Exploring the utility of bedside tests for predicting cardiorespiratory fitness in older adults.

Objectives: Cardiorespiratory fitness (CRF) declines with advancing and has also, independent of age, been shown to be predictive of all-cause mortality, morbidity, and poor clinical outcomes. In relation to the older patient, there is a particular wealth of evidence highlighting the relationship between low CRF and poor surgical outcomes. Cardiopulmonary exercise testing (CPET) is accepted as the gold-standard measure of CRF. However, this form of assessment has significant personnel and equipment demands and is not feasible for those with certain age-associated physical limitations, including joint and cardiovascular comorbidities. As such, alternative ways to assess the CRF of older patients are very much needed. Methods: Sixty-four participants (45% female) with a median age of 74 (65-90) years were recruited to this study via community-based advertisements. All participants completed three tests of physical function: (1) a step-box test; (2) handgrip strength dynamometry; and (3) a CPET on a cycle ergometer; and also had their muscle architecture (vastus lateralis) assessed by B-mode ultrasonography to provide measures of muscle thickness, pennation angle, and fascicle length. Multivariate linear regression was then used to ascertain bedside predictors of CPET parameters from the alternative measures of physical function and demographic (age, gender, body mass index (BMI)) data. Results: There was no significant association between ultrasound-assessed parameters of muscle architecture and measures of CRF. VO2peak was predicted to some extent from fast step time during the step-box test, gender, and BMI, leading to a model that achieved an R 2 of 0.40 (p < 0.001). Further, in aiming to develop a model with minimal assessment demands (i.e., using handgrip dynamometry rather than the step-box test), replacing fast step time with non-dominant HGS led to a model which achieved an R 2 of 0.36 (p < 0.001). Non-dominant handgrip strength combined with the step-box test parameter of fast step time and BMI delivered the most predictive model for VO2peak with an R 2 of 0.45 (p < 0.001). Conclusions: Our findings show that simple-to-ascertain patient characteristics and bedside assessments of physical function are able to predict CPET-derived CRF. Combined with gender and BMI, both handgrip strength and fast step time during a step-box test were predictive for VO2peak. Future work should apply this model to a clinical population to determine its utility in this setting and to explore if simple bedside tests are predictive of important clinical outcomes in older adults (i.e., post-surgical complications).

Appendectomy versus antibiotic treatment for acute appendicitis.

BACKGROUND: Acute appendicitis is one of the most common emergency general surgical conditions worldwide. Uncomplicated/simple appendicitis can be treated with appendectomy or antibiotics. Some studies have suggested possible benefits with antibiotics with reduced complications, length of hospital stay, and the number of days off work. However, surgery may improve success of treatment as antibiotic treatment is associated with recurrence and future need for surgery. OBJECTIVES: To assess the effects of antibiotic treatment for uncomplicated/simple acute appendicitis compared with appendectomy for resolution of symptoms and complications. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registers (World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov) on 19 July 2022. We also searched for unpublished studies in conference proceedings together with reference checking and citation search. There were no restrictions on date, publication status, or language of publication. SELECTION CRITERIA: We included parallel-group randomised controlled trials (RCTs) only. We included studies where most participants were adults with uncomplicated/simple appendicitis. Interventions included antibiotics (by any route) compared with appendectomy (open or laparoscopic). DATA COLLECTION AND ANALYSIS: We used standard methodology expected by Cochrane. We used GRADE to assess the certainty of evidence for each outcome. Primary outcomes included mortality and success of treatment, and secondary outcomes included number of participants requiring appendectomy in the antibiotic group, complications, pain, length of hospital stay, sick leave, malignancy in the antibiotic group, negative appendectomy rate, and quality of life. Success of treatment definitions were heterogeneous although mainly based on resolution of symptoms rather than incorporation of long-term recurrence or need for surgery in the antibiotic group. MAIN RESULTS: We included 13 studies in the review covering 1675 participants randomised to antibiotics and 1683 participants randomised to appendectomy. One study was unpublished. All were conducted in secondary care and two studies received pharmaceutical funding. All studies used broad-spectrum antibiotic regimens expected to cover gastrointestinal bacteria. Most studies used predominantly laparoscopic surgery, but some included mainly open procedures. Six studies included adults and children. Almost all studies aimed to exclude participants with complicated appendicitis prior to randomisation, although one study included 12% with perforation. The diagnostic technique was clinical assessment and imaging in most studies. Only one study limited inclusion by sex (male only). Follow-up ranged from hospital admission only to seven years. Certainty of evidence was mainly affected by risk of bias (due to lack of blinding and loss to follow-up) and imprecision. Primary outcomes It is uncertain whether there was any difference in mortality due to the very low-certainty evidence (Peto odds ratio (OR) 0.51, 95% confidence interval (CI) 0.05 to 4.95; 1 study, 492 participants). There may be 76 more people per 1000 having unsuccessful treatment in the antibiotic group compared with surgery, which did not reach our predefined level for clinical significance (risk ratio (RR) 0.91, 95% CI 0.87 to 0.96; I2 = 69%; 7 studies, 2471 participants; low-certainty evidence). Secondary outcomes At one year, 30.7% (95% CI 24.0 to 37.8; I2 = 80%; 9 studies, 1396 participants) of participants in the antibiotic group required appendectomy or, alternatively, more than two-thirds of antibiotic-treated participants avoided surgery in the first year, but the evidence is very uncertain. Regarding complications, it is uncertain whether there is any difference in episodes of Clostridium difficile diarrhoea due to very low-certainty evidence (Peto OR 0.97, 95% CI 0.24 to 3.89; 1 study, 1332 participants). There may be a clinically significant reduction in wound infections with antibiotics (RR 0.25, 95% CI 0.09 to 0.68; I2 = 16%; 9 studies, 2606 participants; low-certainty evidence). It is uncertain whether antibiotics affect the incidence of intra-abdominal abscess or collection (RR 1.58, 95% CI 0.61 to 4.07; I2 = 19%; 6 studies, 1831 participants), or reoperation (Peto OR 0.13, 95% CI 0.01 to 2.16; 1 study, 492 participants) due to very low-certainty evidence, mainly due to rare events causing imprecision and risk of bias. It is uncertain if antibiotics prolonged length of hospital stay by half a day due to the very low-certainty evidence (MD 0.54, 95% CI 0.06 to 1.01; I2 = 97%; 11 studies, 3192 participants). The incidence of malignancy was 0.3% (95% CI 0 to 1.5; 5 studies, 403 participants) in the antibiotic group although follow-up was variable. Antibiotics probably increased the number of negative appendectomies at surgery (RR 3.16, 95% CI 1.54 to 6.49; I2 = 17%; 5 studies, 707 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Antibiotics may be associated with higher rates of unsuccessful treatment for 76 per 1000 people, although differences may not be clinically significant. It is uncertain if antibiotics increase length of hospital stay by half a day. Antibiotics may reduce wound infections. A third of the participants initially treated with antibiotics required subsequent appendectomy or two-thirds avoided surgery within one year, but the evidence is very uncertain. There were too few data from the included studies to comment on major complications.

