BACKGROUND CONTEXT: Spondylodiscitis management presents significant clinical challenges, particularly in critically ill patients, where the risks and benefits of surgical intervention must be carefully balanced. The optimal timing of surgery in this context remains a subject of debate. PURPOSE: This study aims to evaluate the effectiveness of early surgery versus delayed surgery or conservative management in critically ill patients with de novo pyogenic spondylodiscitis. STUDY DESIGN/SETTING: This is an international, multicenter retrospective cohort study involving 24 centers, primarily in Europe. PATIENT SAMPLE: The study included 192 critically ill patients (65.63% male) with a median age of 69 years, all severely affected by pyogenic spondylodiscitis characterized by an initial CRP level >200 mg/l or the presence of two out of four Systemic Inflammatory Response Syndrome criteria upon admission. OUTCOME MEASURES: The primary outcome was 30-day mortality. Secondary outcomes included length of ICU stay, length of hospital stay, and relapse rates of spondylodiscitis. METHODS: Patients were divided into three groups: early surgery (within three days of admission), delayed surgery (after three days of admission), and conservative therapy. Propensity score matching and multivariate regression analyses were performed to adjust for baseline differences and assess the impact of treatment modalities on mortality and other clinical outcomes. RESULTS: Delayed surgery was associated with significantly lower 30-day mortality (4.05%) compared to early surgery (27.85%) and conservative therapy (27.78%) (p<.001). Delayed surgery also resulted in shorter hospital stays (42.76 days) compared to conservative therapy (55.53 days) and early surgery (26.33 days) (p<.001), and shorter ICU stays (4.52 days) compared to conservative therapy (16.48 days) and early surgery (7.92 days) (p<.001). The optimal window for surgery, minimizing mortality, was identified as ten to fourteen days postadmission (p=.02). Risk factors for increased mortality included age (p<.05), multiple organ failure (p<.05), and vertebral body destruction (p<.05), whereas delayed surgery (p<.05) and the presence of an epidural abscess were associated with reduced mortality (p<.05). CONCLUSIONS: Delayed surgery, optimally between 10 to 14 days postadmission, was associated with lower mortality in critically ill spondylodiscitis patients. These findings highlight the potential benefits of considering surgical timing to improve patient outcomes.

• MeSH
• Anti-Bacterial Agents therapeutic use   MeSH
• Length of Stay MeSH
• Discitis * therapy   mortality   surgery   microbiology   MeSH
• Conservative Treatment MeSH
• Critical Illness MeSH
• Middle Aged MeSH
• Humans MeSH
• Retrospective Studies MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

INTRODUCTION: This study aimed to assess the impact of midline lumbar fusion with cortical bone trajectory screws (MIDLF/CBT) on the multifidus muscles, focusing on the evaluation of their postoperative atrophy. CLINICAL RATIONALE FOR THE STUDY: MIDLF/CBT is a relatively new technique increasingly used to treat spinal instability. Despite its reduced invasiveness compared to traditional posterior lumbar interbody fusion with traditional pedicle screws (PLIF/TP), concerns remain about potential damage to the multifidus muscles that are crucial for spinal stability. Understanding the extent of muscular atrophy post-MIDLF/CBT is vital for improving surgical outcomes, and potentially patient rehabilitation strategies. MATERIAL AND METHODS: This study retrospectively analysed preoperative and postoperative MRI scans of patients who underwent MIDLF/CBT for degenerative segmental spondylolisthesis. The bilateral width of the multifidus muscles at the operated segment and adjacent segments was measured using axial T2-weighted MRI scans. Statistical comparisons were made using a paired t test, with significance set at p < 0.05. RESULTS: The study included 16 patients with an average age of 57 ± 10 years, 10 of whom (62.5%) were women, and featured a mean follow-up period of 37 ± 25 months. Postoperative measurements showed a significant reduction in the width of the multifidus muscles at the operated segment (mean difference -3.3mm, p = 0.02) and the inferior adjacent segment (-7.4 mm, p < 0.01). A decrease in muscle width at the superior adjacent segment was also observed, although this was not statistically significant. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study concluded that MIDLF/CBT results in significant multifidus muscle atrophy at and below the operated segment, potentially impacting postoperative rehabilitation and recovery. These findings highlight the need for further research comparing MIDLF/CBT to other spinal stabilisation techniques. Additionally, incorporating functional electromyographic assessments of paraspinal muscles could provide deeper insights into the long-term consequences of spinal surgeries and helpdevelop new approaches and strategies to mitigate paravertebral muscles atrophy, thus enhancing patient outcomes.

