Erector spinae plane block for postoperative pain.

BACKGROUND: Acute and chronic postoperative pain are important healthcare problems, which can be treated with a combination of opioids and regional anaesthesia. The erector spinae plane block (ESPB) is a new regional anaesthesia technique, which might be able to reduce opioid consumption and related side effects. OBJECTIVES: To compare the analgesic effects and side effect profile of ESPB against no block, placebo block or other regional anaesthetic techniques. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Web of Science on 4 January 2021 and updated the search on 3 January 2022. SELECTION CRITERIA: Randomised controlled trials (RCTs) investigating adults undergoing surgery with general anaesthesia were included. We included ESPB in comparison with no block, placebo blocks or other regional anaesthesia techniques irrespective of language, publication year, publication status or technique of regional anaesthesia used (ultrasound, landmarks or peripheral nerve stimulator). Quasi-RCTs, cluster-RCTs, cross-over trials and studies investigating co-interventions in either arm were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all trials for inclusion and exclusion criteria, and risk of bias (RoB), and extracted data. We assessed risk of bias using the Cochrane RoB 2 tool, and we used GRADE to rate the certainty of evidence for the primary outcomes. The primary outcomes were postoperative pain at rest at 24 hours and block-related adverse events. Secondary outcomes were postoperative pain at rest (2, 48 hours) and during activity (2, 24 and 48 hours after surgery), chronic pain after three and six months, as well as cumulative oral morphine requirements at 2, 24 and 48 hours after surgery and rates of opioid-related side effects. MAIN RESULTS: We identified 69 RCTs in the first search and included these in the systematic review. We included 64 RCTs (3973 participants) in the meta-analysis. The outcome postoperative pain was reported in 38 out of 64 studies; block-related adverse events were reported in 40 out of 64 studies. We assessed RoB as low in 44 (56%), some concerns in 24 (31%) and high in 10 (13%) of the study results. Overall, 57 studies reported one or both primary outcomes. Only one study reported results on chronic pain after surgery. In the updated literature search on 3 January 2022 we found 37 new studies and categorised these as awaiting classification. ESPB compared to no block There is probably a slight but not clinically relevant reduction in pain intensity at rest 24 hours after surgery in patients treated with ESPB compared to no block (visual analogue scale (VAS), 0 to 10 points) (mean difference (MD) -0.77 points, 95% confidence interval (CI) -1.08 to -0.46; 17 trials, 958 participants; moderate-certainty evidence). There may be no difference in block-related adverse events between the groups treated with ESPB and those receiving no block (no events in 18 trials reported, 1045 participants, low-certainty evidence). ESPB compared to placebo block ESPB probably has no effect on postoperative pain intensity at rest 24 hours after surgery compared to placebo block (MD -0.14 points, 95% CI -0.29 to 0.00; 8 trials, 499 participants; moderate-certainty evidence). There may be no difference in block-related adverse events between ESPB and placebo blocks (no events in 10 trials reported; 592 participants; low-certainty evidence). ESPB compared to other regional anaesthetic techniques Paravertebral block (PVB) ESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to PVB (MD 0.23 points, 95% CI -0.06 to 0.52; 7 trials, 478 participants; low-certainty evidence). There is probably no difference in block-related adverse events (risk ratio (RR) 0.27, 95% CI 0.08 to 0.95; 7 trials, 522 participants; moderate-certainty evidence). Transversus abdominis plane block (TAPB) ESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to TAPB (MD -0.16 points, 95% CI -0.46 to 0.14; 3 trials, 160 participants; low-certainty evidence). There may be no difference in block-related adverse events (RR 1.00, 95% CI 0.21 to 4.83; 4 trials, 202 participants; low-certainty evidence). Serratus anterior plane block (SAPB) The effect on postoperative pain could not be assessed because no studies reported this outcome. There may be no difference in block-related adverse events (RR 1.00, 95% CI 0.06 to 15.59; 2 trials, 110 participants; low-certainty evidence). Pectoralis plane block (PECSB) ESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to PECSB (MD 0.24 points, 95% CI -0.11 to 0.58; 2 trials, 98 participants; low-certainty evidence). The effect on block-related adverse events could not be assessed. Quadratus lumborum block (QLB) Only one study reported on each of the primary outcomes. Intercostal nerve block (ICNB) ESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to ICNB, but this is uncertain (MD -0.33 points, 95% CI -3.02 to 2.35; 2 trials, 131 participants; very low-certainty evidence). There may be no difference in block-related adverse events, but this is uncertain (RR 0.09, 95% CI 0.04 to 2.28; 3 trials, 181 participants; very low-certainty evidence). Epidural analgesia (EA) We are uncertain whether ESPB has an effect on postoperative pain intensity at rest 24 hours after surgery compared to EA (MD 1.20 points, 95% CI -2.52 to 4.93; 2 trials, 81 participants; very low-certainty evidence). A risk ratio for block-related adverse events was not estimable because only one study reported this outcome. AUTHORS' CONCLUSIONS: ESPB in addition to standard care probably does not improve postoperative pain intensity 24 hours after surgery compared to no block. The number of block-related adverse events following ESPB was low. Further research is required to study the possibility of extending the duration of analgesia. We identified 37 new studies in the updated search and there are three ongoing studies, suggesting possible changes to the effect estimates and the certainty of the evidence in the future.