Molecular mechanisms underpinning favourable physiological adaptations to exercise prehabilitation for urological cancer surgery.

BACKGROUND: Surgery for urological cancers is associated with high complication rates and survivors commonly experience fatigue, reduced physical ability and quality of life. High-intensity interval training (HIIT) as surgical prehabilitation has been proven effective for improving the cardiorespiratory fitness (CRF) of urological cancer patients, however the mechanistic basis of this favourable adaptation is undefined. Thus, we aimed to assess the mechanisms of physiological responses to HIIT as surgical prehabilitation for urological cancer. METHODS: Nineteen male patients scheduled for major urological surgery were randomised to complete 4-weeks HIIT prehabilitation (71.6 ± 0.75 years, BMI: 27.7 ± 0.9 kg·m2) or a no-intervention control (71.8 ± 1.1 years, BMI: 26.9 ± 1.3 kg·m2). Before and after the intervention period, patients underwent m. vastus lateralis biopsies to quantify the impact of HIIT on mitochondrial oxidative phosphorylation (OXPHOS) capacity, cumulative myofibrillar muscle protein synthesis (MPS) and anabolic, catabolic and insulin-related signalling. RESULTS: OXPHOS capacity increased with HIIT, with increased expression of electron transport chain protein complexes (C)-II (p = 0.010) and III (p = 0.045); and a significant correlation between changes in C-I (r = 0.80, p = 0.003), C-IV (r = 0.75, p = 0.008) and C-V (r = 0.61, p = 0.046) and changes in CRF. Neither MPS (1.81 ± 0.12 to 2.04 ± 0.14%·day-1, p = 0.39) nor anabolic or catabolic proteins were upregulated by HIIT (p > 0.05). There was, however, an increase in phosphorylation of AS160Thr642 (p = 0.046) post-HIIT. CONCLUSIONS: A HIIT surgical prehabilitation regime, which improved the CRF of urological cancer patients, enhanced capacity for skeletal muscle OXPHOS; offering potential mechanistic explanation for this favourable adaptation. HIIT did not stimulate MPS, synonymous with the observed lack of hypertrophy. Larger trials pairing patient-centred and clinical endpoints with mechanistic investigations are required to determine the broader impacts of HIIT prehabilitation in this cohort, and to inform on future optimisation (i.e., to increase muscle mass).

Non-opioid analgesics for the prevention of chronic postsurgical pain: a systematic review and network meta-analysis.

BACKGROUND: Chronic postsurgical pain is common after surgery. Identification of non-opioid analgesics with potential for preventing chronic postsurgical pain is important, although trials are often underpowered. Network meta-analysis offers an opportunity to improve power and to identify the most promising therapy for clinical use and future studies. METHODS: We conducted a PRISMA-NMA-compliant systematic review and network meta-analysis of randomised controlled trials of non-opioid analgesics for chronic postsurgical pain. Outcomes included incidence and severity of chronic postsurgical pain, serious adverse events, and chronic opioid use. RESULTS: We included 132 randomised controlled trials with 23 902 participants. In order of efficacy, i.v. lidocaine (odds ratio [OR] 0.32; 95% credible interval [CrI] 0.17-0.58), ketamine (OR 0.64; 95% CrI 0.44-0.92), gabapentinoids (OR 0.67; 95% CrI 0.47-0.92), and possibly dexmedetomidine (OR 0.36; 95% CrI 0.12-1.00) reduced the incidence of chronic postsurgical pain at ≤6 months. There was little available evidence for chronic postsurgical pain at >6 months, combinations agents, chronic opioid use, and serious adverse events. Variable baseline risk was identified as a potential violation to the network meta-analysis transitivity assumption, so results are reported from a fixed value of this, with analgesics more effective at higher baseline risk. The confidence in these findings was low because of problems with risk of bias and imprecision. CONCLUSIONS: Lidocaine (most effective), ketamine, and gabapentinoids could be effective in reducing chronic postsurgical pain ≤6 months although confidence is low. Moreover, variable baseline risk might violate transitivity in network meta-analysis of analgesics; this recommends use of our methods in future network meta-analyses. SYSTEMATIC REVIEW PROTOCOL: PROSPERO CRD42021269642.