• MeSH
• Lumbar Vertebrae * surgery   diagnostic imaging   MeSH
• Spinal Fusion * methods   MeSH
• Paraspinal Muscles * diagnostic imaging   pathology   MeSH
• Cortical Bone surgery   diagnostic imaging   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging MeSH
• Pedicle Screws MeSH
• Postoperative Complications diagnostic imaging   MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Spondylolisthesis * surgery   diagnostic imaging   MeSH
• Muscular Atrophy * etiology   diagnostic imaging   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

PURPOSE: We set out to develop a publicly available tool that could accurately diagnose spinal muscular atrophy (SMA) in exome, genome, or panel sequencing data sets aligned to a GRCh37, GRCh38, or T2T reference genome. METHODS: The SMA Finder algorithm detects the most common genetic causes of SMA by evaluating reads that overlap the c.840 position of the SMN1 and SMN2 paralogs. It uses these reads to determine whether an individual most likely has 0 functional copies of SMN1. RESULTS: We developed SMA Finder and evaluated it on 16,626 exomes and 3911 genomes from the Broad Institute Center for Mendelian Genomics, 1157 exomes and 8762 panel samples from Tartu University Hospital, and 198,868 exomes and 198,868 genomes from the UK Biobank. SMA Finder's false-positive rate was below 1 in 200,000 samples, its positive predictive value was greater than 96%, and its true-positive rate was 29 out of 29. Most of these SMA diagnoses had initially been clinically misdiagnosed as limb-girdle muscular dystrophy. CONCLUSION: Our extensive evaluation of SMA Finder on exome, genome, and panel sequencing samples found it to have nearly 100% accuracy and demonstrated its ability to reduce diagnostic delays, particularly in individuals with milder subtypes of SMA. Given this accuracy, the common misdiagnoses identified here, the widespread availability of clinical confirmatory testing for SMA, and the existence of treatment options, we propose that it is time to add SMN1 to the American College of Medical Genetics list of genes with reportable secondary findings after genome and exome sequencing.

• MeSH
• Algorithms MeSH
• Exome genetics   MeSH
• Genome, Human genetics   MeSH
• Genomics methods   MeSH
• Humans MeSH
• Survival of Motor Neuron 1 Protein genetics   MeSH
• Survival of Motor Neuron 2 Protein genetics   MeSH
• Sequence Analysis, DNA methods   MeSH
• Exome Sequencing MeSH
• Muscular Atrophy, Spinal * genetics   diagnosis   MeSH
• High-Throughput Nucleotide Sequencing MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

OBJECTIVE: The study objectives were (i) to explore the agreement between the Outcome Measures in Rheumatology (OMERACT) ultrasound lesions of enthesitis and physical examination in assessing enthesitis in patients with spondyloarthritis (SpA) and (ii) to investigate the prevalence and clinical relevance of subclinical enthesitis in this population. METHODS: Twenty rheumatology centers participated in this cross-sectional study. Patients with SpA, including axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA), underwent both ultrasound scan and physical examination of large lower limb entheses. The OMERACT ultrasound lesions of enthesitis were considered, along with a recently proposed definition for "active enthesitis" by our group. Subclinical enthesitis was defined as the presence of "active enthesitis" in ≥1 enthesis in patients with SpA without clinical enthesitis (ie, number of positive entheses on physical examination and Leeds Enthesitis Index score = 0). RESULTS: A total of 4,130 entheses in 413 patients with SpA (224 with axSpA and 189 with PsA) were evaluated through ultrasound and physical examination. Agreement between ultrasound and physical examination ranged from moderate (ie, enthesophytes) to almost perfect (ie, power Doppler and "active enthesitis"). Patellar tendon entheses demonstrated the highest agreement, whereas Achilles tendon insertion showed the lowest. Among 158 (38.3%) of 413 patients with SpA with clinical enthesitis, 108 (68.4%) exhibited no "active enthesitis" on ultrasound. Conversely, of those 255 without clinical enthesitis, 39 (15.3%) showed subclinical enthesitis. Subclinical enthesitis was strongly associated with local structural damage. However, no differences were observed regarding the demographic and clinical profiles of patients with SpA with and without subclinical enthesitis. CONCLUSION: Our study underscores the need for a comprehensive tool integrating ultrasound and physical examination for assessing enthesitis in patients with SpA.

