Estimating Surgical Urethral Length on Intraoperative Robot-Assisted Prostatectomy Images Using Artificial Intelligence Anatomy Recognition.

Objective: To construct a convolutional neural network (CNN) model that can recognize and delineate anatomic structures on intraoperative video frames of robot-assisted radical prostatectomy (RARP) and to use these annotations to predict the surgical urethral length (SUL). Background: Urethral dissection during RARP impacts patient urinary incontinence (UI) outcomes, and requires extensive training. Large differences exist between incontinence outcomes of different urologists and hospitals. Also, surgeon experience and education are critical toward optimal outcomes. Therefore, new approaches are warranted. SUL is associated with UI. Artificial intelligence (AI) surgical image segmentation using a CNN could automate SUL estimation and contribute toward future AI-assisted RARP and surgeon guidance. Methods: Eighty-eight intraoperative RARP videos between June 2009 and September 2014 were collected from a single center. Two hundred sixty-four frames were annotated according to prostate, urethra, ligated plexus, and catheter. Thirty annotated images from different RARP videos were used as a test data set. The dice (similarity) coefficient (DSC) and 95th percentile Hausdorff distance (Hd95) were used to determine model performance. SUL was calculated using the catheter as a reference. Results: The DSC of the best performing model were 0.735 and 0.755 for the catheter and urethra classes, respectively, with a Hd95 of 29.27 and 72.62, respectively. The model performed moderately on the ligated plexus and prostate. The predicted SUL showed a mean difference of 0.64 to 1.86 mm difference vs human annotators, but with significant deviation (standard deviation = 3.28-3.56). Conclusion: This study shows that an AI image segmentation model can predict vital structures during RARP urethral dissection with moderate to fair accuracy. SUL estimation derived from it showed large deviations and outliers when compared with human annotators, but with a small mean difference (<2 mm). This is a promising development for further research on AI-assisted RARP.

How to reduce the complication rate of multiple burr holes surgery in moyamoya angiopathy.

PURPOSE: This study is aimed at analyzing clinical outcome, absence of stroke recurrence, revascularization, and complications and long-term follow-up in the surgical treatment of moyamoya angiopathy (MMA) using the multiple burr holes (MBH) technique with dura opening and arachnoid preservation as a single procedure. To the best of our knowledge, this is the first to describe an MBH technique with arachnoid preservation. METHOD: We retrospectively reviewed all patients operated from June 2001 to March 2021, for a symptomatic and progressive MMA operated with opening of the dura but arachnoid preservation. Clinical examinations were obtained in all patients, and radiological monitoring was performed by cerebral 3D-magnetic resonance angiography (MRA) with perfusion or single-photon emission computed tomography (SPECT) with acetazolamide. RESULTS: In total, 21 consecutive patients (6 children and 15 adults) were included with a mean age of 7.4 years in the pediatric group and 36.9 years in the adult group. Initial presentation was permanent ischemic stroke in 15 cases, transient ischemic attack (TIA) in 5 cases, and cerebral hemorrhage in one case. The MBH with dura opening and arachnoid preservation was performed bilaterally in 9 cases (43%) and unilaterally in 12 cases (57%). One patient died due to intraoperative bilateral ischemic stroke. Of the 20 other patients, 30% demonstrated clinical stability and 70% showed partial or complete recovery. Although one patient experienced a perioperative stroke, we did not observe any pseudomeningocele or postoperative ischemic stroke (IS) recurrence in all surviving cases during the average follow-up period of 55.5 months (range: 1-195). These outcomes emphasize the importance of preoperative monitoring to ensure the effectiveness and safety of the intervention. Postoperative angiography studies showed revascularization in 96.3% of treated hemispheres (100% in the adult group vs 80% in the pediatric group). CONCLUSIONS: Our results on this small cohort suggest that the MBH technique with opening of the dura and arachnoids preservation can prevent recurrent strokes and reduce the risk of pseudomeningocele.

Complete resection of dual ependymoma spinal metastasis using a fixed tubular retractor-a pediatric case report.

