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Introduction: Pain is the most common reason for seeking medical treatment. Despite extensive research efforts and effective analgesics modulating pain, there is still a major therapeutic gap in addressing the root causes of pain. Pain is associated with tissue damage induced by oxidative stress and induction of inflammatory mediators following high consumption of antioxidants. The role of antioxidants in general, and the administration of l-ascorbate in particular, is still controversially discussed and underestimated in the daily clinical practice.The current literature on the therapeutic effect of l-ascorbate, ascorbic acid, and vitamin C on various pain conditions was evaluated against the background of evidence-based medicine. Those articles, obtained from systematic search in PubMed, were critically assessed and rated in terms of evidence level and methodological quality by two independent experts. The primary purpose of this work was to establish specific pain therapy guidance for intravenous l-ascorbate.A PubMed search revealed 14 suitable articles comprising controlled clinical trials and meta-analyses. An additional ten publications could be identified via secondary literature. There is supporting evidence for the efficacy of ascorbate treatment in inflammatory pain conditions, in the complex regional pain syndrome, in post zoster neuralgia, in neuropathic pain, in post-operative pain conditions, and in tumor-related pain. However, the considered studies differ in the type of administration, in dosage, in duration of treatment, as well as in quality of research. Despite all study heterogeneity, it became evident that research of high scientific quality is in support of the efficacy of l-ascorbate in pain treatment.Oxidative stress is present in almost all pain conditions. Because oral administration of most magistral formulas of vitamin C does not provide biological availability, parenteral administration should be preferred and can be supported by an oral dose with high bioavailability on days without intravenous treatment. l-ascorbate should be preferred for parenteral high dosage, rather than ascorbic acid, as it does not release acid valences under physiological conditions.l-ascorbate is an effective, safe, and economically favorable integrative treatment option for various pain conditions, addressing the root cause of tissue damage and inflammatory mediator burst.Methods: Pain is the most common reason for seeking medical treatment. Despite extensive research efforts and effective analgesics modulating pain, there is still a major therapeutic gap in addressing the root causes of pain. Pain is associated with tissue damage induced by oxidative stress and induction of inflammatory mediators following high consumption of antioxidants. The role of antioxidants in general, and the administration of l-ascorbate in particular, is still controversially discussed and underestimated in the daily clinical practice.The current literature on the therapeutic effect of l-ascorbate, ascorbic acid, and vitamin C on various pain conditions was evaluated against the background of evidence-based medicine. Those articles, obtained from systematic search in PubMed, were critically assessed and rated in terms of evidence level and methodological quality by two independent experts. The primary purpose of this work was to establish specific pain therapy guidance for intravenous l-ascorbate.A PubMed search revealed 14 suitable articles comprising controlled clinical trials and meta-analyses. An additional ten publications could be identified via secondary literature. There is supporting evidence for the efficacy of ascorbate treatment in inflammatory pain conditions, in the complex regional pain syndrome, in post zoster neuralgia, in neuropathic pain, in post-operative pain conditions, and in tumor-related pain. However, the considered studies differ in the type of administration, in dosage, in duration of treatment, as well as in quality of research. Despite all study heterogeneity, it became evident that research of high scientific quality is in support of the efficacy of l-ascorbate in pain treatment.Oxidative stress is present in almost all pain conditions. Because oral administration of most magistral formulas of vitamin C does not provide biological availability, parenteral administration should be preferred and can be supported by an oral dose with high bioavailability on days without intravenous treatment. l-ascorbate should be preferred for parenteral high dosage, rather than ascorbic acid, as it does not release acid valences under physiological conditions.l-ascorbate is an effective, safe, and economically favorable integrative treatment option for various pain conditions, addressing the root cause of tissue damage and inflammatory mediator burst.Results: Pain is the most common reason for seeking medical treatment. Despite extensive research efforts and effective analgesics modulating pain, there is still a major therapeutic gap in addressing the root causes of pain. Pain is associated with tissue damage induced by oxidative stress and induction of inflammatory mediators following high consumption of antioxidants. The role of antioxidants in general, and the administration of l-ascorbate in particular, is still controversially discussed and underestimated in the daily clinical practice.The current literature on the therapeutic effect of l-ascorbate, ascorbic acid, and vitamin C on various pain conditions was evaluated against the background of evidence-based medicine. Those articles, obtained from systematic search in PubMed, were critically assessed and rated in terms of evidence level and methodological quality by two independent experts. The primary purpose of this work was to establish specific pain therapy guidance for intravenous l-ascorbate.A PubMed search revealed 14 suitable articles comprising controlled clinical trials and meta-analyses. An additional ten publications could be identified via secondary literature. There is supporting evidence for the efficacy of ascorbate treatment in inflammatory pain conditions, in the complex regional pain syndrome, in post zoster neuralgia, in neuropathic pain, in post-operative pain conditions, and in tumor-related pain. However, the considered studies differ in the type of administration, in dosage, in duration of treatment, as well as in quality of research. Despite all study heterogeneity, it became evident that research of high scientific quality is in support of the efficacy of l-ascorbate in pain treatment.Oxidative stress is present in almost all pain conditions. Because oral administration of most magistral formulas of vitamin C does not provide biological availability, parenteral administration should be preferred and can be supported by an oral dose with high bioavailability on days without intravenous treatment. l-ascorbate should be preferred for parenteral high dosage, rather than ascorbic acid, as it does not release acid valences under physiological conditions.l-ascorbate is an effective, safe, and economically favorable integrative treatment option for various pain conditions, addressing the root cause of tissue damage and inflammatory mediator