Transitional Pain Service: An Update.

PURPOSE OF REVIEW: Chronic Postsurgical Pain (CPSP) and the risk for long-term opioid dependency are known complications following major surgery. The idea of Transitional Pain Service (TPS) has been introduced as an interdisciplinary setting to manage pain in the perioperative continuum. We expand on the basic framework and principles of TPS and summarize the current evidence of the TPS and possible interventions to adress postoperative pain. Areas of future work in TPS-related research are discussed. RECENT FINDINGS: Several studies support the effectiveness of TPS in reducing opioid consumption in the perioperative period and following discharge. Some studies also show an improvement in functional outcome with TPS with patients reporting lower pain severity and pain interference. The TPS aims to halt the progress of acute postoperative pain to CPSP by providing longitudinal support with patient-centered care. While some studies suggest a positive impact of TPS implementation in terms of reduction in postoperative opioid consumption and improvement of some functional outcomes, direct evidence in terms of reduction in the incidence of CPSP is still missing. The cost-effectiveness of TPS and the expansion of TPS through e-health services and digital applications also need to be evaluated.

Multicentric pilot study to standardize clinical whole exome sequencing (WES) for cancer patients.

A growing number of druggable targets and national initiatives for precision oncology necessitate broad genomic profiling for many cancer patients. Whole exome sequencing (WES) offers unbiased analysis of the entire coding sequence, segmentation-based detection of copy number alterations (CNAs), and accurate determination of complex biomarkers including tumor mutational burden (TMB), homologous recombination repair deficiency (HRD), and microsatellite instability (MSI). To assess the inter-institution variability of clinical WES, we performed a comparative pilot study between German Centers of Personalized Medicine (ZPMs) from five participating institutions. Tumor and matched normal DNA from 30 patients were analyzed using custom sequencing protocols and bioinformatic pipelines. Calling of somatic variants was highly concordant with a positive percentage agreement (PPA) between 91 and 95% and a positive predictive value (PPV) between 82 and 95% compared with a three-institution consensus and full agreement for 16 of 17 druggable targets. Explanations for deviations included low VAF or coverage, differing annotations, and different filter protocols. CNAs showed overall agreement in 76% for the genomic sequence with high wet-lab variability. Complex biomarkers correlated strongly between institutions (HRD: 0.79-1, TMB: 0.97-0.99) and all institutions agreed on microsatellite instability. This study will contribute to the development of quality control frameworks for comprehensive genomic profiling and sheds light onto parameters that require stringent standardization.

Complex Regional Pain Syndrome (CRPS) and the Value of Early Detection.

PURPOSE OF REVIEW: The goal of this narrative review is to describe the current understanding of the pathology of Complex Regional Pain Syndrome (CRPS), as well as diagnostic standards and therapeutic options. We will then make the case for early recognition and management. RECENT FINDINGS: CRPS remains an enigmatic pain syndrome, comprising several subtypes. Recent recommendations clarify diagnostic ambiguities and emphasize the importance of standardized assessment and therapy. Awareness of CRPS should be raised to promote prevention, early detection, and rapid escalation of therapy in refractory cases. Comorbidities and health costs (i.e., the socioeconomic impact) must also be addressed early to prevent negative consequences for patients.

Intravenous acetaminophen does not reduce morphine use for pain relief in emergency department patients: A multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Pain is one of the main reasons to present to emergency departments (EDs). Opioids are indispensable for acute pain management but are associated with side effects, misuse, and dependence. The aim of this study was to test whether a single dose of intravenous (IV) acetaminophen (paracetamol) can reduce the use of morphine for pain relief and/or morphine-related adverse events (AEs). METHODS: ED patients >18 years with acute pain (i.e., Numeric Rating Scale [NRS] > 4) were screened for eligibility. Patients with analgesia in the past 6 h, chronic pain, or clinical instability were excluded. Patients were randomized in a 1:1 ratio to receive either morphine 0.1 mg/kg and 1 g acetaminophen IV or morphine 0.1 mg/kg and placebo IV. The intervention was double-blinded. Additional morphine 0.05 mg/kg IV was administered every 15 minutes until pain relief (defined as NRS < 4) and whether the pain recurred. The primary outcome was the mean morphine dose for pain relief. Secondary outcomes were the total amount of morphine given, time to achieve pain relief, and AEs. RESULTS: A total of 220 patients were randomized and 202 evaluated for the primary outcome. The mean morphine dose for pain relief was similar in both groups (acetaminophen 0.15 mg ± 0.07 mg/kg, placebo 0.16 ± 0.07 mg/kg). There were no differences in the total amount of morphine given (acetaminophen 0.19 ± 0.09 mg/kg, placebo 0.19 ± 0.1 mg/kg), the time to achieve pain relief (acetaminophen 30 min [95% CI 17-31 min], placebo 30 min [95% CI 30-35 min]), and the frequency of AEs (overall 27.4%). Time to pain recurrence did not differ significantly between the groups (hazard ratio 1.23 [0.76-1.98], p = 0.40). CONCLUSIONS: In ED patients, acetaminophen had no additional effect on pain control or morphine-sparing effect at the time of first morphine administration. Titrated morphine with the algorithm used was highly effective, with 80% of all patients reporting pain relief within 60 min of starting therapy.