Peripheral Regional Anesthetic Techniques in Cardiac Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this systematic review was to investigate postoperative pain outcomes and adverse events after peripheral regional anesthesia (PRA) compared to no regional anesthesia (RA), placebo, or neuraxial anesthesia in children and adults undergoing cardiac surgery. DESIGN: A systematic review and meta-analysis with an assessment of the risk of bias (Cochrane RoB 1) and certainty of evidence (Grading of Recommendations, Assessment, Development, and Evaluation). SETTING: Randomized controlled trials (RCTs). PARTICIPANTS: Adults and children undergoing heart surgery. INTERVENTIONS: Any kind of PRA compared to no RA or placebo or neuraxial anesthesia. MEASUREMENTS AND MAIN RESULTS: In total, 33 RCTs (2,044 patients) were included-24 of these had a high risk of bias, and 28 were performed in adults. Compared to no RA, PRA may reduce pain intensity at rest 24 hours after surgery (mean difference [MD] -0.81 points, 95% CI -1.51 to -0.10; I2 = 92%; very low certainty evidence). Peripheral regional anesthesia, compared to placebo, may reduce pain intensity at rest (MD -1.36 points, 95% CI -1.59 to -1.13; I2 = 54%; very low certainty evidence) and during movement (MD -1.00 points, 95% CI -1.34 to -0.67; I² = 72%; very low certainty evidence) 24 hours after surgery. No data after pediatric cardiac surgery could be meta-analyzed due to the low number of included trials. CONCLUSIONS: Compared to no RA or placebo, PRA may reduce pain intensity at rest and during movement. However, these results should be interpreted cautiously because the certainty of evidence is only very low.

[Frequency of Chronic Pain after Work-Related Trauma: A Preliminary Status Survey during Workers' Compensation Rehabilitation in a Tertiary Clinic]. / Häufigkeit chronischer Schmerzen nach Arbeitsunfall ­ Eine erste Statuserhebung im BG-lichen Heilverfahren einer Tertiärklinik.

BACKGROUND: Chronic pain after trauma and surgery is a long-term complication. Its relevance for patients within the workers' compensation rehabilitation process has not been adequately investigated. OBJECTIVES: Initial evaluation of frequency of chronic pain after occupational accidents. METHODS: In 2017, surgical inpatients (18-65 y) treated in a tertiary hospital were asked about chronic pain arising from an occupational trauma recognized by statutory occupation insurance (interval 2.8±6.9 years), regardless of care received, first at the time of hospitalization and then by telephone interview 6 months later. The focus was on patients with a work-related trauma (A) within the past month or (B) >6 months. PRIMARY OUTCOME: frequency of work trauma-related chronic pain (>6 months) at the initial interview (point prevalence), secondary outcomes: frequency of chronicity at 6 months (A) and persistence of chronic pain (B). Tertiary outcomes: ability to work, occupational injury classification, burden based on pain intensity, localization, and medication, functional deficits due to the existence of chronic pain, and comorbidity. RESULTS: Out of 415 patients included in the survey, 85% (160/188) reported accident-related chronic pain (predominantly moderate to highly severe in intensity, localized at joints and bones). 90% (131/145) also reported this pain six months later. 67% (64/96) reported chronic pain for the first time. Patients with chronic pain at follow-up (281/369) were less likely to return to work (p=0.003), required analgesics in 60%, were more often comorbid (p<0.002) and had greater functional deficits (p<0.002). CONCLUSION: Despite the preliminary nature of the data, chronic pain seems to be common after occupational trauma and negatively affects the recovery of work ability in the long term. Based on the present observational data, a further differentiated re-evaluation of prospective data considering therapeutic measures is strongly recommended.

Quantitative muscle magnetic resonance imaging depicts microstructural abnormalities but no signs of inflammation or dystrophy in post-COVID-19 condition.

BACKGROUND AND PURPOSE: Post-COVID-19 condition (PCC) has high impact on quality of life, with myalgia and fatigue affecting at least 25% of PCC patients. This case-control study aims to noninvasively assess muscular alterations via quantitative muscle magnetic resonance imaging (MRI) as possible mechanisms for ongoing musculoskeletal complaints and premature exhaustion in PCC. METHODS: Quantitative muscle MRI was performed on a 3 Tesla MRI scanner of the whole legs in PCC patients compared to age- and sex-matched healthy controls, including a Dixon sequence to determine muscle fat fraction (FF), a multi-echo spin-echo sequence for quantitative water mapping reflecting putative edema, and a diffusion-weighted spin-echo echo-planar imaging sequence to assess microstructural alterations. Clinical examination, nerve conduction studies, and serum creatine kinase were performed in all patients. Quantitative muscle MRI results were correlated to the results of the 6-min walk test and standardized questionnaires assessing quality of life, fatigue, and depression. RESULTS: Twenty PCC patients (female: n = 15, age = 48.8 ± 10.1 years, symptoms duration = 13.4 ± 4.2 months, body mass index [BMI] = 28.8 ± 4.7 kg/m2 ) were compared to 20 healthy controls (female: n = 15, age = 48.1 ± 11.1 years, BMI = 22.9 ± 2.2 kg/m2 ). Neither FF nor T2 revealed signs of muscle degeneration or inflammation in either study groups. Diffusion tensor imaging (DTI) revealed reduced mean, axial, and radial diffusivity in the PCC group. CONCLUSIONS: Quantitative muscle MRI did not depict any signs of ongoing inflammation or dystrophic process in the skeletal muscles in PCC patients. However, differences observed in muscle DTI depict microstructural abnormalities, which may reflect potentially reversible fiber hypotrophy due to deconditioning. Further longitudinal and interventional studies should prove this hypothesis.

