Learning Curve of Endoscopic Lumbar Discectomy - A Systematic Review and Meta-Analysis of Individual Participant and Aggregated Data.

STUDY DESIGN: A systematic review and meta-analysis of individual participant and aggregated data. OBJECTIVES: To define the learning curves of endoscopic discectomies using unified statistical methodologies. METHODS: Searches returned 913 records, with 118 full-text articles screened. Studies of endoscopic lumbar spine surgery reporting outcomes by case order were included. Mixed-effects nonlinear, logistic, and beta meta-regressions prdwere conducted to define the learning curves. RESULTS: 13 studies involving 864 patients among 15 surgeons were included in total. For transforaminal endoscopic discectomy, the estimated operating time for the first case was 95 min [CI: 87-104], and the estimated plateau was 66 minutes [CI: 51-81]. An estimated 21 cases [CI: 18-25] were required to overcome 80% of this deficit, but near-plateau performance was expected only after 59 cases [CI: 51-70]. The estimated risk of surgical complications on the first case was 25% [CI: 11%-46%], with an 80% reduction in relative risk requiring an estimated 41 cases. The expected postoperative VAS leg pain score after the first case was 2.7 [CI: 1.8-3.8], with an 80% improvement requiring an estimated 96 cases. Similar numbers were required to overcome the learning curves in interlaminar and biportal endoscopic discectomies. CONCLUSIONS: Approximately 60 cases are required to achieve proficiency in endoscopic lumbar spine surgery, although the greatest part of the learning curve can be overcome with 20 cases. This should be considered when designing implementation programmes for surgeons and service providers that wish to incorporate endoscopic spinal surgery into their practice.

Validation of a surgical simulator and establishment of quantitative performance thresholds-RealSpine simulation system for open lumbar decompressions.

BACKGROUND CONTEXT: The majority of surgical training is conducted in real-world operations. High-fidelity surgical simulators may provide a safer environment for surgical training. However, the extent that it reflects real-world operations and surgical ability is often poorly characterized. PURPOSE: (1) Assess the validity and fidelity of a surgical simulator; (2) Examine the quantitative relationship between simulation performance and markers of real-world ability; (3) Establish thresholds for surgical expertise, and estimate their external validity and accuracy. STUDY DESIGN/SETTING: A cohort study of surgeons at a British neurosurgical center. STUDY SAMPLE: Ten early-career "novice" surgeons and 8 board-certified "expert" neurosurgeons. OUTCOMES MEASURES: (1) Face and content validity, and visual and haptic fidelity; (2) Construct validity; (3) Predictive and discriminative utility of quantitative performance thresholds. METHODS: Participants performed unilateral lumbar decompressions on high-fidelity spinal simulators that replicate the bony and soft tissue anatomy along with physiological processes such as bleeding and CSF leaks. Operating times, measured from first surgical action to either self-perceived satisfactory decompression or the end of allocated time, were recorded. The performance was also assessed independently by 2 blinded spinal subspecialist neurosurgeons using OSATS, a validated surgical assessment tool that utilizes 5-point scales on a variety of technical domains to grade the overall technical proficiency. Validity and fidelity were assessed by expert neurosurgeons using quantitative questionnaires. Construct validity was assessed by ordinal regression of simulation performance against real-world surgical grade and portfolio. Thresholds of expert status by simulation performance was established, and their predictive and discriminative utility assessed by crossvalidation accuracy and AUC-ROC. RESULTS: Operating time and expert assessments of simulation performance (OSATS) were strong and significant prdictors of surrogate markers of real-world surgical ability. The thresholds for expert status were operating time of 15 minutes and modified OSATS score of 15/20. These thresholds predicted expert status with 84.2% and 71.4% accuracy respectively. Strong discriminative ability was demonstrated by AUC-ROC of 0.95 and 0.83 respectively. All expert surgeons agreed that RealSpine simulators demonstrate high face validity, and high visual and haptic fidelity, with overall scores showing statistically significant agreement on these items (all scores at least 4/5, p<.0001). There was less consensus on content validity, but with still significant overall agreement (average score: 3.75/5, p=.023). CONCLUSIONS: Real-world surgical ability and experience can be accurately predicted by defining objective quantitative thresholds on high-fidelity simulations. The thresholds established here, along with other data presented in this paper, may inform objectives and standards to be established in a spinal surgical training curriculum.

