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Purpose: To assess the technical feasibility, safety, and clinical success rate of trans-arterial embolization (TAE) as an emergency treatment for acute lower gastrointestinal bleeding (LGIB)., Materials and Methods: Consecutive patients who received urgent TAE due to active LGIB at five academic centers in Germany were retrospectively analyzed. LGIB was confirmed and localized using contrast-enhanced computed tomography (CT) or endoscopy. Outcome parameters including technical and clinical success rates as well as ischemia-related adverse events were analyzed. Furthermore, treatment-related variables that may affect technical and clinical success were analyzed using a regression model., Results: One hundred and forty-one patients were included. TAE was performed in 91% (128/141) of patients. In 81% (114/141) of patients, TAE was performed due to active bleeding visible at angiography, the remaining 10% (14/141) underwent empiric embolization based on pre-interventional imaging. In 9% (13/141) of patients, no TAE was performed. Microcoils were the most used embolic 48.5% (62/128), followed by glue 23.5% (30/128) and Microparticles (8%; 10/128). In the case of bleeding visible in angiography, the technical success rate was 100% (114/114); the clinical success rate was 93.6% (120/128). Severe ischemia-related adverse events necessitating bowel surgery occurred in 14% (18/128) of all patients after embolization. Thirty-day mortality was 14% (21/141). Regression analysis revealed no significant correlations but a statistical trend toward a higher incidence of bowel resection when glue was used (p = 0.090) and toward a higher 30-day mortality when an unselective embolization was performed (p = 0.057)., Conclusion: TAE for LGIB has a high technical and clinical success rate. Severe ischemia-related adverse events necessitating bowel surgery occurred in 14% of patients without identifying a significant correlation to the embolization technique or an embolic., Key Points: Question Is trans-arterial embolization (TAE) viable as an emergency treatment for acute lower gastrointestinal bleeding (LGIB)? Findings TAE demonstrated a 100% technical and 93.6% clinical success rate in treating acute LGIB, with severe ischemia-related adverse events occurring in 14% of patients. Clinical relevance TAE is highly effective and has an acceptable complication rate in treating lower gastrointestinal bleeding, emphasizing the need for a direct head-to-head comparison between endovascular and endoscopic therapy., (© 2024. The Author(s).)

Background: Surgery represents the only curative treatment option for pancreatic ductal adenocarcinoma (PDAC), but recurrence in more than 85% of patients limits the success of curative-intent tumor resection. Neural invasion (NI), particularly the spread of tumor cells along nerves into extratumoral regions of the pancreas, constitutes a well-recognized risk factor for recurrence. Hence, monitoring and therapeutic targeting of NI offer the potential to stratify recurrence risk and improve recurrence-free survival. Based on the evolutionary conserved dual function of axon and vessel guidance molecules, we hypothesize that the proangiogenic vessel guidance factor placental growth factor (PlGF) fosters NI. To test this hypothesis, we correlated PlGF with NI in PDAC patient samples and functionally assessed its role for the interaction of tumor cells with nerves., Methods: Serum levels of PlGF and its soluble receptor sFlt1, and expression of PlGF mRNA transcripts in tumor tissues were determined by ELISA or qPCR in a retrospective discovery and a prospective validation cohort. Free circulating PlGF was calculated from the ratio PlGF/sFlt1. Incidence and extent of NI were quantified based on histomorphometric measurements and separately assessed for intratumoral and extratumoral nerves. PlGF function on reciprocal chemoattraction and directed neurite outgrowth was evaluated in co-cultures of PDAC cells with primary dorsal-root-ganglia neurons or Schwann cells using blocking anti-PlGF antibodies., Results: Elevated circulating levels of free PlGF correlated with NI and shorter overall survival in patients with PDAC qualifying for curative-intent surgery. Furthermore, high tissue PlGF mRNA transcript levels in patients undergoing curative-intent surgery correlated with a higher incidence and greater extent of NI spreading to tumor-distant extratumoral nerves. In turn, more abundant extratumoral NI predicted shorter disease-free and overall survival. Experimentally, PlGF facilitated directional and dynamic changes in neurite outgrowth of primary dorsal-root-ganglia neurons upon exposure to PDAC derived guidance and growth factors and supported mutual chemoattraction of tumor cells with neurons and Schwann cells., Conclusion: Our translational results highlight PlGF as an axon guidance factor, which fosters neurite outgrowth and attracts tumor cells towards nerves. Hence, PlGF represents a promising circulating biomarker of NI and potential therapeutic target to improve the clinical outcome for patients with resectable PDAC., (© 2024. The Author(s).)

