Decoding the muscle transcriptome of patients with late onset Pompe disease reveals markers of disease progression.

Late-onset Pompe Disease (LOPD) is a rare genetic disorder caused by the deficiency of acid alpha-glucosidase leading to progressive cellular dysfunction due to the accumulation of glycogen in the lysosome. The mechanism of relentless muscle damage - a classic manifestation of the disease - has been extensively studied by analysing the whole muscle tissue; however, little, if any, is known about transcriptional heterogeneity among nuclei within the multinucleated skeletal muscle cells. This is the first report of application of single nuclei RNA sequencing to uncover changes in the gene expression profile in muscle biopsies from eight patients with LOPD and four muscle samples from age and gender matched healthy controls. We matched these changes with histology findings using GeoMx Spatial Transcriptomics to compare the transcriptome of control myofibers from healthy individuals with non-vacuolated (histologically unaffected) and vacuolated (histologically affected) myofibers of LODP patients. We observed an increase in the proportion of slow and regenerative muscle fibers and macrophages in LOPD muscles. The expression of the genes involved in glycolysis was reduced, whereas the expression of the genes involved in the metabolism of lipids and amino acids was increased in non-vacuolated fibers, indicating early metabolic abnormalities. Additionally, we detected upregulation of autophagy genes, and downregulation of the genes involved in ribosomal and mitochondrial function leading to defective oxidative phosphorylation. The upregulation of the genes associated with inflammation, apoptosis and muscle regeneration was observed only in vacuolated fibers. Notably, enzyme replacement therapy - the only available therapy for the disease - showed a tendency to restore metabolism dysregulation, particularly within slow fibers. A combination of single nuclei RNA sequencing and spatial transcriptomics revealed the landscape of normal and the diseased muscle, and highlighted the early abnormalities associated with the disease progression. Thus, the application of these two new cutting-edge technologies provided insight into the molecular pathophysiology of muscle damage in LOPD and identified potential avenues for therapeutic intervention.

Effect of avalglucosidase alfa on disease-specific and general patient-reported outcomes in treatment-naïve adults with late-onset Pompe disease compared with alglucosidase alfa: Meaningful change analyses from the Phase 3 COMET trial.

BACKGROUND: The Phase 3 COMET trial (NCT02782741) comparing avalglucosidase alfa and alglucosidase alfa included health-related quality of life (HRQoL) assessments in treatment-naïve patients with late-onset Pompe disease (LOPD). Here, we further characterize results from disease-specific and general patient-reported outcome (PRO) measures. METHODS: Adults who participated in the COMET trial receiving avalglucosidase alfa or alglucosidase alfa (both 20 mg/kg biweekly) during the 49-week double-blind treatment period were included in the analysis. Proportions of patients exceeding meaningful change thresholds at Week 49 were compared post hoc between treatment groups. PROs and their meaningful change thresholds included: Pompe Disease Severity Scale (PDSS; decrease 1.0-1.5 points), Pompe Disease Impact Scale (PDIS; decrease 1.0-1.5 points), Rasch-built Pompe-specific Activity Scale (R-PAct; change from unable to able to complete activity), 12-item Short Form Health Survey (SF-12; physical component summary [PCS] score: increase ≥6 points, mental component summary [MCS] score: increase ≥7 points), EuroQol 5 Dimension 5 Level (EQ-5D-5L; improvement of ≥1 category), and Patient Global Impression of Change (PGIC; any improvement). RESULTS: The analysis included 99 adult patients (avalglucosidase alfa n = 50; alglucosidase alfa n = 49). Patients who received avalglucosidase alfa had significantly greater odds of achieving a meaningful change versus alglucosidase alfa for the PDSS Shortness of Breath (OR [95% CI] 11.79 [2.24; 62.18]), Fatigue/Pain (6.24 [1.20; 32.54]), Morning Headache (13.98 [1.71; 114.18]), and Overall Fatigue (5.88 [1.37; 25.11]) domains, and were significantly more likely to meet meaningful change thresholds across multiple PDSS domains (all nominal p < 0.05). A numerically greater proportion of patients in the avalglucosidase alfa group were able to complete selected activities of the R-PAct compared with the alglucosidase alfa group. Significantly greater proportions of patients who received avalglucosidase alfa achieved meaningful improvements for EQ-5D-5L usual activities dimension, EQ visual analog scale, and all four PGIC domains. The proportion of patients with improvements in SF-12 PCS and MCS was greater in the avalglucosidase alfa group versus alglucosidase alfa group, but was not significant (p > 0.05). CONCLUSIONS: These analyses show that avalglucosidase alfa improves multiple symptoms and aspects of daily functioning, including breathing and mobility. This supports the clinical relevance of the effects of avalglucosidase alfa on HRQoL for patients with LOPD.

