Tourniquet use for people with peripheral arterial disease undergoing major lower limb amputations.

BACKGROUND: At least 7000 major lower limb amputations (MLLAs) are performed in the UK each year, 80% of which are due to peripheral arterial disease (PAD). Intraoperative blood loss can have a deleterious effect on patient outcomes, and its replacement with transfused blood is not without risk. Tourniquets can be used in lower limb surgical procedures to provide a bloodless surgical field, minimise intraoperative blood loss, and reduce perioperative blood transfusion requirements. Although their safety has been demonstrated in certain orthopaedic operations, their use among people with PAD undergoing MLLA remains controversial. Many clinicians are concerned about tourniquets potentially compromising perfusion of the stump and thereby impacting wound healing through direct tissue injury, damage to the arterial supply of the wound, or both. OBJECTIVES: To assess the safety and effectiveness of tourniquet use in people undergoing MLLA for complications of PAD, specifically with regard to intraoperative blood loss, change in haemoglobin levels, transfusion rates, wound healing, need for revision surgery, and postoperative complications including mortality. SEARCH METHODS: We searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers from inception to 17 May 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing tourniquet use to no tourniquet use among people with PAD undergoing MLLA. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Primary outcomes were intraoperative blood loss, fall in haemoglobin levels, and perioperative blood transfusion requirement. Secondary outcomes were primary wound-healing rates, stump revision rates, other postoperative complications defined as per Clavien-Dindo classification, and postoperative mortality at 30 days and at maximal follow-up. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: One RCT met our inclusion criteria, which was a prospective randomised blinded controlled trial conducted in Sheffield, UK in 2006. In total 64 participants undergoing transtibial amputation for non-reconstructable PAD were randomised to either tourniquet or no tourniquet to assess for intraoperative blood loss, fall in haemoglobin, transfusion requirement, wound healing, stump breakdown and revision. Ten participants were excluded postrandomisation (five from the tourniquet group and five from the no tourniquet group). The reported median volume of intraoperative blood loss was significantly less in the tourniquet group (255 mL (interquartile range (IQR) 150 to 572.5 mL))) compared to the control group (550 mL (IQR 255 to 1050 mL)) (P = 0.014). There was a significantly lower median drop in haemoglobin concentration in the tourniquet group (1.0 g/dL (IQR 0.6 to 2.4 g/dL)) compared to the control group (1.8 g/dL (IRQ 0 to 1.2 g/dL)) (P = 0.035). There was a significantly lower perioperative blood transfusion requirement in the tourniquet group (8 participants, 32%) compared to the control group (14 participants, 48%) (P = 0.047). There were no clear differences in wound breakdown, stump revision, primary wound healing at six weeks, postoperative complications (myocardial infarction, cardiac arrhythmias, pulmonary oedema), and death between groups. We assessed the one included study as at low risk of bias for sequence generation and blinding of outcome assessors; high risk of bias for incomplete outcome data and selective outcome reporting; and unclear risk of bias for allocation concealment, blinding of participants and personnel, and other sources of bias. We assessed the certainty of the evidence as low or very low due to risk of bias, small sample size, and the study being insufficiently powered for most outcomes. AUTHORS' CONCLUSIONS: This review identified only one small historical RCT evaluating tourniquet use in MLLA. Tourniquets appeared to reduce intraoperative blood loss, drop in haemoglobin, and blood transfusion requirements following transtibial amputations for people with PAD. However, it is unclear whether tourniquets affect wound healing, stump revision rates, postoperative complications, or mortality. High-certainty evidence is required to inform clinical decision-making for the use of tourniquets in these patients.

Clinical Effects of Tourniquet Use for Nontraumatic Major Lower Limb Amputation: A Two-Center Retrospective Cohort Study.