• MeSH
• Achilles Tendon diagnostic imaging   MeSH
• Axial Spondyloarthritis diagnostic imaging   MeSH
• Adult MeSH
• Enthesopathy * diagnostic imaging   MeSH
• Physical Examination * MeSH
• Middle Aged MeSH
• Humans MeSH
• Cross-Sectional Studies MeSH
• Arthritis, Psoriatic diagnostic imaging   complications   MeSH
• Spondylarthritis * diagnostic imaging   complications   MeSH
• Ultrasonography * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

Neuroaxiální léčba bolesti slouží jako doplněk analgetické terapie, když běžné analgetické postupy nejsou dostatečně účinné. Znamená to podání léků do epidurálního nebo intratekálního kompartmentu páteřního kanálu. Léky je možné aplikovat jednorázově, krátkodobě kontinuálně pomocí externího dávkovače nebo dlouhodobě prostřednictvím implantované pumpy. Standardně používanými léky jsou lokální anestetika, opioidy, případně v epidurálním prostoru též kortikoidy; tento výčet ale není konečný, zkoušely se i další látky. Neuroaxiální analgezie má řadu rizik, od systémové toxicity přes nežádoucí účinky léků až po neurotoxicitu.

Neuraxial pain treatment serves as an adjunct to analgesic therapy when conventional analgesic procedures are not sufficiently effective. It invol- ves the administration of drugs into the epidural or intrathecal compartment of the spinal canal. The medication can be administered as a single dose, continuously over a short period of time using an external dispenser, or over a long period of time using an implanted pump. The standard drugs used are local anesthetics, opioids, or, in the epidural space, corticosteroids, but this list is not exhaustive; other agents have also been tried. Neuraxial analgesia has some risks, ranging from systemic toxicity, adverse drug reactions and neurotoxicity.

BACKGROUND AND OBJECTIVES: En bloc sacrectomy is associated with sacral root transection causing loss of urinary bladder, rectum, and sexual function. The aim of the study was to determine the position of the pudendal branches (sensorimotor) and pelvic splanchnic nerves (parasympathetic) on the sacral roots relative to the sacrum, and the minimal and maximal defects in the sacral roots that can be reconstructed by grafting after various types of sacrectomy. METHODS: Five cadaveric pelves were dissected bilaterally. The lengths and widths of the S1-S4 roots and their branches were measured. Then, the minimal and maximal defects between the proximal and distal stumps of the sacrificed roots were measured following 3 models of sacrectomy (below S2, below S1, and total sacrectomy). RESULTS: The mean distance of the splanchnic nerves from the S2 and S3 anterior sacral foramina was 17.7 ± 7.3 and 23.6 ± 11.1 mm, respectively, and the mean distance of the pudendal S2 and S3 branches was 36.8 ± 13.7 and 30.2 ± 10.8 mm, respectively. The mean widths of the S2 and S3 roots were 9.3 ± 1.9 and 5.4 ± 1.2 mm, respectively. The mean maximal defects in S2 and S3 roots after various types of sacrectomies were between 61.8 ± 16.3 and 100.7 ± 14.3 mm and between 62.7 ± 20.2 and 84.7 ± 25.1 mm, respectively. There were no statistically significant differences between sides or sexes for all obtained measurements. CONCLUSION: The reconstruction of the S2-S3 roots is anatomically feasible after partial or total sacrectomies in which the resection of the soft tissue does not extend further than approximately 1.5 to 2 cm ventrally from the sacrum.

• MeSH
• Sacrum * surgery   anatomy & histology   innervation   MeSH
• Middle Aged MeSH
• Humans MeSH
• Spinal Nerve Roots * anatomy & histology   surgery   MeSH
• Cadaver * MeSH
• Aged MeSH
• Splanchnic Nerves anatomy & histology   surgery   MeSH
• Plastic Surgery Procedures methods   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Diagnostika místa úniku mozkomíšního moku coby příčiny spontánní intrakraniální hypotenze (SIH) je obecně komplikovaná, zejména pak v případě vzniku likvoro-venózních fistul. Tyto žilní píštěle na rozdíl od ostatních příčin SIH nezpůsobují hromadění tekutiny v epidurálním prostoru, a nelze je tedy diagnostikovat standardními zobrazovacími technikami. Cílem článku je přiblížit radiologické nálezy typické pro diagnózu spontánní intrakraniální hypotenze a role různých technik zobrazování páteře při detekci místa úniku likvoru včetně dynamické CT myelografie.