Erector spinae plane block for postoperative pain.

BACKGROUND: Acute and chronic postoperative pain are important healthcare problems, which can be treated with a combination of opioids and regional anaesthesia. The erector spinae plane block (ESPB) is a new regional anaesthesia technique, which might be able to reduce opioid consumption and related side effects. OBJECTIVES: To compare the analgesic effects and side effect profile of ESPB against no block, placebo block or other regional anaesthetic techniques. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and Web of Science on 4 January 2021 and updated the search on 3 January 2022. SELECTION CRITERIA: Randomised controlled trials (RCTs) investigating adults undergoing surgery with general anaesthesia were included. We included ESPB in comparison with no block, placebo blocks or other regional anaesthesia techniques irrespective of language, publication year, publication status or technique of regional anaesthesia used (ultrasound, landmarks or peripheral nerve stimulator). Quasi-RCTs, cluster-RCTs, cross-over trials and studies investigating co-interventions in either arm were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed all trials for inclusion and exclusion criteria, and risk of bias (RoB), and extracted data. We assessed risk of bias using the Cochrane RoB 2 tool, and we used GRADE to rate the certainty of evidence for the primary outcomes. The primary outcomes were postoperative pain at rest at 24 hours and block-related adverse events. Secondary outcomes were postoperative pain at rest (2, 48 hours) and during activity (2, 24 and 48 hours after surgery), chronic pain after three and six months, as well as cumulative oral morphine requirements at 2, 24 and 48 hours after surgery and rates of opioid-related side effects. MAIN RESULTS: We identified 69 RCTs in the first search and included these in the systematic review. We included 64 RCTs (3973 participants) in the meta-analysis. The outcome postoperative pain was reported in 38 out of 64 studies; block-related adverse events were reported in 40 out of 64 studies. We assessed RoB as low in 44 (56%), some concerns in 24 (31%) and high in 10 (13%) of the study results. Overall, 57 studies reported one or both primary outcomes. Only one study reported results on chronic pain after surgery. In the updated literature search on 3 January 2022 we found 37 new studies and categorised these as awaiting classification. ESPB compared to no block There is probably a slight but not clinically relevant reduction in pain intensity at rest 24 hours after surgery in patients treated with ESPB compared to no block (visual analogue scale (VAS), 0 to 10 points) (mean difference (MD) -0.77 points, 95% confidence interval (CI) -1.08 to -0.46; 17 trials, 958 participants; moderate-certainty evidence). There may be no difference in block-related adverse events between the groups treated with ESPB and those receiving no block (no events in 18 trials reported, 1045 participants, low-certainty evidence). ESPB compared to placebo block ESPB probably has no effect on postoperative pain intensity at rest 24 hours after surgery compared to placebo block (MD -0.14 points, 95% CI -0.29 to 0.00; 8 trials, 499 participants; moderate-certainty evidence). There may be no difference in block-related adverse events between ESPB and placebo blocks (no events in 10 trials reported; 592 participants; low-certainty evidence). ESPB compared to other regional anaesthetic techniques Paravertebral block (PVB) ESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to PVB (MD 0.23 points, 95% CI -0.06 to 0.52; 7 trials, 478 participants; low-certainty evidence). There is probably no difference in block-related adverse events (risk ratio (RR) 0.27, 95% CI 0.08 to 0.95; 7 trials, 522 participants; moderate-certainty evidence). Transversus abdominis plane block (TAPB) ESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to TAPB (MD -0.16 points, 95% CI -0.46 to 0.14; 3 trials, 160 participants; low-certainty evidence). There may be no difference in block-related adverse events (RR 1.00, 95% CI 0.21 to 4.83; 4 trials, 202 participants; low-certainty evidence). Serratus anterior plane block (SAPB) The effect on postoperative pain could not be assessed because no studies reported this outcome. There may be no difference in block-related adverse events (RR 1.00, 95% CI 0.06 to 15.59; 2 trials, 110 participants; low-certainty evidence). Pectoralis plane block (PECSB) ESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to PECSB (MD 0.24 points, 95% CI -0.11 to 0.58; 2 trials, 98 participants; low-certainty evidence). The effect on block-related adverse events could not be assessed. Quadratus lumborum block (QLB) Only one study reported on each of the primary outcomes. Intercostal nerve block (ICNB) ESPB may not have any additional effect on postoperative pain intensity at rest 24 hours after surgery compared to ICNB, but this is uncertain (MD -0.33 points, 95% CI -3.02 to 2.35; 2 trials, 131 participants; very low-certainty evidence). There may be no difference in block-related adverse events, but this is uncertain (RR 0.09, 95% CI 0.04 to 2.28; 3 trials, 181 participants; very low-certainty evidence). Epidural analgesia (EA) We are uncertain whether ESPB has an effect on postoperative pain intensity at rest 24 hours after surgery compared to EA (MD 1.20 points, 95% CI -2.52 to 4.93; 2 trials, 81 participants; very low-certainty evidence). A risk ratio for block-related adverse events was not estimable because only one study reported this outcome. AUTHORS' CONCLUSIONS: ESPB in addition to standard care probably does not improve postoperative pain intensity 24 hours after surgery compared to no block. The number of block-related adverse events following ESPB was low. Further research is required to study the possibility of extending the duration of analgesia. We identified 37 new studies in the updated search and there are three ongoing studies, suggesting possible changes to the effect estimates and the certainty of the evidence in the future.