Objectives: C-C-chemokine receptors (CCRs) are expressed on a variety of immune cells and play an important role in many immune processes, particularly leukocyte migration. Comprehensive preclinical research demonstrated CCR2/CCR5-dependent pathways as pivotal for the pathophysiology of severe COVID-19. Here we report human data on use of a chemokine receptor inhibitor in patients with COVID-19., Methods: Interim results of a 2:1 randomised, placebo-controlled, investigator-initiated trial on the CCR2/CCR5-inhibitor Cenicriviroc (CVC) 150 mg BID orally for 28 d in hospitalised patients with moderate to severe COVID-19 are reported. The primary endpoint is the subject's responder status defined by achieving grade 1 or 2 on the 7-point ordinal scale of clinical improvement on day 15., Results: Of the 30 patients randomised, 18 were assigned to receive CVC and 12 to placebo. Efficient CCR2- and CCR5 inhibition was demonstrated through CCL2 and CCL4 elevation in CVC-treated patients (485% and 80% increase on day 3 compared to the baseline, respectively). In the modified intention-to-treat population, 82.4% of patients (14/17) in the CVC group met the primary endpoint, as did 91.7% (11/12) in the placebo group (OR = 0.5, 95% CI = 0.04-3.41). One patient treated with CVC died of progressive acute respiratory distress syndrome, and the remaining had a favourable outcome. Overall, treatment with CVC was well tolerated, with most adverse events being grade I or II and resolving spontaneously., Conclusions: Our interim analysis provides proof-of-concept data on CVC for COVID-19 patients as an intervention to inhibit CCR2/CCR5. Further studies are warranted to assess its clinical efficacy., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The functional gastrointestinal disorders (FGIDs) have a high prevalence and are associated with high healthcare costs. The diagnosis of these diseases could be difficult and require func-tional tests such as high-resolution manometry (HRM) of the esophagus, anorectal manometry and H2-Breathtests. Due to the COVID-19 Pandemic and the fear of infections there was a marked reduction in the number of performed exams in the last months - nevertheless some exams are necessary, in order to exclude or to diagnose important and dangerous diseases like Achalasia. Goal of this article is to present some new and relevant developments in the field. The HRM of the esophagus is the diagnostic standard for Achalasia, a rare clinical condi-tion associated to dysphagia - new European guidelines suggests a safe strategy in perform-ing the pneumatic dilatation.The intestinal methanogen overgrowth (IMO) is a clinical condition caused by a high production of methane in the small intestine due to overgrowth of Methanobrevibacter smithii, this condition could be in some patients associated with irritable bowel syndrome., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Synchrotron-generated microplanar beams (microbeams) provide the most stereo-selective irradiation modality known today. This novel irradiation modality has been shown to control seizures originating from eloquent cortex causing no neurological deficit in experimental animals. To test the hypothesis that application of microbeams in the hippocampus, the most common source of refractory seizures, is safe and does not induce severe side effects, we used microbeams to induce transections to the hippocampus of healthy rats. An array of parallel microbeams carrying an incident dose of 600 Gy was delivered to the rat hippocampus. Immunohistochemistry of phosphorylated γ-H2AX showed cell death along the microbeam irradiation paths in rats 48 hours after irradiation. No evident behavioral or neurological deficits were observed during the 3-month period of observation. MR imaging showed no signs of radio-induced edema or radionecrosis 3 months after irradiation. Histological analysis showed a very well preserved hippocampal cytoarchitecture and confirmed the presence of clear-cut microscopic transections across the hippocampus. These data support the use of synchrotron-generated microbeams as a novel tool to slice the hippocampus of living rats in a minimally invasive way, providing (i) a novel experimental model to study hippocampal function and (ii) a new treatment tool for patients affected by refractory epilepsy induced by mesial temporal sclerosis.

