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.

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.

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.

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.

Dose reduction in multislice CT by means of bismuth shields: results of in vivo measurements and computed evaluation.

PURPOSE: We investigated the amount of patient dose reduction in the thyroid, lens of the eye and the breast when using bismuth protections in multislice computed tomography (CT) exams as well as their influence on the quality of diagnostic images. MATERIALS AND METHODS: The radiation dose was measured by using thermoluminescence dosimeters. The study was conducted on the two CT scanners installed in our radiology department (64 and eight slices). The shield effects on the CT image were evaluated by measuring the signal-to-noise ratio in a phantom and in vivo, and by verifying the presence of artefacts on patients' images. The obtained organ-dose reduction factors were used to evaluate the effects of shielding on the effective dose. RESULTS: The shielding attenuation ranged from 30% to 60% depending on the CT scan protocols and organs. The difference between shielded and unshielded signal-to-noise ratio was statistically significant but within the standard requirements for quality assurance. Results were in agreement with the radiologists' perception of image quality. The use of the shields allowed up to 38% reduction of effective dose. CONCLUSIONS: Use of bismuth shields significantly decreases both organ and effective radiation dose, with a consequent reduction in health risk for the patient, quantified in 1.4 fewer cases of radiation-induced tumours every 5 years in our centre (12,100 exams/year), in agreement with the risk factors proposed by Publication 60 of the International Commission on Radiological Protection (ICRP). The relative inexpensiveness of these protections, their easy application and their substantial lack of influence on image quality suggest their massive introduction into routine clinical practice.

Intrathecal ropivacaine 5 mg/ml for outpatient knee arthroscopy: a comparison with lidocaine 10 mg/ml.

PURPOSE: The aim of this prospective, randomised, blind study was to compare the evolution of spinal block produced with 50 mg lidocaine 10 mg/ml and 10 mg ropivacaine 5 mg/ml for outpatient knee arthroscopy. METHODS: Thirty outpatients undergoing knee arthroscopy received 50 mg of lidocaine 10 mg/ml (n=15) or 10 mg of ropivacaine 5 mg/ml (n=15) intrathecally. The evolution of spinal block was recorded until home discharge, while the occurrence of transient neurologic symptoms (TNS) was evaluated through phone-call follow-ups. RESULTS: The median onset time was 15 (10-21) min with lidocaine and 24 (11-37) min with ropivacaine (P=0.109). Spinal lidocaine resulted in a faster resolution of sensory block [148 (130-167) min vs. 188 (146-231) (P=0.022)], unassisted ambulation with crutches [176 (144-208) min vs. 240 (179-302) min (P=0.014)], and voiding [208 (163-254) min vs. 293 (242-343) min (P=0.001)] than ropivacaine. Recovery of motor function required 113 (95-131) min with lidocaine and 135 (87-183) with ropivacaine (P=0.219). Six lidocaine patients reported TNS (40%) as compared with no patient receiving ropivacaine (0%) (P=0.005). CONCLUSIONS: Spinal block produced with 10 mg ropivacaine 5 mg/ml is as effective as that produced by 50 mg of lidocaine 10 mg/ml. Recovery of unassisted ambulation and spontaneous voiding occurred earlier with lidocaine, but this was associated with a markedly higher incidence of TNS.

Continuous lumbar epidural infusion of levobupivacaine: effects of small-or large-volume regimen of infusion.

BACKGROUND: The question of whether the dose, concentration or volume of a local anesthetic solution is the relevant determinant of the spread and quality of post-operative epidural analgesia is still open. In this prospective, randomized, double-blind study, we compared the effects of a large volume-low concentration with a small-volume-high-concentration lumbar epidural infusion of levobupivacaine. METHODS: Seventy patients scheduled for total hip replacement were enrolled. After surgery, patients were randomly allocated to receive a continuous epidural infusion of levobupivacaine (10.5 mg/h) using either 0.125% levobupivacaine infused at 8.4 ml/h (low concentration group, n=35) or 0.75% levobupivacaine infused at 1.4 ml/h (high concentration group, n=35). We blindly recorded the degree of pain relief at rest and during movement every 8 h for the first two post-operative days, as well as hip flexion, motor block, rescue analgesic consumption and adverse events. RESULTS: No difference in pain relief was observed between groups as estimated with the areas under the curve of the verbal Numerical Rating Scale for pain over time, both at rest and during movement. Similarly, there was no difference between groups in hip flexion degree, motor blockade and hemodynamic stability. CONCLUSIONS: Continuous lumbar epidural infusion of 0.75% levobupivacaine was as effective as continuous lumbar epidural infusion of 0.125% levobupivacaine, when administered at the same hourly dose of 10.5 mg, in achieving adequate analgesia both at rest and during movement, without differences in the incidence of hypotension and motor blockade.