burst.Discussion: Pain is the most common reason for seeking medical treatment. Despite extensive research efforts and effective analgesics modulating pain, there is still a major therapeutic gap in addressing the root causes of pain. Pain is associated with tissue damage induced by oxidative stress and induction of inflammatory mediators following high consumption of antioxidants. The role of antioxidants in general, and the administration of l-ascorbate in particular, is still controversially discussed and underestimated in the daily clinical practice.The current literature on the therapeutic effect of l-ascorbate, ascorbic acid, and vitamin C on various pain conditions was evaluated against the background of evidence-based medicine. Those articles, obtained from systematic search in PubMed, were critically assessed and rated in terms of evidence level and methodological quality by two independent experts. The primary purpose of this work was to establish specific pain therapy guidance for intravenous l-ascorbate.A PubMed search revealed 14 suitable articles comprising controlled clinical trials and meta-analyses. An additional ten publications could be identified via secondary literature. There is supporting evidence for the efficacy of ascorbate treatment in inflammatory pain conditions, in the complex regional pain syndrome, in post zoster neuralgia, in neuropathic pain, in post-operative pain conditions, and in tumor-related pain. However, the considered studies differ in the type of administration, in dosage, in duration of treatment, as well as in quality of research. Despite all study heterogeneity, it became evident that research of high scientific quality is in support of the efficacy of l-ascorbate in pain treatment.Oxidative stress is present in almost all pain conditions. Because oral administration of most magistral formulas of vitamin C does not provide biological availability, parenteral administration should be preferred and can be supported by an oral dose with high bioavailability on days without intravenous treatment. l-ascorbate should be preferred for parenteral high dosage, rather than ascorbic acid, as it does not release acid valences under physiological conditions.l-ascorbate is an effective, safe, and economically favorable integrative treatment option for various pain conditions, addressing the root cause of tissue damage and inflammatory mediator burst.Conclusions: Pain is the most common reason for seeking medical treatment. Despite extensive research efforts and effective analgesics modulating pain, there is still a major therapeutic gap in addressing the root causes of pain. Pain is associated with tissue damage induced by oxidative stress and induction of inflammatory mediators following high consumption of antioxidants. The role of antioxidants in general, and the administration of l-ascorbate in particular, is still controversially discussed and underestimated in the daily clinical practice.The current literature on the therapeutic effect of l-ascorbate, ascorbic acid, and vitamin C on various pain conditions was evaluated against the background of evidence-based medicine. Those articles, obtained from systematic search in PubMed, were critically assessed and rated in terms of evidence level and methodological quality by two independent experts. The primary purpose of this work was to establish specific pain therapy guidance for intravenous l-ascorbate.A PubMed search revealed 14 suitable articles comprising controlled clinical trials and meta-analyses. An additional ten publications could be identified via secondary literature. There is supporting evidence for the efficacy of ascorbate treatment in inflammatory pain conditions, in the complex regional pain syndrome, in post zoster neuralgia, in neuropathic pain, in post-operative pain conditions, and in tumor-related pain. However, the considered studies differ in the type of administration, in dosage, in duration of treatment, as well as in quality of research. Despite all study heterogeneity, it became evident that research of high scientific quality is in support of the efficacy of l-ascorbate in pain treatment.Oxidative stress is present in almost all pain conditions. Because oral administration of most magistral formulas of vitamin C does not provide biological availability, parenteral administration should be preferred and can be supported by an oral dose with high bioavailability on days without intravenous treatment. l-ascorbate should be preferred for parenteral high dosage, rather than ascorbic acid, as it does not release acid valences under physiological conditions.l-ascorbate is an effective, safe, and economically favorable integrative treatment option for various pain conditions, addressing the root cause of tissue damage and inflammatory mediator burst.Graphical Abstract: Pain is the most common reason for seeking medical treatment. Despite extensive research efforts and effective analgesics modulating pain, there is still a major therapeutic gap in addressing the root causes of pain. Pain is associated with tissue damage induced by oxidative stress and induction of inflammatory mediators following high consumption of antioxidants. The role of antioxidants in general, and the administration of l-ascorbate in particular, is still controversially discussed and underestimated in the daily clinical practice.The current literature on the therapeutic effect of l-ascorbate, ascorbic acid, and vitamin C on various pain conditions was evaluated against the background of evidence-based medicine. Those articles, obtained from systematic search in PubMed, were critically assessed and rated in terms of evidence level and methodological quality by two independent experts. The primary purpose of this work was to establish specific pain therapy guidance for intravenous l-ascorbate.A PubMed search revealed 14 suitable articles comprising controlled clinical trials and meta-analyses. An additional ten publications could be identified via secondary literature. There is supporting evidence for the efficacy of ascorbate treatment in inflammatory pain conditions, in the complex regional pain syndrome, in post zoster neuralgia, in neuropathic pain, in post-operative pain conditions, and in tumor-related pain. However, the considered studies differ in the type of administration, in dosage, in duration of treatment, as well as in quality of research. Despite all study heterogeneity, it became evident that research of high scientific quality is in support of the efficacy of l-ascorbate in pain treatment.Oxidative stress is present in almost all pain conditions. Because oral administration of most magistral formulas of vitamin C does not provide biological availability, parenteral administration should be preferred and can be supported by an oral dose with high bioavailability on days without intravenous treatment. l-ascorbate should be preferred for parenteral high dosage, rather than ascorbic acid, as it does not release acid valences under physiological conditions.l-ascorbate is an effective, safe, and economically favorable integrative treatment option for various pain conditions, addressing the root cause of tissue damage and inflammatory mediator burst. [ABSTRACT FROM AUTHOR]

