An Altered Metabolism in Leukocytes Showing in vitro igG Memory From SARS-CoV-2-Infected Patients.

Coronavirus disease 2019 (COVID 19) is a systemic infection that exerts a significant impact on cell metabolism. In this study we performed metabolomic profiling of 41 in vitro cultures of peripheral blood mononuclear cells (PBMC), 17 of which displayed IgG memory for spike-S1 antigen 60-90 days after infection. By using mass spectrometry analysis, a significant up-regulation of S-adenosyl-Homocysteine, Sarcosine and Arginine was found in leukocytes showing IgG memory. These metabolites are known to be involved in physiological recovery from viral infections and immune activities, and our findings might represent a novel and easy measure that could be of help in understanding SARS-Cov-2 effects on leukocytes.

What to Do, and What Not to Do, When Diagnosing and Treating Breakthrough Cancer Pain (BTcP): Expert Opinion.

Clinical management of breakthrough cancer pain (BTcP) is still not satisfactory despite the availability of effective pharmacological agents. This is in part linked to the lack of clarity regarding certain essential aspects of BTcP, including terminology, definition, epidemiology and assessment. Other barriers to effective management include a widespread prejudice among doctors and patients concerning the use of opioids, and inadequate assessment of pain severity, resulting in the prescription of ineffective drugs or doses. This review presents an overview of the appropriate and inappropriate actions to take in the diagnosis and treatment of BTcP, as determined by a panel of experts in the field. The ultimate aim is to provide a practical contribution to the unresolved issues in the management of BTcP. Five 'things to do' and five 'things not to do' in the diagnosis and treatment of BTcP are proposed, and evidence supporting said recommendations are described. It is the duty of all healthcare workers involved in managing cancer patients to be mindful of the possibility of BTcP occurrence and not to underestimate its severity. It is vital that all the necessary steps are carried out to establish an accurate and timely diagnosis, principally by establishing effective communication with the patient, the main information source. It is crucial that BTcP is treated with an effective pharmacological regimen and drug(s), dose and administration route prescribed are designed to suit the particular type of pain and importantly the individual needs of the patient.

The prevention of analgesic opioids abuse: expert opinion.

Opioids are drugs of reference for the treatment of moderate to severe pain. Their proper use and a periodic assessment of the patient are crucial to prevent misuse. A multidisciplinary group suggests strategies for all stakeholders involved in the management of pain and suggests the importance of the doctor-patient relationship.

Opioid risk addiction in the management of chronic pain in primary care: the addition risk questionnaire.

OBJECTIVE: Chronic pain is one of the most common complaints for people seeking medical care, with a series of potential detrimental effects on the individual and his social texture. Despite the heavy impact of chronic pain on patients' quality of life, epidemiological data suggest that chronic pain is often untreated or undertreated. An accurate diagnostic flow and appropriate treatment should be considered as key factors for optimal management of patients with chronic pain. Opioids are recommended for treatment of chronic cancer pain (CCP) and chronic non-cancer pain (CNCP) in guidelines and can safely and effectively relieve pain in a number of patients with chronic pain. Conversely, fears of addiction and adverse events could result in ineffective pain management. Recent epidemiological and clinical data demonstrate that only low percentages of patients treated with opioids for chronic pain have a risk to develop addiction, with a prevalence rate similar to that observed in the general population. METHODS: Despite the iatrogenic risk can be considered as low, validated tools for the early identification of patients at higher risk of addiction can help health professionals in the overall management of chronic pain. CONCLUSIONS: Due to the increasing relevance of primary care physicians in chronic pain management, we propose a 28-item questionnaire to validate specifically conceived for GPs' and aimed at the preliminary evaluation of the risk of addiction in patients with chronic pain.

Intrathecal 1% 2-chloroprocaine vs. 0.5% bupivacaine in ambulatory surgery: a prospective, observer-blinded, randomised, controlled trial.