There are no specific guidelines regarding best treatment for focal, distant metastasis in ependymoma in the context of a well-controlled primary site. A combination using maximal safe resection and adjuvant radiotherapy is usually advised. As wound healing might be hindered by repeated radiotherapy, and delay future radiation treatment if needed, there is a growing interest in less invasive surgeries to reduce post-operative pain and wound healing complications. Those approaches have been extensively used and studied in adult but never in the pediatric population. Here, we present a pediatric case of a 12-year-old boy known for a posterior fossa ependymoma completely resected 18 months earlier who presented with a dual lumbosacral intradural ependymoma metastasis. A single-stage complete resection was achieved using a fixed tubular retractor with no complication. Post-operative course was favorable with rapid healing and discharge, minimal post-operative pain, and a rapid return to normal activities. Re-irradiation could be performed 2 weeks later without any problem. To our knowledge, this is the first report of the use of minimally invasive techniques to achieve complete resection of dual intradural metastasis of an ependymoma in the pediatric population. We demonstrate its feasibility and safety as well as its advantages.

WDR5, BRCA1, and BARD1 Co-regulate the DNA Damage Response and Modulate the Mesenchymal-to-Epithelial Transition during Early Reprogramming.

Differentiated cells are epigenetically stable, but can be reprogrammed to pluripotency by expression of the OSKM transcription factors. Despite significant effort, relatively little is known about the cellular requirements for reprogramming and how they affect the properties of induced pluripotent stem cells. We have performed high-content screening with small interfering RNAs targeting 300 chromatin-associated factors and extracted colony-level quantitative features. This revealed five morphological phenotypes in early reprogramming, including one displaying large round colonies exhibiting an early block of reprogramming. Using RNA sequencing, we identified transcriptional changes associated with these phenotypes. Furthermore, double knockdown epistasis experiments revealed that BRCA1, BARD1, and WDR5 functionally interact and are required for the DNA damage response. In addition, the mesenchymal-to-epithelial transition is affected in Brca1, Bard1, and Wdr5 knockdowns. Our data provide a resource of chromatin-associated factors in early reprogramming and underline colony morphology as an important high-dimensional readout for reprogramming quality.

Partial cauda equina syndrome after an uneventful minimally invasive microdiscectomy in a patient with Crohn's disease.

Cauda equina syndrome is a serious condition resulting from dysfunction of the lumbosacral nerve roots and characterized by impairment of bladder, bowel, sexual and lower limb functions. We report the case of a 48-year-old woman who had Crohn's disease for more than twenty years. The patient was undergoing immunotherapy with infliximab and developed a partial cauda equina syndrome after an uneventful minimally invasive microdiscectomy (L5-S1) that completely cured her sciatica. A postoperative magnetic resonance imaging examination showed root clumping but no compressive lesion. We discuss a possible relationship between the cauda equina syndrome and the patient's active Crohn's disease, treatment and surgery.

Involvement of mTOR and Regulation by AMPK in Early Iodine Deficiency-Induced Thyroid Microvascular Activation.

Iodine deficiency (ID) induces TSH-independent microvascular activation in the thyroid via the reactive oxygen species/nitric oxide-hypoxia-inducible factor-1α/vascular endothelial growth factor (VEGF) pathway. We hypothesized the additional involvement of mammalian target of rapamycin (mTOR) as a positive regulator of this pathway and AMP-activated protein kinase (AMPK) as a negative feedback regulator to explain the transient nature of ID-induced microvascular changes under nonmalignant conditions. mTOR and AMPK involvement was investigated using an in vitro model (human thyrocytes in primary cultures) and 2 murine models of goitrogenesis (normal NMRI and RET-PTC mice [a papillary thyroid cancer model]). In NMRI mice, ID had no effect on the phosphorylation of ribosomal S6 kinase (p70S6K), a downstream target of mTOR. However, rapamycin inhibited ID-induced thyroid blood flow and VEGF protein expression. In the RET-PTC model, ID strongly increased the phosphorylation of p70S6K, whereas rapamycin completely inhibited the ID-induced increase in p70S6K phosphorylation, thyroid blood flow, and VEGF-A expression. In vitro, although ID increased p70S6K phosphorylation, the ID-stimulated hypoxia-inducible factor/VEGF pathway was inhibited by rapamycin. Activation of AMPK by metformin inhibited ID effects both in vivo and in vitro. In AMPK-α1 knockout mice, the ID-induced increase in thyroid blood flow and VEGF-A protein expression persisted throughout the treatment, whereas both parameters returned to control values in wild-type mice after 4 days of ID. In conclusion, mTOR is required for early ID-induced thyroid microvascular activation. AMPK negatively regulates this pathway, which may account for the transient nature of ID-induced TSH-independent vascular effects under benign conditions.

Involvement of nitric oxide in iodine deficiency-induced microvascular remodeling in the thyroid gland: role of nitric oxide synthase 3 and ryanodine receptors.