Cannabinoids are multitarget substances. Currently available are dronabinol (synthetic delta-9-tetrahydrocannabinol, THC), synthetic cannabidiol (CBD) the respective substances isolated and purified from cannabis, a refined extract, nabiximols (THC:CBD = 1.08:1.00); and nabilone, which is also synthetic and has properties that are very similar to those of THC. Cannabinoids have a role in the treatment of cancer as palliative interventions against nausea, vomiting, pain, anxiety, and sleep disturbances. THC and nabilone are also used for anorexia and weight loss, whereas CBD has no orexigenic effect. The psychotropic effects of THC and nabilone, although often undesirable, can improve mood when administered in low doses. CBD has no psychotropic effects; it is anxiolytic and antidepressive. Of particular interest are glioma studies in animals where relatively high doses of CBD and THC demonstrated significant regression of tumor volumes (approximately 50% to 95% and even complete eradication in rare cases). Concomitant treatment with X-rays or temozolomide enhanced activity further. Similarly, a combination of THC with CBD showed synergistic effects. Although many questions, such as on optimized treatment schedules, are still unresolved, today's scientific results suggest that cannabinoids could play an important role in palliative care of brain tumor patients. [ABSTRACT FROM AUTHOR]

Objective To evaluate the effectiveness of tapentadol prolonged release (PR) vs. oxycodone/naloxone PR in non-opioid-pretreated patients with severe chronic low back pain with a neuropathic pain component. Methods Eligible patients (average pain intensity [numerical rating scale-3 ( NRS-3)] ≥6; pain DETECT positive/unclear) were randomized to twice-daily tapentadol PR 50 mg or oxycodone/naloxone PR 10 mg/5 mg. After a 21-day titration (maximum twice-daily doses: tapentadol PR 250 mg, or oxycodone/naloxone PR 40 mg/20 mg plus oxycodone PR 10 mg), target doses were continued for 9 weeks. The primary effectiveness endpoint was the change in NRS-3 from baseline to final evaluation; the exact repeated confidence interval ( RCI) for tapentadol PR minus oxycodone/naloxone PR was used to establish noninferiority (upper limit <1.3) and superiority (confirmatory analyses). Results For the primary effectiveness endpoint, tapentadol PR was noninferior to oxycodone/naloxone PR (97.5% RCI: [−1.820, −0.184]; P < 0.001). This exact RCI also yielded evidence of superiority for tapentadol PR vs. oxycodone/naloxone PR (significantly greater reduction in pain intensity; P = 0.003). Improvements (baseline to final evaluation) in pain DETECT and Neuropathic Pain Symptom Inventory scores were significantly greater with tapentadol PR vs. oxycodone/naloxone PR (all P ≤ 0.005). Conclusions The study was formally shown to be positive and demonstrated, in the primary effectiveness endpoint, the noninferiority for tapentadol PR vs. oxycodone/naloxone PR. The effectiveness of tapentadol PR was superior to that of oxycodone/naloxone PR by means of clinical relevance and statistical significance (confirmatory evidence of superiority). Tapentadol PR was associated with significantly greater improvements in neuropathic pain-related symptoms and global health status than oxycodone/naloxone PR and with a significantly better gastrointestinal tolerability profile. Tapentadol PR may be considered a first-line option for managing severe chronic low back pain with a neuropathic pain component. [ABSTRACT FROM AUTHOR]