[Application possibilities of digital tools in postoperative pain therapy]. / Einsatzmöglichkeiten digitaler Tools in der postoperativen Schmerztherapie.

BACKGROUND: Recently, digital tools, such as smartphone-based applications and the use of artificial intelligence have increasingly found their way into pain medicine. This could enable new treatment approaches in postoperative pain management. Therefore, this article provides an overview of various digital tools and their potential application options in postoperative pain management. MATERIAL AND METHODS: An orienting literature search was carried out in the MEDLINE and Web of Science databases, and a targeted selection of essential key publications was made in order to provide a structured presentation of different current possible applications and a discussion based on the most recent knowledge. RESULTS: Today, possible applications of digital tools, even if they mostly have only a model character, include pain documentation and assessment, patient self-management and education, pain prediction, decision support for medical staff, and supportive pain therapy, for example in the form of virtual reality and videos. These tools offer advantages such as individualized treatment concepts, addressing specific patient groups, reduction of pain and analgesics, and the potential for early warning or detection of postoperative pain. Furthermore, the challenges of the technical implementation and appropriate user training are highlighted. CONCLUSION: The use of digital tools, although so far integrated in clinical routine in a relatively selective and exemplary manner, promises to be an innovative approach for personalized postoperative pain therapy in the future. Future studies and projects should help to integrate the promising research approaches into everyday clinical practice.

MHC-E-Restricted CD8+ T Cells Target Hepatitis B Virus-Infected Human Hepatocytes.

Currently 247 million people are living with chronic hepatitis B virus infection (CHB), and the development of novel curative treatments is urgently needed. Immunotherapy is an attractive approach to treat CHB, yet therapeutic approaches to augment the endogenous hepatitis B virus (HBV)-specific T cell response in CHB patients have demonstrated little success. In this study, we show that strain 68-1 rhesus macaque (RM) CMV vaccine vectors expressing HBV Ags engender HBV-specific CD8+ T cells unconventionally restricted by MHC class II and the nonclassical MHC-E molecule in RM. Surface staining of human donor and RM primary hepatocytes (PH) ex vivo revealed the majority of PH expressed MHC-E but not MHC class II. HBV-specific, MHC-E-restricted CD8+ T cells from RM vaccinated with RM CMV vaccine vectors expressing HBV Ags recognized HBV-infected PH from both human donor and RM. These results provide proof-of-concept that MHC-E-restricted CD8+ T cells could be harnessed for the treatment of CHB, either through therapeutic vaccination or adoptive immunotherapy.

Chronic Pain Following Fracture-Related Surgery: Posttraumatic Rather Than Postsurgical Origin Promotes Chronification-A Prospective Observational Study With 1-Year Follow-up.

BACKGROUND: Chronic posttraumatic/postsurgical pain (CPSP) is common after traumatic or surgical damage. Exposure to both trauma and surgery, with the potential for repeated bone and nerve damage, may increase the risk of CPSP after fracture-related surgery. But the (long-term) incidences of CPSP and neuropathic CPSP and the ensuing burdens are unknown. Therefore, the patients were prospectively assessed within 1 year, and the patient-specific characteristics were explored. METHODS: Between 2017 and 2018, 127 patients (age: 52.9 ± 17.1 years, male: 55.1%) with traumatic fractures needing osteosynthesis (extremities: 91.3%) were assessed posttrauma (before surgery), postsurgery at days 1 to 5, 6 weeks, 3 and 12 months. The primary outcomes are as follows: incidence at 3 and 12 months of CPSP (defined as pain intensity on a numerical rating scale [NRS: 0-10] ≥3), secondary exploration: neuropathic CPSP (NRS ≥3 and Douleur Neuropathique 4 interview [DN4i] score ≥3 [Douleur Neuropathique interview: 0-7]); burden: quality of life (QoL, the EuroQOL five dimensions questionnaire [EQ-5D-3L] descriptive system); and inter alia, the number of analgesics (trial registration: DRKS00011601). RESULTS: The incidence of CPSP was 57.1% (52/91, n/N) at 3 and 42.7% (35/82) at 12 months postsurgery, including neuropathic CPSP 7.7% (4/52) and 17.1% (6/35), respectively. Descriptively, posttraumatic higher pain intensity at rest (difference of 0.9 ± 1.8 NRS) and the need for more frequent analgesics (by 34.3%) were associated with CPSP a year after surgery compared to those without. As soon as week 6, these patients had developed descriptively a 15% more impaired QoL, with 25% more impairment after 1 year. The patients with CPSP presented with at least 1 neuropathic symptom 12 months later in 68.6% (24/35) of cases, mainly with an early posttraumatic occurrence (without fulfilling the definition of neuropathic CPSP). CONCLUSIONS: After early fracture-related surgery, high incidences of CPSP (43%) were prospectively observed 1 year postsurgery, up to approximately 1 in 5 patients who had neuropathic CPSP. At the same time, CPSP was accompanied with an impacted QoL and analgesic dependence, both indicating clinical relevance. Moreover, the high incidence and the early posttraumatic occurrence of more intense pain suggest that the initial fracture-related trauma, rather than the surgical trauma, may predominantly trigger CPSP at Y1 (1 year). Therefore, these exploratory results set the direction of required future research. A future clinical hypothesis might be: treat first what hurts first.