Single-cell transcriptome analysis reveals subtype-specific clonal evolution and microenvironmental changes in liver metastasis of pancreatic adenocarcinoma and their clinical implications.

BACKGROUND: Intratumoral heterogeneity (ITH) and tumor microenvironment (TME) of pancreatic ductal adenocarcinoma (PDAC) play important roles in tumor evolution and patient outcomes. However, the precise characterization of diverse cell populations and their crosstalk associated with PDAC progression and metastasis is still challenging. METHODS: We performed single-cell RNA sequencing (scRNA-seq) of treatment-naïve primary PDAC samples with and without paired liver metastasis samples to understand the interplay between ITH and TME in the PDAC evolution and its clinical associations. RESULTS: scRNA-seq analysis revealed that even a small proportion (22%) of basal-like malignant ductal cells could lead to poor chemotherapy response and patient survival and that epithelial-mesenchymal transition programs were largely subtype-specific. The clonal homogeneity significantly increased with more prevalent and pronounced copy number gains of oncogenes, such as KRAS and ETV1, and losses of tumor suppressor genes, such as SMAD2 and MAP2K4, along PDAC progression and metastasis. Moreover, diverse immune cell populations, including naïve SELLhi regulatory T cells (Tregs) and activated TIGIThi Tregs, contributed to shaping immunosuppressive TMEs of PDAC through cellular interactions with malignant ductal cells in PDAC evolution. Importantly, the proportion of basal-like ductal cells negatively correlated with that of immunoreactive cell populations, such as cytotoxic T cells, but positively correlated with that of immunosuppressive cell populations, such as Tregs. CONCLUSION: We uncover that the proportion of basal-like subtype is a key determinant for chemotherapy response and patient outcome, and that PDAC clonally evolves with subtype-specific dosage changes of cancer-associated genes by forming immunosuppressive microenvironments in its progression and metastasis.

Description of Roseibium sediminicola sp. nov. Isolated from Sediment of a Tidal Flat on the Yellow Sea Coast.

A Gram-stain-negative, aerobic, rod-shaped, motile, flagellated bacterial strain, designated as CAU 1639T, was isolated from the tidal flat sediment on the Yellow Sea in the Republic of Korea. Growth of the isolate was observed at 20-37 °C, at pH 5.0-10.5 and with 0-7% (w/v) NaCl. The genomic DNA G + C content was 60.8%. Phylogenetic analysis, grounded on 16S rRNA gene sequencing, revealed that strain CAU 1639T was closely related to species within the genus Roseibium. It shared the highest similarity with Roseibium album CECT 5095T, followed by Roseibium aggregatum IAM 12614T and Roseibium salinum Cs25T, with 16S rRNA gene sequence similarity ranging from 98.0-98.4%. It was observed that the average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values ranged between 72.5-79.5 and 20.0-22.9%, respectively. The polyphasic taxonomic analysis reveals that strain CAU 1639T represents a novel species in the genus Roseibium with the proposed name Roseibium sediminicola sp. nov. The type strain is CAU 1639T (= KCTC 82430T = MCCC 1K06081T).

Successful Treatment of Eosinophilic Enterocolitis in an Adult Patient With Adalimumab.

Eosinophilic gastrointestinal diseases are increasing in prevalence, but understanding of their causes and effective treatments remain elusive, especially in adults. We present a case of eosinophilic gastroenteritis and colitis with extraintestinal manifestations that was successfully treated with a tumor necrosis factor α inhibitor, adalimumab.

Lumbar decompression and fusion for symptomatic spinal stenosis in a patient with chronic thoracic sensory level from prior transverse myelitis: a case report.