Ultrasound vs nerve stimulation multiple injection technique for posterior popliteal sciatic nerve block.

In this prospective, randomised, observer-blinded study we evaluated whether ultrasound guidance can shorten the onset time of popliteal sciatic nerve block as compared to nerve stimulation with a multiple injection technique. Forty-four ASA I-III patients undergoing posterior popliteal sciatic nerve block with 20 ml of 0.75% ropivacaine were randomly allocated to nerve stimulation or ultrasound guided nerve block. A blinded observer recorded onset of sensory and motor blocks, success rates, the need for fentanyl intra-operatively, the requirement for general anaesthesia, procedure-related pain, patient satisfaction and side-effects. Onset times for sensory and motor blocks were comparable. The success rate was 100% for ultrasound guided vs 82% for nerve stimulation (p = 0.116). Ultrasound guidance reduced needle redirections (p = 0.01), were associated with less procedural pain (p = 0.002) and required less time to perform (p = 0.002). Ultrasound guidance reduced the time needed for block performance and procedural pain.

Effectiveness and safety of a novel gel dressing in the management of neuropathic leg ulcers in diabetic patients: a prospective double-blind randomized trial.

Neuropathic leg ulcers (NLUs) affect more than 10% of diabetic patients with peripheral neuropathy and represent the most common cause of ulceration of the leg in these patients. Though their pathogenesis is well known, related to the chronic neuropathic edema, the management of NLUs, mainly based on elastocompression, is still controversial, with lower healing rates than nondiabetic venous leg ulcers. The authors tested if a novel gel formulation, containing amino acids and hyaluronic acid (Vulnamin)gel; Errekappa, Milan, Italy), will improve the outcomes of NLUs when used together with elastocompression. Thirty patients affected by NLU were randomized into 2 groups, both treated with 4-layer elastocompressive bandaging: patients in group A were topically treated with the application of Vulnamin) gel, whereas patients in group B received only the inert gel vehicle. The healing rate at 3 months was evaluated as the primary endpoint, whereas the secondary endpoints were healing time, reduction in ulcer area and ulceration score in 4 weeks, number of infective complications, and overall satisfaction of patients. Healing rate was significantly (P < .05) higher in patients in group A when compared with those in group B; healing time, patients' satisfaction, and reduction in ulcer area and ulceration score in 4 weeks were also higher in patients in group A. However, no significant differences were found in the prevalence of infections and other adverse events. The use of Vulnamin) gel with elastocompression is safe and effective in the management of NLUs of diabetic patients.

Antiangiogenic and anticolorectal cancer effects of metronomic irinotecan chemotherapy alone and in combination with semaxinib.

Metronomic chemotherapy refers to the administration of chemotherapy at low, nontoxic doses on a frequent schedule with no prolonged breaks. The aim of the study is to rationally develop a CPT-11 metronomic regimen in preclinical settings of colon cancer. In vitro cell proliferation, apoptosis and thrombospondin-1/vascular endothelial growth factor (TSP-1/VEGF) expression analyses were performed on endothelial (HUVEC, HMVEC-d) and colorectal cancer (HT-29, SW620) cells exposed for 144 h to metronomic concentrations of SN-38, the active metabolite of CPT-11. HT-29 human colorectal cancer xenograft model was used, and tumour growth, microvessel density and VEGF/TSP-1 quantification was performed in tumours. In vitro and in vivo combination studies with the tyrosine inhibitor semaxinib were also performed. SN-38 preferentially inhibited endothelial cell proliferation alone and interacted synergistically with semaxinib; it induced apoptosis and increased the expression and secretion of TSP-1. Metronomic CPT-11 alone and combined with semaxinib significantly inhibits tumour growth in the absence of toxicity, which was accompanied by decreases in microvessel density and increases in TSP-1 gene expression in tumour tissues. In vitro results show the antiangiogenic properties of low-concentration SN-38, suggesting a key role of TSP-1 in this effect. In vivo, the CPT-11 metronomic schedule is effective against tumour and microvessel growth without toxic effect on mice.

