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Development and clinical significance of the musculus dorsoepitrochlearis in men
Musculus dorsoepitrochlearis is a typical muscle variation, which, if in full extent, is represented by the muscular or fibromuscular slip detached from the anteroinferior border of the musculus latissimus dorsi. It passes over the axilla under the axillary fascia crossing the medial side of the brachial plexus and continues as a septum intermusculare mediale brachii distally to the medial epicondyle of humerus. Its full extent is rarely developed-the connection into the intermuscular septum being mostly absent. Muscular slips from the musculus latissimus then insert on various structures in the axilla, often on the crest of greater tubercle of humerus or into the musculus pectoralis major (this variation is known as the axillary arch of Langer) or to other neighboring structures (coracoid process, fasciae of muscles). In our observations, 209 patients with traumatic lesions of the brachial plexus underwent surgical procedure. The presence of the musculus dorsoepitrochlearis has been observed. It was found in the form of various slips from the musculus latissimus dorsi in 4 patients. In 3 of those 4 patients, the innervation was derived from the nervus thoracodorsalis. We also presented 2 case reports of patients with clinical symptoms caused by compression of nerves in the axilla by the dorsoepitrochlear strip. Clin. Anat. 22:481-488, 2009. © 2009 Wiley-Liss, Inc.
The Effect of Denosumab on Pain and Radiological Improvement in Giant Cell Tumours of the Spine in the Acute Setting
Study Design Retrospective Cohort Study. Objectives The current recommended treatment for Giant Cell Tumour (GCT) of the spine is en bloc excision. Denosumab is a monoclonal antibody reducing osteoclast activity that shows promising results when used as a neo – adjuvant treatment. However, the current literature remains limited. The purpose of this study was to assess the effect of denosumab on tumour characteristics and symptom relief in the acute phase of treatment of spinal GCT. Methods We performed a retrospective review of 16 patients treated with denosumab as neo-adjuvant and stand - alone treatment. MRI and PET tumour characteristics were taken before and after treatment and patients were interviewed for subjective pain responses. Results Following treatment, all patients showed improvement of pain, of which 68.7% of patients were pain free with 43.75% noting improvement within 48 hours. Mean relative volumetric reduction in tumour volume was 37.3% ( P < .001). Eight patients showed high grade of Bilsky classification (Epidural spinal cord compression scale - ESCC) with seven of them showing significant improvement to low grade of ESCC ( P = .016). Median baseline PET Standardised Uptake Value (SUV)max was 14.57 and post treatment was 4.8 ( P < .001). Conclusions This study provides necessary insight to the limited literature on the use of denosumab for spinal GCT in the acute phase. The clinical and radiographic responses observed demonstrate the critical role that neo-adjuvant denosumab has by reducing the tumour burden around critical adjacent neurovascular structures before eventual resection, significant pain improvement even with presence of fractured vertebra.
Clinical Anatomy of the Sacral Nerve Roots and Its Relevance to Their Reconstruction After Sacrectomy
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.
Anatomy of the superior hypogastric plexus and its relevance to anterior lumbar interbody fusion
OBJECTIVE Retrograde ejaculation (RE) is a known complication of anterior lumbar interbody fusion (ALIF) and results from injury to the superior hypogastric plexus (SHP) during intervertebral disc exposure. Yet, there has been no recommendation for SHP mobilization. Thus, the aim of this study was to describe the anatomy of the SHP and vessels at the L5–S1 level, and to evaluate the possibility of SHP mobilization and its retraction to the side. METHODS Twelve formaldehyde-embalmed cadavers (6 female and 6 male; mean age 65.5 years [range 60–77 years]) were dissected. Distances from the SHP and middle sacral vessels to the midline were measured at the L5–S1 level. The relationship of the great vessel bifurcations and common iliac vessels to the SHP were noted. The extent of lateral retraction of the SHP following mobilization was measured in relation to the midline. Moreover, the positions of the SHP and middle sacral vessels relative to the midline at the L5–S1 level were determined. RESULTS The SHP formed below the aortic bifurcation and was present at the L5–S1 level in all cases. The SHP overlaid the midline with a left-sided shift. There were 4 cases (33.3%) in which lateral retraction was not achievable because the plexus divided into hypogastric nerves at the L5–S1 level or was too wide for safe mobilization. In the remaining cases, retraction on the left side was achievable up to 15.3 mm from the midline, while retraction to the right side was limited to 5.3 mm from the midline. The types of SHP morphological arrangement included single cord (41.7%), plexiform (41.7%), and fiber (16.6%). CONCLUSIONS Based on the more extensive left-sided shift of the SHP at the L5–S1 level and frequent presence of the third left splanchnic lumbar nerve, attempting retraction to the left side is recommended. If it is not feasible, the SHP should be split at the midline, with both components mobilized laterally.