BACKGROUND: To investigate the effect of tourniquet use on outcomes after major lower limb amputation (MLLA) due to peripheral arterial disease or complications from diabetes mellitus. METHODS: In this 2-center retrospective observational study, vascular patients who underwent MLLA between January 1, 2016 and December 31, 2020 at 2 UK hospitals were identified using operating theater databases. Hospital databases were used to access medical records, operation notes, and laboratory reports. The use of a tourniquet in each MLLA was noted. The primary outcome was postoperative hemoglobin (Hb) drop (g/L). Secondary outcomes were units of allogeneic blood transfused perioperatively, 90-day revision rates, 90-day wound breakdown rates, surgical site infection (SSI) rates (at 30 days), and 90-day mortality. A follow-up index (a measure of follow-up completeness) was calculated for all 30-day and 90-day outcomes. RESULTS: Four hundred seventy two patients underwent MLLA, of which 124 had a tourniquet applied. The median postoperative Hb drop was significantly lower in the tourniquet group compared to the nontourniquet group (13 [interquartile range 5-22] g/L vs. 20 [interquartile range 11-28] g/L; P ≤ 0.001). Thirty three point one percent (41) of tourniquet patients received a blood transfusion perioperatively, compared to 35.6% (124) of nontourniquet patients (P = 0.82). Sixteen percent (76) of patients required surgical revision within 90 days, with no significant difference between the tourniquet and nontourniquet group (20.2% tourniquet vs. 14.7% no tourniquet; P = 0.15). SSI rates (12.0% tourniquet vs. 10.6% no tourniquet, P = 0.66) and 90-day mortality (6.5% tourniquet vs. 10.1% no tourniquet; P = 0.23) were similar. Multivariable regression demonstrated that tourniquet use was independently associated with a reduced hemoglobin drop (ß = -4.671, 95% confidence interval -7.51 to -1.83, P ≤ 0.001) but was not associated with wound breakdown, revision surgery, or SSI. Hypertension, SSI, and below-knee amputation using the skew flap technique were all significant predictors of revision surgery. All follow-up indices were ≥ 0.97. CONCLUSIONS: Tourniquet use in MLLA was associated with a significantly lower fall in postoperative Hb without evidence of harm in terms of SSI, wound breakdown/revision rates, or mortality.

A cluster of children with facial nerve palsy in a high prevalence area for COVID-19.

BACKGROUND: COVID-19 is a disease of varying presentation and neurological sequelae of the disease are being studied. Following a cluster of paediatric facial nerve palsy (FNP) cases in an area of South Wales with a high prevalence of COVID-19, we conducted an opportunistic study to determine whether there has been an increase of incidence of FNP and if there is an association between the FNP and COVID-19 in children. METHODS: We performed a retrospective review of the incidence of FNP between 2015 and 2020 across two hospitals within the health board. The incidence was compared with that in 2020 including a cluster of six children in 14 weeks, presenting to Royal Glamorgan Hospital between June and October. RESULTS: There were 48 cases of children with FNP across both hospital within the study years. Seven (7) cases in 2020. The incidence was not statistically different in comparison to other years. Five out of six of these children in 2020 had antibody testing for COVID-19. All serology testing (100%) returned negative for SARS-CoV- 2 antibodies. CONCLUSIONS: In high prevalence area for COVID-19, cases of children with FNP have not shown a commensurate increase. we have found no causal link between COVID-19 and FNP in children. While this is a small study, larger cohort studies are needed to support this finding. As new strains of COVID-19 are being reported in UK, South Africa and Brazil, physicians need to continue to be vigilant for consistent pattern of signs and symptoms, especially in children.

Low Stress Ion Conductance Microscopy of Sub-Cellular Stiffness.

Directly examining subcellular mechanics whilst avoiding excessive strain of a live cell requires the precise control of light stress on very small areas, which is fundamentally difficult. Here we use a glass nanopipet out of contact with the plasma membrane to both exert the stress on the cell and also accurately monitor cellular compression. This allows the mapping of cell stiffness at a lateral resolution finer than 100 nm. We calculate the stress a nanopipet exerts on a cell as the sum of the intrinsic pressure between the tip face and the plasma membrane plus its direct pressure on any glycocalyx, both evaluated from the gap size in terms of the ion current decrease. A survey of cell types confirms that an intracellular pressure of approximately 120 Pa begins to detach the plasma membrane from the cytoskeleton and reveals that the first 0.66 ± 0.09 µm of compression of a neuron cell body is much softer than previous methods have been able to detect.

Pipette-surface interaction: current enhancement and intrinsic force.

