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Hemodialysis Patients Make Long-Lived Antibodies against SARS-CoV-2 that May Be Associated with Reduced Reinfection.
No full textConscious sedation for office hysteroscopy: A systematic review and meta-analysis.
No full textOBJECTIVE
To evaluate the role of conscious sedation on pain control in office hysteroscopy.
METHODS
MEDLINE, EMBASE, CINAHL and CENTRAL were searched from inception to the 30th October 2020 in order to perform a systematic review and meta-analysis of all randomized controlled trials investigating women undergoing office hysteroscopic procedures, allocated to either conscious sedation or a suitable comparator, where the outcome was pain. Data regarding adverse events, feasibility and satisfaction/acceptability were also collected. The Risk of Bias 2 tool was used to assess study quality. Standard mean differences (SMD) or Odds Ratios (OR), and their 95% confidence intervals (CIs) were calculated for continuous (e.g. mean pain) and dichotomous (e.g. side-effects) outcomes, respectively.
RESULTS
The literature search returned 339 results, of which seven studies were included for systematic review, with five studies having data suitable for meta-analysis. Intravenous conscious sedation, when compared with local anesthesia, reduced pain during (SMD -0.26, 95% CI -0.51 to -0.01), but not after (SMD -0.18, 95% CI -0.43 to 0.07) office hysteroscopy. No significant difference in side-effects were noted (OR 15.58, 95% CI 0.08 to 2891.91). Intravenous conscious sedation, when compared to an oral analgesic and antispasmodic, was associated with increased pain, both during (SMD 1.03, 95% CI 0.56 to 1.49) and after (SMD 0.49, 95% CI 0.04 to 0.93) hysteroscopy and had significantly more side-effects (OR 134.33, 95% CI 16.14 to 1118.17). Inhalational conscious sedation (70% NO/30% O), when compared to oral analgesia and anxiolysis, showed the greatest reduction in pain during hysteroscopy (SMD -1.04, 95% CI -1.57 to -0.52), however side-effects were not reported. Whilst patients and hysteroscopists were more satisfied with deeper levels of sedation, resulting side-effects, such as delirium, increased the level of post-procedural attention required, leading to a significantly lower level of satisfaction amongst nursing staff.
CONCLUSION
The routine use of conscious sedation in contemporary hysteroscopic practice should be avoided in the absence of any clear reduction in pain and a higher risk of side-effects
Two-stage reconstruction of infected Charcot foot using internal fixation : a promising functional limb salvage technique.
No full textAIMS
In our unit, we adopt a two-stage surgical reconstruction approach using internal fixation for the management of infected Charcot foot deformity. We evaluate our experience with this functional limb salvage method.
METHODS
We conducted a retrospective analysis of prospectively collected data of all patients with infected Charcot foot deformity who underwent two-stage reconstruction with internal fixation between July 2011 and November 2019, with a minimum of 12 months' follow-up.
RESULTS
We identified 23 feet in 22 patients with a mean age of 56.7 years (33 to 70). The mean postoperative follow-up period was 44.7 months (14 to 99). Limb salvage was achieved in all patients. At one-year follow-up, all ulcers have healed and independent full weightbearing mobilization was achieved in all but one patient. Seven patients developed new mechanical skin breakdown; all went on to heal following further interventions. Fusion of the hindfoot was achieved in 15 of 18 feet (83.3%). Midfoot fusion was achieved in nine of 15 patients (60%) and six had stable and painless fibrous nonunion. Hardware failure occurred in five feet, all with broken dorsomedial locking plate. Six patients required further surgery, two underwent revision surgery for infected nonunion, two for removal of metalwork and exostectomy, and two for dynamization of the hindfoot nail.
CONCLUSION
Two-stage reconstruction of the infected and deformed Charcot foot using internal fixation and following the principle of 'long-segment, rigid and durable internal fixation, with optimal bone opposition and local antibiotic elusion' is a good form of treatment provided a multidisciplinary care plan is delivered. Cite this article: 2021;103-B(10):1611-1618
Host Immune-Metabolic Adaptations Upon Mycobacterial Infections and Associated Co-Morbidities.
No full textMycobacterial diseases are a major public health challenge. Their causative agents include, in order of impact, members of the complex (causing tuberculosis), (causing leprosy), and non-tuberculous mycobacterial pathogens including Macrophages are mycobacterial targets and they play an essential role in the host immune response to mycobacteria. This review aims to provide a comprehensive understanding of the immune-metabolic adaptations of the macrophage to mycobacterial infections. This metabolic rewiring involves changes in glycolysis and oxidative metabolism, as well as in the use of fatty acids and that of metals such as iron, zinc and copper. The macrophage metabolic adaptations result in changes in intracellular metabolites, which can post-translationally modify proteins including histones, with potential for shaping the epigenetic landscape. This review will also cover how critical tuberculosis co-morbidities such as smoking, diabetes and HIV infection shape host metabolic responses and impact disease outcome. Finally, we will explore how the immune-metabolic knowledge gained in the last decades can be harnessed towards the design of novel diagnostic and therapeutic tools, as well as vaccines
Comparative analysis of major incident triage tools in children: a UK population-based analysis.