A strategic neurological research agenda for Europe: Towards clinically relevant and patient-centred neurological research priorities.

BACKGROUND AND PURPOSE: Neurological disorders constitute a significant portion of the global disease burden, affecting >30% of the world's population. This prevalence poses a substantial threat to global health in the foreseeable future. A lack of awareness regarding this high burden of neurological diseases has led to their underrecognition, underappreciation, and insufficient funding. Establishing a strategic and comprehensive research agenda for brain-related studies is a crucial step towards aligning research objectives among all pertinent stakeholders and fostering greater societal awareness. METHODS: A scoping literature review was undertaken by a working group from the European Academy of Neurology (EAN) to identify any existing research agendas relevant to neurology. Additionally, a specialized survey was conducted among all EAN scientific panels, including neurologists and patients, inquiring about their perspectives on the current research priorities and gaps in neurology. RESULTS: The review revealed the absence of a unified, overarching brain research agenda. Existing research agendas predominantly focus on specialized topics within neurology, resulting in an imbalance in the number of agendas across subspecialties. The survey indicated a prioritization of neurological disorders and research gaps. CONCLUSIONS: Building upon the findings from the review and survey, key components for a strategic and comprehensive neurological research agenda in Europe were delineated. This research agenda serves as a valuable prioritization tool for neuroscientific researchers, as well as for clinicians, donors, and funding agencies in the field of neurology. It offers essential guidance for creating a roadmap for research and clinical advancement, ultimately leading to heightened awareness and reduced burden of neurological disorders.

Improving outcome measures in late onset Pompe disease: Modified Rasch-Built Pompe-Specific Activity scale.

BACKGROUND AND PURPOSE: The Rasch-Built Pompe-Specific Activity (R-PAct) scale is a patient-reported outcome measure specifically designed to quantify the effects of Pompe disease on daily life activities, developed for use in Dutch- and English-speaking countries. This study aimed to validate the R-PAct for use in other countries. METHODS: Four other language versions (German, French, Italian, and Spanish) of the R-PAct were created and distributed among Pompe patients (≥16 years old) in Germany, France, Spain, Italy, and Switzerland and pooled with data of newly diagnosed patients from Australia, Belgium, Canada, the Netherlands, New Zealand, the USA, and the UK and the original validation cohort (n = 186). The psychometric properties of the scale were assessed by exploratory factor analysis and Rasch analysis. RESULTS: Data for 520 patients were eligible for analysis. Exploratory factor analysis suggested that the items separated into two domains: Activities of Daily Living and Mobility. Both domains independently displayed adequate Rasch model measurement properties, following the removal of one item ("Are you able to practice a sport?") from the Mobility domain, and can be added together to form a "higher order" factor as well. Differential item functioning (DIF)-by-language assessment indicated DIF for several items; however, the impact of accounting for DIF was negligible. We recalibrated the nomogram (raw score interval-level transformation) for the updated 17-item R-PAct scale. The minimal detectable change value was 13.85 for the overall R-PAct. CONCLUSIONS: After removing one item, the modified-R-PAct scale is a valid disease-specific patient-reported outcome measure for patients with Pompe disease across multiple countries.

