference in median postoperative FAAM ADL (98% vs 98%, P = .67), FAAM sport (88% vs 91%, P = .43), SF-12 PCS (55 vs 54, P = .93), Tegner score (5 vs 5, P = .64), or patient satisfaction (9 vs 9, P = .82). There was significantly higher SF-12 MCS (55.7 vs 57.6, P = .02) in the BR-ST group. Eight patients underwent subsequent ipsilateral ankle surgery, of which one patient (BR-ST group) was revised for recurrent lateral ankle instability. CONCLUSION: At median 5 years, patients treated for ATFL injury of the lateral ankle with Broström repair with suture tape augmentation demonstrated similar patient-reported outcomes to those treated with Broström repair alone. LEVEL OF EVIDENCE: Level II, retrospective cohort study.

ACLR and military service: time to rethink?

Anterior cruciate ligament (ACL) rupture is a common injury that affects young, active individuals, normally managed with reconstruction in this age group. Current UK Armed Forces policy precludes prospective applicants from joining with an anterior cruciate ligament reconstruction (ACLR). This isdue to the perceived risk of premature osteoarthritis (OA), graft rupture or clinical failure, all of which could make the service person medically non-deployable.The most recent evidence shows that an ACL rupture without associated significant meniscal or osteochondral defect has a similar likelihood of developing OA as to that of the uninjured knee after reconstruction at 20 years postoperatively.Applicants should be considered for service following an ACL rupture without significant concurrent meniscal or osteochondral defect who have undergone ACLR and 18 months of rehabilitation. We recommend these applicants to be graded P2 Medically Fully Deployable (MFD) as per the Joint Service Publication (JSP) guidance for service personnel who undergo ACLR.

Abdominal Aortic Junctional Tourniquet - Stabilized (AAJTS) can be applied both successfully and rapidly by Combat Medical Technicians (CMTs).

BACKGROUND: 'Non-compressible' haemorrhage is the leading cause of preventable battlefield death, often requiring surgical or radiological intervention, which is precluded in the pre-hospital environment. One-fifth of such bleeds are junctional and therefore potentially survivable. We examine the use of the Abdominal Aortic Junctional Tourniquet - Stabilized (AAJTS) among UK Combat Medical Technicians (CMTs) as a device to control junctional haemorrhage with external compression of the abdominal aorta-compression of junctional haemorrhage previously considered 'non-compressible.' This follows animal studies showing that the AAJTS achieves control of haemorrhage and improves physiological parameters. METHODS: CMTs were selected and applied the AAJTS to each other following a 1-hour training package. A consultant radiologist-operated hand-held ultrasound monitored flow changes in the subjects' common femoral artery. CMTs were then surveyed for their opinions as to utility and function. RESULTS: 21 CMTs were screened and 17 CMTs participated with 34 total applications (16 day and 18 low-light). 27/34 (79%) achieved a successful application. The median application time was 75 s in daylight and 57 s in low-light conditions. There was no significant difference in Body Mass Index (p=0.23), median systolic blood pressure (p=0.19), nor class of CMT (p=0.10) between successful and unsuccessful applications. Higher systolic blood pressure was associated with longer application times (p=0.03). Users deemed the device easy to use (median score 4.4 on a 5-point Likert scale). CONCLUSION: CMTs can use AAJTS successfully after a 1-hour training session in the majority of applications. Application was successful in both daylight and low-light conditions. Self-reported usability ratings were high.

Image-Guided Transvaginal and Transabdominal Drain Placement for Surgical Navigation in a Patient with Tubo-Ovarian Abscess and Obstructed Hemivagina and Ipsilateral Renal Anomaly Syndrome.

BACKGROUND: We describe a minimally invasive, image-guided technique for obstructed hemivagina and ipsilateral renal anomaly (OHVIRA) syndrome complicated by tubo-ovarian abscess (TOA). CASE: A 15-year-old female adolescent with OHVIRA syndrome presented with TOA. Magnetic resonance imaging of the abdomen/pelvis showed a loculated pelvic mass and fluid collection near the obstructed left hemivagina. Tissue quality and ill-defined surgical planes prevented surgical excision. A transabdominal drain was placed via laparoscopic port by Interventional Radiology. She later underwent transvaginal and transabdominal drain placement into the hemivaginal collection using computed tomography and ultrasound guidance, allowing for surgical excision of the vaginal septum, drainage and excision of the TOA, and neosalpingostomy. SUMMARY AND CONCLUSION: Because of the anatomic complexity in OHVIRA syndrome, preoperative minimally invasive techniques with Interventional Radiology collaboration can assist intraoperative anatomic navigation for successful surgical treatment.