No full textINTRODUCTION
Triage is a key principle in the effective management of major incidents. There is currently a paucity of evidence to guide the triage of children. The aim of this study was to perform a comparative analysis of nine adult and paediatric triage tools, including the novel 'Sheffield Paediatric Triage Tool' (SPTT), assessing their ability in identifying patients needing life-saving interventions (LSIs).
METHODS
A 10-year (2008-2017) retrospective database review of the Trauma Audit Research Network (TARN) Database for paediatric patients (15. Primary analysis was conducted on patients with complete prehospital physiological data with planned secondary analyses using first recorded data. Performance characteristics were evaluated using sensitivity, specificity, undertriage and overtriage.
RESULTS
15 133 patients met TARN inclusion criteria. 4962 (32.8%) had complete prehospital physiological data and 8255 (54.5%) had complete first recorded physiological data. The majority of patients were male (69.5%), with a median age of 11.9 years. The overwhelming majority of patients (95.4%) sustained blunt trauma, yielding a median ISS of 9 and overall, 875 patients (17.6%) received at least one LSI. The SPTT demonstrated the greatest sensitivity of all triage tools at identifying need for LSI (92.2%) but was associated with the highest rate of overtriage (75.0%). Both the Paediatric Triage Tape (sensitivity 34.1%) and JumpSTART (sensitivity 45.0%) performed less well at identifying LSI. By contrast, the adult Modified Physiological Triage Tool-24 (MPTT-24) triage tool had the second highest sensitivity (80.8%) with tolerable rates of overtriage (70.2%).
CONCLUSION
The SPTT and MPTT-24 outperform existing paediatric triage tools at identifying those patients requiring LSIs. This may necessitate a change in recommended practice. Further work is needed to determine the optimum method of paediatric major incident triage, but consideration should be given to simplifying major incident triage by the use of one generic tool (the MPTT-24) for adults and children
The clinical profile and associated mortality in people with and without diabetes with Coronavirus disease 2019 on admission to acute hospital services.
No full textINTRODUCTION
To assess if in adults with COVID-19, whether those with diabetes and complications (DM+C) present with a more severe clinical profile and if that relates to increased mortality, compared to those with diabetes with no complications (DM-NC) and those without diabetes.
METHODS
Service-level data was used from 996 adults with laboratory confirmed COVID-19 who presented to the Queen Elizabeth Hospital Birmingham, UK, from March to June 2020. All individuals were categorized into DM+C, DM-NC, and non-diabetes groups. Physiological and laboratory measurements in the first 5 days after admission were collated and compared among groups. Cox proportional hazards regression models were used to evaluate associations between diabetes status and the risk of mortality.
RESULTS
Among the 996 individuals, 104 (10.4%) were DM+C, 295 (29.6%) DM-NC and 597 (59.9%) non-diabetes. There were 309 (31.0%) in-hospital deaths documented, 40 (4.0% of total cohort) were DM+C, 99 (9.9%) DM-NC and 170 (17.0%) non-diabetes. Individuals with DM+C were more likely to present with high anion gap/metabolic acidosis, features of renal impairment, and low albumin/lymphocyte count than those with DM-NC or those without diabetes. There was no significant difference in mortality rates among the groups: compared to individuals without diabetes, the adjusted HRs were 1.39 (95% CI 0.95-2.03, p = 0.093) and 1.18 (95% CI 0.90-1.54, p = 0.226) in DM+C and DM-C, respectively.
CONCLUSIONS
Those with COVID-19 and DM+C presented with a more severe clinical and biochemical profile, but this did not associate with increased mortality in this study
Theta rhythmicity governs human behavior and hippocampal signals during memory-dependent tasks.
No full textMemory formation and reinstatement are thought to lock to the hippocampal theta rhythm, predicting that encoding and retrieval processes appear rhythmic themselves. Here, we show that rhythmicity can be observed in behavioral responses from memory tasks, where participants indicate, using button presses, the timing of encoding and recall of cue-object associative memories. We find no evidence for rhythmicity in button presses for visual tasks using the same stimuli, or for questions about already retrieved objects. The oscillations for correctly remembered trials center in the slow theta frequency range (1-5 Hz). Using intracranial EEG recordings, we show that the memory task induces temporally extended phase consistency in hippocampal local field potentials at slow theta frequencies, but significantly more for remembered than forgotten trials, providing a potential mechanistic underpinning for the theta oscillations found in behavioral responses
Omega-3 supplementation during unilateral resistance exercise training in older women: A within subject and double-blind placebo-controlled trial.