BACKGROUND: Many patients with transverse myelitis suffer from sensory loss below the spinal level of the lesion. This is commonly associated with chronic neuropathic pain. However, the presence of somatic pain below a complete thoracic sensory level after transverse myelitis is exceptionally rare, and it is unclear if surgical decompression is an effective form of treatment for these patients. CASE PRESENTATION: In this report, we describe a 22-year-old Caucasian female who suffered from chronic lumbar back pain despite a complete thoracic sensory level secondary to prior transverse myelitis. Imaging demonstrated multilevel central stenosis below the sensory level, and her pain improved after surgical decompression. To our knowledge, this is the first reported case of symptomatic lumbar stenosis below a sensory level after transverse myelitis successfully treated with surgical decompression. CONCLUSION: This is the first reported case of a patient with symptomatic lumbar stenosis after transverse myelitis whose lower back pain and quality of life improved following surgical decompression and fusion. This case provides evidence that typical lumbago is possible in patients with sensory loss from transverse myelitis, and standard lumbar decompression may provide benefit for these patients.

Dual-Targeted Therapy with Upadacitinib and Ustekinumab in Medically Complex Crohn's Disease.

BACKGROUND AND AIMS: Ongoing efforts to break the therapeutic ceiling in inflammatory bowel disease include combination therapy approaches. Dual-targeted therapy (DTT) has been reported in case reports and small case series. This report describes our experience with ustekinumab (UST) and upadacitinib (UPA) as DTT in patients with Crohn's disease (CD). METHODS: In this retrospective, observational study, we reviewed medical records of patients with CD treated with combined UST and UPA between April 2021 and July 2022. Clinical remission was defined as Harvey-Bradshaw Index (HBI) ≤ 4, and clinical response was defined as decrease in HBI ≥ 3 or physician's assessment of clinical response. RESULTS: We identified 10 CD patients treated with UST/UPA, with median follow-up period of 10 months (interquartile range (IQR) 7.3-12). Median age was 35.5 years (IQR 28.3-43.8) and median number of prior biologic treatment exposures was 4 (IQR 4-5). Indications for UST/UPA were active CD (n = 6), extraintestinal manifestations (EIM) (n = 2), and both active CD and EIM (n = 2). Five of six patients with active CD achieved clinical remission with UST/UPA. Two patients with active EIM (joint pain) achieved resolution of their symptoms. One patient exhibited improvement in both conditions. Three patients developed mild respiratory symptoms and one experienced bowel obstruction. Two patients developed nausea resulting in de-escalation of treatment interval or discontinuation altogether. CONCLUSION: Based on our case series, combination therapy with UST and UPA may be effective and appears safe in refractory Crohn's disease and for patients with co-existing extraintestinal manifestations.

Genomic characterization of an esthesioneuroblastoma with spinal metastases: illustrative case.

BACKGROUND: Esthesioneuroblastoma (ENB) is a rare neoplasm of the sinonasal tract. Currently, the optimal treatment includes maximal resection combined with radiotherapy and/or chemotherapy. Although ENBs often recur and have an aggressive clinical course, spinal metastases are extremely rare and the underlying molecular mechanisms are poorly understood. OBSERVATIONS: Here, the authors describe a 50-year-old male with an aggressive ENB, initially treated with resection and chemotherapy/radiation, who developed multiple thoracic and lumbar spinal metastases. The authors performed targeted exome sequencing on both the resected primary tumor and biopsied spinal metastases, which revealed 12 total variants of unknown clinical significance in genes associated with the PI3K/AKT/mTOR pathway, chromatin remodeling, DNA repair, and cell proliferation. Six of these variants were restricted to the metastatic lesion and included missense mutations with predicted functional effects in GRM3, DNMT3B, PLCG2, and SPEN. LESSONS: This report discusses the potential impact of these variants on tumor progression and metastasis, as well as the implications for identifying potential new biomarkers and therapies.

Single-cell RNA Sequencing Reveals Novel Cellular Factors for Response to Immunosuppressive Therapy in Aplastic Anemia.