Diagnostic and prognostic value of α-synuclein seed amplification assay kinetic measures in Parkinson's disease: a longitudinal cohort study
Background: α-synuclein seed amplification assay (SAA) positivity has been proposed as a diagnostic biomarker for Parkinson's disease. However, studies of the prognostic value of this biomarker have been limited to small, single-centre studies over short follow-up periods. We aimed to assess the diagnostic and prognostic value of quantitative CSF α-synuclein SAA kinetic measures in Parkinson's disease. Methods: In this longitudinal cohort study, we collected and analysed data from participants with Parkinson's disease, progressive supranuclear palsy, and healthy controls enrolled in three cohorts: the UK parkinsonism cohort, the Parkinson's Progression Markers Initiative (PPMI) international observational study, and the Tübingen Parkinson's disease cohort. Baseline CSF α-synuclein SAA data and longitudinal clinical data were collected between Jan 1, 2005, and Nov 1, 2023. The following seeding kinetic measures were calculated from the α-synuclein SAA curve for each SAA-positive sample: time to threshold (TTT) for a positive SAA result; maximum Thioflavin T fluorescence during the reaction time (MaxThT); and area under the fluorescence curve during the reaction time (AUC). We compared seeding kinetic measures between sporadic Parkinson's disease and progressive supranuclear palsy, and between sporadic Parkinson's disease and monogenic Parkinson's disease. We used time-to-event analyses to assess the ability of α-synuclein SAA kinetic measures to predict an unfavourable outcome in Parkinson's disease, adjusting for sex, age, and disease duration at SAA testing. Findings: We analysed data from 1631 participants: newly generated data from the UK parkinsonism cohort (Parkinson's disease, n=66; progressive supranuclear palsy, n=52; controls, n=9) and previously generated data from the PPMI (Parkinson's disease, n=1036; controls, n=239) and Tübingen (Parkinson's disease, n=229) cohorts. In the UK parkinsonism cohort, α-synuclein SAA was positive in 63 (96%) of 66 Parkinson's disease samples and eight (15%) of 52 progressive supranuclear palsy samples, with six (75%) of eight positive progressive supranuclear palsy samples having distinct low and slow seeding kinetics (low MaxThT and high TTT) as a marker of Lewy body co-pathology. TTT was faster in GBA1-associated Parkinson's disease compared with sporadic Parkinson's disease in both the PPMI (p=0·04) and Tübingen (p=0·01) cohorts. In the PPMI cohort, after excluding individuals who had an unfavourable outcome at the time of baseline SAA testing, an unfavourable outcome was observed in 593 (73%) of 810 participants with α-synuclein SAA-positive Parkinson's disease during a median follow-up period of 4·5 years (IQR 2–9). TTT at baseline predicted only cognitive decline (Montreal Cognitive Assessment score ≤21) as a component of an unfavourable outcome in Parkinson's disease in both the PPMI (n=824, hazard ratio [HR] 2·36 [95% CI 1·60–3·46], p=0·001) and Tübingen (n=135, 2·17 [1·07–4·41], p=0·03) cohorts. TTT also predicted cognitive decline in a subgroup of participants with Parkinson's disease in the PPMI cohort who were Alzheimer's disease biomarker negative (n=355, HR 1·80 [95% CI 1·03–3·18], p=0·04). Interpretation: Assessing α-synuclein SAA kinetic measures might aid in the diagnostic differentiation of Parkinson's disease from progressive supranuclear palsy with Lewy body co-pathology. Furthermore, faster seeding kinetics are found in GBA1-Parkinson's disease and predict cognitive decline in Parkinson's disease independently of Alzheimer's disease co-pathology. Funding: Medical Research Council, PSP Association. Copyright: © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
Tremor Asymmetry and the Development of Bilateral Phase-Specific Deep Brain Stimulation for Postural Tremor.