Background: Cardiovascular Magnetic Resonance (CMR) imaging with adenosine stress is an important diagnostic tool in patients with known or suspected coronary artery disease (CAD). However, the method is not yet established for CAD patients with pacemakers (PM) in clinical practice. A possible reason is that no recommendations exist for PM setting (paused pacing or asynchronous mode) during adenosine stress. We elaborated a protocol for rhythm management in clinical routine for PM patients that considers heart rate changes under adenosine using a test infusion of adenosine in selected patients., Methods: 47 consecutive patients (mean age 72.3 ± 10,0 years) with MR conditional PM and known or suspected CAD who underwent CMR in clinical routine were studied in this prospective observational study. PM indications were sinus node dysfunction (SND, n = 19; 40,4%), atrioventricular (AV) block (n = 26; 55.3%) and bradyarrhythmia in permanent atrial fibrillation (AF, n = 2; 4.3%). In patients with SND, normal AV-conduction and resting HR >45 bpm at the time of CMR and in AF the PM was deactivated for the scan. In intermittent AV-block a test infusion of adenosine was given prior to the scan. All patients with permanent higher degree sinuatrial or AV-block or deterioration of AV-conduction in the adenosine test were paced asynchronously during CMR, in patients with preserved AV-conduction under adenosine the pacemaker was deactivated. CMR protocol included cine imaging, adenosine stress perfusion and late gadolinium enhancement., Results: The adenosine test was able to differentiate between mandatory PM stimulation during CMR and safe deactivation of the device. In patients with permanent sinuatrial or AV-block (n = 11; 23.4%) or deterioration of AV conduction in the adenosine test (n = 5, 10.6%) asynchronous pacing above resting heart rate did not interfere with intrinsic rhythm, no competitive stimulation was seen during the scan. 10 of 15 (66,7%) patients with intermittent AV-block showed preserved AV-conduction under adenosine. As in SND and AF deactivation of the PM showed to be safe during CMR, no bradycardia was observed., Conclusion: Our protocol for rhythm management during adenosine stress CMR showed to be feasible and safe and may be recommended for pacemaker patients undergoing routine CMR.

There are only limited data on the impact of device-related artifacts on image quality in cardiovascular magnetic resonance imaging (CMR) in patients with pacemakers (PM). Adenosine stress perfusion, T1-weighted imaging and flow measurement as well as valve characterization have not been evaluated previously concerning artifact burden. We aimed to assess image quality in all routinely used CMR sequences. We analyzed 2623 myocardial segments in CMR scans of 61 patients with MR conditional PM (mean age 72.1 ± 11.5 years), 23 (37.7%) with right sided, 38 (62.3%) with left-sided devices. There were no relevant artifacts in patients with right-sided devices irrespective of the imaging sequence. In left-sided implants no PM-induced artifacts were found in first pass perfusion sequence, flow analysis and T1 weighted imaging. Only few patients with left-sided devices showed significant PM-artifacts in aortic (3/38, 7.9%)/mitral (n = 2/38, 5.3%) valve imaging and STIR (n = 3/35, 8.6%). In STIR only 14/805 (1.7%) segments were involved. In left-sided PM SSFP cine sequences had more artifact burden than LGE with 377/1505 (25.0%) vs. 162/1505 (10.8%) myocardial segments involved by relevant artifacts respectively (p < 0.001). Apart from cine and LGE imaging in anterior myocardial segments with left-sided implants presence of MRI conditional pacemakers does not affect CMR image quality in multimodal CMR examinations to a significant extent. Our data supports evidence that reduced image quality does not need to be a major concern in PM patients undergoing CMR.