BACKGROUND: This prospective, observer-blinded, randomised, multicentre study aimed at determining the non-inferiority of 50 mg of plain 1% 2-chloroprocaine vs. 10 mg of 0.5% plain bupivacaine in terms of sensory block onset time at T10 after spinal injection. The study hypothesis was that the difference in onset times of sensory block to T10 between the two drugs is ≤ 4 min. METHODS: One hundred and thirty patients undergoing lower abdominal or lower limb procedures (≤ 40 min) were randomised to receive one of two treatments: 50 mg of plain 1% 2-chloroprocaine (Group C, n = 66) or 10 mg of plain 0.5% bupivacaine (Group B, n = 64). Times to sensory and motor block onsets, maximum sensory block level, readiness for surgery, regression of sensory and motor blocks, first analgesic requirements, unassisted ambulation, home discharge, and side effects after 24 h and 7 days were registered blindly. RESULTS: Chloroprocaine was comparable with plain 0.5% bupivacaine in terms of time to sensory block at T10 level. Group C showed faster onsets of motor block (5 vs. 6 min), maximum sensory block level (8.5 vs. 14 min), resolution of sensory (105 vs. 225 min) and motor (100 vs. 210 min) blocks, unassisted ambulation (142.5 vs. 290.5 min), first analgesic requirement (120 vs. 293.5 min), and home discharge (150 vs. 325 min) (all comparisons, P < 0.05). No chloroprocaine patient developed transient neurological symptoms. CONCLUSION: Spinal anaesthesia with 50 mg of plain 1% 2-chloroprocaine is similar to 10 mg of plain 0.5% bupivacaine in terms of onset of sensory block at T10 but shows quicker recovery from anaesthesia than with 0.5% bupivacaine.

Pilot double-blinded study to assess efficacy and tolerability of morphine sulphate oral solution (Oramorph®) given preoperatively as add-on therapy within a multimodal postoperative pain approach in patients undergoing laparoscopic cholecystectomy.

BACKGROUND: This study aims at investigating the effect of a single pre-operative oral administration of morphine sulphate (Oramorph®) on pain after laparoscopic cholecystectomy (LC). METHODS: Forty-one ASA I-III patients, aged 18-65 years, undergoing LC were randomly, double-blindly allocated to treatment (N.=20, 30mg Oramorph®, group M) or placebo (N.=21, group P). General anesthesia was maintained with propofol and remifentanil. All patients received ketamine 0.2 mg/kg iv at induction, intraoperative ketorolac 30mg iv and tramadol postoperatively (iv PCA: bolus 50 mg, lock-out 30 min, max 100 mg/4 hours). Numerical rating scale for pain (NRS), White's fast track and PADSS scores, tramadol consumption and adverse events were recorded for the first 24h. All patients underwent State Trait Anxiety Inventory (STAI) and Mini Mental State Examination (MMSE). RESULTS: Anthropometric characteristics, MMSE, STAI, ASA status, NRS rest, White's and PADDS scores, PONV incidence were similar. Group M showed significantly lower NRS on movement during the first 3 hours after awakening. Cumulative tramadol consumption was lower in group M than in group P (185±142 mg versus 263±199 mg, P=0.199). CONCLUSION: Within a multimodal approach, a single preoperative oral administration of 30 mg of morphine sulphate in patients undergoing LC did not improve pain at rest, but improved NRS on movement during the first 3 hours after awakening. Group P required a higher mean dose of tramadol compared to Group M, although not significantly. The safety profile of Oramorph® allowed fast extubation and awakening times as well as prompt home discharge within 6 hours from surgery.

Ectopic expression of FSH receptor isoforms in neoplastic but not in endothelial cells from pancreatic neuroendocrine tumors.

