Urgent Endovascular Aortic Repair Requiring Coverage of the Left Subclavian Artery.

BACKGROUND: Evaluation of the optimal left subclavian artery (LSA) management during thoracic endovascular aortic repair (TEVAR) involving the distal aortic arch in an urgent setting. METHODS: A total of 52 patients with acute aortic syndromes underwent TEVAR (March 2017 to May 2021) requiring proximal landing in the distal aortic arch. Decision for partial or complete LSA ostial endograft coverage, with or without additional bypassing, was made depending upon the aortic pathology and vascular anatomy. We focused on the patency of the circle of Willis and the unilateral dominance of one carotid or a vertebral artery: 35% underwent complete (complete LSA group) and 17% partial LSA coverage (partial LSA group), whereas in 48% the LSA was reached only by the bare springs of the endograft (control group). A total of 22% of the complete LSA group underwent LSA bypass before TEVAR, whereas 11% underwent cerebrospinal fluid drainage. Endpoints were 30-day and 1-year mortality, stroke, spinal cord ischemia (SCI), and malperfusion. RESULTS: Technical success was achieved in 96%. The endograft length was 171 ± 34 (complete LSA group) versus 151 ± 22 (partial LSA group) versus 181 ± 52 mm (control group), covering 6 ± 2 versus 5 ± 1 versus 7 ± 2 intercostal arteries. The 30-day mortality, stroke and SCI rates did not differ. One patient with arm malperfusion underwent LSA bypass post-TEVAR. After 1 year, aortic interventions occurred in 6 (complete LSA group) versus 22 (partial LSA group) versus 13% (control group). One-year mortality (0 vs. 0 vs. 8%), stroke (6 vs. 0 vs. 4%), and SCI (0 vs. 0 vs. 4%) were similar between groups. CONCLUSION: With an adequate analysis of vascular anatomy, coverage of the LSA for TEVAR is safe and may offer results similar to TEVAR starting distal to the LSA.

Shoulder complaints and incidence of shoulder pathologies after contralateral major amputation in the mid and long-term.

INTRODUCTION: Amputations of the upper extremity are rare but present a life-altering event that is accompanied with considerable restrictions for the affected patients. Even with functional prosthesis, tasks of the amputated limb are usually transferred to the unaffected arm which could result in complaints of the unaffected shoulder in the mid and long term. We therefore aimed to investigate musculoskeletal pain and morphological degenerative changes of the shoulder following a contralateral amputation. MATERIALS AND METHODS: We included all patients with a major amputation treated at our institution with a minimum of three years since the amputation. All patients received an MRI of both shoulders and were investigated using validated scores for the upper extremity and physical activity (SSV, ASES, DASH, GPAQ, SF-36). Results of the MRIs were investigated for morphological changes by two blinded investigators comparing the side of the amputation and the unharmed upper extremity and results were correlated to the time since amputation and their physical activity. RESULTS: A total of 20 patients with a mean age of 56 ± 19.9 years (range, 23-82 years) could be included in the study. The mean time since the amputation was 26.3 ± 19 years (range, 3-73 years). On the unharmed upper extremity, the mean SSV was 61.9 ± 24.6, the mean ASES-Score 54.5 ± 20.3, the Constant-score of 63.7 ± 40.4 and a DASH-score of 47.6 ± 23.8. The MRI of the unharmed shoulder showed significant more full-thickness rotator cuff tears and joint effusion compared to the side of the amputation. Significant differences in the degree of a glenohumeral arthritis, AC-joint arthritis, or partial rotator cuff tears could not be found between shoulders. CONCLUSION: Amputations of the upper extremity are associated with a high disability of the unharmed upper extremity and more full thickness rotator cuff tears compared to the side of the amputation. However, the small number of patients and rotator cuff injuries should be kept in mind when interpreting the data. LEVEL OF EVIDENCE: IV (retrospective case series).

FYCO1 Increase and Effect of Arimoclomol-Treatment in Human VCP-Pathology.