Proteomic features of skeletal muscle adaptation to resistance exercise training as a function of age.

Resistance exercise training (RET) can counteract negative features of muscle ageing but older age associates with reduced adaptive capacity to RET. Altered muscle protein networks likely contribute to ageing RET adaptation; therefore, associated proteome-wide responses warrant exploration. We employed quantitative sarcoplasmic proteomics to compare age-related proteome and phosphoproteome responses to RET. Thigh muscle biopsies were collected from eight young (25 ± 1.1 years) and eight older (67.5 ± 2.6 years) adults before and after 20 weeks supervised RET. Muscle sarcoplasmic fractions were pooled for each condition and analysed using Isobaric Tags for Relative and Absolute Quantification (iTRAQ) labelling, tandem mass spectrometry and network-based hub protein identification. Older adults displayed impaired RET-induced adaptations in whole-body lean mass, body fat percentage and thigh lean mass (P > 0.05). iTRAQ identified 73 differentially expressed proteins with age and/or RET. Despite possible proteomic stochasticity, RET improved ageing profiles for mitochondrial function and glucose metabolism (top hub; PYK (pyruvate kinase)) but failed to correct altered ageing expression of cytoskeletal proteins (top hub; YWHAZ (14-3-3 protein zeta/delta)). These ageing RET proteomic profiles were generally unchanged or oppositely regulated post-RET in younger muscle. Similarly, RET corrected expression of 10 phosphoproteins altered in ageing, but these responses were again different vs. younger adults. Older muscle is characterised by RET-induced metabolic protein profiles that, whilst not present in younger muscle, improve untrained age-related proteomic deficits. Combined with impaired cytoskeletal adhesion responses, these results provide a proteomic framework for understanding and optimising ageing muscle RET adaptation.

Combined high-voltage pulsed radiofrequency and ozone therapy versus ozone therapy alone in treating postherpetic neuralgia: a retrospective comparison.

Postherpetic neuralgia (PHN) is a devastating disease with extraordinarily poor treatment outcomes. Both pulsed radiofrequency (PRF) and ozone have good effects on the treatment of the disease. However, whether PRF and ozone have a synergistic effect on PHN remains unclear. Therefore, this study aimed to assess the therapeutic effects of ozone alone and in combination with PRF in the treatment of PHN. Ninety-one patients with PHN were assigned into two groups: PRF combined with ozone (PRF + ozone group, n = 44) and ozone therapy alone (ozone group, n = 47). In PRF + ozone group, the high-voltage, long-duration PRF was applied to the target dorsal root ganglions. Then ozonated water (11.5 µg/mL) was injected through the inner cannula. In the ozone group, all other processes were the same as those in the PRF + ozone group apart from the electrical stimulation. The therapeutic efficacy was evaluated by visual analog scale and tactile sensation at pre-treatment and post-treatment 3, 6, and 12 months. Compared with pre-treatment data, the visual analog scale score was significantly decreased in both groups after treatment. Compared with the ozone group, the visual analog scale score was significantly decreased in the PRF + ozone group at 3, 6, and 12 months. Similarly, the tactile sensation was also significantly decreased at post-treatment when compared to pre-treatment. However, there were no statistical differences between the two groups. Regression analysis results showed that the history of diabetes mellitus and age had significant negative and positive effects, respectively, on the treatment results. To conclude, the administration of PRF + ozone and ozone therapy alone could both improve pain symptoms. Moreover, treatment effects and total efficacy rates tended to be higher for the combination of PRF and ozone than ozone alone. This conclusion was especially true for long-term therapeutic effects.

Dexmedetomidine prevents spatial learning and memory impairment induced by chronic REM sleep deprivation in rats.

The study was attempted to investigate the effect on and mechanisms of action of dexmedetomidine with regard to learning and memory impairment in rats with chronic rapid eye movement (REM) sleep deprivation. A total of 50 male Sprague Dawley rats were randomly divided into five groups. Modified multiple platform method was conducted to cause the sleep deprivation of rats. Dexmedetomidine and midazolam were administered by intraperitoneal injection. Learning and memory ability was assessed through Morris water maze. Morphological changes of rat hippocampal neurons and synaptic were detected by transmission electron microscope and Golgi staining. The gene expression in hippocampus of each group was detected by RNA-seq and verified by RT-PCR and western blot. REM Sleep-deprived rats exhibited spatial learning and memory deficits. Furthermore, there was decreased density of synaptic spinous in the hippocampal CA1 region of the sleep deprivation group compared with the control. Additionally, transmission electron microscopy showed that the synaptic gaps of hippocampal neurons in REM sleep deprivation group were loose and fuzzy. Interestingly, dexmedetomidine treatment normalized these events to control levels following REM sleep deprivation. Molecular biological methods showed that Alox15 expression increased significantly after REM sleep deprivation as compared to control, while dexmedetomidine administration reversed the expression of Alox15. Dexmedetomidine alleviated the spatial learning and memory dysfunction induced with chronic REM sleep deprivation in rats. This protective effect may be related to the down-regulation of Alox15 expression and thereby the enhancement of synaptic structural plasticity in the hippocampal CA1 area of rats. Supplementary Information: The online version contains supplementary material available at 10.1007/s41105-023-00450-8.