The plant pathogen enzyme AldC is a long-chain aliphatic aldehyde dehydrogenase.

Aldehyde dehydrogenases are versatile enzymes that serve a range of biochemical functions. Although traditionally considered metabolic housekeeping enzymes because of their ability to detoxify reactive aldehydes, like those generated from lipid peroxidation damage, the contributions of these enzymes to other biological processes are widespread. For example, the plant pathogen Pseudomonas syringae strain PtoDC3000 uses an indole-3-acetaldehyde dehydrogenase to synthesize the phytohormone indole-3-acetic acid to elude host responses. Here we investigate the biochemical function of AldC from PtoDC3000. Analysis of the substrate profile of AldC suggests that this enzyme functions as a long-chain aliphatic aldehyde dehydrogenase. The 2.5 Å resolution X-ray crystal of the AldC C291A mutant in a dead-end complex with octanal and NAD+ reveals an apolar binding site primed for aliphatic aldehyde substrate recognition. Functional characterization of site-directed mutants targeting the substrate- and NAD(H)-binding sites identifies key residues in the active site for ligand interactions, including those in the "aromatic box" that define the aldehyde-binding site. Overall, this study provides molecular insight for understanding the evolution of the prokaryotic aldehyde dehydrogenase superfamily and their diversity of function.

Incidence, Time Course and Influence on Quality of Life of Intensive Care Unit-Acquired Weakness Symptoms in Long-Term Intensive Care Survivors.

PURPOSE: Intensive care unit-acquired weakness (ICUAW) can manifest as muscle weakness or neuropathy-like symptoms, with diagnosis remaining a challenge. Uncertainties surround the long-term cause and sequelae. Therefore, the purpose was to assess incidence, time course and long-term influence on quality of life (QoL) of symptoms in ICU survivors. METHODS: After ethical approval and registration (www.drks.de: DRKS00011593), in a single-center cohort study all patients admitted to the ICU in 2007-2017 in a German university hospital were screened. Out of 1,860 patients (≥7d ICU care including ventilation support for ≥72 h, at least 6mo-10y after ICU) 636 were deceased, 912 survivors were contacted. RESULTS: 149 former patients (age: 63.5 ± 13.1y; males: 73%; duration in ICU: 20.8 ± 15.7d; duration of ventilation: 16.5 ± 13.7 h; time post-ICU: 4.4 ± 2.7y, 5-10y: 43%) consented to be interviewed concerning occurrence, duration, recovery and consequences of ICUAW-associated muscle weakness or neuropathy-like symptoms after ICU. In 75% at least 1 persistent or previous symmetrical symptom was reported (myopathy-like muscle weakness: 43%; neuropathy-like symptoms: 13%; both: 44%) and rated as incidence of ICUAW. However, only 18% of participants had received an ICUAW diagnosis by their physicians, although 62% had persistent symptoms up to 10y after ICU (5-10y: 46%). Only 37% of participants reported a complete recovery of symptoms, significantly associated with an initially low number of symptoms after ICU (p < 0.0001), myopathy-like symptoms (p = 0.024), and younger age at the time of ICU admission (55.7 ± 13.1 vs. 62.6 ± 10.6y, p < 0.001). ICUAW still impaired the QoL at the time of the interview in 74% of affected survivors, with 30% reporting severe impairment. CONCLUSION: ICUAW symptoms were disturbingly common in the majority of long-term survivors, indicating that symptoms persist up to 10y and frequently impair QoL. However, only a small number of patients had been diagnosed with ICUAW. Trial registry: Deutsches Register Klinischer Studien (DRKS), https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011593, registration number: DRKS00011593.

Pectoral nerve blocks for breast surgery: A meta-analysis.

BACKGROUND: Pectoral nerve blocks (PECS block) might be an interesting new regional anaesthetic technique in patients undergoing breast surgery. OBJECTIVE: The aim of this meta-analysis was to investigate postoperative pain outcomes and adverse events of a PECS block compared with no treatment, sham treatment or other regional anaesthetic techniques in women undergoing breast surgery. DESIGN: We performed a systematic review of randomised controlled trials (RCT) with meta-analysis and risk of bias assessment. DATA SOURCES: The databases MEDLINE, CENTRAL (until December 2019) and clinicaltrials.gov were systematically searched. ELIGIBILITY CRITERIA: All RCTs investigating the efficacy and adverse events of PECS compared with sham treatment, no treatment or other regional anaesthetic techniques in women undergoing breast surgery with general anaesthesia were included. RESULTS: A total of 24 RCTs (1565 patients) were included. PECS (compared with no treatment) block might reduce pain at rest [mean difference -1.14, 95% confidence interval (CI), -2.1 to -0.18, moderate quality evidence] but we are uncertain regarding the effect on pain during movement at 24 h after surgery (mean difference -1.79, 95% CI, -3.5 to -0.08, very low-quality evidence). We are also uncertain about the effect of PECS block on pain at rest at 24 h compared with sham block (mean difference -0.83, 95% CI, -1.80 to 0.14) or compared with paravertebral block (PVB) (mean difference -0.18, 95% CI, -1.0 to 0.65), both with very low-quality evidence. PECS block may have no effect on pain on movement at 24 h after surgery compared with PVB block (mean difference -0.56, 95% CI, -1.53 to 0.41, low-quality evidence). Block-related complications were generally poorly reported. CONCLUSION: There is moderate quality evidence that PECS block compared with no treatment reduces postoperative pain intensity at rest. The observed results were less pronounced if patients received a sham block. Furthermore, PECS blocks might be equally effective as PVBs. Due to mostly low-quality or very low-quality evidence level, further research is warranted. PROTOCOL REGISTRATION: CRD42019126733.