BACKGROUND: Tremor phase-locked deep brain stimulation (DBS) has been shown to modulate symptom severity in postural tremor, including essential and dystonic tremor, with less energy than existing systems. Previous studies focused on unilateral stimulation; it remains unknown how tremor asymmetry interacts with stimulation in the context of bilateral phase-locked DBS. METHODS: Archival limb acceleration from nine essential tremor patients was analyzed for asymmetries in tremor amplitude, frequency, and instability, and their relationship with continuous high-frequency DBS (cDBS). Bilateral phase-locked DBS was tested in one essential tremor and one dystonic tremor patient. RESULTS: Postural tremor is asymmetric, with larger tremor power linked to smaller amplitude and frequency stability in one hand. These asymmetries were significantly reduced during cDBS, with greater effects on larger amplitude tremors. Bilateral phasic DBS effects were also asymmetric. CONCLUSIONS: This study enhances understanding of tremor asymmetry and its relationship with DBS, offering insights for patient-specific tremor treatments. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Ultrahigh frequencies of peripherally matured LGI1- and CASPR2-reactive B cells characterize the cerebrospinal fluid in autoimmune encephalitis
Intrathecal synthesis of central nervous system (CNS)-reactive autoantibodies is observed across patients with autoimmune encephalitis (AE), who show multiple residual neurobehavioral deficits and relapses despite immunotherapies. We leveraged two common forms of AE, mediated by leucine-rich glioma inactivated-1 (LGI1) and contactin-associated protein-like 2 (CASPR2) antibodies, as human models to comprehensively reconstruct and profile cerebrospinal fluid (CSF) B cell receptor (BCR) characteristics. We hypothesized that the resultant observations would both inform the observed therapeutic gap and determine the contribution of intrathecal maturation to pathogenic B cell lineages. From the CSF of three patients, 381 cognate-paired IgG BCRs were isolated by cell sorting and scRNA-seq, and 166 expressed as monoclonal antibodies (mAbs). Sixty-two percent of mAbs from singleton BCRs reacted with either LGI1 or CASPR2 and, strikingly, this rose to 100% of cells in clonal groups with ≥4 members. These autoantigen-reactivities were more concentrated within antibody-secreting cells (ASCs) versus B cells ( P < 0.0001), and both these cell types were more differentiated than LGI1- and CASPR2-unreactive counterparts. Despite greater differentiation, autoantigen-reactive cells had acquired few mutations intrathecally and showed minimal variation in autoantigen affinities within clonal expansions. Also, limited CSF T cell receptor clonality was observed. In contrast, a comparison of germline-encoded BCRs versus the founder intrathecal clone revealed marked gains in both affinity and mutational distances ( P = 0.004 and P < 0.0001, respectively). Taken together, in patients with LGI1 and CASPR2 antibody encephalitis, our results identify CSF as a compartment with a remarkably high frequency of clonally expanded autoantigen-reactive ASCs whose BCR maturity appears dominantly acquired outside the CNS.
Next-generation phenotyping of inherited retinal diseases from multimodal imaging with Eye2Gene
Rare eye diseases such as inherited retinal diseases (IRDs) are challenging to diagnose genetically. IRDs are typically monogenic disorders and represent a leading cause of blindness in children and working-age adults worldwide. A growing number are now being targeted in clinical trials, with approved treatments increasingly available. However, access requires a genetic diagnosis to be established sufficiently early. Critically, the timely identification of a genetic cause remains challenging. We demonstrate that a deep learning algorithm, Eye2Gene, trained on a large multimodal imaging dataset of individuals with IRDs (n = 2,451) and externally validated on data provided by five different clinical centres, provides better-than-expert-level top-five accuracy of 83.9% for supporting genetic diagnosis for the 63 most common genetic causes. We demonstrate that Eye2Gene’s next-generation phenotyping can increase diagnostic yield by improving screening for IRDs, phenotype-driven variant prioritization and automatic similarity matching in phenotypic space to identify new genes. Eye2Gene is accessible online (app.eye2gene.com) for research purposes.