Introduction: Ganglionic local opioid analgesia (GLOA) at the superior cervical ganglion (SCG) is performed for pain control and is known to be an effective procedure. In this study, we evaluated the spread of the injectate in the area of the SCG. Our expectation was that there would be a correlation between the area and volume of the injectate spread and post-procedural outcome measures. Methods: This was a retrospective blinded review of magnetic resonance imaging (MRI) scans. Assessors evaluated the anatomical area of fluid spread, the furthermost spread from midline, any hampered spread and contact of contrast fluid with other structures. The efficacy of GLOA and complications were estimated. Results: The main solution spread reached from the C1 to C3 vertebrae. The furthest spread in the lateral and sagittal planes was 21.2 and 15.2 mm, respectively. The furthest craniocaudal spread was 63.5 mm. In 53.3% and 33% of interventions, the solution was found in the parapharyngeal space and in its "medial compartment," respectively. A correlation was found between pain relief and both solution spread and volume of solution spread. No hampered spread was recorded. A negative correlation between pain reduction and number of GLOA was observed. Higher pre-procedural pain intensity was correlated with higher pain reduction. We estimated pain relief in 93% of procedures correctly. No correlation between post-procedural Numerical Rating Scale (NRS) scores and different needle approaches was found. Conclusion: For the transoral blocking technique, a strict laterodorsal needle direction is recommended to prevent possible block failures. A total volume of 2 ml injected into the parapharyngeal space and its "medial compartment" is recommended. Higher volumes may lead to uncontrolled distribution patterns. Trial registration: Clinicaltrials.gov identifier NCT05257655; date of registration 2022-02-25; patient enrollment date from 2023-01-09 to 2023-08-31. Plain Language Summary: The injection of low-dose opioids (mainly buprenorphine or sufentanil) to different sympathetic ganglia has been termed "ganglionic local opioid analgesia" (GLOA). This form of therapy has been successfully used for numerous, often protracted diseases that severely impair the patient's quality of life, such as trigeminal neuralgia. For example, as part of a multimodal approach for pain management, GLOA at the superior cervical ganglion should be considered for pain treatment in patients suffering from trigeminal neuralgia with high pre-procedural pain scores. [ABSTRACT FROM AUTHOR]

Background : Additional benefits of passive exposures to intermittent hypoxia and hyperoxia on cognitive performance and functional exercise capacity have been demonstrated in geriatric patients who performed a multimodal training program. The main goal of the present study was to evaluate effects of adding intermittent hypoxic-hyperoxic training (IHHT) to a multimodal training intervention (MTI) on mobility and perceived health in old individuals at a Geriatric Day Hospital. Methods: Thirty-four patients between 64 and 92 years participated in the double blind, randomized and controlled clinical trial. The elderly patients attended in a 5-7 weeks lasting MTI (strength, endurance, balance, reaction, flexibility, coordination, and cognitive exercises) and performed IHHT (breathing 10-14% oxygen for 4-7 min followed by 2–4 min 30–40% oxygen) in the Hypoxic Group (HG) or placebo treatment with ambient air in the Normoxic Group (NG) in parallel. Before and after all treatments, mobility was assessed by the Tinetti Mobility Test (TMT), the Timed-Up-and-Go Test (TUG) and Barthel-Index, while perceived health was assessed by one part of the EQ-5D Test, the EQ visual analogue scale (EQ VAS). Results: After the MTI plus IHHT or normoxia sessions, results of the TMT, TUG, Barthel Index and EQ-VAS revealed no significant difference between HG and NG (+ 14.9% vs + 15.4%, p = 0.25; - 21% vs - 26.3%, p = 0.51; + 4.2% vs+ 3.6%, p = 0.56; + 37.9% vs+ 33.9%, p = 0.24;). Conclusions: IHHT added to MTI did not elicit additional improvements in perceived health and mobility compared to MTI alone. [ABSTRACT FROM AUTHOR]