Aim: This study was carried out to evaluate the outcome of patients in different hospitals with the aim to plan future structural and management changes., Methods: All the anaesthesiological and surgical procedures were observed for a 2 weeks period in a major teaching hospital (A), in a major nonteaching hospital (B) and in a minor nonteaching hospital (C) in all the patients requiring anaesthesia. The main and the co-existing diseases and the surgical and anaesthesiological treatments they received were evaluated to determine the outcome. The ASA class, the duration of the procedure, the length of staying in hospital, the transfusions of blood or derivatives, the adverse events for each patient were also observed., Results: The results showed that the patients admitted to the teaching hospital were classified in higher ASA risk classes and had surgery of longer duration, with a higher ratio of major surgery. The outcome was satisfactory in all the 3 hospitals, with a 2 days length of stay respectively in 30% (A and B) and 50% (C) of the patients. The rate of mortality was low: only 3 patients in hospital A and no patient in B and C died in a period of 2 days following surgery. Hospitals B and C showed a large use of modern techniques such as autologous blood transfusion and central and peripheral anaesthetic blocks, with a better cost-benefit ratio than the major teaching hospital., Conclusions: This study showed good results, but it should be repeated in a few years in order to evaluate any change and possible improvement in the management and outcome of the patients.

Methods: 50 ASA I-IV patients (62-90 aged, mean 78.54 +/- 6.48) were submitted to subarachnoidal selective anaesthesia with hyperbaric 1% bupivacaine and morphine for hip surgery. The aim of the study was to evaluate the clinical effectiveness of this anaesthetic technique. Ketamine 0.25 mg/kg and propofol 0.5 mg/kg were administered intravenously before positioning the patients homolaterally to the sick hip. The subarachnoidal puncture was effected at L2-L3 or L3-L4 level with a 22 gauge Quinke or Whitacre needle. The mean dose of bupivacaine was 7.72 +/- 0.81 mg and the mean dose of morphine was 0.23 +/- 0.03 mg. No patient needed general anaesthesia; 3 patients needed small boluses of ketamine and propofol or fentanyl (50 gamma) before the end of surgery. Ephedrine (5 mg) was administered to 5 patients to counteract hypotension by sympathetic block. Only one patient needed extra analgesia up to 8 hours after surgery (Ketorolac 60 mg)., Results: The morphine side effects were 3 cases of itch (6%), 4 cases of drowsiness (8%), 5 cases of nausea and vomiting (10%), 1 case of herpes labialis (2%); the subarachnoidal puncture caused one case of headache., Conclusions: The authors believe that such an easily executable anaesthetic technique is safe enough even in elderly patients.

For monitoring of vecuronium profound neuromuscular blockade post-tetanic count (PTC) following tetanic stimulation at frequency of 50 and 100 Hz was employed in 25 ASA I-II patients submitted to elective surgery, to evaluate the differences between the two patterns of stimulation and the possible clinical utility of the latter pattern of stimulation. The drugs employed for anaesthesia were: diazepam 0.15 mg kg-1 in premedication, thiopental 4-5 mg kg-1 for induction, suxamethonium 1.5 mg kg-1 for tracheal intubation. Anaesthesia was maintained with N2 + O2 (2:1). Analgesia was obtained with fentanyl at usual doses, and muscular relaxation with vecuronium. The ulnar nerve was stimulated at the wrist with Digistim III Plus and the responses evaluated by tactile method. The pattern of stimulation used was a cyclic one, as described by Howardy Hansen et al. The first dose of vecuronium (0.06 mg kg-1) was administered at recovery from suxamethonium (clinically evaluated) and the other doses (0.06 mg kg-1) when the third response to a train of four appeared. The results show that the PTC following 100 Hz tetanus was greater than the PTC following 50 Hz tetanic stimulation (P < 0.01). The results also show that PTC following 100 Hz tetanus leads to underestimate neuromuscular blockade; yet maybe it has any clinical employment in selected surgical situations such as middle ear and eye surgery, microvascular surgery, neurosurgery.