Novel 0D-nanocarbon-silica ceramic composites: sol-gel synthesis and high-temperature evolution.

Herein we report the synthesis of novel 0D-nanocarbon-based silicon-containing ceramic composites by a facile salt-free synthesis method followed by polymer-to-ceramic transformation. 0D-nanocarbon-silica composites were synthesized via a one-pot sol-gel process using tetramethyl orthosilicate (TMOS) and functionalized nanodiamonds and converted subsequently via pyrolysis under an argon atmosphere into nanodiamond/silica nanocomposites. The thermal conversion of the nanodiamond phase to a multilayer fullerene phase was carefully investigated by integral and local characterization methods such as vibrational spectroscopy, X-ray diffraction, BET, SEM and HRTEM. The incorporation of nanodiamonds in a silica matrix enhances the crystallization temperature of the silica phase, as α-cristobalite, to 1500 °C, while their full graphitization is shifted to T > 1700 °C under an argon atmosphere. The thermal decomposition of the nanodiamond/silica composites leads to the formation of materials with a high specific surface area (up to 562 m2 g-1) and a mesoporous structure. No carbothermal reaction of composing phases was identified. The results obtained in the present study allow for designing advanced and highly-defined mesoporous 0D-nanocarbon-containing composites with tailored structural features and multifunctional property profiles.

Intradural non-calcified thoracic disc herniation causing spontaneous intracranial hypotension: a case report.

BACKGROUND: Spontaneous intracranial hypotension (SIH) is a rare pathology caused by a cerebrospinal fluid (CSF) leak. If intractable by conventional methods (i.e. bedrest, analgesics, or epidural blood patching) it may lead to the inability of the patient to cope with daily life and eventually to life-threatening complications. Recently, calcified discogenic microspurs or dorsal osteophytes were identified as a major cause for ventral CSF loss through vertical longitudinal dural slits. We report a rare case of intractable SIH due to an intradural disc herniation at the thoracolumbar junction (without signs of calcification) and its management. CASE PRESENTATION: A 46-year old woman suffered from orthostatic headache (sudden onset, no history of trauma) due to intractable SIH for over 2 month (without neurologic deficits). There was no clinical amelioration by conservative measures (analgesics, bedrest) and serial unspecific epidural blood patches (repeated for 3 times). She was diagnosed with an intradural disc herniation at the thoracolumbar junction causing a CSF leak. Surgical exploration by a translaminar and transdural approach with removal of the disc herniation and closure of the CSF leak was performed with immediate cessation of orthostatic symptoms. Histological workup revealed non-calcified intervertebral disc material. After 3 months of follow-up and no evidence for clinical relapse the patient returned to work. CONCLUSIONS: We report the rare phenomenon of an intradural non-calcified disc sequester at the thoracolumbar junction as the cause of a ventral dural tear leading to a CSF leak with intractable SIH. This is of particular interest as the major cause of ventral dural leakage is thought to arise from calcified discogenic microspurs or dorsal osteophytes. Furthermore, we comprehensively describe a short and reasonable diagnostic and surgical approach of this rare pathology, which may particularly be of use in daily clinical routine in neurological wards and general surgical spine centers not facing such pathologies on a regular basis.

[The preanaesthetic care of patients with renal disorder]. / Präoperative Betreuung des nierenkranken Patienten.