Introduction: Computed tomography (CT)-guided coeliac plexus neurolysis (CPN) is considered effective at controlling pain in patients with intra-abdominal malignancies. The primary objective was to correlate pain outcomes with the spread of neurolytic solution in the coeliac area and to evaluate the predictive value for the spread of injectate for pain outcomes and side effects. Methods: Blinded CT scans were reviewed. The coeliac area was divided into nine quadrants. Assessors evaluated quadrants according to contrast spread, needle tip position, and the contact between the injectate and other organs and plexuses. Efficacy of CPN and complications were estimated. Results: In 54.9% there was complete spread of the neurolytic in the coeliac area with no correlation between pain relief and spread of injectate. In 85% the neurolytic had contact with viscera with no correlation with pain relief or complications. There was no correlation between needle tip position and spread of the neurolytic and contact of the neurolytic with viscera. In 71.6% the injectate was found to have spread into "other" plexuses. In 13.3% hampered spread of the injectate was observed. There was no correlation between patterns of injectate spread and pain relief, pain relief and spread of injectate in any particular quadrants, and expected and documented post-procedural pain scores. Conclusions: Based on the spread of contrast medium clinicians can neither correctly anticipate the pain relief or post-procedural NRS, nor the duration of pain relief and complications. It is not essential to have the perfect sickle-shaped spread of the injectate for adequate pain control. Plain language summary: CT-guided coeliac plexus neurolysis is considered effective at controlling pain in patients with intra-abdominal malignancies. Based on the spread of contrast medium clinicians can neither correctly anticipate the pain relief or post-procedural NRS, nor the duration of pain relief and complications. It is not essential to have the perfect sickle-shaped spread of the injectate for adequate pain control. [ABSTRACT FROM AUTHOR]

Introduction: Prevalence rates of chronic abdominal pain (CAP) and breakthrough cancer pain (BTcP) are high in patients with intra-abdominal malignancies. As part of a multimodal approach, CT-guided coeliac plexus blockade (CPB) and CT-guided coeliac plexus neurolysis (CPN) are commonly used pain management strategies. The aim of this study was to evaluate pain outcomes among patients with intra-abdominal malignancies who underwent CPB and/or CPN. Methods: Patients with intra-abdominal malignancies who underwent CPB and/or CPN for pain control at the general hospital Klagenfurt am Wörthersee from 2010 to 2019 were enrolled. Results: A total of 84 procedures (24 CPB and 60 CPN) were performed on 52 patients; 62% of these patients had pancreatic cancer. CPN led to significant pain reduction and decreased BTcP intensity. Patients receiving repeated CPN showed higher individual pain reduction. Higher pre-procedural pain intensity was correlated with higher pain reduction. No difference in pain reduction in patients receiving a diagnostic CPB prior to CPN compared to patients without a diagnostic CPB was found. Higher pain reduction after CPN led to longer-lasting pain relief. The time frame from diagnosis to CPN was 472 (± 416) days. Patients experienced a mean duration of pain prior to CPN of 330 (± 53) days. The time frame from diagnosis to CPN was shorter in patients with pancreatic cancer compared to other intra-abdominal malignancies. In 58% of patients pain medication was stable or was reduced after CPN; 16% of patients complained about pain during the procedure; no major complications occurred. There was no correlation between median survival after CPN and pain outcomes. Conclusions: In patients with intra-abdominal malignancy-related CAP, CPN is a safe and effective procedure which can provide long-lasting significant relief of background pain and BTcP. As part of a multimodal approach, CPN should be considered as an earlier option for pain management in these patients. Plain Language Summary: In patients with intra-abdominal malignancy-related abdominal pain, CT-guided coeliac plexus neurolysis is a safe and effective procedure. It can provide long-lasting significant relief of background pain and breakthrough cancer pain. As part of a multimodal approach, coeliac plexus neurolysis should be considered as an earlier option for pain management in patients with intractable abdominal cancer pain. [ABSTRACT FROM AUTHOR]

Chloroprocaine is a short-acting local anaesthetic with a rapid onset of action and an anaesthesia duration up to 60 min. In this pivotal study success rates, onset and remission of motor and sensory block and safety of chloroprocaine 2% was compared to ropivacaine 0.75% for short-duration distal upper limb surgery with successful block rates as primary outcome. The study was designed as a prospective, randomised, multi-centre, active-controlled, double-blind, parallel-group, non-inferiority study, performed in 4 European hospitals with 211 patients scheduled for short duration distal upper limb surgery under axillary plexus block anaesthesia. Patients received either ultrasound guided axillary block with 20 ml chloroprocaine 2%, or with 20 ml ropivacaine 0.75%. Successful block was defined as block without any supplementation in the first 45 min calculated from the time of readiness for surgery. 90.8% patients achieved a successful block with chloroprocaine 2% and 92.9% patients with Ropivacaine 0.75%, thus non-inferiority was demonstrated (10% non inferiority margin; 95% CI − 0.097, 0.039; p = 0.02). Time to onset of block was not significantly different between the groups. Median time to motor and sensory block regression was significantly shorter as was time to home discharge (164 [155–170] min for chloroprocaine versus 380 [209–450] for the ropivacaine group, p < 0.001). For short-duration surgical procedures, the short-acting Chloroprocaine 2% may be used, with success rates non-inferior to ropivacaine and a favourable safety profile. Trial registration: The trial was registered at Clinicaltrials.gov with registration number NCT02385097 (March 11th, 2015) and European Clinical Trial Database with the EudraCT number 2014-002519-40 (July 7th, 2015, Austria—BASG). [ABSTRACT FROM AUTHOR]