Dominant VCP-mutations cause a variety of neurological manifestations including inclusion body myopathy with early-onset Paget disease and frontotemporal dementia 1 (IBMPFD). VCP encodes a ubiquitously expressed multifunctional protein that is a member of the AAA+ protein family, implicated in multiple cellular functions ranging from organelle biogenesis to ubiquitin-dependent protein degradation. The latter function accords with the presence of protein aggregates in muscle biopsy specimens derived from VCP-patients. Studying the proteomic signature of VCP-mutant fibroblasts, we identified a (pathophysiological) increase of FYCO1, a protein involved in autophagosome transport. We confirmed this finding applying immunostaining also in muscle biopsies derived from VCP-patients. Treatment of fibroblasts with arimoclomol, an orphan drug thought to restore physiologic cellular protein repair pathways, ameliorated cellular cytotoxicity in VCP-patient derived cells. This finding was accompanied by increased abundance of proteins involved in immune response with a direct impact on protein clearaqnce as well as by elevation of pro-survival proteins as unravelled by untargeted proteomic profiling. Hence, the combined results of our study reveal a dysregulation of FYCO1 in the context of VCP-etiopathology, highlight arimoclomol as a potential drug and introduce proteins targeted by the pre-clinical testing of this drug in fibroblasts.

ANO5-related muscle diseases: From clinics and genetics to pathology and research strategies.

Anoctamin-5 (ANO5) is a multi-pass membrane protein localized to the sarcolemma and the sarcoplasmic reticulum. Mutations were linked to rare autosomal recessive muscle diseases. Here, we summarize the clinical spectrum, imaging data and molecular research findings as well as results of animal modeling, which significantly moved forward the understanding of mechanisms underlying ANO5-related muscle diseases. Given that precise histological information on inflammatory processes taking place in patient-derived muscle are still lacking, an (immuno)histological study on biopsies derived from six ANO5-patients was performed showing focal accumulation of necrotic fibers, mild fiber-size variances and myophagocytosis. In addition, MRI data of four ANO5-patients (including a 10-year follow-up in one patient) are presented and discussed in the context of previously published MRI-findings. Hence, data presented in this article combining a review of the literature with own myopathological findings address scientific trends and open questions on ANO5-related muscle diseases, which would be of significant interest for a wide neuromuscular diseases community. To conclude, a clear genotype-phenotype correlation does not exist, and ANO5-related muscle disorders might represent the next entity of a clinical continuum with varying degree of muscle cell pathologies. In addition, results of pre-clinical studies allowed the definition of suitable cell and animal models characterized by certain histological and functional pathologies resembling the human phenotype. These models might serve as suitable systems for testing of interventional concepts in future.

A Highly Reliable Convolutional Neural Network Based Soft Tissue Sarcoma Metastasis Detection from Chest X-ray Images: A Retrospective Cohort Study.

INTRODUCTION: soft tissue sarcomas are a subset of malignant tumors that are relatively rare and make up 1% of all malignant tumors in adulthood. Due to the rarity of these tumors, there are significant differences in quality in the diagnosis and treatment of these tumors. One paramount aspect is the diagnosis of hematogenous metastases in the lungs. Guidelines recommend routine lung imaging by means of X-rays. With the ever advancing AI-based diagnostic support, there has so far been no implementation for sarcomas. The aim of the study was to utilize AI to obtain analyzes regarding metastasis on lung X-rays in the most possible sensitive and specific manner in sarcoma patients. METHODS: a Python script was created and trained using a set of lung X-rays with sarcoma metastases from a high-volume German-speaking sarcoma center. 26 patients with lung metastasis were included. For all patients chest X-ray with corresponding lung CT scans, and histological biopsies were available. The number of trainable images were expanded to 600. In order to evaluate the biological sensitivity and specificity, the script was tested on lung X-rays with a lung CT as control. RESULTS: in this study we present a new type of convolutional neural network-based system with a precision of 71.2%, specificity of 90.5%, sensitivity of 94%, recall of 94% and accuracy of 91.2%. A good detection of even small findings was determined. DISCUSSION: the created script establishes the option to check lung X-rays for metastases at a safe level, especially given this rare tumor entity.

Body mass index and abdominal wall thickness correlate with perforator caliber in free abdominal tissue transfer for breast reconstruction.