Iodine deficiency (ID) induces microvascular changes in the thyroid gland via a TSH-independent reactive oxygen species-hypoxia inducible factor (HIF)-1α-vascular endothelial growth factor (VEGF) pathway. The involvement of nitric oxide (NO) in this pathway and the role of calcium (Ca(2+)) and of ryanodine receptors (RYRs) in NO synthase 3 (NOS3) activation were investigated in a murine model of goitrogenesis and in 3 in vitro models of ID, including primary cultures of human thyrocytes. ID activated NOS3 and the production of NO in thyrocytes in vitro and increased the thyroid blood flow in vivo. Using bevacizumab (a blocking antibody against VEGF-A) in mice, it appeared that NOS3 is activated upstream of VEGF-A. L-nitroarginine methyl ester (a NOS inhibitor) blocked the ID-induced increase in thyroid blood flow in vivo and NO production in vitro, as well as ID-induced VEGF-A mRNA and HIF-1α expression in vitro, whereas S-nitroso-acetyl-penicillamine (a NO donor) did the opposite. Ca(2+) is involved in this pathway as intracellular Ca(2+) flux increased after ID, and thapsigargin activated NOS3 and increased VEGF-A mRNA expression. Two of the 3 known mammalian RYR isoforms (RYR1 and RYR2) were shown to be expressed in thyrocytes. RYR inhibition using ryanodine at 10µM decreased ID-induced NOS3 activation, HIF-1α, and VEGF-A expression, whereas RYR activation with ryanodine at 1nM increased NOS3 activation and VEGF-A mRNA expression. In conclusion, during the early phase of TSH-independent ID-induced microvascular activation, ID sequentially activates RYRs and NOS3, thereby supporting ID-induced activation of the NO/HIF-1α/VEGF-A pathway in thyrocytes.

Pathogenesis of vestibular schwannoma in ring chromosome 22.

BACKGROUND: Ring chromosome 22 is a rare human constitutional cytogenetic abnormality. Clinical features of neurofibromatosis type 1 and 2 as well as different tumour types have been reported in patients with ring chromosome 22. The pathogenesis of these tumours is not always clear yet. METHODS: We report on a female patient with a ring chromosome 22 presenting with severe mental retardation, autistic behaviour, café-au-lait macules and facial dysmorphism. Peripheral blood lymphocytes were karyotyped and array CGH was performed on extracted DNA. At the age of 20 years she was diagnosed with a unilateral vestibular schwannoma. Tumour cells were analyzed by karyotyping, array CGH and NF2 mutation analysis. RESULTS: Karyotype on peripheral blood lymphocytes revealed a ring chromosome 22 in all analyzed cells. A 1 Mb array CGH experiment on peripheral blood DNA showed a deletion of 5 terminal clones on the long arm of chromosome 22. Genetic analysis of vestibular schwannoma tissue revealed loss of the ring chromosome 22 and a somatic second hit in the NF2 gene on the remaining chromosome 22. CONCLUSION: We conclude that tumours can arise by the combination of loss of the ring chromosome and a pathogenic NF2 mutation on the remaining chromosome 22 in patients with ring chromosome 22. Our findings indicate that patients with a ring 22 should be monitored for NF2-related tumours starting in adolescence.

Results from a prospective, randomized, controlled study evaluating the acceptability and effects of routine pre-IVF counselling.

BACKGROUND: The aim of this study was to evaluate a model of routine pre-IVF counselling focusing on the narrative capacities of couples. The acceptability of counselling, the effects on emotional factors and the participants' assessments were considered. METHODS: The study included 141 consecutive childless couples preparing for their first IVF. Randomization was carried out through sealed envelopes attributing participants to counselled and non-counselled groups and was accepted by 100 couples. Another 12 couples refused randomization because they wanted counselling and 29 because they did not. Questionnaires including the State-Trait Anxiety Inventory, the Beck Depression Inventory and assessments of help were mailed to couples before IVF and counselling, and after the IVF outcome. RESULTS: Counselling was accepted by 79% (112/141) of couples. There was no significant effect of counselling on anxiety and depression scores which were within normal ranges at both times. Counselling provided help for 86% (75/87) of initially non-demanding subjects and 96% (25/26) of those initially requesting a session. Help was noted in areas of psychological assistance, technical explanations and discussing relationships. CONCLUSIONS: This model of routine counselling centred on the narrative provides an acceptable form of psychological assistance for pre-IVF couples.