There is an intrinsic repulsion between glass and cell surfaces that allows noninvasive scanning ion conductance microscopy (SICM) of cells and which must be overcome in order to form the gigaseals used for patch clamping investigations of ion channels. However, the interactions of surfaces in physiological solutions of electrolytes, including the presence of this repulsion, for example, do not obviously agree with the standard Derjaguin-Landau-Verwey-Overbeek (DLVO) colloid theory accurate at much lower salt concentrations. In this paper we investigate the interactions of glass nanopipettes in this high-salt regime with a variety of surfaces and propose a way to resolve DLVO theory with the results. We demonstrate the utility of this understanding to SICM by topographically mapping a live cell's cytoskeleton. We also report an interesting effect whereby the ion current though a nanopipette can increase under certain conditions upon approaching an insulating surface, rather than decreasing as would be expected. We propose that this is due to electroosmotic flow separation, a high-salt electrokinetic effect. Overall these experiments yield key insights into the fundamental interactions that take place between surfaces in strong solutions of electrolytes.

From the other side of the GP's desk: a patient perspective on the Fuller report.

As the recommendations of the Fuller Review are implemented and the new system of integrated care boards becomes established, it has never been more important to involve the voices of patients and communities as we shape the future of general practice. Here, a patient offers a perspective on how we can harness multiple viewpoints and apply the principles of human-centred design to bring solutions to the challenges of access and prevention that are grounded in local communities.

Is Simultaneous Bilateral Knee Replacement a Safe Approach for Patients with Bilateral Knee Osteoarthritis? A Prospective Case-control Study.

BACKGROUND: Total knee arthroplasty (TKA) is the standard treatment for terminal knee osteoarthritis. Simultaneous bilateral total knee arthroplasty (STKA) can be a cost-effective and practical option for patients with degenerative joint disease affecting both knees. The purpose of this study was to assess complication rates and functional outcomes following simultaneous versus staged bilateral total knee replacement. MATERIAL AND METHODS: Approximately 60 individuals who experienced debilitating knee osteoarthritis were enrolled in a prospective study with a randomized comparative design. Out of these, 30 patients underwent simultaneous total knee arthroplasty (STKA), while the remaining 30 individuals underwent two separate surgeries with a gap of 3-6 months between each procedure for both knees. After excluding 7 patients from both groups, a total of 53 patients were included in the study and followed up for at least 12 months. RESULTS: Pre-operative demographic parameters were equated between both groups. The overall number of systemic complications was higher in the simultaneous group compared with the stagedone. Systemic complications were correlated with the elderly and high-risk populations. However, simultaneous procedures were safe in a low-risk group with shorter hospitalization and operative times. CONCLUSIONS: 1. Simultaneous bilateral total knee arthroplasty (TKA) is considered safe and feasible mainly for younger individuals with ASA 1 or 2 health status. 2. Patients undergoing simultaneous bilateral TKA experience significantly reduced hospital stays. 3. The procedure may not be advisable for elderly patients at a higher risk of systemic complications.

Neck of femur fracture: who gets a total hip replacement? A review of 230 eligible patients.

PURPOSE: To investigate patient-specific factors that predict Total Hip Replacement (THR) in patients with fracture neck of femur (NOF), fulfilling the National Institute of Health and Care Excellence (NICE) criteria. METHODS: Hip fracture database from a district general hospital and university hospital was retrospectively reviewed to identify patients fulfilling NICE criteria for THR after fracture NOF. Patient demographics, Nottingham Hip Fracture score (NHFS), complications, re-operations, revision, 30 days and one-year mortality was obtained from patient-records. Independent predictors correlating with the outcome of surgery were identified. A logistic regression analysis was used to predict the type of surgery in these patients. RESULTS: A total of 230 (114 WMH and 116 MH) were identified; 133 (57.8 per-cent) received hip hemiarthroplasty (HA), and 97 (42.2 per-cent) received THR. Patients receiving THR (mean 73.5 years, 95% CI 72-74.8) were significantly younger in comparison to patients receiving HA (mean 81.7 years, 95% CI 80.5-82.8). A negative correlation is noted between NHFS and type of surgery (Pearson's correlation - 0.537, p < 0.01), implying higher NHFS decreased the likelihood of receiving THR. Regression analysis showed NHFS (p-0.001) and walking ability (p-0.001) as significant predictors for the type of surgery (Nagelkerke R2-0.472). A log-rank test showed higher estimated survival time in patients with THR in comparison to HA (p-value 0.002). CONCLUSIONS: NHFS and walking ability can be used as an adjunct to the NICE criteria for selecting patients for THR after fracture NOF. Carefully selected patients treated with THR survive longer and have a better outcome in comparison to HA.