Fibrinolysis or hypercoagulation during radical prostatectomy? An evaluation of thrombelastographic parameters and standard laboratory tests.

BACKGROUND AND OBJECTIVES: Radical prostatectomy is at high risk for intraoperative and postoperative bleeding due to surgical trauma, release of urokinase and tissue type plasminogen activator. We conducted this prospective, observational multi-centre study to assess the degree of systemic fibrinolysis or hypercoagulation in the perioperative period. We studied serial changes in standard laboratory values and in thrombelastographic (TEG; Haemoscope Corporation, Skokie, IL, USA) parameters including lysis at 30 and 60 min (LY-30, LY-60), alpha-angle (alpha) and maximum amplitude. METHODS: In all, 49 patients undergoing radical retropubic prostatectomy in five Italian University Hospitals were included. Blood samples were taken before surgery (T1), at the removal of the prostate (T2), 4 h after surgery (T3) and then 1 day after surgery (T4). Native blood samples were analysed using a thrombelastograph Haemoscope 5000 (Haemoscope Corporation). RESULTS: We did not see any relevant activation of fibrinolysis during any stage. Intraoperatively, we showed even more activated blood coagulation with consumption of fibrinogen and a reduced TEG percentage clot lysis. Only at the first postoperative sample point we saw a trend towards a more fibrinolytic state indicated by increasing partial thromboplastin time, LY-30 and LY-60 values, and a peak of the fibrin degradation product D-dimers. This is consistent with a normal reaction to the hypercoagulable state before and is unlikely to be due to an intraoperative tissue type plasminogen activator release. We found no evidence of an uncontrolled activation of fibrinolysis on the day after surgery. On the contrary, alpha-values which indicate the rate of clot formation and which increase during hypercoagulation showed the tendency to rise slightly compared with the preoperative value. CONCLUSION: Neither standard coagulation parameters nor TEG values showed any significant activation of fibrinolysis or of hypercoagulation in the preoperative period. Nevertheless, hypercoagulation seems to have a substantial clinical impact as it has been shown that cardiovascular complications and pulmonary embolism were the most common causes of death after retropubic prostatectomy.

Pyrazinoate excretion in the chimpanzee. Relation to urate disposition and the actions of uricosuric drugs.

These experiments were designed to define the renal disposition of pyrazinoic acid in a nonhuman primate that is phylogenetically close to man and to relate this to the effects of pyrazinoate on urate excretion. The renal clearance of pyrazinoate was almost always greater than the simultaneous glomerular filtration rate at plasma concentrations ranging from 1.9 to 960 mug/ml. Some inhibitors of tubular secretion, probenecid, MK-282 (an experimental, potent uricosuric drug), p-aminohippurate, iodopyracet, sulfinpyrazone, and mersalyl, reduced clearances of pyrazinoate to values far below filtration rate. Chlorothiazide, allopurinol, and salicylate did not. The clearance of pyrazinoate was not influenced by changes in urine flow. It is concluded that pyrazinoate is actively secreted and actively reabsorbed. Pyrazinoate had a dual effect on urate excretion. At concentrations in plasma less than 10 mug/ml there was a concentration related fall in urate/inulin clearance ratio, reaching values of 10-20% of control. Over the range of 10-100 mug/ml in plasma, the clearance of urate remained maximally depressed. At higher concentrations of pyrazinoate there was a concentration related increase in urate/inulin clearance ratio such that at pyrazinoate levels above 600 mug/ml a definite uricosuric response was obtained. Prior administration of pyrazinoate to give plasma levels of 20-140 mug/ml completely or almost completely prevented uricosuric responses to probenecid, PAH, chlorothiazide, and sulfinpyrazone. Iodopyracet, mersalyl, salicylate and N-acetyl-4-dibutylsulfamoyl-3-trifluoromethylbenzenesulfonamide (MK-282) retained significant uricosuric action, but the activities were probably less than normal. The results are consistent with a model of urate transport involving high rates of bidirectional transtubular flux.