INTRODUCTION: The aim of the study was to investigate the relationship of BMI and abdominal wall thickness (AWT) with the diameter of the dominant deep inferior epigastric artery perforator (DIEP) as well as DIEA branching pattern in preoperatively performed computed tomography angiography (CTA). PATIENTS AND METHODS: We conducted a retrospective study including all patients undergoing DIEP flap breast reconstruction with available CTAs from November 2013 to April 2018 in our department. The caliber-strongest DIEP was detected after passage of the rectus fascia as well as the superficial inferior epigastric artery (SIEA) and correlated with the AWT 5 cm above and below the umbilicus, lateral at the level of the umbilicus and at the level of the anterior superior iliac spine (ASIS), and with BMI. RESULTS: Seventy-seven patients met the inclusion criteria (age: 47.3 ± 8.9 years). We observed a significant relationship (p < 0.05) between DIEP (mean ∅ = 2.98 mm) and BMI (r = 0.353), the AWT supra- and infraumbilical (r ≥ 0.32), and the AWT lateral at the level of the umbilicus and ASIS (r ≥ 0.25). In addition, there was a highly significant correlation (p < 0.01) between SIEA and BMI (r = 0.389) and between the AWT lateral at the level of ASIS (r ≥ 0.41). CONCLUSION: We demonstrated a correlation of the diameter of the dominant DIEP with both BMI and AWT. Focusing on the diameter, in patients with a high AWT at the level of the ASIS, the SIEA, if present, may represent an alternative therapeutic option.

Diagnosis of leptomeningeal disease in diffuse large B-cell lymphomas of the central nervous system by flow cytometry and cytopathology.

Reliable detection of leptomeningeal disease has the potential of facilitating the diagnosis of central nervous system (CNS) lymphoma and is important for therapeutic considerations. Currently, the standard diagnostic procedure for the detection of lymphoma in the cerebrospinal fluid is cytopathology. To improve the limited specificity and sensitivity of cytopathology, flow cytometry has been suggested as an alternative. Here, we evaluated multi-parameter flow cytometry in combination with conventional cytopathology in cerebrospinal fluid (CSF) samples from 30 patients with primary CNS lymphoma and seven patients with secondary CNS lymphoma. Overall, in 11 of 37 (29.7%) patients with CNS lymphoma, lymphoma cells were detected in CSF by flow cytometry, while cytopathology was less sensitive displaying unequivocally malignant CSF cells in only seven of all 37 (18.9%) patients. Six (16.2%) patients showed cytopathological results suspicious of lymphoma; however, in only one of these patients, the diagnosis of CSF lymphoma cells could be confirmed by flow cytometry. In primary CNS lymphomas (PCNSL), seven of 30 (23.3%) patients were positive for CSF lymphoma cells in flow cytometry, in contrast to four (13.3%) patients with PCNSL with definitely positive cytopathology. In summary, our results suggest that multi-parameter flow cytometry increases the sensitivity and specificity of leptomeningeal disease detection in CNS lymphomas. Both methods should be applied concurrently for complementary diagnostic assessment in patients with CNS lymphoma.

Detection of free immunoglobulin light chains in cerebrospinal fluids of patients with central nervous system lymphomas.

Diagnosis of central nervous system (CNS) lymphoma depends on histopathology of brain biopsies, because no reliable disease marker in the cerebrospinal fluid (CSF) has been identified yet. B-cell lymphomas such as CNS lymphomas are clonally restricted and express either kappa or lambda immunoglobulin light chains. The aim of this study was to find out a potential diagnostic value of free immunoglobulin light chains released into the CSF of CNS lymphoma patients. Kappa (kappa) and lambda (lambda) free immunoglobulin light chains (FLC) were measured in CSF and serum samples collected from 21 patients with primary and secondary CNS lymphomas and 14 control patients with different neurologic disorders. FLC concentrations and ratios were compared between patient groups and were further analyzed in correlation with clinical, cytopathological, and radiological findings. FLC concentrations for all patients were lower in CSF when compared to serum. In patients with CNS lymphoma, the FLC ratios in CSF were higher (range 392-0.3) compared to control patients (range 3.0-0.3). Irrespective of cytopathological proven lymphomatous meningitis, in 11/21 lymphoma CSF samples the FLC ratios were markedly above 3.0 indicating a clonally restricted B-cell population. Increased FLC ratios in CSF were found in those patients showing subependymal lymphoma contact as detected in magnetic resonance imaging. In summary, this is the first report demonstrating that a significant proportion of patients with CNS lymphomas display a markedly increased FLC ratio in the CSF.