Intraperitoneal ozone injection prevents REM sleep deprivation - induced spatial learning and memory deficits by suppressing the expression of Sema3A in the hippocampus in rats.

Objectives: Sleep deprivation is a common health problem in modern society and is negatively associated with deleterious effects on cognitive functions such as learning and memory ability. This study was undertaken to provide a detailed account of the effect of chronic ozone intraperitoneal injection on the deleterious effects of sleep deprivation on brain function in rats. Materials and Methods: Sleep deprivation was induced using the modified multiple platform model. The rats received REM sleep deprivation with an intraperitoneal injection of ozone or midazolam for 28 days. The effects of ozone on REM sleep deprivation-induced hippocampus-dependent learning and memory deficits were studied by the following approaches: Morris water maze (MWM) tests were used to evaluate spatial learning and memory of rats. Morphological changes in the brain were evaluated using hematoxylin and eosin (HE) staining. RNA-sequence was performed to seek a common mechanism. The expression of the targeted gene was examined by qPCR and Western blotting. Results: Ozone intraperitoneal injection reversed spatial learning and memory deficits associated with REM sleep deprivation, ameliorating pathological brain damage and down-regulating the hippocampal expression of Sema3A in rats after REM sleep deprivation. Conclusion: Ozone intraperitoneal injection alleviated sleep deprivation-induced spatial learning and memory deficits by protecting hippocampal neurons via down-regulation of the expression of Sema3A in the hippocampus.

Electroacupuncture Alleviates Thalamic Pain in Rats by Suppressing ADCY1 Protein Upregulation.

BACKGROUND: Thalamic pain (TP), also known as central post-stroke pain, is a chronic neuropathic pain syndrome that follows a stroke and is a severe pain that is usually intractable. No universally applicable and effective therapies have been proposed. Emerging studies have reported that electroacupuncture (EA) can potentially be used as an effective therapy for the treatment of neuropathic pain. However, whether EA influences TP and if so, by what potential mechanism, remains poorly understood. OBJECTIVE: The aim of this study was to detect the efficacy of EA and explore possible mechanisms for treating TP. STUDY DESIGN: Controlled animal study. SETTING: The laboratory at the Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine. METHODS: Male Sprague Dawley rats were randomly divided into 3 groups (n = 15 / group): sham-operated (SH) group, thalamic pain model (TP) group, EA treatment (EA) group. After the TP rat model was successfully established, EA was used for intervention. During the experiment, the mechanical pain thresholds of rats were detected among the groups. The right thalamus of the rats was extracted on postoperative day 28 for RNA-sequencing (RNA-Seq) analysis to find the changes in gene expression in different groups of rats. The key genes were screened using reverse transcription-polymerase chain reaction (RT-PCR) detection and subsequently identified with western blotting and immunofluorescence. RESULTS: The mechanical withdrawal threshold (MWT) value of the right facial skin in the TP group and the EA group decreased significantly on the 3rd day after surgery, compared to the SH group (P < 0.01). From 7 to 28 days, the MWT value increased continually in the EA group; however, there was no significant change in the TP group. The results of RNA-seq showed that compared to the TP group, 377 genes changed in the EA group. Moreover, ADCY1 expression increased significantly in the TP group as compared to the SH group, while EA treatment reversed the expression of ADCY1. LIMITATIONS: In addition to ADCY1, the mechanism(s) of other signaling pathways in TP need to be explored in future research. CONCLUSIONS: EA treatment may promote the recovery of TP model rat by regulating ADCY1 expression.

Repeatability of Contrast-Enhanced Ultrasound to Determine Renal Cortical Perfusion.

Alterations in renal perfusion play a major role in the pathogenesis of renal diseases. Renal contrast-enhanced ultrasound (CEUS) is increasingly applied to quantify renal cortical perfusion and to assess its change over time, but comprehensive assessment of the technique's repeatability is lacking. Ten adults attended two renal CEUS scans within 14 days. In each session, five destruction/reperfusion sequences were captured. One-phase association was performed to derive the following parameters: acoustic index (AI), mean transit time (mTT), perfusion index (PI), and wash-in rate (WiR). Intra-individual and inter-operator (image analysis) repeatability for the perfusion variables were assessed using intra-class correlation (ICC), with the agreement assessed using a Bland-Altman analysis. The 10 adults had a median (IQR) age of 39 years (30-46). Good intra-individual repeatability was found for mTT (ICC: 0.71) and PI (ICC: 0.65). Lower repeatability was found for AI (ICC: 0.50) and WiR (ICC: 0.56). The correlation between the two operators was excellent for all variables: the ICCs were 0.99 for PI, 0.98 for AI, 0.87 for mTT, and 0.83 for WiR. The Bland-Altman analysis showed that the mean biases (± SD) between the two operators were 0.03 ± 0.16 for mTT, 0.005 ± 0.09 for PI, 0.04 ± 0.19 for AI, and -0.02 ± 0.11 for WiR.

Dressings and topical agents for the management of open wounds after surgical treatment for sacrococcygeal pilonidal sinus.