Aplastic anemia (AA) is a lethal hematological disorder; however, its pathogenesis is not fully understood. Although immunosuppressive therapy (IST) is a major treatment option for AA, one-third of patients do not respond to IST and its resistance mechanism remains elusive. To understand AA pathogenesis and IST resistance, we performed single-cell RNA sequencing (scRNA-seq) of bone marrow (BM) from healthy controls and patients with AA at diagnosis. We found that CD34+ early-stage erythroid precursor cells and PROM1+ hematopoietic stem cells were significantly depleted in AA, which suggests that the depletion of CD34+ early-stage erythroid precursor cells and PROM1+ hematopoietic stem cells might be one of the major mechanisms for AA pathogenesis related with BM-cell hypoplasia. More importantly, we observed the significant enrichment of CD8+ T cells and T cell-activating intercellular interactions in IST responders, indicating the association between the expansion and activation of T cells and the positive response of IST in AA. Taken together, our findings represent a valuable resource offering novel insights into the cellular heterogeneity in the BM of AA and reveal potential biomarkers for IST, building the foundation for future precision therapies in AA.

Ozanimod-Exposed Patients with Ulcerative Colitis Undergoing Total Colectomy Exhibit Unique Lymph Node Histologic Changes.

INTRODUCTION: Ozanimod regulates lymphocyte egress from the spleen and lymph nodes into the systemic circulation. The histologic changes which occur in the lymph nodes of patients on ozanimod is unknown. MATERIALS AND METHODS: This retrospective study included patients with UC undergoing total colectomy for treatment-refractory disease who received ozanimod and a cohort of patients with UC undergoing colectomy who did not have ozanimod exposure. Histology of the lymph nodes from the mesentery of colectomy specimens was reviewed and multiple features were scored by experienced pathologists. RESULTS: Six (13%) ozanimod-treated patients with UC required surgery for treatment-refractory disease. Colectomy specimen data were available for 5 patients (1 patient had surgery at an outside center). Lymph node specimens from 6 control patients with UC who had colectomy were examined. Histologic examination of lymph nodes showed that patients treated with ozanimod had significantly greater extent of dilated sinuses (p=0.03) and greater degrees of sinus histiocytosis (p=0.03) compared with control patients. In addition, there was a trend towards more Castleman-like angiotrophic hyperplasia, plasma cell infiltration and subcortical interfollicular expansion in ozanimod treated patients. CONCLUSION: This study identifies unique histologic changes in the lymph nodes of patients with UC treated with ozanimod. The presence of sinus histiocytosis and dilated sinuses is in keeping with the known mechanism of action of ozanimod and suggests that blocking lymphocyte egression from lymph nodes was insufficient to ameliorate disease severity in these patients. The possibility of Castleman-like features identified in several of the cases, needs to be further investigated.

Upadacitinib Is Effective and Safe in Both Ulcerative Colitis and Crohn's Disease: Prospective Real-World Experience.

BACKGROUND & AIMS: Upadacitinib is a novel selective Janus kinase 1 inhibitor that has shown efficacy in the treatment of moderate to severe ulcerative colitis (UC) and Crohn's disease (CD), and has received Food and Drug Administration approval for UC. We report a large real-world experience with upadacitinib in UC and CD. METHODS: We performed a prospective analysis of clinical outcomes on upadacitinib in patients with UC and CD using predetermined intervals at weeks 0, 2, 4, and 8 as part of a formalized treatment protocol at our institution. We used the Simple Clinical Colitis Activity Index and the Harvey-Bradshaw index, as well as C-reactive protein and fecal calprotectin to assess efficacy, and also recorded treatment-related adverse events and serious adverse events. RESULTS: A total of 105 patients were followed up for 8 weeks on upadacitinib, 84 of whom (44 UC patients, 40 CD patients) were initiated because of active luminal or perianal disease and included in the analysis. One hundred percent previously received anti-tumor necrosis factor therapy, and 89.3% had received 2 or more advanced therapies. At 4 and 8 weeks of treatment for UC, 19 of 25 (76.0%) and 23 of 27 (85.2%) achieved clinical response and 18 of 26 (69.2%) and 22 of 27 (81.5%) achieved clinical remission, respectively. Of those who previously were tofacitinib-exposed, 7 of 9 (77.8%) achieved clinical remission by 8 weeks. In CD, 13 of 17 (76.5.%) achieved clinical response and 12 of 17 (70.6%) achieved clinical remission by 8 weeks. Of those with increased fecal calprotectin and C-reactive protein levels, 62% and 64% normalized by week 8, respectively. Results were seen as early as week 2 in both UC and CD, with clinical remission rates of 36% and 56.3.%, respectively. Acne was the most commonly reported adverse event, occurring in 24 of 105 patients (22.9%). CONCLUSIONS: In this large real-world experience in medically resistant patients with UC or CD, we report that upadacitinib is rapidly effective and safe, including in those who had prior tofacitinib exposure. This study was approved by the Institutional Review Board at the University of Chicago (IRB20-1979).