A Cluster of Children with Facial Nerve Palsy in High Prevalence Area for COVID-19.

OBJECTIVES: COVID-19 is a disease of varying presentation and neurological sequelae of the disease are being studied. Following a cluster of paediatric facial nerve palsy (FNP) cases in an area of South Wales with a high prevalence of COVID-19, we conducted an opportunistic study to determine whether there has been an increase in incidence of FNP and if there is an association between the FNP and COVID-19 in children. STUDY DESIGN: A retrospective cohort study. Using the case series from 2020 and comparing it with previous years. METHODS: We reviewed the incidence of FNP between 2015-2020 across two hospitals within the health board. The incidence was compared with that in 2020 including a cluster of six children in 14 weeks, presenting to the Royal Glamorgan Hospital between June and October. RESULTS: There were 48 cases of children with FNP across both hospital within the study years. Seven (7) cases in 2020. The incidence was not statistically different in comparison to other years.Five out of six of these children in 2020 had antibody testing for COVID-19. All serology testing (100%) returned negative for SARS-CoV- 2 antibodies.In high prevalence area for COVID-19, cases of children with FNP have not shown a commensurate increase. we have found no causal link between COVID-19 and FNP in children. While this is a small study, larger cohort studies are needed to support this finding. CONCLUSION: As new strains of COVID-19 are being reported in UK, South Africa and Brazil, physicians need to continue to be vigilant for consistent pattern of signs and symptoms, especially in children.

Procalcitonin Increase Is Associated with the Development of Critical Care-Acquired Infections in COVID-19 ARDS.

Secondary bacterial infection in COVID-19 patients is associated with increased mortality and disproportionately affects critically ill patients. This single-centre retrospective observational study investigates the comparative efficacy of change in procalcitonin (PCT) and other commonly available biomarkers in revealing or predicting microbiologically proven secondary infection in critical COVID-19 patients. Adult patients admitted to an intensive care unit (ICU) with confirmed SARS-CoV-2 infection between 9 March 2020 and 5 June 2020 were recruited to the study. For daily biomarker and secondary infection, laboratory-confirmed bloodstream infection (LCBI) and ventilator-associated pneumonia/tracheobronchitis (VAP/VAT) data were collected. We observed a PCT rise in 53 (81.5%) of the patients, a C-reactive protein (CRP) rise in 55 (84.6%) and a white blood cell count (WBC) rise in 61 (93.8%). Secondary infection was confirmed in 33 (50.8%) of the patients. A PCT rise was present in 97.0% of patients with at least one confirmed VAP/VAT and/or LCBI event. CRP and WBC rises occurred in 93.9% and 97.0% of patients with confirmed VAP/VAT and/or LCBI, respectively. Logistic regression analysis found that, when including all biomarkers in the same model, there was a significant association between PCT rise and the occurrence of LCBI and/or VAP/VAT (OR = 14.86 95%CI: 2.20, 342.53; p = 0.021). Conversely, no statistically significant relationship was found between either a CRP rise (p = 0.167) or a WBC rise (p = 0.855) and the occurrence of VAP/VAT and/or LCBI. These findings provide a promising insight into the usefulness of PCT measurement in predicting the emergence of secondary bacterial infection in ICU.

Differences in Inflammatory Marker Kinetics between the First and Second Wave of COVID-19 Patients Admitted to the ICU: A Retrospective, Single-Center Study.

BACKGROUND: We sought to determine if there was a difference in the longitudinal inflammatory response measured by white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), and ferritin levels between the first and the second COVID-19 wave of ICU patients. METHODS: In a single-center retrospective observational study, ICU patients were enrolled during the first and second waves of the COVID-19 pandemic. Data were collected on patient demographics, comorbidities, laboratory results, management strategies, and complications during the ICU stay. The inflammatory response was evaluated using WBC count, CRP, PCT, and Ferritin levels on the day of admission until Day 28, respectively. Organ dysfunction was measured by the SOFA score. RESULTS: 65 patients were admitted during the first and 113 patients during the second wave. WBC and ferritin levels were higher in the second wave. CRP and PCT showed markedly different longitudinal kinetics up until day 28 of ICU stay between the first and second wave, with significantly lower levels in the second wave. Steroid and immunomodulatory therapy use was significantly greater in the second wave. Mortality was similar in both waves. CONCLUSIONS: We found that there was a significantly reduced inflammatory response in the second wave, which is likely to be attributable to the more widespread use of immunomodulatory therapies.