BACKGROUND: Sacrococcygeal pilonidal sinus disease is a common debilitating condition that predominantly affects young adults, with a profound impact on their activities of daily living. The condition is treated surgically, and in some cases the wound in the natal cleft is left open to heal by itself. Many dressings and topical agents are available to aid healing of these wounds. OBJECTIVES: To assess the effects of dressings and topical agents for the management of open wounds following surgical treatment for sacrococcygeal pilonidal sinus in any care setting. SEARCH METHODS: In March 2021, we searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and we scanned reference lists of included studies, reviews, meta-analyses and health technology reports to identify additional studies. There were no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We included parallel-group randomised controlled trials (RCTs) only. We included studies with participants who had undergone any type of sacrococcygeal pilonidal sinus disease surgery and were left with an open wound. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: We included 11 RCTs comprising 932 participants. Two studies compared topical negative pressure wound therapy (TNPWT) with conventional open wound healing, two studies compared platelet-rich plasma with sterile absorbent gauze, and the other seven studies compared various dressings and topical agents. All studies were at high risk of bias in at least one domain, whilst one study was judged to be at low risk of bias in all but one domain. All studies were conducted in secondary care. Mean participant ages were between 20 and 30 years, and nearly 80% of participants were male. No studies provided data on quality of life, cost-effectiveness, pain at first dressing change or proportion of wounds healed at 6 or 12 months, and very few adverse effects were recorded in any study. It is unclear whether TNPWT reduces time to wound healing compared with conventional open wound healing (comparison 1), as the certainty of evidence is very low. The two studies provided conflicting results, with one study showing benefit (mean difference (MD) -24.01 days, 95% confidence interval (CI) -35.65 to -12.37; 19 participants), whilst the other reported no difference. It is also unclear whether TNPWT has any effect on the proportion of wounds healed by 30 days (risk ratio (RR) 3.60, 95% CI 0.49 to 26.54; 19 participants, 1 study; very low-certainty evidence). Limited data were available for our secondary outcomes time to return to normal daily activities and recurrence rate; we do not know whether TNPWT has any effect on these outcomes. Lietofix cream may increase the proportion of wounds that heal by 30 days compared with an iodine dressing (comparison 4; RR 8.06, 95% CI 1.05 to 61.68; 205 participants, 1 study; low-certainty evidence). The study did not provide data on time to wound healing. We do not know whether hydrogel dressings reduce time to wound healing compared with wound cleaning with 10% povidone iodine (comparison 5; MD -24.54 days, 95% CI -47.72 to -1.36; 31 participants, 1 study; very low-certainty evidence). The study did not provide data on the proportion of wounds healed. It is unclear whether hydrogel dressings have any effect on adverse effects as the certainty of the evidence is very low. Platelet-rich plasma may reduce time to wound healing compared with sterile absorbent gauze (comparison 6; MD -19.63 days, 95% CI -34.69 to -4.57; 210 participants, 2 studies; low-certainty evidence). No studies provided data on the proportion of wounds healed. Platelet-rich plasma may reduce time to return to normal daily activities (MD -15.49, 95% CI -28.95 to -2.02; 210 participants, 2 studies; low-certainty evidence). Zinc oxide mesh may make little or no difference to time to wound healing compared with placebo (comparison 2; median 54 days in the zinc oxide mesh group versus 62 days in the placebo mesh group; low-certainty evidence). We do not know whether zinc oxide mesh has an effect on the proportion of wounds healed by 30 days as the certainty of the evidence is very low (RR 2.35, 95% CI 0.49 to 11.23). It is unclear whether gentamicin-impregnated collagen sponge reduces time to wound healing compared with no dressing (comparison 7; MD -1.40 days, 95% CI -5.05 to 2.25; 50 participants, 1 study; very low-certainty evidence). The study did not provide data on the proportion of wounds healed. Dialkylcarbamoyl chloride (DACC)-coated dressings may make little or no difference to time to wound healing compared with alginate dressings (comparison 8; median 69 (95% CI 62 to 72) days in the DACC group versus 71 (95% CI 69 to 85) days in the alginate group; 1 study, 246 participants; low-certainty evidence). One study compared a polyurethane foam hydrophilic dressing with an alginate dressing (comparison 3) whilst another study compared a hydrocolloid dressing with an iodine dressing (comparison 9). It is unclear whether either intervention has any effect on time to wound healing as the certainty of evidence is very low. AUTHORS' CONCLUSIONS: At present, the evidence that any of the dressings or topical agents contained in this review have a benefit on time to wound healing, the proportion of wounds that heal at a specific time point or on any of the secondary outcomes of our review ranges from low certainty to very low certainty. There is low-certainty evidence on the benefit on wound healing of platelet-rich plasma from two studies and of Lietofix cream and hydrogel dressings from single studies. Further studies are required to investigate these interventions further.

Blood Component Requirements and Erythrocyte Transfusion and Mortality Related to Hemoglobin Deficit in Phase III Trial of Hemoglobin-Based Oxygen Carrier: HBOC-201.