Targeting patient recovery priorities in degenerative cervical myelopathy: design and rationale for the RECEDE-Myelopathy trial-study protocol.

INTRODUCTION: Degenerative cervical myelopathy (DCM) is a common and disabling condition of symptomatic cervical spinal cord compression secondary to degenerative changes in spinal structures leading to a mechanical stress injury of the spinal cord. RECEDE-Myelopathy aims to test the disease-modulating activity of the phosphodiesterase 3/phosphodiesterase 4 inhibitor Ibudilast as an adjuvant to surgical decompression in DCM. METHODS AND ANALYSIS: RECEDE-Myelopathy is a multicentre, double-blind, randomised, placebo-controlled trial. Participants will be randomised to receive either 60-100 mg Ibudilast or placebo starting within 10 weeks prior to surgery and continuing for 24 weeks after surgery for a maximum of 34 weeks. Adults with DCM, who have a modified Japanese Orthopaedic Association (mJOA) score 8-14 inclusive and are scheduled for their first decompressive surgery are eligible for inclusion. The coprimary endpoints are pain measured on a visual analogue scale and physical function measured by the mJOA score at 6 months after surgery. Clinical assessments will be undertaken preoperatively, postoperatively and 3, 6 and 12 months after surgery. We hypothesise that adjuvant therapy with Ibudilast leads to a meaningful and additional improvement in either pain or function, as compared with standard routine care. STUDY DESIGN: Clinical trial protocol V.2.2 October 2020. ETHICS AND DISSEMINATION: Ethical approval has been obtained from HRA-Wales.The results will be presented at an international and national scientific conferences and in a peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN Number: ISRCTN16682024.

Risankizumab-rzaa: A New Therapeutic Option for the Treatment of Crohn's Disease.

OBJECTIVE: To review the pharmacologic and clinical profile of risankizumab-rzaa in the treatment of Crohn's disease (CD). DATA SOURCES: A PubMed search was performed from inception to August 2022 using keywords risankizumab, risankizumab-rzaa, interleukin-23 inhibitor, and Crohn's disease. Information was obtained from package inserts as well as published abstracts. STUDY SELECTION AND DATA EXTRACTION: Phase 2 and 3 studies plus relevant literature on risankizumab-rzaa pharmacologic and clinical profile were reviewed. DATA SYNTHESIS: Risankizumab-rzaa approval was based on ADVANCE, MOTIVATE, and FORTIFY. In these 3 phase 3 studies involving patients with moderate to severe CD, risankizumab-rzaa, when compared with placebo, resulted in clinical remission and endoscopic response in a significantly higher proportion of patients in both the induction and maintenance phase. In addition, risankizumab-rzaa met the secondary endpoints of clinical response, endoscopic improvement, corticosteroid-free remission, and mucosal healing. Common adverse events noted include nasopharyngitis, arthralgia, headache, abdominal pain, and nausea. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Risankizumab-rzaa is the first selective IL-23 inhibitor approved for CD and provides an additional therapeutic option for patients, particularly those who have been previously treated with other advanced inflammatory bowel disease therapies. Additional studies are required to determine how to best position risankizumab-rzaa in both bio-naïve and bio-experienced patients with CD. CONCLUSIONS: Risankizumab-rzaa is the most recent therapeutic advance for CD. It has a selective mechanism of action with a similar safety profile comparable with other currently approved advanced therapies.