Does clonidine 50 microg improve cervical plexus block obtained with ropivacaine 150 mg for carotid endarterectomy? A randomized, double-blinded study.

STUDY OBJECTIVE: To evaluate the effects of adding 50 microg clonidine to 150 mg ropivacaine for superficial cervical plexus block in patients undergoing elective carotid endarterectomy (TEA). DESIGN: Randomized, double-blind study. SETTING: Departments of Anesthesia and Vascular Surgery of a university hospital. PATIENTS: 40 ASA physical status II and III patients undergoing elective TEA during superficial cervical plexus block. INTERVENTIONS: Superficial cervical plexus block was placed using 20 mL of 0.75% ropivacaine alone (Ropi group, n = 20) or with the addition of 50 microg clonidine (Ropi-Clonidine group, n = 20). If required, analgesic supplementation was given with local infiltration with 1% lidocaine and intravenous fentanyl (50-microg boluses). Nerve block profile, need for intraoperative analgesic supplementation, and time to first analgesic request were recorded. MEASUREMENTS AND MAIN RESULTS: Median (range) onset time was 10 minutes (5-25 min) in the Ropi group and 5 minutes (5-20 min) in the Ropi-Clonidine group (P < 0.05). Intraoperative consumption of both 1% lidocaine and fentanyl was higher in patients of the Ropi group (15 mL [0-25 mL] and 250 microg [50-300 microg]) than in patients of the Ropi-Clonidine group (8 mL [0-20 mL] and 0 microg [0-150 microg]; P < 0.05 and P < 0.05, respectively). First postoperative analgesic request occurred after 17 hours (10-24 hrs) in the Ropi group and 20 hours (10-24 hrs) in the Ropi-Clonidine group (P > 0.05). CONCLUSIONS: Adding 50 microg clonidine to 150 mg ropivacaine for superficial cervical plexus block shortened the onset time and improved the quality of surgical anesthesia in patients undergoing elective TEA.

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.

Does intracellular sodium regulate sodium transport across the mucosal surface of frog skin?

A method has been devised to functionally remove the serosal membrane of frog skin. Skins treated in this way have no spontaneous potential. However, if sodium gradients are placed across the tissues diffusion potentials and hence short-circuit currents of either sign, depending on the direction of the gradient, could be recorded. These short-circuit currents were completely imhibited by amiloride only from the mucosal face. However, the concentration of amiloride causing 50% inhibition of the short-circuit curent (Km) in treated skins was 2.3 . 10(-3)M, when a sodium gradient was applied from serosa to mucosa, whereas both in untreated skins without a sodium gradient and in treated skins with a mucosal to serosal sodium gradient, the Km of amiloride was 2 . 10(-7)-4 . 10(-7)M. The mechanism by which amiloride is able to inhibit the short-circuit currents of either sign is discussed.

Electroencephalographic background desynchronization during cerebral blood flow reduction.

OBJECTIVE: The aim of this study is to evaluate the usefulness of a spectral function detecting cerebral hypoperfusion. METHODS: Continuous electroencephalographic monitoring was employed during 47 consecutive carotid endarterectomies. Patients were assigned to 3 different groups according to the entity of electroencephalographic changes during carotid clamping (major changes: group A; moderate changes: group B; no change: group C). The desynchronization function, indicating the reduction of the 8-15 Hz band power, and the desynchronization index were calculated. RESULTS: Group A function decreased within 20s from clamping, with a constant slope (7.14). Desynchronization indexes were: 76.85% (group A), 40.23% (group B) and 15.29% (group C). Difference among groups was statistically significant (P < 0.0001). A case of syncope due to asystole is also reported, showing the same pattern in the descending phase of the function. CONCLUSIONS: The stereotyped time course of the desynchronization function describes the cerebral reaction to significant blood flow reduction. Values of desynchronization index exceeding 65% seem to correctly detect patients with cerebral hypoxic risk. SIGNIFICANCE: The analysis of the 8-15 Hz band desynchronization is helpful in the evaluation of cerebral hypoperfusion during carotid endarterectomy. This method could be employed in monitoring different clinical situations of ischemia.

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.