Building a Covid-19 secure intensive care unit: A human-centred design approach
Background The Covid-19 pandemic has highlighted weaknesses in the National Health Service critical care provision including both capacity and infrastructure. Traditionally, healthcare workspaces have failed to fully incorporate Human-Centred Design principles resulting in environments that negatively affect the efficacy of task completion, patient safety and staff wellbeing. In the summer of 2020, we received funds for the urgent construction of a Covid-19 secure critical care facility. The aim of this project was to design a pandemic resilient facility centred around both staff and patient requirements and safety, within the available footprint. Methods We developed a simulation exercise, underpinned by Human-Centred Design principles, to evaluate intensive care designs through Build Mapping, Tasks Analysis and Qualitative data. Build Mapping involved taping out sections of the design and mocking up with equipment. Task Analysis and qualitative data were collected following task completion. Results 56 participants completed the build simulation exercise generating 141 design suggestions (69 task related, 56 patient and relative related, 16 staff related). Suggestions translated to 18 multilevel design improvements; five significant structural changes (Macro level) including wall moves and lift size change. Minor improvements were made at a Meso and Micro design level. Critical care design drivers identified included functional drivers (visibility, Covid-19 secure environment, workflow, and task efficiency) and behavioural drivers (learning and development, light, humanising intensive care and design consistency). Conclusion Success of clinical tasks, infection control, patient safety and staff/patient wellbeing are highly dependent on clinical environments. Primarily, we have improved clinical design by focusing on user requirements. Secondly, we developed a replicable approach to exploring healthcare build plans revealing significant design changes, that may have only been identified once built.
Musculoskeletal impairments after critical illness: A protocol for a qualitative study of the experiences of patients, family and health care professionals
AbstractBackgroundSurvivors of critical care are at risk of long‐term disability from musculoskeletal (MSK) impairments. These can have a biopsychosocial impact on the patient and their families with a reduction in health‐related quality of life, increased health care utilization, caregiving roles and associated psychological distress.AimsTo understand the experiences of patients living with MSK impairments following critical illness, and family and health care professionals supporting them, to inform the development of a future intervention to improve MSK health following critical illness.Study DesignA four‐site qualitative case study approach will be taken, with each of the four hospital sites and associated community services representing a case site. We will conduct semi‐structured interviews with 10–15 patients/family members and 10–15 health care professionals about their experiences of MSK impairment following critical illness. Interviews will be audio recorded, transcribed verbatim and analysed using reflexive thematic analysis within a descriptive phenomenological approach. Alongside interview data, analysis of publicly available policy documentation, patient‐facing materials and information from service leads at the four sites will be conducted. Discourse analysis will be used for this case study documentation.ResultsThis protocol describes a qualitative study exploring the experiences of patients living with MSK impairments following critical illness, and the family and health care professionals supporting them.Relevance to Clinical PracticeData analysis will illuminate their experiences and enable data richness to contribute to the qualitative body of evidence of intensive care unit (ICU) survivors. These findings will inform the development of a complex intervention for MSK rehabilitation after critical illness.
Patient Harm and Institutional Avoidability of Out-of-Hours Discharge From Intensive Care: An Analysis Using Mixed Methods*
OBJECTIVES: Out-of-hours discharge from ICU to the ward is associated with increased in-hospital mortality and ICU readmission. Little is known about why this occurs. We map the discharge process and describe the consequences of out-of-hours discharge to inform practice changes to reduce the impact of discharge at night. DESIGN: This study was part of the REcovery FoLlowing intensive CarE Treatment mixed methods study. We defined out-of-hours discharge as 16:00 to 07:59 hours. We undertook 20 in-depth case record reviews where in-hospital death after ICU discharge had been judged “probably avoidable” in previous retrospective structured judgment reviews, and 20 where patients survived. We conducted semistructured interviews with 55 patients, family members, and staff with experience of ICU discharge processes. These, along with a stakeholder focus group, informed ICU discharge process mapping using the human factors–based functional analysis resonance method. SETTING: Three U.K. National Health Service hospitals, chosen to represent different hospital settings. SUBJECTS: Patients discharged from ICU, their families, and staff involved in their care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Out-of-hours discharge was common. Patients and staff described out-of-hours discharge as unsafe due to a reduction in staffing and skill mix at night. Patients discharged out-of-hours were commonly discharged prematurely, had inadequate handover, were physiologically unstable, and did not have deterioration recognized or escalated appropriately. We identified five interdependent function keys to facilitating timely ICU discharge: multidisciplinary team decision for discharge, patient prepared for discharge, bed meeting, bed manager allocation of beds, and ward bed made available. CONCLUSIONS: We identified significant limitations in out-of-hours care provision following overnight discharge from ICU. Transfer to the ward before 16:00 should be facilitated where possible. Our work highlights changes to help make day time discharge more likely. Where discharge after 16:00 is unavoidable, support systems should be implemented to ensure the safety of patients discharged from ICU at night.