This article summarizes recommendations made by six pain specialists who discussed the rationale for ziconotide intrathecal analgesia (ITA) and the requirement for evidence‐based guidance on its use, from a European perspective. Riemser Pharma GmbH (Greifswald, Germany), which holds the European marketing authorization for ziconotide, hosted the meeting. The group agreed that ITA is under‐used in Europe, adding that ziconotide ITA has potential to be a first‐line alternative to morphine; both are already first‐line options in the USA. Ziconotide ITA (initiated using a low‐dose, slow‐titration approach) is suitable for many patients with noncancer‐ or cancer‐related chronic refractory pain and no history of psychosis. Adopting ziconotide as first‐line ITA could reduce opioid usage in these patient populations. The group advocated a risk‐reduction strategy for all candidate patients, including compulsory prescreening for neuropsychosis, and requested US–European alignment of the licensed starting dose for ziconotide: the low‐and‐slow approach practiced in the USA has a better tolerability profile than the fixed high starting dose licensed in Europe. Of note, an update to the European Summary of Product Characteristics is anticipated in early 2021. The group acknowledged that the Polyanalgesic Consensus Conference (PACC) treatment algorithms for ziconotide ITA provide useful guidance, but recommendations tailored specifically for European settings are required. Before a consensus process can formally begin, the group called for additional European prospective studies to investigate ziconotide in low‐and‐slow dosing strategies, in different patient settings. Such data would enable European guidance to have the most appropriate evidence at its core. [ABSTRACT FROM AUTHOR]

A complex inflammatory process mediated by proinflammatory cytokines and prostaglandins commonly occurs in the synovial tissue of patients with joint trauma (JT), osteoarthritis (OA), and rheumatoid arthritis (RA). This study systematically investigated the distinct expression profile of prostaglandin E2 (PGE2), its processing enzymes (COX-2), and microsomal PGES-1 (mPGES-1) as well as the corresponding prostanoid receptor subtypes (EP1-4) in representative samples of synovial tissue from these patients (JT, OA, and RA). Quantitative TaqMan®-PCR and double immunofluorescence confocal microscopy of synovial tissue determined the abundance and exact immune cell types expressing these target molecules. Our results demonstrated that PGE2 and its processing enzymes COX-2 and mPGES-1 were highest in the synovial tissue of RA, followed by the synovial tissue of OA and JT patients. Corresponding prostanoid receptor, subtypes EP3 were highly expressed in the synovium of RA, followed by the synovial tissue of OA and JT patients. These proinflammatory target molecules were distinctly identified in JT patients mostly in synovial granulocytes, in OA patients predominantly in synovial macrophages and fibroblasts, whereas in RA patients mainly in synovial fibroblasts and plasma cells. Our findings show a distinct expression profile of EP receptor subtypes and PGE2 as well as the corresponding processing enzymes in human synovium that modulate the inflammatory process in JT, OA, and RA patients. [ABSTRACT FROM AUTHOR]

Background: The aim of this retrospective analysis was to evaluate the clinical feasibility of the supraclavicular ultrasound‐guided cannulation of the brachiocephalic vein in infants weighing less than 1500 g. Methods: The ultrasound probe was placed in the supraclavicular region so as to obtain the optimum sonographic long‐axis view of the brachiocephalic vein. By using an in‐plane approach the brachiocephalic vein was cannulated by using a 24‐gauge intravenous cannula under real‐time ultrasound guidance into the vein followed by the insertion of a 2‐French single lumen catheter using the Seldinger technique. Results: Forty‐six brachiocephalic vein cannulations in infants weighing between 0.55 and 1.5 kg (Median: 1.2; 95%‐CI: 0.9‐1.2) were included. Ultimate success rate was 89.1% (41 out of 46). One cannulation attempt was required in 30 (65.2%) patients, 2 in 6 (13%) and 3 in 5 (10.8%), respectively. Smaller weight babies did not require significantly more cannulation attempts. The probability of successful cannulation on the first attempt increased significantly from 40% (2010) to more than 80% (2019) over the time course of this series. Median catheter dwell time was 15 days (95%‐CI: 9‐20) with one catheter being removed prematurely after 8 days due to obstruction. Conclusion: Supracalvicular in‐plane real‐time ultrasound‐guided cannulation of the brachiocephalic vein seems to be a convenient and feasible option to provide large‐bore central venous access for very small and sick babies. [ABSTRACT FROM AUTHOR]