FSH receptor (FSHR) expression is restricted to gonads, where it drives FSH-dependent cell differentiation; in addition, FSHR plays an important role in the regulation of ovarian angiogenesis. Recently, FHSR expression has been shown in blood vessels of various tumors. However, pancreatic neuroendocrine tumors (p-NET), which have high-degree blood supply, were not included in that study. The aim of this study was to evaluate FSHR expression in p-NET. FSHR expression was evaluated in tumor samples from 30 patients with p-NET by immunohistochemistry and Western blot; fluorescence microscopy was used to localize FSHR in specific cells from tissue samples. von Willebrand factor (vWF) and chromograninA (chrA) was used as blood vessel and NET cells marker, respectively, to co-localize FSHR. FSHR expression was detected in all p-NET by immunohistochemistry. Western blot confirmed FSHR expression on p- NET although different FSHR isoforms, ranging from 240 kD to 55 kD were found in the samples studied. Surprisingly, FSHR co-localized with chrA but not with vWF, suggesting that neoplastic cells of neuroendocrine origin rather than blood vessels expressed FSHR. No relationship was found between degree of FSHR expression and histology of p-NET. FSHR may be aberrantly expressed in neoplastic cells from p-NET and not in tumor blood vessels; however, its biological significance as well as its clinical relevance remains to be elucidated.

Treatment of a transorbital penetrating injury: a particular endovascular approach.

The management of craniocerebral penetrating injury currently represents a challenge for neurosurgeons and neuroradiologists and requires innovative planning. This report describes the case of a worker admitted to hospital with an intracranial piece of concrete-cutting saw stuck through the right eye. At the time of admission the patient was conscious and this fact influenced the choice of a particular approach. This patient escaped without neurological deficit or complications, except for the inevitable removal of an eye.

Prospective randomized comparison of ultrasound-guided and neurostimulation techniques for continuous interscalene brachial plexus block in patients undergoing coracoacromial ligament repair.

BACKGROUND: There are few data comparing the onset time of interscalene brachial plexus block performed using ultrasound (US) guidance or nerve stimulation (NS) technique for elective coracoacromial ligament repair. METHODS: Fifty ASA I-III patients were randomly allocated to receive a continuous interscalene brachial plexus block with 20 ml of 1% ropivacaine with either NS or US guidance. The time of block performance, number of skin punctures and needle redirections, inadvertent vascular punctures, and procedure-related pain scores were recorded. The onsets of sensory and motor blocks in the distribution of radial, axillary, and musculocutaneous nerves were blindly assessed every 5 min until 30 min from the end of local anaesthetic (LA) injection. Intraoperative fentanyl, general anaesthesia (GA) requirements, postoperative pain scores, LA consumption, and patients' requirements for subcutaneous morphine during the first 24 h were compared. RESULTS: Block onset times were similar. The time to complete the block and the number of skin punctures and vascular punctures were significantly lower in Group US. There were no differences in needle redirections, incidence of paraesthesiae, intraoperative fentanyl consumption, and requirements for GA or postoperative morphine. The US group required significantly less LA only at 16 h after surgery and had lower pain scores at rest at 24 h after surgery. CONCLUSIONS: Block onset times and success rate were similar whether NS or US was used, although US guidance allowed shorter procedural times, fewer needle punctures, and fewer vascular punctures.

Tramadol and 0.5% levobupivacaine for single-shot interscalene block: effects on postoperative analgesia in patients undergoing shoulder arthroplasty.