BACKGROUND: Hemoglobin-based oxygen carriers (HBOCs) may cause coagulopathy, changes in total hemoglobin (THb), and affect mortality. Low total hemoglobin concentrations [THb] during hemorrhage may worsen outcomes. STUDY QUESTION: The database of the Hemopure HEM-0115 phase III trial was queried to determine the use of platelets, plasma, or cryoprecipitate and compare transfusion requirements and coagulation studies between patients randomized to erythrocyte transfusion or HBOC-201 infusion. Modeling of hemoglobin (Hb) changes produced by HBOC-201, erythrocyte, and blood product administration were related to [THb], coagulopathy, and mortality. DATA SOURCES: Hemopure HEM-0115 phase III trial database. STUDY DESIGN: Retrospective and Novel Hemoglobin Deficit Formulas Tested Against Existing Database. RESULTS: The HBOC-201 database (n = 688) demonstrated less than 6% of subjects in both groups were administered non-Hb containing blood products (fresh frozen plasma, platelets, or cryoprecipitate) and low rates of coagulopathies in both erythrocyte and HBOC-201 arms. There were no differences in mortality in elective orthopedic patients administered up to 10 bags HBOC-201 (equivalent to 3 units erythrocytes). Low total [Hb] and lack of adequate oxygen carrying capacity was found to be an independent predictor of morbidity/mortality. CONCLUSIONS: The elective use of HBOC-201 for orthopedics versus erythrocytes demonstrated low incidence of blood product requirements in both cohorts and no differences in mortality up to the HBOC-201 equivalent of 3 units erythrocytes. High total Hb may be important to maintain in acute hemorrhage and [Hb] deficit, whereas later in recovery might not be as crucial. Future trauma trials may benefit from the use of HBOC-201 containing 13 g/dL in prehospital management, when erythrocytes are commonly not available.

Potential Molecular Mechanisms of Electroacupuncture With Spatial Learning and Memory Impairment Induced by Chronic Pain on a Rat Model.

BACKGROUND: It is frequently reported that neuropathic pain is associated with abnormalities in brain function and structure as well as cognitive deficits. However, the contributing mechanisms have remained elusive. OBJECTIVES: We aimed to investigate the systemic ultrastructural changes of the peripheral nervous system (PNS) and central nervous system (CNS) in rats with trigeminal neuralgia (TN) induced by cobra venom, as well as the effects and mechanisms of electroacupuncture (EA) and pregabalin (PGB) on TN. STUDY DESIGN: This study used an experimental design in rats. SETTING: The research took place in the laboratory at the Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine. METHODS: Male Sprague-Dawley rats were randomly divided into 4 groups (n = 12/group): cobra venom (CV), PGB, EA, and sham-operated (SHAM). The development of pain-related behaviors and spatial learning and memory abilities were measured using video recordings and Morris water maze tests, respectively. The ultrastructural changes of the PNS and CNS were examined using transmission electron microscopy. We also screened the differentially expressed genes and proteins in the prefrontal cortex  and hippocampus using  ribonucleic acid sequencing and isobaric tag for relative and absolute quantitation techniques, respectively. Data for the behavioral tests and molecular biology were analyzed with a one-way analysis of variance. RESULTS: The rats in the CV group exhibited long-lasting pain-like behaviors, cognitive deficits, and systemic ultrastructural changes. Both EA and PGB alleviated the chronic pain syndrome, but EA also inhibited the chronic pain-induced cognitive dysfunction and restored normal cellular structures, while PGB was associated with no improvements. Transcriptomic and proteomic analyses revealed marcks, pak2 and acat1 were altered in rats with TN but were adjusted back to baseline by EA but not by PGB. LIMITATIONS: We examined systemic ultrastructural alterations at different levels of the nervous system; however, the detailed timeline of the damage process was not explicitly delineated.  Moreover, the current study provides only preliminary evidence for the neurobiological mechanisms of cognitive impairment resulting from chronic pain.  Further research is still necessary (using models such as gene knockout rats and cell cultures) before a detailed mechanism can be postulated. CONCLUSIONS: EA treatment may offer significant advantages when compared to PGB for the treatment of cognitive impairment associated with chronic pain. Moreover, marcks, pak2 and acat1 may be the potential therapeutic targets of EA.

Curcumin Enhances Fed-State Muscle Microvascular Perfusion but Not Leg Glucose Uptake in Older Adults.

Therapeutic interventions aimed at enhancing blood flow may combat the postprandial vascular and metabolic dysfunction that manifests with chronological ageing. We compared the effects of acute curcumin (1000 mg) coupled with an oral nutritional supplement (ONS, 7.5 g protein, 24 g carbohydrate and 6 g fat) versus a placebo and ONS (control) on cerebral and leg macrovascular blood flow, leg muscle microvascular blood flow, brachial artery endothelial function, and leg insulin and glucose responses in healthy older adults (n = 12, 50% male, 73 ± 1 year). Curcumin enhanced m. tibialis anterior microvascular blood volume (MBV) at 180 and 240 min following the ONS (baseline: 1.0 vs. 180 min: 1.08 ± 0.02, p = 0.01 vs. 240 min: 1.08 ± 0.03, p = 0.01), and MBV was significantly higher compared with the control at both time points (p < 0.05). MBV increased from baseline in the m. vastus lateralis at 240 min after the ONS in both groups (p < 0.05), and there were no significant differences between groups. Following the ONS, leg blood flow and leg vascular conductance increased, and leg vascular resistance decreased similarly in both conditions (p < 0.05). Brachial artery flow-mediated dilation and middle cerebral artery blood flow were unchanged in both conditions (p > 0.05). Similarly, the curcumin and control groups demonstrated comparable increases in glucose uptake and insulin in response to the ONS. Thus, acute curcumin supplementation enhanced ONS-induced increases in m. tibialis anterior MBV without potentiating m. vastus lateralis MBV, muscle glucose uptake, or systemic endothelial or macrovascular function in healthy older adults.