Diffusion tensor imaging reveals changes in non-fat infiltrated muscles in late onset Pompe disease.

MRI is a helpful tool for monitoring disease progression in late-onset Pompe disease (LOPD). Our study aimed to evaluate if muscle diffusion tensor imaging (mDTI) shows alterations in muscles of LOPD patients with <10% fat-fraction. We evaluated 6 thigh and 7 calf muscles (both legs) of 18 LOPD and 29 healthy controls (HC) with muscle diffusion tensor imaging (mDTI), T1w, and mDixonquant sequences in a 3T MRI scanner. The quantitative mDTI-values axial diffusivity (λ1 ), mean diffusivity (MD), radial diffusivity (RD), and fractional anisotropy (FA) as well as fat-fraction were analyzed. 6-Minute Walk Test (6-MWT) data were correlated to diffusion metrics. We found that mDTI showed significant differences between LOPD and HC in diffusion parameters (P < .05). Thigh muscles with <10% fat-fraction showed significant differences in MD, RD, and λ1-3 . MD positively correlated with 6-MWT (P = .06). To conclude, mDTI reveals diffusion restrictions in muscles of LOPD with and without fat-infiltration and reflects structural changes prior to fatty degeneration.

Can a Simple Geriatric Assessment Predict the Outcome of TURP?

PURPOSE: To determine the impact of a simple preoperative geriatric assessment on the outcome in older patients with recurrent urinary retention who underwent desobstructive surgery. PATIENTS AND METHODS: Patients aged 75 years or older with recurrent urinary retention referred for TURP entered this prospective, multicentre study. Several demographic, intra- and postoperative parameters were assessed. Preoperative geriatric assessment was performed by the 7-item Canadian Study of Health and Ageing (CSHA) frailty scale (1: very fit, 7: severely frail; completion takes less than a minute). The main outcome parameters were successful voiding rates at discharge and 3 months postoperatively. RESULTS: A total of 54 patients were recruited; 42 (77.8%) patients had a CSHA index of 1-3 and were considered as "fit", the remaining 12 (22.2%) formed the "frail" group (CSHA index 4-7). Age was identical in both cohorts (79.5 ± 3.7 vs. 79.7 ± 3.3 years); differences were demonstrable for the American Society of Anesthesiologists (ASA) score (p = 0.001), the number of daily medications (>4: 32 vs. 75%, p = 0.02), falls within the past 6 months (12 vs. 33%), and the necessity of home/nursing care (5 vs. 42%, p = 0.004). Intra- and perioperative complications, duration of postoperative catheterization, and length of hospitalization were identical in both cohorts. The success rate at discharge was 80.6% in fit and 75.0% in frail patients; the respective values at 3 months were 95.2 and 83.3%. CONCLUSIONS: A simple 1-min geriatric assessment tool can predict - to a certain extent - the outcome of desobstructive surgery in older patients with recurrent urinary retention. Fit patients achieve an excellent outcome while frail patients might benefit from a more in-depth urodynamic/geriatric evaluation.

[Long-term effectiveness of topical analgesics]. / Langzeiteffektivität topisch applizierter Analgetika.

BACKGROUND: Neuropathic pain consistently presents a significant therapeutic challenge. Topically applied analgesics have the advantage of showing low systemic side effects, but data on long-term effectiveness are lacking. Consequently, interviews were carried out with all patients being treated with topical analgesics in hospital. METHODS: Ethics 16-5690, German Clinical Trials Register (DRKS) 00011877. Between 2008 and 2017 a total of 265 patients were treated at least once with either capsaicin 8% (C), lidocaine 5% (L) and/or perineural botulinum toxin type A (B). From this sample, 205 patients (77%) were interviewed by telephone for feedback on pain reduction (first/last treatment: low/moderate/very good), the possible reduction of analgesic prescription and if applicable the reasons for discontinuation of use (time of interview C: 26 ± 19 months, L: 61 ± 23 months, B: 11 ± 6 months after start). Further pretreatment data and diagnoses were obtained from the in-house documentation system. Responders or long-term responders were defined as patients with at least one moderate pain reduction after the first or last treatment, as long as the effect was adequately maintained. RESULTS: In all treatment groups (56 ± 13 years, 62% male, C: 80, L: 84, B: 58 patients) patients with a long history of pain (C: 60 ± 73 months, L: 59 ± 66 months, B: 67 ± 71 months) and high pain intensity (numeric rating scale, NRS, C: 7 ± 2, L: 7 ± 2, B: 6 ± 2), were predominant. The highest primary and long-term responder rates were exhibited by L (57%/60%, B: 52%/37%, C: 23%/15%). With B, long-term responders were most frequently able to reduce analgesic use (74%, C: 58%, L: 38%). DISCUSSION: Despite the long duration of the disease, the most used off-label topical drugs L and B demonstrated a high primary response rate (in contrast to C), with most benefiting from long-term treatment.