Acute and subacute effects of a synthetic kisspeptin analog, C6, on serum concentrations of luteinizing hormone, follicle stimulating hormone, and testosterone in prepubertal bull calves.

Kisspeptin (KP) is a neuropeptide integral in regulating puberty and gonadotropin releasing hormone. Compound 6 (C6), a KP analog, is more potent in vitro, has a longer half-life, and may have greater therapeutic applications than KP. To determine the acute and subacute effects of KP and C6 on serum concentrations of luteinizing hormone (LH), follicle stimulating hormones (FSH), and testosterone (T), prepubertal bull calves [12.1 ±â€¯1.1 (SD) weeks of age; 91.2 ±â€¯10.8 kg BW] were assigned to one of three treatment groups [Saline (n = 4), KP (n = 4; 20 nmoles), or C6 (n = 4; 20 nmoles). Treatments were administered intramuscularly once daily for four consecutive days. Blood samples were collected every 15 min for 6 h immediately following treatment administration on Day 1 (acute) and Day 4 (subacute). Serum concentrations of LH, FSH, and T were determined by radioimmunoassay. For each day, effects of treatment, time, and interactions on LH and FSH concentrations and pulse parameters were analyzed using procedures for repeated measures with JMP Software (SAS Inst. Inc., Cary, NC). There was a treatment × time interaction during Day 1 (P < 0.0001) and Day 4 (P = 0.02) such that LH concentrations were greatest following administration of C6 (albeit diminished during Day 4). Number of LH pulses were least (P = 0.02) and LH nadirs were highest (P = 0.04) following administration of C6 (P = 0.02). There was no effect of treatment (P = 0.95) or treatment × time interaction (P = 0.10) on serum FSH concentrations during Day 1. During Day 4 FSH concentrations (P = 0.02) and number of FSH pulses (P = 0.02) were least following administration of C6. There was no effect of treatment (P = 0.33), time (P = 0.19) or treatment × time interaction (P = 0.44) on T concentrations. In conclusion, acute and subacute C6 increased LH concentrations and subacute C6 decreased FSH concentrations and pulse parameters. Despite suppression of FSH with subacute daily administration of C6, altered frequency and timing of treatment with KP analogs may have application to affect the onset of puberty in livestock.

Non-battle injury among repatriated UK armed forces since cessation of combat operations: a prospective observational study.

AIM: To describe the mechanisms, burden of injury, inpatient management and rehabilitation requirements of wounded military personnel at the UK Role 4 (R4) facility within the first 12 months following cessation of combat operations in Afghanistan. METHODS: All aeromedical evacuations were recorded prospectively between October 2014 and October 2015. Demographic, logistical and clinical data were derived manually from referring medical unit and patient movement requests in addition to host nation and R4 medical records. RESULTS: Ninety-five patients were repatriated to R4 following traumatic injury: 98.9% (n=94) were male, and median age was 27 years (IQR 25-36 years). The most common mechanisms of injury (MOIs) were sports 26.3% (n=25), falls <2 m 11.6% (n=11) and road traffic collisions 9.8% (n=9). The most common anatomical regions of injury were isolated lower limb 24.1% (n=22), isolated hand 20.0% (n=19) and polytrauma 14.7% (n=14). Median Injury Severity Score was 4 (IQR 4-9), mean 8 (range 1-41). Eleven patients (11.6%) were discharged to rehabilitation units, of whom 7 (63.6%) required neurorehabilitation. CONCLUSION: Although service personnel sustain civilian-type injuries, the specific rehabilitation goals and shift in the acute rehabilitation requirements for military personnel must be considered in the absence of enduring combat operations. It is notable that permanent medical downgrading secondary to trauma still occurs outside of warfare. The colocation of civilian major trauma services and R4 has ensured a mutually beneficial partnership that contributes to institutional memory and improves the coordination of patient pathways. The importance of relevant resource allocation, training, support and logistical considerations remain, even during the current scale of military activity overseas.

STAT4 expression and activation is increased during mitosis in vitro and in vivo in skin- and mucosa-derived cell types: implications in neoplastic and inflammatory skin diseases.