Objective: To identify variables that influence pain reduction following peripheral nerve field stimulation (PNFS) in order to identify a potential responder profile. Methods: Exploratory univariate and multivariate (random forest) analyses were performed separately on 2 randomized controlled trials and a registry; all included patients with chronic back pain, mainly failed back surgery syndrome. An international expert panel judged the clinical relevance of variables to identify responders by consensus. Results: Variables identified that may help predict PNFS success in patients with back pain include patient and pain characteristics (age, time since onset of pain and spinal surgery, pain medication history, position and size of pain area, pain severity, mixed nociceptive/neuropathic pain, health‐related quality of life, depression, functional disability, and leg pain status), implant procedure variables (the number and position of leads, paresthesia coverage, and amount of pain relief during the trial), and programming (number of programs, cathodes, and anodes; pulse rate; pulse width; and percentage of device usage). Conclusions: While these analyses are exploratory and restricted to a limited sample size, they suggest variables that may play a role in predicting a therapeutic response. These results, however, are informative only and should be cautiously interpreted. Future research to validate the variables in a clinical study is needed. [ABSTRACT FROM AUTHOR]

Objective: Dysphagia is a common disorder in neurological and non-neurological intensive care unit (ICU) patients and can lead to aspiration pneumonia, prolonged ventilation, and delayed extubation. Dysphagia is an independent predictor of increased mortality. In dysphagic stroke patients with tracheotomy, the use of pharyngeal electric stimulation (PES), an emerging technique to treat dysphagia, has been shown to improve airway protection and shorten time to decannulation. The objective of this study was to determine whether patients who receive PES have a lower prevalence of pneumonia and frequency of reintubation.Design: Secondary analysis of a non-blinded interventional subject sample from a large clinical study with a historical age, pathology, and severity-matched control group.Setting: ICU of a tertiary care medical center.Patients: In this pilot non-blinded study, a group of 15 intubated patients in a general and a neurologic ICU received PES while orally intubated during ICU stay. A control group (n = 25) matched for age, type, and region of pathology, and severity of illness expressed by Simplified Acute Physiology Score and Therapeutic Intervention Scoring System was used to compare for pneumonia and need for reintubation.Main Results: Patients treated with PES had significantly lower prevalence of pneumonia (4 vs 21, p = 0.00046) and frequency of reintubation (0 vs 6, p = 0.046) when compared to controls.Conclusion: Although limited by its small size and non-blinded design, this is the first study demonstrating the benefits of PES in ICU patients still orally intubated, thus offering a potential new method to reduce morbidity, mortality, and economic burden in a mixed ICU population. In order to further investigate and strengthen our findings, a statistically powered, randomized controlled study is recommended. [ABSTRACT FROM AUTHOR]

The importance of arterial oxygen saturation for the prediction of acute mountain sickness (AMS) is still a matter of debate. Reasons for discrepancies may result from varying laboratory or field conditions and their interactions. Thus, we analyzed data from our prior high-altitude studies, including participants of a broad range of age of both sexes (20 males and 20 females, aged between 20 and 67 years) under strictly standardized conditions of pre-exposure and acute exposure to real high altitude (3480 m). A set of resting cardiovascular, respiratory, hematological, and metabolic variables were recorded at high altitude (Testa Grigia, Plateau Rosa, 3480 m; Swiss-Italian boarder) after performing pretests at low altitude (Innsbruck, 600 m, Austria). Our analyses indicate that (1) smaller changes in resting minute ventilation (VE) and a larger decrease of peripheral oxygen saturation (SpO2) during the first 3 hours of acute exposure to high altitude were independent predictors for subsequent development of AMS (90% correct prediction), (2) there are no differences of responses between sexes, and (3) there is no association of responses with age. Considering the independent effects of both responses (VE and SpO2) may be of clinical/practical relevance. Moreover, the presented data derived from a broad age range of both sexes might be of interest for comparative purposes. [ABSTRACT FROM AUTHOR]

Background: The aim of this retrospective analysis was to evaluate the clinical effectiveness of the supraclavicular ultrasound-guided cannulation of the brachiocephalic vein in preterm infants.Methods: The ultrasound probe was placed in the supraclavicular region so as to obtain the optimum sonographic long-axis view of the brachiocephalic vein. By using a strict in-plane approach the brachiocephalic vein was cannulated by advancing a 22- or 24-gauge iv cannula from lateral to medial under the long axis of the ultrasound probe under real-time ultrasound guidance into the vein.Results: One hundred and forty-two cannulations in infants weighing between 0.59 and 2.5 kg (median: 2.1; CI: 2.0 to 2.2) were included. Ultimate success rate was 94% (134 of 142). One cannulation attempt was required in 100 (70%) patients, two attempts in 21 (15%), and three attempts in 13 (9%). The smaller the weight of the infant the more attempts were needed. More attempts also were needed for the right brachiocephalic vein, which was primarily targeted in 75 (53%) neonates. One (1%) inadvertent arterial puncture was noted.Conclusions: This supraclavicular, in-plane, real-time, ultrasound-guided cannulation of the brachiocephalic vein seems to be a convenient and effective method to insert central venous catheters in preterm infants. [ABSTRACT FROM AUTHOR]