Intensity of Withdrawal Symptoms During Opioid Taper in Patients with Chronic Pain-Individualized or Fixed Starting Dosage?

OBJECTIVE: Controlled opioid withdrawal is recommended for patients with chronic noncancer pain (CNCP) with insufficient pain reduction or intolerable side effects while on opioid treatment. Few studies have investigated the management of opioid withdrawal (OW). Most common are protocols with an individualized starting dosage (ISD), calculated from the last opioid intake. After two cases of overdose, we introduced a novel withdrawal protocol using a low fixed starting dosage (FSD) for safety reasons. The present study compares the intensity of withdrawal symptoms using the Subjective Opioid Withdrawal Scale (SOWS) and incidences of serious adverse events (SAE) and dropouts in each taper schedule in 195 CNCP patients with OW in an inpatient facility. METHODS: Two protocols were compared: FSD (2014-2016): N = 68, starting dose: 90 mg morphine/d; and ISD (2010-2014): N = 127, starting dose: 70% of the patient's daily morphine equivalent dose (MED). Outcome criteria: primary: mean daily SOWS score during the first 10 days (16 questions, daily score 0-64); secondary: change in pain intensity on a numeric rating scale (0-10), rate of dropouts and SAEs. Statistics: Student test, Mann-Whitney U test, chi-square test, analysis of variance, P < 0.05. RESULTS: The mean daily SOWS score was lower in the FSD group (14.9 ± 9.4 vs 16.1 ± 10, P < 0.05) due to a lower rate of high-intensity withdrawal symptoms (12.4% vs 17.6%, P < 0.01), particularly in patients on >180 mg MED (9.7% vs 18.4%, P < 0.01). Pain intensity decreased after withdrawal, and the incidence of SAEs and dropouts was low in both groups. CONCLUSIONS: The FSD protocol provides a lesser burden of withdrawal symptoms and equal patient safety. It can be recommended for OW in CNCP patients.

Adductor canal blocks for postoperative pain treatment in adults undergoing knee surgery.

BACKGROUND: Peripheral regional anaesthesia techniques are well established for postoperative pain treatment following knee surgery. The adductor canal block (ACB) is a new technique, which can be applied as a single shot or by catheter for continuous regional analgesia. OBJECTIVES: To compare the analgesic efficacy and adverse events of ACB versus other regional analgesic techniques or systemic analgesic treatment for adults undergoing knee surgery. SEARCH METHODS: We searched CENTRAL, MEDLINE, and Embase, five other databases, and one trial register on 19 September 2018; we checked references, searched citations, and contacted study authors to identify additional studies. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) comparing single or continuous ACB versus other regional analgesic techniques or systemic analgesic treatment. Inclusion was independent of the technique used (landmarks, peripheral nerve stimulator, or ultrasound) and the level of training of providers. DATA COLLECTION AND ANALYSIS: We used Cochrane's standard methodological procedures. Our primary outcomes were pain intensity at rest and during movement; rate of accidental falls; and rates of opioid-related adverse events. We used GRADE to assess the quality of evidence for primary outcomes. MAIN RESULTS: We included 25 RCTs (1688 participants) in this review (23 trials combined within meta-analyses). In 18 studies, participants underwent total knee arthroplasty (TKA), whereas seven trials investigated patients undergoing arthroscopic knee surgery. We identified 11 studies awaiting classification and 11 ongoing studies. We investigated the following comparisons. ACB versus sham treatment We included eight trials for this comparison. We found no significant differences in postoperative pain intensity at rest (2 hours: standardized mean difference (SMD) -0.56, 95% confidence interval (CI) -1.20 to 0.07, 4 trials, 208 participants, low-quality evidence; 24 hours: SMD -0.49, 95% CI -1.05 to 0.07, 6 trials, 272 participants, low-quality evidence) or during movement (2 hours: SMD -0.59, 95% CI -1.5 to 0.33; 3 trials, 160 participants, very low-quality evidence; 24 hours: SMD 0.03, 95% CI -0.26 to 0.32, 4 trials, 184 participants, low-quality evidence). Furthermore, they noted no evidence of a difference in postoperative nausea between groups (24 hours: risk ratio (RR) 1.91, 95% CI 0.48 to 7.58, 3 trials, 121 participants, low-quality evidence). One trial reported that no accidental falls occurred 24 hours postoperatively (low-quality evidence). ACB versus femoral nerve block We included 15 RCTs for this comparison. We found no evidence of a difference in postoperative pain intensity at rest (2 hours: SMD -0.74, 95% CI -1.76 to 0.28, 5 trials, 298 participants, low-quality evidence; 24 hours: SMD 0.04, 95% CI -0.09 to 0.18, 12 trials, 868 participants, high-quality evidence) or during movement (2 hours: SMD -0.47, 95% CI -1.86 to 0.93, 2 trials, 88 participants, very low-quality evidence; 24 hours: SMD 0.56, 95% CI -0.00 to 1.12, 9 trials, 576 participants, very low-quality evidence). They noted no evidence of a difference in postoperative nausea (24 hours: RR 1.22, 95% CI 0.42 to 3.54, 2 trials, 138 participants, low-quality evidence) and no evidence that the rate of accidental falls during postoperative care was significantly different between groups (24 hours: RR 0.20, 95% CI 0.04 to 1.15, 3 trials, 172 participants, low-quality evidence). AUTHORS' CONCLUSIONS: We are currently uncertain whether patients treated with ACB suffer from lower pain intensity at rest and during movement, fewer opioid-related adverse events, and fewer accidental falls during postoperative care compared to patients receiving sham treatment. The same holds true for the comparison of ACB versus femoral nerve block focusing on postoperative pain intensity. The overall evidence level was mostly low or very low, so further research might change the conclusion. The 11 studies awaiting classification and the 11 ongoing studies, once assessed, may alter the conclusions of this review.