Treatment of Femoral Head Osteonecrosis with Ozone Therapy: Pilot Trial of a New Therapeutic Approach.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a progressive and painful disorder due to impaired blood supply to the femoral head, yet little is known about the effect of ozone therapy in femoral head necrosis. OBJECTIVES: We aimed to evaluate the clinical and radiographic outcomes of ozone therapy in the treatment of ONFH. STUDY DESIGN: Nonrandomized clinical trial. SETTINGS: The study was conducted in a single-center, academic institution. METHODS: A total of 71 patients (107 hip joints) with Association Research Circulation Osseous (ARCO) stage-I, II, III, and IV ONFH were included and assigned to undergo either intraarticular O2-O3 mixture hip injections with ozonated autohemotherapy (ozone therapy group, n = 39, 58 hip joints) or protected weight bearing (control group, n = 32, 49 hip joints). The primary outcomes included the Visual Analog Scale (VAS) for pain intensity and Harris Hip Score (HHS) for hip function. The secondary outcomes included bone marrow edema examination, and conversion to total hip arthroplasty (THA). RESULTS: Ozone therapy effectively improves VAS for pain intensity and HHS during the follow-up period compared to the control group. Ozone therapy showed a significant resolution of bone marrow edema of the femoral head compared to the control group (P < 0.001). Thirteen of the 49 hips (26.53%) in the control group underwent THA, whereas only 6 hips (10.34%) in the ozone therapy group required THA during a 30-month follow-up (P = 0.041). The cumulative analysis revealed a low rate of conversion to THA in the ozone therapy group (logrank test; P = 0.022). LIMITATIONS: The study is limited by a single treatment protocol in addition to the lack of a randomized design. CONCLUSIONS: Ozone therapy was associated with significant pain relief, improvement in hip function, and bone marrow edema resolution that may delay the need for THA in patients affected by ONFH.Institutional Review Board (IRB) approval number: HK2018-10-28.Clinical trials registration number: ChiCTR1900023449.

Green Tea Extract Concurrent with an Oral Nutritional Supplement Acutely Enhances Muscle Microvascular Blood Flow without Altering Leg Glucose Uptake in Healthy Older Adults.

Postprandial macro- and microvascular blood flow and metabolic dysfunction manifest with advancing age, so vascular transmuting interventions are desirable. In this randomised, single-blind, placebo-controlled, crossover trial, we investigated the impact of the acute administration of green tea extract (GTE; containing ~500 mg epigallocatechin-3-gallate) versus placebo (CON), alongside an oral nutritional supplement (ONS), on muscle macro- and microvascular, cerebral macrovascular (via ultrasound) and leg glucose/insulin metabolic responses (via arterialised/venous blood samples) in twelve healthy older adults (42% male, 74 ± 1 y). GTE increased m. vastus lateralis microvascular blood volume (MBV) at 180 and 240 min after ONS (baseline: 1.0 vs. 180 min: 1.11 ± 0.02 vs. 240 min: 1.08 ± 0.04, both p < 0.005), with MBV significantly higher than CON at 180 min (p < 0.05). Neither the ONS nor the GTE impacted m. tibialis anterior perfusion (p > 0.05). Leg blood flow and vascular conductance increased, and vascular resistance decreased similarly in both conditions (p < 0.05). Small non-significant increases in brachial artery flow-mediated dilation were observed in the GTE only and middle cerebral artery blood flow did not change in response to GTE or CON (p > 0.05). Glucose uptake increased with the GTE only (0 min: 0.03 ± 0.01 vs. 35 min: 0.11 ± 0.02 mmol/min/leg, p = 0.007); however, glucose area under the curve and insulin kinetics were similar between conditions (p > 0.05). Acute GTE supplementation enhances MBV beyond the effects of an oral mixed meal, but this improved perfusion does not translate to increased leg muscle glucose uptake in healthy older adults.

Neuropathic Pain Creates Systemic Ultrastructural Changes in the Nervous System Corrected by Electroacupuncture but Not by Pregabalin.

PURPOSE: It is unclear whether neuropathological structural changes in the peripheral nervous system and central nervous system can occur in the spared nerve injury model. In this study, we investigated the pathological changes in the nervous system in a model of neuropathic pain as well as the effects of electroacupuncture (EA) and pregabalin (PGB) administration as regards pain relief and tissue repair. PATIENTS AND METHODS: Forty adult male SD rats were equally and randomly divided into 4 groups: spared nerve injury group (SNI, n = 10), SNI with electroacupuncture group (EA, n = 10), SNI with pregabalin group (PGB, n =10) and sham-operated group (Sham, n=10). EA and PGB were given from postoperative day (POD) 14 to 36. EA (2 Hz and 100 Hz alternating frequencies, intensities ranging from 1-1.5-2 mA) was applied to the left "zusanli" (ST36) and "Yanglingquan" (GB34) acupoints for 30 minutes. The mechanical withdrawal thresholds (MWTs) were tested with von Frey filaments. Moreover, the organizational and structural alterations of the bilateral prefrontal cortex, hippocampus, sciatic nerves and the thoracic, lumbar spinal cords and dorsal root ganglions (DRGs) were examined via light and electron microscopy. RESULTS: MWTs of left hind paw demonstrated a remarkable decrease in the SNI model (P < 0.05). In the SNI model, ultrastructural changes including demyelination and damaged neurons were observed at all levels of the peripheral nervous system (PNS) and central nervous system (CNS). In addition, EA improved MWTs and restored the normal structure of neurons. However, the effect was not found in the PGB treatment group. CONCLUSION: Chronic pain can induce extensive damage to the central and peripheral nervous systems. Meanwhile, EA and PGB can both alleviate chronic pain syndromes in rats, but EA also restores the normal cellular structures, while PGB is associated with no improvement.