The authors critically examine the preoperative management, the various anaesthetic techniques, the perioperative undesired effects in eighty six ASA I-II paediatric patients (age 6 months-11 years) submitted to ambulatorial anaesthesia for minor surgery or endoscopy. The importance of the psychological approach to patients and parents is enhanced. The preoperative screening included physical examination, ECG and simple laboratory tests. Various anaesthetic techniques (tracheal intubation and muscle relaxation with mechanical ventilation or spontaneous breathing) and many variously combined anaesthetic drugs (propofol 2 mg/kg, ketamine 1.5 mg/kg, diazepam 0.15 mg/kg, thiopental 3-4 mg/kg, halothane 1-2 MAC, fentanyl 1 microgram/kg) were employed depending on the quality of the surgical procedure and the conditions and the age of the patient. The results show that arousal was always rapid and smooth. The residual analgesia was sufficient in 74 cases; the other patients received rectal paracetamol 250 mg. No major complication was observed and only 6 patients were discharged 1 day later on account of vomiting or low Steward score. In conclusion outpatient paediatric anaesthesia has no contraindication for ASA I-II patients, shows no major complication and is well accepted by the patients and their patients.

The authors report their own experience in three cases of paediatric phaeochromocytoma. Before surgery the patients received alpha-adrenergic blocking drugs; two of them also received calcium channels blocking drugs and in one of them was employed a beta-adrenergic blocking drug too. Before surgery the patients received blood and plasma expandera infusions for two weeks. Hypertension during surgery was treated with phentolamine infusion. The employment of an invasive haemodynamic monitoring was very important. The authors believe that such management, already employed in adult patients, is the best choice in paediatric patients too.

The Authors report their own experience in three patients that showed reduced sensitivity to atracurium or vecuronium. Two patients were affected by neoplastic diseases and one by hand trauma. Doses of 0.5 mg/kg of atracurium and 0.08 mg/kg of vecuronium were unable to establish a complete neuromuscular blockade. The Authors review the main clinical situations in which resistance to non-depolarizing muscle relaxants is known: burns, hepatic diseases, chronic therapy with anticonvulsant drugs. Possibly, such events are due to fast elimination of the drug, or to an increased number of acetylcholine nicotinic receptors, or to an unknown acutely acting circulating factor, or to increased binding of the drug to plasma proteins. Up to date, no well-established explanation is available.

Vecuronium bromide was employed in 26 pediatric patients; 18 received vecuronium infusion and 11 intermittent bolus administration. The aim of the study was to evaluate the pharmacodynamics of the drug, the lack of cumulative properties, the best infusion rate, the possible advantage of the infusion technique. Neuromuscular blockade monitoring was performed in all patients. In the results, vecuronium shows lack of cumulative properties. The best infusion rate was 0.13 +/- 0.02 mg/kg/h. The continuous infusion allows the employment of lesser doses of the drug than the intermittent administration.

The authors report personal experience in two patients undergoing thoracotomy after previous pneumonectomy. They examine the risks and the complications of such surgical procedure (right ventricular failure, respiratory failure). Management consists of restriction of liquid infusions, digitalis administration, use of drugs that have little effect on haemodynamics, epidural analgesia by morphine.

Onset time and duration of action were monitored in three groups of 13 patients each, using different patterns of neuromuscular stimulation (single twitch stimulation, STS at 10 sec intervals and train of four, TOF, at 10, and 20 sec intervals) to assess: 1) the correspondence between the single twitch and the first TOF twitch; 2) the importance of the stimulation interval. The results show that onset time is longer and the duration of action is shorter when STS or TOF is used at 20 sec intervals in comparison to TOF at 10 sec intervals.