Prevalence of phenotypes of acute respiratory distress syndrome in critically ill patients with COVID-19: a prospective observational study.

BACKGROUND: In acute respiratory distress syndrome (ARDS) unrelated to COVID-19, two phenotypes, based on the severity of systemic inflammation (hyperinflammatory and hypoinflammatory), have been described. The hyperinflammatory phenotype is known to be associated with increased multiorgan failure and mortality. In this study, we aimed to identify these phenotypes in COVID-19-related ARDS. METHODS: In this prospective observational study done at two UK intensive care units, we recruited patients with ARDS due to COVID-19. Demographic, clinical, and laboratory data were collected at baseline. Plasma samples were analysed for interleukin-6 (IL-6) and soluble tumour necrosis factor receptor superfamily member 1A (TNFR1) using a novel point-of-care assay. A parsimonious regression classifier model was used to calculate the probability for the hyperinflammatory phenotype in COVID-19 using IL-6, soluble TNFR1, and bicarbonate levels. Data from this cohort was compared with patients with ARDS due to causes other than COVID-19 recruited to a previous UK multicentre, randomised controlled trial of simvastatin (HARP-2). FINDINGS: Between March 17 and April 25, 2020, 39 patients were recruited to the study. Median ratio of partial pressure of arterial oxygen to fractional concentration of oxygen in inspired air (PaO2/FiO2) was 18 kpa (IQR 15-21) and acute physiology and chronic health evaluation II score was 12 (10-16). 17 (44%) of 39 patients had died by day 28 of the study. Compared with survivors, patients who died were older and had lower PaO2/FiO2. The median probability for the hyperinflammatory phenotype was 0·03 (IQR 0·01-0·2). Depending on the probability cutoff used to assign class, the prevalence of the hyperinflammatory phenotype was between four (10%) and eight (21%) of 39, which is lower than the proportion of patients with the hyperinflammatory phenotype in HARP-2 (186 [35%] of 539). Using the Youden index cutoff (0·274) to classify phenotype, five (63%) of eight patients with the hyperinflammatory phenotype and 12 (39%) of 31 with the hypoinflammatory phenotype died. Compared with matched patients recruited to HARP-2, levels of IL-6 were similar in our cohort, whereas soluble TNFR1 was significantly lower in patients with COVID-19-associated ARDS. INTERPRETATION: In this exploratory analysis of 39 patients, ARDS due to COVID-19 was not associated with higher systemic inflammation and was associated with a lower prevalence of the hyperinflammatory phenotype than that observed in historical ARDS data. This finding suggests that the excess mortality observed in COVID-19-related ARDS is unlikely to be due to the upregulation of inflammatory pathways described by the parsimonious model. FUNDING: US National Institutes of Health, Innovate UK, and Randox.

A hybrid scanning mode for fast scanning ion conductance microscopy (SICM) imaging.

We have developed a new method of controlling the pipette for scanning ion conductance microscopy to obtain high-resolution images faster. The method keeps the pipette close to the surface during a single line scan but does not follow the exact surface topography, which is calculated by using the ion current. Using an FPGA platform we demonstrate this new method on model test samples and then on live cells. This method will be particularly useful to follow changes occurring on relatively flat regions of the cell surface at high spatial and temporal resolutions.

Zero electron kinetic energy spectroscopy of the para-fluorotoluene cation.

Zero electron kinetic energy (ZEKE) spectroscopy is employed to gain information on the vibrational energy levels of the para-fluorotoluene (pFT) cation. Vibrationally resolved spectra are obtained following excitation through a range of intermediate vibrational energy levels in the S1 state. These spectra allow the observation of different cationic vibrational modes, whose assignment is achieved both from a knowledge of the S1 vibrational states and also by comparison with density functional calculations. In one notable case, clean ZEKE spectra were obtained from two overlapped S1 features. From the authors' data, the adiabatic ionization energy of pFT was derived as 70,946+/-4 cm(-1). The information on the cationic energy levels obtained will be useful in untangling the intramolecular vibrational redistribution dynamics of pFT in the S1 state.