Peptide Processing Is Critical for T-Cell Memory Inflation and May Be Optimized to Improve Immune Protection by CMV-Based Vaccine Vectors.

Cytomegalovirus (CMV) elicits long-term T-cell immunity of unparalleled strength, which has allowed the development of highly protective CMV-based vaccine vectors. Counterintuitively, experimental vaccines encoding a single MHC-I restricted epitope offered better immune protection than those expressing entire proteins, including the same epitope. To clarify this conundrum, we generated recombinant murine CMVs (MCMVs) encoding well-characterized MHC-I epitopes at different positions within viral genes and observed strong immune responses and protection against viruses and tumor growth when the epitopes were expressed at the protein C-terminus. We used the M45-encoded conventional epitope HGIRNASFI to dissect this phenomenon at the molecular level. A recombinant MCMV expressing HGIRNASFI on the C-terminus of M45, in contrast to wild-type MCMV, enabled peptide processing by the constitutive proteasome, direct antigen presentation, and an inflation of antigen-specific effector memory cells. Consequently, our results indicate that constitutive proteasome processing of antigenic epitopes in latently infected cells is required for robust inflationary responses. This insight allows utilizing the epitope positioning in the design of CMV-based vectors as a novel strategy for enhancing their efficacy.

Efficacy and safety of dexmedetomidine in peripheral nerve blocks: A meta-analysis and trial sequential analysis.

BACKGROUND: The duration of analgesia provided by nerve blocks is limited if local anaesthetics are administered alone. Therefore, several additives, including dexmedetomidine (DEX), have been investigated in order to prolong postoperative analgesia following single-shot regional anaesthesia. OBJECTIVES: The aim of this meta-analysis was to assess the efficacy and safety of the addition of perineural DEX to local anaesthetics compared with local anaesthetics alone or local anaesthetics combined with systemic administration of DEX. DESIGN: A systematic review of randomised controlled trials (RCT) with meta-analysis, trial sequential analysis and assessment of the quality of evidence by the GRADE approach. DATA SOURCES: The databases MEDLINE, CENTRAL and EMBASE (to May 2017) were systematically searched. ELIGIBILITY CRITERIA: All RCTs investigating the efficacy and safety of perineural DEX combined with local anaesthetics compared with local anaesthetics alone or local anaesthetics in combination with systemic DEX in peripheral nerve blocks of adults undergoing surgery were included. RESULTS: A total of 46 RCTs (3149 patients) were included. Patients receiving perineural DEX combined with local anaesthetics had a longer duration of analgesia than local anaesthetics alone [mean difference 4.87 h; 95% confidence interval (95% CI) 4.02 to 5.73; P < 0.001; I = 100%; moderate-quality evidence]. The most important adverse events in the DEX group were intraoperative bradycardia [risk ratio 2.83; 95% CI 1.50 to 5.33; P = 0.035; I = 40%; very low-quality evidence] and hypotension (risk ratio 3.42; 95% CI 1.24 to 9.48; P = 0.002; I = 65%; very low quality evidence). In contrast, there were no differences in the duration of analgesia between perineural or intravenous DEX combined with local anaesthetics (mean difference 0.98 h; 95% CI -0.12 to 2.08; P = 0.08; I = 0%). CONCLUSION: This meta-analysis demonstrated that DEX in combination with local anaesthetics increases postoperative analgesia for around 5 h. However, there are higher risks of intraoperative hypotension and bradycardia. Findings on side effects are associated with high uncertainty. Initial evidence suggests no difference in the duration of analgesia associated with systemic or perineural DEX. TRIAL REGISTRATION: CRD42016042486.

Native Mass Spectrometry Analysis of Oligomerization States of Fluorescence Recovery Protein and Orange Carotenoid Protein: Two Proteins Involved in the Cyanobacterial Photoprotection Cycle.

The orange carotenoid protein (OCP) and fluorescence recovery protein (FRP) are present in many cyanobacteria and regulate an essential photoprotection cycle in an antagonistic manner as a function of light intensity. We characterized the oligomerization states of OCP and FRP by using native mass spectrometry, a technique that has the capability of studying native proteins under a wide range of protein concentrations and molecular masses. We found that dimeric FRP is the predominant state at protein concentrations ranging from 3 to 180 µM and that higher-order oligomers gradually form at protein concentrations above this range. The OCP, however, demonstrates significantly different oligomerization behavior. Monomeric OCP (mOCP) dominates at low protein concentrations, with an observable population of dimeric OCP (dOCP). The ratio of dOCP to mOCP, however, increases proportionally with protein concentration. Higher-order OCP oligomers form at protein concentrations beyond 10 µM. Additionally, native mass spectrometry coupled with ion mobility allowed us to measure protein collisional cross sections and interrogate the unfolding of different FRP and OCP oligomers. We found that monomeric FRP exhibits a one-stage unfolding process, which could be correlated with its C-terminal bent crystal structure. The structural domain compositions of FRP and OCP are compared and discussed.