BACKGROUND: The aim of this study was to evaluate the efficacy of tramadol as an adjuvant to the local anaesthetic solution in patients undergoing shoulder arthroscopy for rotator cuff tear after middle interscalene block (MIB). METHODS: We enrolled 120 patients (ASA I-II), scheduled for arthroscopic surgery for rotator cuff tear. The patients were sedated with midazolam 0.02 mg/kg and haloperidol 2 mg i.v. before performing MIB. All subjects underwent a MIB with 0.4 mL/kg of 0.5% levobupivacaine. After computerized randomization, all patients were allocated in 1 of 3 groups, each including 40 subjects. Group Placebo (Group P) received 0.4 mL/kg of 0.5% levobupivacaine plus isotonic sodium chloride for MIB and isotonic sodium chloride i.m. Group "Perineural Tramadol" (Group TPN) received 0.4 ml/Kg of 0.5% levobupivacaine plus 1.5 mg/kg of tramadol perineurally and isotonic sodium chloride i.m. Group "Intramuscular Tramadol" (Group TIM) received 0.4 ml/Kg of 0.5% levobupivacaine plus isotonic sodium chloride perineurally and 1.5 mg/kg of tramadol i.m. RESULTS: The MIB onset times were not statistically different in the three groups. The duration of analgesia was significantly longer in Groups TPN and TIM, where tramadol was administered, either i.m. or perineurally, compared with the placebo group. A significant statistical difference was found in the duration of analgesia between the group TPN and TIM. CONCLUSION: The addition of tramadol to the local anaesthetic solution administered for MIB provided a longer duration of analgesia compared with placebo and i.m tramadol administration in patients undergoing arthroscopic surgery for rotator cuff tear.

The nerve stimulation technique versus the loss of resistance technique for the posterior approach to lumbar plexus block: a randomized, prospective, observer-blinded, pilot study.

BACKGROUND: This prospective, randomized, observer-blinded, pilot study compares the effects of the nerve stimulation guidance technique (NS) with the loss of resistance technique (LOR) on readiness for surgery during the posterior approach to lumbar plexus block. METHODS: Thirty ASA status I-III patients who were 18-85 years old and who were undergoing hip fracture repair were enrolled. After parasacral sciatic nerve block, patients were randomly allocated to receive a continuous posterior lumbar plexus block using nerve stimulation (n=15) or a continuous psoas compartment block using the loss of resistance technique (n=15) with 20 ml of 1.5% mepivacaine. A blinded observer monitored for sensory and motor block onsets every 5 minutes. We defined readiness for surgery as complete numbness to the pinprick test and complete motor block on the surgical side. If incomplete, the lumbar plexus block was supplemented with 10 mL of 1.5% mepivacaine through the catheter before surgery. Intraoperative fentanyl or general anesthesia requirements, pain scores, local anesthetic consumption, morphine requirements for breakthrough pain and side effects were monitored. RESULTS: The mean time to readiness for surgery was 12±6 min Group NS and 22±6 min in Group LOR (P=0.03). Three patients in Group NS and 9 patients in Group LOR required additional boluses of local anesthetic through the lumbar plexus catheter before surgery (P=0.113). CONCLUSION: Nerve stimulation allowed faster readiness for surgery than loss of resistance. Nevertheless, the two techniques seem to be comparable in terms of local anesthetic consumption, morphine requirements and pain scores.

Intrathecal atropine to prevent postoperative nausea and vomiting after Cesarean section: a randomized, controlled trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common adverse effect of intrathecal morphine, especially after Cesarean section. This randomized controlled trial investigated the effects of intrathecal administration of a small-dose of atropine on postoperative nausea and vomiting after Cesarean section. METHODS: Parturients with ASA physical status class I-II scheduled for elective Cesarean section and consenting to spinal anesthesia were enrolled. They received 0.5% hyperbaric bupivacaine 12.5 mg, morphine 200 µg and one of the following three solutions: atropine 100 µg intrathecally and saline intravenously; saline intrathecally and atropine 100 µg intravenously; saline only both intravenously and intrathecally. We examined the incidence and severity of PONV, pain ratings and the need for analgesics. RESULTS: We followed 204 parturients. The incidence of PONV was 15%, 37% and 49% in the three groups, respectively (P<0.001). The relative risk reduction for PONV when using intrathecal atropine was 69% vs. placebo and 59% vs. intravenous atropine. No differences were noted in terms of postoperative pain. CONCLUSION: Intrathecal atropine had a significant antiemetic effect, making it a useful adjunct for intrathecal opioid-related PONV.