Brain health and national neurological societies: Results of the European Academy of Neurology survey on brain health awareness and areas of implementation for European countries.

BACKGROUND AND PURPOSE: The European Academy of Neurology (EAN) has adhered to the global plan for reducing the burden of neurological disorders and promoting brain health launched by the World Health Organisation (WHO), the WHO Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders. This study reports the results of an EAN survey among national neurological societies (NNSs) on their awareness of brain health policies. METHODS: The EAN survey on the current state of national brain health policies was conducted among the 47 presidents of the NNSs affiliated with the EAN, with the aim of developing the best strategy for close collaboration among stakeholders. RESULTS: From June 2023 to February 2024, 36/47 responses (77%) were collected. Among respondents, 67% were in contact with their Ministry of Health and 78% were aware of and in contact with one or more national neurological patient organisation, while 17% had no contacts with any association. Ninety-two percent declared a high to medium degree of awareness of the need to support brain health and of brain health plans and strategies in their country. CONCLUSIONS: Our findings suggest good awareness of the importance of brain health and of the strategies implemented at the national level among the EAN-affiliated NNSs and representatives. Efforts towards improvement may be directed towards cooperation between NNSs and political institutions, as well as patient organisations, to optimise brain and global public health and neurological care in each country.

Start, switch and stop (triple-S) criteria for enzyme replacement therapy of late-onset Pompe disease: European Pompe Consortium recommendation update 2024.

BACKGROUND AND PURPOSE: Two novel enzyme replacement therapies (ERTs), studied in phase 3 trials in late-onset Pompe patients, reached marketing authorization by the European Medicines Agency in 2022 and 2023. The European Pompe Consortium (EPOC) updates and extends the scope of the 2017 recommendations for starting, switching and stopping ERT. METHODS: The European Pompe Consortium consists of 25 neuromuscular and metabolic experts from eight European countries. This update was performed after an in-person meeting, three rounds of discussion and voting to provide a consensus recommendation. RESULTS: The patient should be symptomatic, that is, should have skeletal muscle weakness or respiratory muscle involvement. Muscle magnetic resonance imaging findings showing substantial fat replacement can support the decision to start in a patient-by-patient scenario. Limited evidence supports switching ERT if there is no indication that skeletal muscle and/or respiratory function have stabilized or improved during standard ERT of 12 months or after severe infusion-associated reactions. Switching of ERT should be discussed on a patient-by-patient shared-decision basis. If there are severe, unmanageable infusion-associated reactions and no stabilization in skeletal muscle function during the first 2 years after starting or switching treatment, stopping ERT should be considered. After stopping ERT for inefficacy, restarting ERT can be considered. Six-monthly European Pompe Consortium muscle function assessments are recommended. CONCLUSIONS: The triple-S criteria on ERT start, switch and stop include muscle magnetic resonance imaging as a supportive finding and the potential option of home infusion therapy. Six-monthly long-term monitoring of muscle function is highly recommended to cover insights into the patient's trajectory under ERT.

Continuous stellate ganglion block for ventricular arrhythmias: case series, systematic review, and differences from thoracic epidural anaesthesia.