BACKGROUND: The signal transducer and activator of transcription-4 (STAT4/Stat4) is a transcription factor known to convey signals from interleukin-12, interleukin-23, and interferon-alpha/beta to the nucleus, resulting in activation of dendritic cells, T-helper cell differentiation and production of interferon-gamma. OBJECTIVE: To demonstrate a novel role for STAT4 in cell mitosis. RESULTS: Phosphoserine STAT4 (pSerSTAT4) is increased in cells undergoing mitosis and is distributed throughout the cytoplasm during this stage of the cell cycle, whilst phosphotyrosine STAT4 (pTyrSTAT4) is confined to the chromosomal compartment. This distinct pattern of pSerSTAT4 during mitosis is seen in vitro in human keratinocytes and in other cell types. This is also present in vivo in cells undergoing mitosis in normal skin, psoriasis and squamous cell carcinoma. Inhibition of STAT4 phosphorylation by lisofylline and depletion of STAT4 by RNA interference results in a delay in progression of mitosis and leads to a reduction in cells completing cytokinesis. CONCLUSION: Our data demonstrate that STAT4 plays a role in enabling the normal and timely division of cells undergoing mitosis.

The impact of sleep deprivation in military surgical teams: a systematic review.

BACKGROUND: Fatigue in military operations leads to safety and operational problems due to a decrease in alertness and performance. The primary method of counteracting the effects of sleep deprivation is to increase nightly sleep time, which in operational situations is not always feasible. History has taught us that surgeons and surgical teams are finite resources that cannot operate on patients indefinitely. METHODS: A systematic review was conducted using the search terms 'sleep' and 'deprivation' examining the impact of sleep deprivation on cognitive performance in military surgical teams. Studies examining outcomes on intensive care patients and subjects with comorbidities were not addressed in this review. RESULTS: Sleep deprivation in any 'out-of-hours' surgery has a significant impact on overall morbidity and mortality. Sleep deprivation in surgeons and surgical trainees negatively impacts cognitive performance and puts their own and patients' health at risk. All published research lacks consensus when defining 'sleep deprivation' and 'rested' states. It is recognised that it would be unethical to conduct a well-designed randomised controlled trial, to determine the effects of fatigue on performance in surgery; however, there is a paucity between surrogate markers and applying simulated results to actual clinical performance. This requires further research. Recommended methods of combating fatigue include: prophylactically 'sleep-banking' prior to known periods of sleep deprivation, napping, use of stimulant or alerting substances such as modafinil, coordinated work schedules to reduce circadian desynchronisation and regular breaks with enforced rest periods. CONCLUSIONS: A forward surgical team will become combat-ineffective after 48 hours of continuous operations. This systematic review recommends implementing on-call periods of no more than 12 hours in duration, with adequate rest periods every 24 hours. Drug therapies and sleep banking may, in the short term, prevent negative effects of acute sleep deprivation.

Demystifying damage control in musculoskeletal trauma.

Trauma care has evolved rapidly over the past decade. The benefits of operative fracture management in major trauma patients are well recognised. Concerns over early total care arose when applied broadly. The burden of additional surgical trauma could constitute a second hit, fuelling the inflammatory response and precipitating a decline into acute respiratory distress syndrome, sepsis and multiple organ dysfunction syndrome. Temporary external fixation aimed to deliver the benefits of fracture stabilisation without the risk of major surgery. This damage control orthopaedics approach was advocated for those in extremis and a poorly defined borderline group. An increasing understanding of the physiological response to major trauma means there is now a need to refine our treatment options. A number of large scale retrospective reviews indicate that early definitive fracture fixation is beneficial in the majority of major trauma patients. It is recommended that patients are selected appropriately on the basis of their response to resuscitation. The hope is that this approach (dubbed 'safe definitive fracture surgery' or 'early appropriate care') will herald an era when care is individualised for each patient and their circumstances. The novel Damage Control in Orthopaedic Trauma Surgery course at The Royal College of Surgeons of England aims to equip senior surgeons with the insights and mindset necessary to contribute to this key decision making process as well as also the technical skills to provide damage control interventions when needed, relying on the improved techniques of damage control resuscitation and advances in the understanding of early appropriate care.

Targeting protein kinase C in sarcoma.

Protein kinase C (PKC) is a family of serine/threonine tyrosine kinases that regulate many cellular processes including division, proliferation, survival, anoikis and polarity. PKC is abundant in many human cancers and aberrant PKC signalling has been demonstrated in cancer models. On this basis, PKC has become an attractive target for small molecule inhibition within oncology drug development programmes. Sarcoma is a heterogeneous group of mesenchymal malignancies. Due to their relative insensitivity to conventional chemotherapies and the increasing recognition of the driving molecular events of sarcomagenesis, sarcoma provides an excellent platform to test novel therapeutics. In this review we provide a structure-function overview of the PKC family, the rationale for targeting these kinases in sarcoma and the state of play with regard to PKC inhibition in the clinic.