The preoperative evaluation of patients with renal disease does not begin with the anaesthesiologist's visit, but with the evaluation and care given by the primary physician. To decrease postoperative morbidity and mortality, an optimal preoperative preparation is essential. The kidney is highly sensitive to perioperative hypoperfusion. Basically the medullary oxygenation with its high rate of oxygen extraction (about 79% of the delivered oxygen) is vulnerable to hypoxia, which may lead to acute tubular necrosis. The main goal of perioperative care is to avoid hypoperfusion and therefore hypoxia of the kidney. A perioperative equalized intravascular fluid balance (normovolaemia) seems to be the most effective strategy to prevent postoperative renal dysfunction. On the other side, the anaesthesia management depends on the renal function. The dosage of anaesthetics must be adapted to an impaired renal capacity. Accurate assessment of the renal function relies on laboratory determinations. The most useful laboratory tests are those related to the glomerular filtration rate (GFR), which represents the renal function. The measurement of the creatinine clearance is the most precise method available for clinically assessing overall renal function (really GFR). Measurement of creatinine clearance by 24-hour urine collection is uncomfortable and highly error-prone. For the estimation of GFR, the use of the Cockroft-Gault or the MDRD (Modification of Diet in Renal Disease) formula is recommended. The renal impairment is grouped according to the glomerular function, estimated by the named formula. Other important parameters to estimate the effects of an advanced renal dysfunction are the haemoglobin and the serum concentration of potassium and sodium. If possible, elective operative interventions should be carried out during a stable phase of the disease. Appropriate treatment of concomitant symptoms, such as hypertonia, is essential and contributes to a reduction of post operative renal dysfunction. Timely consultation with the responsible anaesthesist can prevent unnecessary delay of the intervention.

Evaluation of a standardized internet-based and telephone-based patient monitoring system for pain therapy with transdermal fentanyl.

The aim of the present observational 4-week study was to document the feasibility and utility of telephone-based or Internet-based pain monitoring in patients with chronic cancer or noncancer pain, such as nociceptive or neuropathic pain, using transdermal fentanyl. Pain intensity, treatment tolerability, activities of daily living, quality of life, and patient and physician satisfaction were evaluated in 60 (60% women, 42% opioid-naive) chronic pain patients who were switched from oral pain therapy to transdermal fentanyl therapy because of persisting severe pain. When the total dataset of all patient entries was analyzed, treatment with transdermal fentanyl led to decreases in maximal and mean pain scores as reported by the patients (-14% and -19%, respectively, last observation carried forward vs. baseline). Pain reduction was more pronounced in opioid-naive than in opioid-experienced patients (-35% and -25% vs. baseline, respectively; P=0.03). Overall, impairment of daily activities was reduced by 23% with transdermal fentanyl. No effect was observed with regard to quality of life and use of rescue pain medication. Transdermal fentanyl was generally well tolerated. Most patients (60%) preferred the telephone-based to the Internet-based or Internet combined with telephone questionnaires. Patient preference was driven by age, whereby younger patients tended to prefer the Internet and older patients the telephone (mean age, 45 and 54 y, respectively; difference n.s.). Internet-based and telephone-based monitoring of the efficacy and tolerability of opioid treatment for chronic pain was feasible in daily practice and generally well accepted by patients and physicians. Future research will determine the relative contribution of these 2 new options for patient-physician interaction and delineate their role in improving chronic pain control.

Rac and Cdc42 play distinct roles in regulating PI(3,4,5)P3 and polarity during neutrophil chemotaxis.

Neutrophils exposed to chemoattractants polarize and accumulate polymerized actin at the leading edge. In neutrophil-like HL-60 cells, this asymmetry depends on a positive feedback loop in which accumulation of a membrane lipid, phosphatidylinositol (PI) 3,4,5-trisphosphate (PI[3,4,5]P3), leads to activation of Rac and/or Cdc42, and vice versa. We now report that Rac and Cdc42 play distinct roles in regulating this asymmetry. In the absence of chemoattractant, expression of constitutively active Rac stimulates accumulation at the plasma membrane of actin polymers and of GFP-tagged fluorescent probes for PI(3,4,5)P3 (the PH domain of Akt) and activated Rac (the p21-binding domain of p21-activated kinase). Dominant negative Rac inhibits chemoattractant-stimulated accumulation of actin polymers and membrane translocation of both fluorescent probes and attainment of morphologic polarity. Expression of constitutively active Cdc42 or of two different protein inhibitors of Cdc42 fails to mimic effects of the Rac mutants on actin or PI(3,4,5)P3. Instead, Cdc42 inhibitors prevent cells from maintaining a persistent leading edge and frequently induce formation of multiple, short lived leading edges containing actin polymers, PI(3,4,5)P3, and activated Rac. We conclude that Rac plays a dominant role in the PI(3,4,5)P3-dependent positive feedback loop required for forming a leading edge, whereas location and stability of the leading edge are regulated by Cdc42.