Cellular plasticity and immune microenvironment of malignant pleural effusion are associated with EGFR-TKI resistance in non-small-cell lung carcinoma.

Malignant pleural effusion (MPE) is a complication of lung cancer that can be used as an alternative method for tissue sampling because it is generally simple and minimally invasive. Our study evaluated the diagnostic potential of non-small-cell lung carcinoma (NSCLC)-associated MPE in terms of understanding tumor heterogeneity and identifying response factors for EGFR tyrosine kinase inhibitor (TKI) therapy. We performed a single-cell RNA sequencing analysis of 31,743 cells isolated from the MPEs of 9 patients with NSCLC (5 resistant and 4 sensitive to EGFR TKI) with EGFR mutations. Interestingly, lung epithelial precursor-like cells with upregulated GNB2L1 and CAV1 expression were enriched in the EGFR TKI-resistant group. Moreover, GZMK upregulated transitional effector T cells, and plasmacytoid dendritic cells were significantly enriched in the EGFR TKI-resistant patients. Our results suggest that cellular plasticity and immunosuppressive microenvironment in MPEs are potentially associated with the TKI response of patients with EGFR-mutated NSCLC.

Adalimumab-Adbm: The First Interchangeable Biosimilar for the Treatment of Inflammatory Diseases.

OBJECTIVE: The objective of the study was to review the pharmacologic and clinical profile of adalimumab-adbm (BI 695501), the first interchangeable biosimilar for treatment of inflammatory diseases. DATA SOURCES: A PubMed search was conducted from inception to December 2021 using the keywords BI 695501 and adalimumab-adbm. Information was also obtained from published abstracts and package inserts. STUDY SELECTION AND DATA EXTRACTION: Phase 1, 2 and 3 studies plus relevant literature on adalimumab-adbm pharmacologic and clinical profile were reviewed. DATA SYNTHESIS: Adalimumab-adbm approval was based on a series of phase 3 VOLTAIRE trials, which evaluated the biosimilar's efficacy and safety in the treatment of moderate to severe Crohn's disease, rheumatoid arthritis, and psoriasis. Interchangeability status was granted based on data from the VOLTAIRE-X trial. The VOLTAIRE and VOLTAIRE-X studies demonstrated comparable efficacy and safety between adalimumab-adbm and reference adalimumab. Common adverse events included infections and injection site reactions. Similar to reference adalimumab, adalimumab-adbm contains black box warnings related to serious infections and malignancy. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Adalimumab-adbm is the first interchangeable biosimilar to be approved for inflammatory diseases and has the potential to improve patient access to treatment while decreasing medication-related costs. However, it will not be commercially available for patient use until 2023 and its adoption into clinical practice may face potential barriers seen with other biosimilars. CONCLUSION: As an interchangeable biosimilar with comparable efficacy and safety to reference adalimumab, adalimumab-adbm is an important advance toward cost-effective management of inflammatory diseases.

Prevalence of olfactory dysfunction and quality of life in hospitalised patients 1 year after SARS-CoV-2 infection: a cohort study.