Keywords: Altitude; systemic blood pressure; sex differences EN Altitude systemic blood pressure sex differences 1 2 2 08/24/22 20220701 NES 220701 Teaser Proper regulation of the systemic blood pressure is crucial for human health and may be affected in changing environmental conditions, e.g. during high-altitude exposure. Travelling to high altitude, i.e. >2500 m, increases systemic blood pressure (BP) at rest and during exercise in normotensive and hypertensive subjects.[1] Although sex differences in BP regulation are well established,[2] evidence on the interaction with acute high-altitude exposure is scarce. Heart rate (HR) and peripheral oxygen saturation (SpO SB 2 sb ) were determined by finger pulse oximetry (Onyx, NONIN) and systemic BP by the use of a wrist blood pressure monitor (OMRON R3). [Extracted from the article]

Synovial injury and healing are complex processes including catabolic effects by proinflammatory cytokines and anabolic processes by anti-inflammatory mediators. Here we examined the expression of pro- versus anti-inflammatory mediators in synovium of patients with diagnostic arthroscopy (control), joint trauma (JT), osteoarthritis (OA), and rheumatoid arthritis (RA). Synovial samples from these patients were subjected to RT-PCR and double immunofluorescence confocal microscopy of pro- and anti-inflammatory mediators as well as immune cell markers. Interestingly, pro- and anti-inflammatory mediators were expressed predominantly in granulocytes in patients with JT and in macrophages, lymphocytes, and plasma cells in patients with OA and RA. Interestingly, parallel to the severity of inflammation, proinflammatory mediators IL-1β, TNF-α, and 5-LOX specific mRNA as well as immunoreactive (IR) cells were significantly more abundant in patients with RA and JT than in those with OA. However, anti-inflammatory mediators 15-LOX, FPR2, and IL-10 specific mRNA as well as IR cells were significantly more abundant in patients with OA than in those with JT and RA. These findings show that upregulation of proinflammatory mediators contributes to the predominantly catabolic inflammatory process in JT and RA synovium, whereas upregulation of anabolic anti-inflammatory mediators counteracts inflammation resulting in the inferior inflammatory process in OA synovium. [ABSTRACT FROM AUTHOR]

Background The supraclavicular ultrasound ( US)-guided cannulation of the brachiocephalic vein ( BCV) is one option of central venous line placement in infants. Aim The aim of this prospective study was to evaluate whether there was an association between the optimum ultrasonographic view as obtained of the entire longitudinal extension of the right BCV and the ease of supraclavicular cannulation when using a strict in-plane technique via a linear US probe in small infants. Methods The US probe was placed in the right supraclavicular region. If the optimum obtainable sonographic view presented the entire longitudinal extension of the right BCV demonstrating clearly its path caudally alongside the pleura, it was graded as I. If, however, only a circular view, i.e., the initial part of the right BCV was obtainable via US, it was graded as II. The right BCV was cannulated by advancing a 22-gauge i.v. cannula from lateral to medial strictly under the long axis of the US probe under direct US vision into the vein. Results Seventy-nine infants weighing between 0.8 and 4.5 kg (Median: 3.4 ± 0.09) were included. In 50 (63.3%) patients, the sonographic view was graded as I and in 29 (36.7%) as II. The proportion of patients successfully cannulated on the first attempt was significantly smaller in patients graded as II, i.e., circular, sonographic view of the right BCV than in patients graded as I, i.e., sonographic view of the entire longitudinal extension of the right BCV (41% vs 90%; chi-square analysis: P < 0.01). Conclusion The sonographic view obtainable of the entire longitudinal extension of the right BCV resulted in significantly fewer required cannulation attempts. [ABSTRACT FROM AUTHOR]

Annually, thousands of air travellers visit high altitude destinations to enjoy hiking tours to attractions in surrounding areas. However, many of them are not adequately trained, not sufficiently acclimatized and/or may suffer from pre-existing diseases. To prevent adverse health effects and unpleasant experiences at high altitude, simple submaximal exercise testing at low altitude for the prediction of exercise tolerance at high altitude would be helpful. Therefore, 40 healthy males and females performed submaximal exercise tests at low (600 m) and high altitude (3500 m). We demonstrate that exercise tolerance during acute exposure to high altitude can be predicted by the individual heart rate response to submaximal exercise assessed at low altitude. [ABSTRACT FROM AUTHOR]