No full textBACKGROUND & AIMS
The skeletal muscle anabolic effects of n-3 polyunsaturated fatty acids (n-3 PUFA) appear favoured towards women; a property that could be exploited in older women who typically exhibit poor muscle growth responses to resistance exercise training (RET). Here we sought to generate novel insights into the efficacy and mechanisms of n-3 PUFA alongside short-term RET in older women.
METHODS
We recruited 16 healthy older women (Placebo n = 8 (PLA): 67±1y, n-3 PUFA n = 8: 64±1y) to a randomised double-blind placebo-controlled trial (n-3 PUFA; 3680 mg/day versus PLA) of 6 weeks fully-supervised progressive unilateral RET (i.e. 6 × 8 reps, 75% 1-RM, 3/wk). Strength was assessed by knee extensor 1-RM and isokinetic dynamometry ∼ every 10 d. Thigh fat free mass (TFFM) was measured by DXA at 0/3/6 weeks. Bilateral vastus lateralis (VL) biopsies at 0/2/4/6 weeks with deuterium oxide (DO) dosing were used to determine MPS responses for 0-2 and 4-6 weeks. Further, fibre cross sectional area (CSA), myonuclei number and satellite cell (SC) number were assessed, alongside muscle anabolic/catabolic signalling via immunoblotting.
RESULTS
RET increased 1-RM equally in the trained leg of both groups (+23 ± 5% n-3 PUFA vs. +25 ± 5% PLA (both P < 0.01)) with no significant increase in maximum voluntary contraction (MVC) (+10 ± 6% n-3 PUFA vs. +13 ± 5% PLA). Only the n-3 PUFA group increased TFFM (3774 ± 158 g to 3961 ± 151 g n-3 PUFA (P < 0.05) vs. 3406 ± 201 g to 3561 ± 170 PLA) and type II fibre CSA (3097 ± 339 μm to 4329 ± 264 μm n-3 PUFA (P < 0.05) vs. 2520 ± 316 μm to 3467 ± 303 μm in PL) with RET. Myonuclei number increased equally in n-3 PUFA and PLA in both type I and type II fibres, with no change in SC number. N-3 PUFA had no added benefit on muscle protein synthesis (MPS), however, during weeks 4-6 of RET, absolute synthesis rates (ASR) displayed a trend to increase with n-3 PUFA only (5.6 ± 0.3 g d to 7.1 ± 0.5 g d n-3 PUFA (P = 0.09) vs. 5.5 ± 0.5 g d to 6.5 ± 0.5 g d PLA). Further, the n-3 PUFA group displayed greater 4EBP1 activation after acute RE at 6 weeks.
CONCLUSION
n3-PUFA enhanced RET gains in muscle mass through type II fibre hypertrophy, with data suggesting a role for MPS rather than via SC recruitment. As such, the present study adds to a literature base illustrating the apparent enhancement of muscle hypertrophy with RET in older women fed adjuvant n3-PUFA
Cenerimod, a selective S1P receptor modulator, improves organ-specific disease outcomes in animal models of Sjögren's syndrome.
No full textBACKGROUND
Sjögren's syndrome is a systemic autoimmune disease characterized by immune cells predominantly infiltrating the exocrine glands and frequently forming ectopic lymphoid structures. These structures drive a local functional immune response culminating in autoantibody production and tissue damage, associated with severe dryness of mucosal surfaces and salivary gland hypofunction. Cenerimod, a potent, selective and orally active sphingosine-1-phosphate receptor 1 modulator, inhibits the egress of lymphocytes into the circulation. Based on the mechanism of action of cenerimod, its efficacy was evaluated in two mouse models of Sjögren's syndrome.
METHODS
Cenerimod was administered in two established models of Sjögren's syndrome; firstly, in an inducible acute viral sialadenitis model in C57BL/6 mice, and, secondly, in the spontaneous chronic sialadenitis MRL/lpr mouse model. The effects of cenerimod treatment were then evaluated by flow cytometry, immunohistochemistry, histopathology and immunoassays. Comparisons between groups were made using a Mann-Whitney test.
RESULTS
In the viral sialadenitis model, cenerimod treatment reduced salivary gland immune infiltrates, leading to the disaggregation of ectopic lymphoid structures, reduced salivary gland inflammation and preserved organ function. In the MRL/lpr mouse model, cenerimod treatment decreased salivary gland inflammation and reduced T cells and proliferating plasma cells within salivary gland ectopic lymphoid structures, resulting in diminished disease-relevant autoantibodies within the salivary glands.
CONCLUSIONS
Taken together, these results suggest that cenerimod can reduce the overall autoimmune response and improve clinical parameters in the salivary glands in models of Sjögren's syndrome and consequently may reduce histological and clinical parameters associated with the disease in patients