Six weeks of high-intensity interval training enhances contractile activity induced vascular reactivity and skeletal muscle perfusion in older adults.

Impairments in muscle microvascular function are associated with the pathogenesis of sarcopenia and cardiovascular disease. High-intensity interval training (HIIT) is an intervention by which a myriad of beneficial skeletal muscle/cardiovascular adaptations have been reported across age, including capillarisation and improved endothelial function. Herein, we hypothesised that HIIT would enhance muscle microvascular blood flow and vascular reactivity to acute contractile activity in older adults, reflecting HIIT-induced vascular remodelling. In a randomised controlled-trial, twenty-five healthy older adults aged 65-85 years (mean BMI 27.0) were randomised to 6-week HIIT or a no-intervention control period of an equal duration. Measures of microvascular responses to a single bout of muscle contractions (i.e. knee extensions) were made in the m. vastus lateralis using contrast-enhanced ultrasound during a continuous intravenous infusion of Sonovue™ contrast agent, before and after the intervention period, with concomitant assessments of cardiorespiratory fitness and resting blood pressure. HIIT led to improvements in anaerobic threshold (13.2 ± 3.4 vs. 15.3 ± 3.8 ml/kg/min, P < 0.001), dynamic exercise capacity (145 ± 60 vs. 159 ± 59 W, P < 0.001) and resting (systolic) blood pressure (142 ± 15 vs. 133 ± 11 mmHg, P < 0.01). Notably, HIIT elicited significant increases in microvascular blood flow responses to acute contractile activity (1.8 ± 0.63 vs. 2.3 ± 0.8 (arbitrary contrast units (AU), P < 0.01)), with no change in any of these parameters observed in the control group. Six weeks HIIT improves skeletal muscle microvascular responsiveness to acute contractile activity in the form of active hyperaemia-induced by a single bout of resistance exercise. These findings likely reflect reports of enhanced large vessel distensibility, improved endothelial function, and muscle capillarisation following HIIT. Moreover, our findings illustrate that HIIT may be effective in mitigating deleterious alterations in muscle microvascular mediated aspects of sarcopenia.

Cocoa Flavanols Adjuvant to an Oral Nutritional Supplement Acutely Enhances Nutritive Flow in Skeletal Muscle without Altering Leg Glucose Uptake Kinetics in Older Adults.

Ageing is associated with postprandial muscle vascular and metabolic dysfunction, suggesting vascular modifying interventions may be of benefit. Reflecting this, we investigated the impact of acute cocoa flavanol (450-500 mg) intake (versus placebo control) on vascular (via ultrasound) and glucose/insulin metabolic responses (via arterialised/venous blood samples and ELISA) to an oral nutritional supplement (ONS) in twelve healthy older adults (50% male, 72 ± 4 years), in a crossover design study. The cocoa condition displayed significant increases in m. vastus lateralis microvascular blood volume (MBV) in response to feeding at 180 and 240-min after ONS consumption (baseline: 1.00 vs. 180 min: 1.09 ± 0.03, p = 0.05; 240 min: 1.13 ± 0.04, p = 0.002), with MBV at these timepoints significantly higher than in the control condition (p < 0.05). In addition, there was a trend (p = 0.058) for MBV in m. tibialis anterior to increase in response to ONS in the cocoa condition only. Leg blood flow and vascular conductance increased, and vascular resistance decreased in response to ONS (p < 0.05), but these responses were not different between conditions (p > 0.05). Similarly, glucose uptake and insulin increased in response to ONS (p < 0.05) comparably between conditions (p > 0.05). Thus, acute cocoa flavanol supplementation can potentiate oral feeding-induced increases in MBV in older adults, but this improvement does not relay to muscle glucose uptake.

Multimodal sleep, an innovation for treating chronic insomnia: case report and literature review.

The authors present the clinical case of a 67-year-old man with severe insomnia for 5 years with an exacerbation about 1 year before consultation. He did not have enough concentration and energy for his daily work and developed depression and anxiety because of his excessive daytime sleepiness. During his insomniac state, a drug treatment provided partial relief, but the effects were not long-lasting. Consequently, the drug dosage increased, and major side effects gradually manifested. We decided to use a completely new therapeutic strategy for this patient to improve his sleep quality and mental symptoms. In time, the patient could stop oral medications and that is multimodal sleep. After the end of multimodal sleep, the patient typically experiences improvement in sleep quality and architecture. Additionally, the dosage of hypnotics used before multimodal sleep is discontinued without severe withdrawal symptoms. CITATION: Zhang J-F, Williams JP, Zhao Q-N, et al. Multimodal sleep, an innovation for treating chronic insomnia: case report and literature review. J Clin Sleep Med. 2021;17(8):1737-1742.