A phase II study of sirolimus, tacrolimus and rabbit anti-thymocyte globulin as GVHD prophylaxis after unrelated-donor PBSC transplant.

We report on a prospective phase II trial of 32 patients who underwent unrelated-donor hematopoietic cell transplantation, with a tacrolimus, sirolimus and rabbit anti-thymoctye globulin GVHD prophylactic regimen. The primary study endpoint was incidence of grades II-IV acute (aGVHD), with 80% power to detect a 30% decrease compared with institutional historical controls. Median age at transplant was 60 (19-71). In total, 23 patients (72%) received reduced-intensity conditioning, whereas the remainder received full-intensity regimens. Median follow-up for surviving patients was 35 months (range: 21-49). The cumulative incidence of aGVHD was 37.3%, and the 2-year cumulative incidence of chronic GVHD was 63%. We observed thrombotic microangiopathy in seven patients (21.8%), one of whom also developed sinusoidal obstructive syndrome (SOS). Four of the 32 patients (12.5%) failed to engraft, and 3 of these 4 died. As a result, enrollment to this trial was closed before the targeted accrual of 60 patients. Two-year OS was 65.5% and EFS was 61.3%. Two-year cumulative incidence of relapse was 12.5% and non-relapse mortality (NRM) was 15.6%. NRM and aGVHD rates were lower than historical rates. However, the unexpectedly high incidence of graft failure requires caution in the design of future studies with this regimen.

Hereditary leukemia due to rare RUNX1c splice variant (L472X) presents with eczematous phenotype.

Deleterious mutations in the RUNX1 gene cause hereditary leukemia due to a rare syndrome called Familial platelet Disorder with Associated Myeloid Malignancy (FPDMM). We describe the characteristics of a family with FPDMM due to a novel RUNX1 mutation (L472X), located in the most 3-prime end of the gene reported to date. Our 36-year old proband presented with incidentally detected thrombocytopenia and a family history suggestive of FPDMM. Contrary to previously described families, affected members of our kindred express an eczematous phenotype, reportedly most severe in members who develop leukemia. Pedigree analysis shows that the L472X mutation tracks with thrombocytopenia, acute leukemia, and eczema. The L472X mutation produces a stably expressed RUNX1 protein product with a corresponding decrease in wild type RUNX1 expression. Our data supports the inclusion of eczema in the FPDMM phenotype and suggests the possibility that the RUNX1 L472X mutant causes the type of dominant negative affect that is associated with an elevated risk of leukemia in FPDMM families.

Consensus statement on decision making in junctional trauma care.

Improvised explosive devices (IEDs) cause 60% of all UK fatalities in the current campaign in Afghanistan. Shorter evacuation timelines now deliver patients at the edge of the physiological envelope of survivability meaning that the available time period for haemorrhage control and initial wound surgery is short--often no more than 75 minutes. The concepts and practise of 'right turn resuscitation', damage control general and orthopaedic surgery, on-table 'ITU' pause/catch-up and then further resuscitative surgery are commonplace. In Helmand in 2011, multiple team operating is now the norm on these casualties with up to seven surgeons and three anaesthetists simultaneously involved in the operative care of one patient. This usually involves one consultant orthopaedic surgeon and trainee per lower limb, a plastic surgeon on the upper limb or faceleyes and two general surgeons obtaining proximal vascular control or in-cavity haemorrhage control. A combined meeting in 2010 of the Lower Limb and Torso Trauma Working Groups of the Academic Department of Military Surgery and Trauma produced 25 clear, didactic statements to provide advice to the consultant team. The fundamental message is that bleeding is always a surgical problem. Some adjuncts are available; pressure (direct and indirect), compressive bandaging, haemostatic dressings and tourniquets. However, only formal surgical control, by whatever means is definitive. Early proximal control is mandatory: in all cases, rapidly obtain the most distally appropriate proximal control above the zone of injury.

Initial extremity war wound debridement: a multidisciplinary consensus.

A joint meeting of the Limb Trauma and Wounds Working Groups resulted in the establishment of 29 consensus recommendations for the conduct of initial extremity war wound debridement. Pre-operative, operative and post-operative phases of debridement were considered along with wound irrigation and dressings. Wounds where a different surgical approach is required, such as superficial soft tissue wounds at one end of the spectrum and complex wounds sustained in close proximity to explosions at the other, were also discussed. The recommendations represent the consensus opinion of orthopaedic, vascular and plastic surgeons, as well as nursing officers, from across the Defence Medical Services and are intended to provide useful guidance to the deploying surgeon, regardless of their own personal experience.