OBJECTIVES: To determine the long-term prevalence of olfactory and/or gustatory dysfunction (OD±GD), associated risk factors and impact on quality of life (QoL) in previously hospitalised patients with COVID-19 1 year after infection. DESIGN: A single-centre cohort study. SETTING: Patients admitted at a large central London hospital with COVID-19 infection between 10 February 2020 and 22 May 2020. PARTICIPANTS: 150 adult subjects with previously confirmed SARS-CoV-2 infection were recruited between 10 December 2020 and 29 January 2021. Participants were predominantly male (102/150, 68.0%); mean age 58.0±15.9 years and 41.2% (56/136) were of black, Asian and minority ethnic backgrounds. MAIN OUTCOME MEASURES: EQ-5D-5L values and Sino-Nasal Outcome Test-22 (SNOT-22) scores. RESULTS: Long-term prevalence of OD±GD was 12.8% (19/149) at median time of 264.5 days following SARS-CoV-2 infection onset. Patients with OD±GD had a significantly higher median total SNOT-22 score (46.1; Q1-Q3: 23.0-60.0; 95% CI 23.0 to 60.0) compared with those without (16.0; Q1-Q3: 5.0-30.5; 95% CI 12.0 to 18.0) (p=0.0002), reflecting poorer QoL, particularly psychological well-being (p=0.0004), which was not alleviated with time (p=0.4977). Median EQ-5D-5L value was not significantly different between patients with OD±GD (0.70; Q1-Q3: 0.38-0.83; 95% CI 0.38 to 0.83) and those without (0.83; Q1-Q3: 0.61-0.94; 95% CI 0.75 to 0.89) (p=0.0627). Age, sex, ethnicity, smoking status, highest C reactive protein value, intubation and ventilation, and oxygen supplementation were not found to influence OD±GD (p>0.05). CONCLUSIONS: 12.8% of previously hospitalised patients with COVID-19 in London still report persistent problems with smell or taste up to a year after infection, impacting their QoL. Increased holistic support including psychological therapy and olfactory rehabilitation for affected patients may help to reduce long-term morbidity.

Cell-cell adhesion impacts epithelia response to substrate stiffness: Morphology and gene expression.

Monolayer epithelial cells interact constantly with the substrate they reside on and their surrounding neighbors. As such, the properties of epithelial cells are profoundly governed by the mechanical and molecular cues that arise from both the substrate and contiguous cell neighbors. Although both cell-substrate and cell-cell interactions have been studied individually, these results are difficult to apply to native confluent epithelia, in which both jointly regulate the cell phenotype. Specifically, it remains poorly understood about the intertwined contributions from intercellular adhesion and substrate stiffness on cell morphology and gene expression, two essential microenvironment properties. Here, by adjusting the substrate modulus and altering the intercellular adhesion within confluent kidney epithelia, we found that cell-substrate and cell-cell interactions can mask each other's influence. For example, we found that epithelial cells exhibit an elongated morphological phenotype only when the substrate modulus and intercellular adhesions are both reduced, whereas their motility can be upregulated by either reduction. These results illustrate that combinatorial changes of the physical microenvironment are required to alter cell morphology and gene expression.

Surgical management and outcomes in spinal intradural arachnoid cysts: the experience from two tertiary neurosurgical centres.

PURPOSE: Evaluation of the presentation and outcomes of different surgical treatment approaches for spinal intradural arachnoid cysts (SIAC). METHODS: Cases were identified from electronic records of two major neurosurgical centres in London over the last 10 years (October 2009-October 2019) that have been surgically treated in both institutions. Clinical findings, surgical technique, and recurrence by procedure were statistically analysed. Statistical analysis was performed with STATA 13.1 Software. RESULTS: A total of 42 patients with SIAC were identified for this study with a mean age at the time of surgery of 53.6 years and a male:female ratio of 8:13. There were 31 patients with primary SIACs and 11 with secondary SIACs. The most common presenting symptom was paraesthesia (n = 27). The most common location of the cyst was in the thoracic region (n = 33). Syrinx was present in 26.2% of SIACs (n = 11). Resection was associated with significantly better postoperative pain compared to other surgical techniques (p = 0.01), significantly poorer postoperative urinary function (p = 0.029), and lower rates of sensory recovery in patients who presented preoperatively with sensory deficit (p = 0.041). No significant difference was seen in symptomatic outcomes between patients with primary and secondary SIACs. CONCLUSION: Resection and drainage are both effective methods of managing SIACs. In this observational study, resection was associated with significantly reduced pain postoperatively when compared with drainage, however also with significantly less improvement in postoperative urinary function. Therefore, resection should be the gold standard management option for SIACs, with drainage as an option where resection is unsafe, and drainage should also be considered in patients presenting with urinary dysfunction.