Diagnosis of the site of cerebrospinal fluid leak as a cause of spontaneous intracranial hypotension (SIH) is generally complicated, especially in the case of liquor-venous fistulas. These venous fistulas, unlike other causes of SIH, do not cause fluid accumulation in the epidural space and thus cannot be diagnosed by standard techniques. The aim of this article is to review the radiological findings typical for the diagnosis of spontaneous intracranial hypotension and the role of various spinal imaging techniques in the detection of the site of liquor leak including dynamic CT myelography.

Radiologicky izolovaný syndrom je definován jako náhodně zjištěný obraz na magnetické rezonanci typický pro roztroušenou sklerózu u pacienta, který nemá žádné klinické příznaky pro toto onemocnění. Tento termín byl poprvé použit včetně definice kritérií v roce 2009. Cílem nových revidovaných kritérií radiologicky izolovaného syndromu z roku 2023 je zajistit přesnou a rychlejší diagnostiku, než umožňovala původní kritéria z roku 2009. Nová kritéria vyžadují alespoň jedno T2 hypersignální ložisko v jedné ze čtyř typických lokalizací pro roztroušenou sklerózu spolu se dvěma z následujících tří znaků: míšní léze, oligoklonální pásy omezené na mozkomíšní mok nebo nové T2 hypersignální ložisko nebo po podání kontrastní látky zvýrazňující se ložisko pozorované na následném vyšetření magnetickou rezonancí. V diagnostice radiologicky izolovaného syndromu se stanovují rizikové faktory pro konverzi do klinicky definitivní roztroušené sklerózy a hrozícího těžšího průběhu onemocnění. Jedná se o nižší věk pacienta, lokalizaci ložisek (infratentoriálně a intramedulárně) a přítomnost oligoklonálních pásů v mozkomíšním moku nepřítomných v séru. To je důležité pro zvážení léčebné intervence. Nedávné klinické studie ukázaly, že perorální léčba modifikující průběh onemocnění může u pacientů s radiologicky izolovaným syndromem oddálit první klinickou příhodu nebo jí zabránit. Tento posun diagnostiky a zvažování léčby již v preklinickém stadiu vytváří enormní tlak na precizní diagnostiku a management, aby tito náhodně vytypovaní pacienti byli směřováni do RS center, kde budou dále podrobně vyšetřeni. Revidovaná McDonaldova diagnostická kritéria pro roztroušenou sklerózu z roku 2024 budou klasifikovat osoby s pozitivními dalšími markery z mozkomíšního moku a pokročilými MR biomarkery jako osoby s preklinickou RS, což zdůrazňuje důležitost preciznosti v diagnostice a edukaci jak radiologů, tak neurologů, jakým způsobem postupovat, aby se pacient dostal včas do sledování v centrech vysoce specializované péče pro pacienty s roztroušenou sklerózou.

Radiologically isolated syndrome (RIS) is defined as an incidental finding on magnetic resonance imaging (MRI) that is typical of multiple sclerosis (MS) in a patient without clinical symptoms of the disease. This term, along with its definition criteria, was first introduced in 2009. The newly revised 2023 RIS criteria aim to provide a more accurate and faster diagnosis compared to the original 2009 criteria. These criteria require at least one T2-hyperintense lesion in one of the four typical locations for MS, along with two of the following three features: spinal cord lesions, oligoclonal bands confined to the cerebrospinal fluid (but absent in the serum), or a new T2-hyperintense lesion (or, after contrast administration, a prominent lesion visible on follow-up MRI scans). An MRI diagnosis of RIS establishes a risk factor for conversion to clinically definite MS and a more severe disease course. These risk factors include the patient’s age, the location of the lesions (infratentorial and intramedullary) and the presence of oligoclonal bands in the cerebrospinal fluid. These factors are critical when considering therapeutic interventions. Recent clinical trials have demonstrated that oral disease-modifying therapies can delay or prevent the first clinical event in patients with RIS. This shift in diagnosis and treatment considerations to preclinical stages places enormous pressure on ensuring precise diagnosis and management. It is essential that such patients are referred to MS centers for further specialized investigations. The forthcoming Revised McDonald Criteria of 2024 will classify individuals with additional cerebrospinal fluid markers and advanced MRI biomarkers as having preclinical MS. This highlights the importance of precise diagnosis and the need for radiologists and neurologists to familiarize themselves with the appropri- ate steps to ensure patients are monitored at highly specialized MS care centers.