AIMS: Percutaneous stellate ganglion block (PSGB) through single-bolus injection and thoracic epidural anaesthesia (TEA) have been proposed for the acute management of refractory ventricular arrhythmias (VAs). However, data on continuous PSGB (C-PSGB) are scant. The aim of this study is to report our dual-centre experience with C-PSGB and to perform a systematic review on C-PSGB and TEA. METHODS AND RESULTS: Consecutive patients receiving C-PSGB at two centres were enrolled. The systematic literature review follows the latest Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. Our case series (26 patients, 88% male, 60 ± 16 years, all with advanced structural heart disease, left ventricular ejection fraction 23 ± 11%, 32 C-PSGBs performed, with a median duration of 3 days) shows that C-PSGB is feasible and safe and leads to complete VAs suppression in 59% and to overall clinical benefit in 94% of cases. Overall, 61 patients received 68 C-PSGBs and 22 TEA, with complete VA suppression in 63% of C-PSGBs (61% of patients). Most TEA procedures (55%) were performed on intubated patients, as opposed to 28% of C-PSGBs (P = 0.02); 63% of cases were on full anticoagulation at C-PSGB, none at TEA (P < 0.001). Ropivacaine and lidocaine were the most used drugs for C-PSGB, and the available data support a starting dose of 12 and 100 mg/h, respectively. No major complications occurred, yet TEA discontinuation rate due to side effects was higher than C-PSGB (18 vs. 1%, P = 0.01). CONCLUSION: Continuous PSGB seems feasible, safe, and effective for the acute management of refractory VAs. The antiarrhythmic effect may be accomplished with less concerns for concomitant anticoagulation compared with TEA and with a lower side-effect related discontinuation rate.

Distribution of Exonic Variants in Glycogen Synthesis and Catabolism Genes in Late Onset Pompe Disease (LOPD).

Pompe disease (PD) is a monogenic autosomal recessive disorder caused by biallelic pathogenic variants of the GAA gene encoding lysosomal alpha-glucosidase; its loss causes glycogen storage in lysosomes, mainly in the muscular tissue. The genotype-phenotype correlation has been extensively discussed, and caution is recommended when interpreting the clinical significance of any mutation in a single patient. As there is no evidence that environmental factors can modulate the phenotype, the observed clinical variability in PD suggests that genetic variants other than pathogenic GAA mutations influence the mechanisms of muscle damage/repair and the overall clinical picture. Genes encoding proteins involved in glycogen synthesis and catabolism may represent excellent candidates as phenotypic modifiers of PD. The genes analyzed for glycogen synthesis included UGP2, glycogenin (GYG1-muscle, GYG2, and other tissues), glycogen synthase (GYS1-muscle and GYS2-liver), GBE1, EPM2A, NHLRC1, GSK3A, and GSK3B. The only enzyme involved in glycogen catabolism in lysosomes is α-glucosidase, which is encoded by GAA, while two cytoplasmic enzymes, phosphorylase (PYGB-brain, PGL-liver, and PYGM-muscle) and glycogen debranching (AGL) are needed to obtain glucose 1-phosphate or free glucose. Here, we report the potentially relevant variants in genes related to glycogen synthesis and catabolism, identified by whole exome sequencing in a group of 30 patients with late-onset Pompe disease (LOPD). In our exploratory analysis, we observed a reduced number of variants in the genes expressed in muscles versus the genes expressed in other tissues, but we did not find a single variant that strongly affected the phenotype. From our work, it also appears that the current clinical scores used in LOPD do not describe muscle impairment with enough qualitative/quantitative details to correlate it with genes that, even with a slightly reduced function due to genetic variants, impact the phenotype.

Prevalence, clinical features, and radiological pattern of artery of Percheron infarction: a challenging diagnosis.

PURPOSE: Occlusion of artery of Percheron (AOP), a rare variant of paramedian branches of posterior cerebral artery, results in a characteristic pattern of ischemic lesions in bilateral paramedian thalami with or without midbrain and anterior thalami involvement. AIM: To evaluate the prevalence, the clinical, and the imaging features of AOP infarction in a single comprehensive stroke center experience. METHODS: We retrospectively search in our stroke center database, patients with ischemic lesions in the AOP distribution. We collected clinical features and time between hospital admission and diagnosis. Imaging findings were categorized following a pre-selected classification. RESULTS: Of 2830 ischemic stroke admitted in our center, we identified 15 patients with AOP infarction (0.53%). Clinical manifestations were variable, but oculomotor disturbances, particularly vertical gaze palsy, were the most observed, followed by consciousness impairment, varying from drowsiness to coma. The most frequent imaging pattern was bilateral paramedian thalamic infarction with midbrain infarction, and the V-sign was recognized in 6 cases from this group. In 8 patients a fetal origin of the PCA was observed. The average time from first hospital admission to diagnosis was 28.09 h. CONCLUSIONS: The prevalence of AOP infarction in our center was 0.53%. Diagnosis of AOP infarction can be challenging and should be suspected in case of sudden altered consciousness.

Contactin 1, a Potential New Antigen Target in Membranous Nephropathy: A Case Report.

Several novel antigens have recently been characterized in membranous nephropathy (MN), but those involved in the rare cases of MN associated with inflammatory neuropathies remain elusive. Although several antibodies have been identified in the serum, there is no evidence so far for their deposition in glomeruli. We report the case of a 73-year-old woman who was referred because of subacute onset of proximal asymmetric lower limb weakness together with ataxic gait. She was diagnosed with inflammatory neuropathy. Testing showed an estimated glomerular filtration rate of 73mL/min/1.73m2, hypoalbuminemia (2.89g/dL), and proteinuria (3.6g/d). Autoantibodies (antinuclear antibody, anti-extractable nuclear antigen antibody, anti-double stranded DNA antibody, lupus anticoagulant, anticardiolipin antibody, antineutrophil cytoplasmic antibody) were undetectable. Serum immunoglobulin and complement levels were normal. A kidney biopsy with electron microscopy examination showed a classical picture of MN. Testing for antibodies to phospholipase A2 receptor (PLA2R) gave negative results in the serum, and PLA2R and THSD7A antigens were not detected in kidney tissue. Anti-contactin 1 (CNTN1) antibody was detected by enzyme-linked immunosorbent assay at a 1:100 dilution of serum and shown to be mostly of IgG4 subclass by Western blot. CNTN1 antigen was colocalized with IgG4 within immune deposits by confocal microscopy. This observation suggests a pathophysiological link between inflammatory neuropathies and MN. CNTN1 should be considered as a potential candidate antigen involved in MN and tested in PLA2R-negative forms associated with inflammatory neuropathies.

European Academy of Neurology guidance for developing and reporting clinical practice guidelines on rare neurological diseases.

BACKGROUND AND PURPOSE: Rare diseases affect up to 29 million people in the European Union, and almost 50% of them affect the nervous system or muscles. Delays in diagnosis and treatment onset and insufficient treatment choices are common. Clinical practice guidelines (CPGs) may improve the diagnosis and treatment of patients and optimize care pathways, delivering the best scientific evidence to all clinicians treating these patients. Recommendations are set for developing and reporting high-quality CPGs on rare neurological diseases (RNDs) within the European Academy of Neurology (EAN), through a consensus procedure. METHODS: A group of 27 experts generated an initial list of items that were evaluated through a two-step Delphi consensus procedure and a face-to-face meeting. The final list of items was reviewed by an external review group of 58 members. RESULTS: The consensus procedure yielded 63 final items. Items are listed according to the domains of the AGREE instruments and concern scope and purpose, stakeholder involvement, rigour of development, and applicability. Additional items consider reporting and ethical issues. Recommendations are supported by practical examples derived from published guidelines and are presented in two tables: (1) items specific to RND CPGs, and general guideline items of special importance for RNDs, or often neglected; (2) items for guideline development within the EAN. CONCLUSIONS: This guidance aims to provide solutions to the issues specific to RNDs. This consensus document, produced by many experts in various fields, is considered to serve as a starting point for further harmonization and for increasing the quality of CPGs in the field of RNDs.

Preaponeurotic endoscopic repair (REPA) of diastasis recti: a single surgeon's experience.

BACKGROUND: Diastasis recti is a pathology that affects not only the abdominal wall but also the stability of lumbopelvic muscles, consequently altering urinary and digestive functionality. Preaponeurotic endoscopic repair (REPA) is an endoscopic alternative to tummy tuck for the treatment of diastasis. In this study, the outcomes of REPA application by a single surgeon are presented. METHODS: A total of 172 patients underwent REPA for the treatment of diastasis recti between August 2017 and December 2019. One hundred twenty-four patients were followed for at least one year. Sixty-three patients responded to a survey on satisfaction and quality of life 12 months after surgery. RESULTS: Three (2.4%) recurrences occurred, of which two occurred in the same patient. The main postoperative complications observed were 12 (9.7%) seromas, 3 (2.4%) haematomas, a single wound infection, 3 (2.4%) cases of skin fold formation, and a case of trophic skin lesion that required negative pressure therapy. Quality of life after surgery, as reported by 63 patients who responded to the survey, was satisfactory. CONCLUSIONS: REPA is a safe and effective technique for diastasis recti treatment, representing a valid alternative to abdominoplasty. Since there is no need to access the peritoneal cavity and the mesh is onlay, there are no risks of bowel damage or adhesions between the intestine and prosthesis.

Sleep and sleep-modifying factors in chronic migraine patients during the COVID-19 lockdown.

AIMS: The objective of the present study was to evaluate sleep features and sleep-modifying factors in patients with chronic migraine (CM) during the first Italian COVID-19 lockdown. MATERIAL AND METHODS: The study was based on an e-mail survey addressed to CM patients of our headache center. The survey investigated demographic, life-style, sleep, psychological, and migraine features during the first COVID-19 lockdown period and the month before. The outcomes were sleep quality (measured using PSQI) and variation in sleep quality, duration, and latency. RESULTS: Ninety-two patients were included. The mean PSQI was 11.96. Sleep quality was improved in 14.1%, stable in 47.8%, and worsened in 38.0%. Sleep latency was reduced in 5.4%, stable in 46.7%, and increased in 47.8%. Sleep duration was reduced in 29.3%, stable in 34.8%, and increased in 35.9%. Significant associations were found with age, work/study, remote working, job loss, meal quality change, smoking variation, COVID-19 province prevalence, home-inhabitant relationship, ratio of house size/number of people, stress, state anxiety, anxiety/depression variation, future concern variation, computer hours, internet hours, and television hours. CONCLUSION: The study described sleep features of chronic migraineurs during COVID-19 lockdown, pinpointing the main factors involved in sleep quality and sleep changes. Our findings revealed that migraineurs' sleep was closely linked with life-style and psychological features. Several modifiable factors came to light and they should be considered in order to develop an optimal management of CM. An appropriate and more aware treatment of sleep problems could be a way to improve migraineurs' life.

Ischemic stroke and reperfusion therapies in diabetic patients.

INTRODUCTION: The study aimed to identify the main prognostic factors in diabetic patients with ischemic stroke undergoing reperfusion therapies (RT). METHODS: This retrospective study included 170 diabetic patients: 62 treated with intravenous thrombolysis (IVT) alone and 108 with mechanical thrombectomy (MT). Among MT patients, 29 underwent IVT. We collected clinical, laboratory, and radiological data. The outcomes were 3-month functional impairment (measured by modified Rankin scale, mRs), discharge neurological severity (measured by National Institutes of Health Stroke Scale score, NIHSS), 3-month mortality, intracranial hemorrhage (ICH), and symptomatic intracranial hemorrhage (SICH). We performed a general analysis for all RT and sub-group analyses for IVT and MT. RESULTS: A lower mRs was associated with lower glycemia and admission NIHSS (aNIHSS) in all RT and MT; lower aNIHSS and younger age in IVT. Mortality increased with hyperglycemia, aNIHSS, and age in all RT; age and aNIHSS in IVT; hyperglycemia and systolic pressure in MT. A lower discharge NIHSS was related with lower aNIHSS, thrombolysis, and no thrombectomy in all RT; lower aNIHSS in IVT; lower aNIHSS and thrombolysis in MT. ICH was associated with elevated aNIHSS, older age, and lower platelets in all RT; lower platelets and older age in IVT; higher aNIHSS in MT. SICH depended on longer thrombectomy duration in all RT; no metformin use in IVT; higher weight in MT. CONCLUSION: The study shed light on diabetic patients and stroke RT highlighting the protective effect of metformin in IVT and the role of glycemia, weight, and combined treatment in MT.

Safety of Ultrasound-Guided Serratus Anterior and Erector Spinae Fascial Plane Blocks: A Retrospective Analysis in Patients Undergoing Cardiac Surgery While Receiving Anticoagulant and Antiplatelet Drugs.

OBJECTIVES: Chest wall blocks are an effective strategy for postoperative pain control in minimally invasive cardiac surgery, but, in the absence of clinical trials evaluating their safety in the presence of anticoagulant and antiplatelet drugs, it still is recommended to follow the same guidelines developed for the neuraxial procedures and for peripheral blocks. DESIGN: Retrospective observational study. SETTING: AOU Città della Salute e della Scienza di Torino, University of Turin, Italy. PARTICIPANTS: Between March 28, 2019 and October 19, 2020, 70 patients who underwent mitral valve surgery via right minithoracotomy were enrolled: 35 treated with continuous erector spinae plane block (ESPB) and 35 with continuous serratus anterior plane block (SAPB). INTERVENTIONS: The primary objective was the evaluation of the number of blocks performed or catheters removed while coagulation was abnormal or antithrombotic and anticoagulant therapies were in progress. MEASUREMENTS AND MAIN RESULTS: Eleven patients (15.7%) received fascial plane block with international normalized ratio (INR) > 1.40, four patients (5.71%) with a platelet count <80 × 103, and one patient received ESPB block during dual-antiplatelet therapy. In 16 patients (22.9%), the catheter was removed with an INR > 1.40, in five patients (7.1%) with a platelet count <80 × 103, and in 53 patients (75.71%) despite low-molecular-weight heparin at therapeutic dose. The median antagonist dose of vitamin K at the time of catheter removal was 2.5 mg (range 2.5-3.44 mg) in both groups. No major adverse effects directly attributable to the blocks were observed. CONCLUSIONS: The authors did not find any problems related to the use of continuous ESPB and SAPB, although they were performed in the presence of anticoagulation and in a context with a high risk of bleeding such as cardiac surgery.

Hemophagocytic lymphohistiocytosis following gene replacement therapy in a child with type 1 spinal muscular atrophy.

WHAT IS KNOWN AND OBJECTIVE: Onasemnogene abeparvovec (OA) is the first gene replacement therapy for the treatment of paediatric patients with bi-allelic mutations in the SMN1 gene. Efficacy and safety of OA have been assessed in several studies with promising results, despite rare side effects have been described. CASE SUMMARY: A 3-year-old child with spinal muscular atrophy was treated with OA and subsequently developed fever, widespread erythematous skin lesions and hepatosplenomegaly. Laboratory tests were suggestive for Hemophagocytic lymphohistiocytosis (HLH). WHAT IS NEW AND CONCLUSION: To our knowledge, this is the first case of HLH following gene replacement therapy with OA, described in literature.

Transversus thoracic plane block and rectus sheath block for left ventricular assist device implantation via full median sternotomy: A case report.

BACKGROUND: Traditionally, pain management after left ventricular assist device (LVAD) implantation via median sternotomy have been based on intravenous opioids but, in the era of enhanced recovery after surgery, a multimodal opioid-sparing analgesia could represent a valid alternative reducing opioids related side effects. CASE REPORT: We described the successfully use of an opioid-sparing regimen for pain management after LVAD implantation via median sternotomy based on two ultrasound-guided fascial plane wall blocks. Bilateral ultrasound-guided transversus thoracic plane block was performed to manage sternotomy pain; additionally, unilateral left ultrasound-guided rectus sheath block was performed to provide somatic pain relief for left abdominal wall structures superficial to the peritoneum within which the LVAD driveline was inserted. The patient was extubated on Day 1 and good quality analgesia (numerical rating scale <3) was obtained, without using nonsteroidal antiinflammatory drugs or opioids. The patient was discharged from Intensive Care Unit on Day 3 and during hospitalization (lasted 24 days) there was no need for rescue analgesia administration.

Awake cardiac surgery using the novel pectoralis-intercostal-rectus sheath (PIRS) plane block and subxiphoid approach.

BACKGROUND: Postoperative pain after cardiac surgery is a very important issue and affects recovery, risk of postoperative complications and quality of life. The pain management has been traditionally based on intravenous opioids with growing evidence suggesting the use of opioid-free and opioid-sparing techniques to reduce its adverse effects. CASE PRESENTATION: We report the case of a 75-year-old frail patient underwent awake mediastinal revision with subxiphoid access due to deep sternal wound infection using a pectoralis-intercostal rectus sheath (PIRS) plane block. During the procedure the patient never reported pain receiving acetaminophen 1 g every 8 h for postoperative pain management without others pain relievers. CONCLUSION: Ultrasound guided PIRS block could be an effective and safe analgesic technique to manage sternal and subxiphoid drainage pain in patients undergoing cardiac surgery via subxiphoid approach.

Chronic postsurgical pain and quality of life after right minithoracotomy mitral valve operations.

OBJECTIVES: Chronic postsurgical pain (CPSP) is a relatively common complication after cardio-thoracic operations with well-known consequences in terms of return to normal activities and quality of life. Little is known about the prevalence and severity of CPSP after minimally invasive cardiac surgery. The aim of this study was to measure the rate of CPSP in patients undergoing right minithoracotomy mitral valve (MV) surgery and to compare the effectiveness of different approaches to pain control. METHODS: A prospective observational study was conducted between March 2019 and September 2020. All patients undergoing right minithoracotomy MV surgery treated with morphine, continuous serratus anterior plane block (SAPB), or continuous erector spinae plane block (ESPB) were included. The Brief Pain Inventory questionnaire was used to evaluate 6-month CPSP and quality of life. RESULTS: A total of 100 patients were enrolled: postoperative pain control was obtained with morphine in 26 cases, with SAPB in 37 cases, and with ESPB in 37 cases. Median intensive care unit and hospital length of stay were 1 day and 6 days, respectively. Pain severity index was lower than 10 in 81 patients, and no differences were recorded between groups (p = .59). No patients reported chronic use of medications for pain management or severe pain interference in daily activities at follow-up. DISCUSSION: Right minithoracotomy approach is not burdened by a high incidence of CPSP: pain severity index was lower than 10 in more than 90% of patients. Then, in our experience, chronic pain seems not to be related to the type of perioperative analgesia adopted.

Pimozide and pancreatic cancer in diabetic chorea: a case report.

PURPOSE/AIM: Diabetic chorea is a rare movement disorder associated with diabetes mellitus. We report the case of a patient that benefited from pimozide and died of pancreatic cancer. CASE REPORT: A 70-year-old woman presented with pollakiuria and involuntary movements of left limbs since three months. Laboratory tests revealed high serum levels of glycemia and glycated haemoglobin. She was admitted to internal medicine department and discharged one week later: insulin was administered with normalization of blood glucose levels and the involuntary movements gradually disappeared. Three weeks later she was admitted to neurological department due to the recurrence of the involuntary movements. Glycemia and other routine laboratory tests were normal. Neurological examination showed choreic movements involving left limbs. MRI showed a hyperintensity on T1- and T2-weighted sequences of right putamen and caudate nucleus head. Haloperidol was administered without improvement, it was successively substituted with tetrabenazine and the patient was discharged with an unvaried clinical picture. Two months later tetrabenazine was discontinued because of inefficacy and pimozide was started. The choreic movements considerably diminished after few days. Four months later, a pancreatic cancer was diagnosed and the patient died in the same month. CONCLUSION: Clinical and radiological features were suggestive of diabetic chorea. Our patient benefited exclusively from pimozide, it could be reasonable to use pimozide in resistant form and also propose it as first choice treatment. Another important element is the diagnosis of pancreatic cancer some months after chorea onset: a causal link could exist.