BACKGROUND: Severe combined immunodeficiency (SCID) is a fatal but treatable inborn error of immunity (IEI). Newborn screening (NBS) using T-cell receptor excision circles (TREC) has been adopted globally, with very few countries incorporating kappa recombination excision circles (KREC) to also detect early B-cell development disorders, such as X-linked agammaglobulinemia (XLA). OBJECTIVE: To evaluate the effectiveness of a 2-year pilot SCID NBS program in the Czech Republic, emphasising the utility of combined TREC/KREC screening. METHODS: Between January 2022 and December 2023, a dual TREC/KREC NBS pilot was conducted across the Czech Republic, alongside spinal muscular atrophy (SMA) screening. Approximately 200,000 newborns were screened using quantitative real-time PCR on dried blood spots collected 48-72 h after birth. RESULTS: The pilot referred 58 newborns, identifying 21 cases of IEI, including two SCID cases, with an overall incidence of TREC/KREC screenable IEI of 10.5/100,000 newborns. SCID incidence was 1/100,000. KREC screening proved invaluable, detecting 10 cases of congenital agammaglobulinemia including novel non-XLA forms, which increased the estimated incidence of agammaglobulinemia in the Czech Republic sixfold. Over one-third of low KREC results were linked to maternal immunosuppression. CONCLUSION: The Czech pilot demonstrated the effectiveness of integrated TREC/KREC NBS in detecting both T- and B-cell immunodeficiencies. As of 2024, SCID and SMA screening are included in the nationwide NBS, with KREC screening significantly improving early detection of B-cell disorders.

• MeSH
• Agammaglobulinemia diagnosis   MeSH
• B-Lymphocytes immunology   MeSH
• Genetic Diseases, X-Linked MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Neonatal Screening * methods   MeSH
• Pilot Projects MeSH
• Receptors, Antigen, T-Cell * genetics   MeSH
• Severe Combined Immunodeficiency * diagnosis   genetics   epidemiology   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

BACKGROUND: Age-related neurodegenerative diseases (NDs) pose a formidable challenge to healthcare systems worldwide due to their complex pathogenesis, significant morbidity, and mortality. Scope and Approach: This comprehensive review aims to elucidate the central role of the microbiotagut- brain axis (MGBA) in ND pathogenesis. Specifically, it delves into the perturbations within the gut microbiota and its metabolomic landscape, as well as the structural and functional transformations of the gastrointestinal and blood-brain barrier interfaces in ND patients. Additionally, it provides a comprehensive overview of the recent advancements in medicinal and dietary interventions tailored to modulate the MGBA for ND therapy. CONCLUSION: Accumulating evidence underscores the pivotal role of the gut microbiota in ND pathogenesis through the MGBA. Dysbiosis of the gut microbiota and associated metabolites instigate structural modifications and augmented permeability of both the gastrointestinal barrier and the blood-brain barrier (BBB). These alterations facilitate the transit of microbial molecules from the gut to the brain via neural, endocrine, and immune pathways, potentially contributing to the etiology of NDs. Numerous investigational strategies, encompassing prebiotic and probiotic interventions, pharmaceutical trials, and dietary adaptations, are actively explored to harness the microbiota for ND treatment. This work endeavors to enhance our comprehension of the intricate mechanisms underpinning ND pathogenesis, offering valuable insights for the development of innovative therapeutic modalities targeting these debilitating disorders.

• MeSH
• Dysbiosis metabolism   MeSH
• Blood-Brain Barrier metabolism   MeSH
• Humans MeSH
• Brain * metabolism   MeSH
• Neurodegenerative Diseases * microbiology   metabolism   MeSH
• Brain-Gut Axis * physiology   MeSH
• Probiotics MeSH
• Aging * MeSH
• Gastrointestinal Microbiome * physiology   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH