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Purpose: This study aimed to determine the occurrence of incidental obturator hernia and clinical risk factors of their appearance in patients undergoing totally extraperitoneal (TEP) inguinal hernioplasty., Methods: Data were collected retrospectively from patients who underwent TEP inguinal hernioplasty between June 2020 and December 2022., Results: A total of 251 patients were included in the study. Obturator hernias were found in 21 patients (8.4%). At admission, no patient presented clinical signs of an obturator hernia. There was a significant predominance of women in the obturator hernia compared to the non-obturator hernia group (28.6% vs. 10.9%, respectively, p=0.018). There was no correlation between age (p=0.479) and BMI (p=0.771) and the occurrence of obturator hernia. Additional obturator hernia repair within the TEP inguinal hernioplasty procedure did not influence the overall length of the surgery (60.86 minutes) compared to the standard TEP inguinal hernioplasty (61.09 minutes, p=0.876)., Conclusions: The TEP inguinal hernioplasty allows the detection and repair of incidental obturator hernia. Through thorough inspection of the obturator canal, an asymptomatic obturator hernia can be detected and adequately treated within the same procedure, without the impact on the surgery duration, when performed by an experienced hernia surgeon., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Purpose: We aimed to determine the surgical indications and postoperative outcomes among pediatric patients with lobar cerebral cavernous malformations (CCMs)., Methods: We retrospectively reviewed pediatric patients operated on for lobar CCM between March 2010 and August 2021. Indications for surgery included (1) intracranial hemorrhage, (2) symptomatic superficially located lesion, and (3) asymptomatic CCM in non-eloquent area in case of strong parental preferences. Patients presenting with seizures were assessed using Engel Epilepsy Surgery Outcome Scale., Results: Twenty-one patients were included. The predominant symptoms were seizures (57.1%), headaches (33.3%), and focal neurological deficits (23.8%). Patients were qualified for surgery due to symptomatic intracranial hemorrhage (47.6%), drug-resistant epilepsy (28.6%), and focal neurological deficits (9.5%). Three patients (14.3%) were asymptomatic. A gross total resection of CCM with the surrounding hemosiderin rim was achieved in all patients. The mean follow-up was 52 months. No patient experienced surgery-related complications. In all individuals with a preoperative first episode of seizures or focal neurological deficits, the symptoms subsided. All six patients with drug-resistant epilepsy improved to Engel classes I (67%) and II (33%)., Conclusion: Surgical removal of symptomatic lobar CCMs in properly selected candidates remains a safe option. Parental preferences may be considered a sole qualifying criterion for asymptomatic lobar CCM excision., (© 2024. The Author(s).)

Purpose: Since new evidence regarding the impact of Wendler glottoplasty (WG) on the voice in transgender women became available in the literature in recent years, we aimed to perform an updated systematic review and meta-analysis to determine the actual safety and efficacy of WG in the process of vocal feminization., Methods: PubMed, Embase, and Cochrane were searched for English-language articles published until July 4, 2023. Studies were found eligible if they evaluated the impact of WG on the acoustic-aerodynamic measures and quality of voice in transgender women., Results: Twenty-three studies were identified. After exclusion of three studies due to incomplete data, 20 studies including 656 patients were included in the meta-analysis. After WG, there was a significant increase of fundamental frequency, speaking fundamental frequency, and lower limit of the frequency range (p < 0.001). Concurrently, a significant reduction of frequency range and maximum phonation time was observed (p < 0.001). No significant differences were found between the pre- and postoperative values regarding the Grade, Roughness, Breathiness, Asthenia, and Strain scale score (p = 0.339). The overall score in the Trans Woman Voice Questionnaire (TWVQ) significantly improved after WG (p < 0.001)., Conclusions: WG is an effective voice feminization method in transgender women, associated with a high procedural success and low risk of postoperative complications. Significantly improved TWVQ score after surgery suggests its positive impact on the voice-related quality of life. Postoperative decrease of maximum phonation time and frequency range does not seem to significantly impact the effectiveness of voice production., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

We conducted a comparative cross-sectional study to compare the prevalence of exposure to workplace violence and intimate partner violence (IPV) in 125 female sex workers (FSWs) and 125 age-matched control women working in other professions (non-FSWs) and their children in El Alto, Bolivia. Violence exposure was assessed using the Demographic Health Survey Domestic Violence Module. To determine associations between work type and violence exposure, we conducted multivariate logistic regression. One-third of working mothers experienced sexual IPV, regardless of their profession. FSWs experienced higher rates of severe physical IPV and workplace violence. Children of FSWs were approximately three times more likely to be exposed to violence in the workplace. In Bolivia, strategies to reduce exposure to violence within the home and in FSW workplaces are paramount to minimizing negative impacts on women and their children. These findings have implications for policies to improve education, living wages, and social interventions to prevent and mitigate violence against women and children., (© Copyright 2023 Springer Publishing Company, LLC.)

There remains much debate about the correct management of incidentally found brain tumors in the pediatric population. This study aimed to evaluate the efficacy and safety of surgical treatment of incidentally found pediatric brain tumors. A retrospective analysis of pediatric patients who underwent surgical resection of incidentally found brain tumors between January 2010 and April 2016 was performed. A total of seven patients were included. The median age at the time of diagnosis was 9.7 years. The reasons for performing neuroimaging were as follows: impeded speech development ( n = 2), shunt control ( n = 1), paranasal sinuses control ( n = 1), behavior changes ( n = 1), head trauma ( n = 1), and preterm birth ( n = 1). Five patients underwent gross total tumor resection (71.4%), while subtotal resection was performed in two patients (28.6%). There was no surgery-related morbidity. Patients were followed up for a mean of 79 months. One patient with atypical neurocytoma experienced tumor recurrence 45 months following primary resection. All patients remained neurologically intact. The majority of pediatric incidentally found brain tumors were histologically benign. Surgery remains a safe therapeutic approach associated with favorable long-term outcomes. Considering the expected long lifetime of pediatric patients, as well as the psychological burden associated with having a brain tumor as a child, surgical resection can be considered an initial approach.

This study aimed to systematically review the literature to determine the efficacy and safety of transoral robotic surgery (TORS) in the management of submandibular gland (SMG) sialolithiasis. PubMed, Embase, and Cochrane were searched for English-language articles evaluating TORS in the management of SMG stones published up to 12 September 2022. Nine studies with a total of 99 patients were included. Eight patients underwent TORS followed by sialendoscopy (TS); 11 patients underwent sialendoscopy followed by TORS and sialendoscopy (STS); 4 patients underwent sialendoscopy followed by TORS only (ST); and 4 patients underwent TORS without sialendoscopy (T). The mean operative time amounted to 90.97 min. The mean procedure success rate reached 94.97%, with the highest for ST (100%) and T (100%), followed by the TS (95.04%) and STS (90.91%) variants. The mean follow-up time was 6.81 months. Transient lingual nerve injury occurred in 28 patients (28.3%) and was resolved in all of them within the mean of 1.25 months. No permanent lingual nerve injury was reported. TORS is a safe and effective management modality for hilar and intraparenchymal SMG sialoliths, with high procedural success in terms of successful sialolith removal, SMG preservation, and reduced risk of permanent postoperative lingual nerve damage.

Purpose: While Ruptured Arteriovenous Malformation Grading Scale (RAGS) has recently been validated in children, the literature lacks validation on adults exclusively. Therefore, we aimed to determine the validity of RAGS on the external multicenter adult cohort and compare its accuracy with other scales., Methods: A retrospective analysis was performed in five neurosurgical departments to extract patients who presented with the first episode of acute brain arteriovenous malformation (bAVM) rupture between 2012 and 2019. Standard logistic regression and area under the receiver operating curve (AUROC) calculations were performed to determine the value of the following scales: intracerebral hemorrhage (ICH), AVM-associated ICH (AVICH), Spetzler-Martin (SM), Supplemented SM (Supp-SM), Hunt and Hess (HH), Glasgow Coma Scale (GCS), World Federation of Neurological Surgeons (WFNS), and RAGS to predict change in categorical and dichotomized modified Rankin Scale (mRS) across three follow-up periods: within the 6 months, 6 months to 1 year, and above 1 year., Results: Sixty-one individuals with a mean age of 43.6 years were included. The RAGS outperformed other grading scales during all follow-up time frames. It showed AUROC of 0.78, 0.74, and 0.71 at the first 6 months, between 6 and 12 months, and after 12 months of follow-up, respectively, when categorized mRS was applied, while corresponding values were 0.79, 0.76, and 0.73 for dichotomized mRS, respectively., Conclusion: The RAGS constitutes a reliable scale predicting clinical outcomes following bAVM rupture among adults. Furthermore, the RAGS proved its generalizability across medical centers with varying treatment preferences., (© 2022. The Author(s).)

Objective: The Chicago Chiari Outcome Scale (CCOS) serves as a standardized clinical outcome evaluation tool among patients with Chiari malformation type I (CM-I). While the reliability of this scale has been proven for pediatric patients, the literature lacks CCOS validation when used solely in adults. Therefore, this study aimed to determine the validity of the CCOS in an external cohort of adult patients., Methods: The authors retrospectively analyzed the medical records of symptomatic patients with CM-I who underwent posterior fossa decompression between 2010 and 2018 in six neurosurgical departments. Each patient was clinically assessed at the latest available follow-up. Gestalt outcome was determined as improved, unchanged, or worsened compared with the preoperative clinical state. Additionally, the CCOS score was calculated for each patient based on the detailed clinical data. To verify the ability of the CCOS to determine clinical improvement, the area under the receiver operating characteristic (AUROC) curve was evaluated. A logistic regression analysis using all four components of the CCOS (pain symptoms, nonpain symptoms, functionality, and complications) was performed to establish predictors of the improved outcome., Results: Seventy-five individuals with a mean age of 42 ± 15.32 years were included in the study. The mean follow-up duration was 52 ± 33.83 months. Considering gestalt outcome evaluation, 41 patients (54.7%) were classified as improved, 24 (32%) as unchanged, and 10 (13.3%) as worsened. All patients with a CCOS score of 14 or higher improved, while all those with a CCOS score of 8 or lower worsened. The AUROC was 0.986, suggesting almost perfect accuracy of the CCOS in delineating clinical improvement. A CCOS score of 13 showed high sensitivity (0.93) and specificity (0.97) for identifying patients with clinical improvement. Additionally, a meaningful correlation was found between higher CCOS scores in each component and better outcomes. Patient stratification by total CCOS score showed that those categorized as improved, unchanged, and worsened scored prevalently between 13 and 16 points, 10 and 12 points, and 4 and 9 points, respectively., Conclusions: In this adult cohort, the CCOS was found to be almost perfectly accurate in reflecting postoperative clinical improvement. Moreover, all four CCOS components (pain symptoms, nonpain symptoms, functionality, and complications) significantly correlated with patient clinical outcomes.

This study aimed to evaluate the predictive value of motor evoked potentials (MEP) in the resection of pediatric intradural extramedullary (IDEM) tumors. Additionally, we aimed to assess the impact of MEP alerts on the extent of tumor resection. Medical records of pediatric patients who underwent resection of IDEM tumors with the assistance of MEP between March 2011 and October 2020 were reviewed. The occurrence of postoperative motor deficits was correlated with intraoperative MEP alerts. Sixteen patients were included. MEP alerts appeared in 2 patients (12.5%), being reflective of new postoperative motor deficits. Among the remaining 14 patients without any intraoperative MEP alerts, no motor decline was found. Accordingly, MEP significantly predicted postoperative motor deficits, reaching sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100% (p < 0.001). In the absence of MEP alerts, 11 out of 14 patients (78.6%) underwent GTR, while no patient with intraoperative IONM alerts underwent GTR (p = 0.025). Although MEP alerts limit the extent of tumor resection, the high sensitivity and PPV of MEP underline its importance in avoiding iatrogenic motor deficits. Concurrently, high specificity and NPV ensure safer tumor excision. Therefore, MEP can reliably support surgical decisions in pediatric patients with IDEM tumors.

Recently, contrast-enhanced ultrasound (CEUS) has become a promising tool in distinguishing benign from malignant parotid gland tumors. However, its usefulness in differentiating various benign parotid tumors has not been determined so far. This study aimed to systematically review the literature to determine the utility of CEUS in the preoperative differentiation between pleomorphic adenomas (PAs) and Warthin's tumors (WTs) of the parotid gland. PubMed, Embase, and Cochrane were searched for English-language articles published until 21 July 2022. Fifteen studies were included. On CEUS examination, a significantly greater percentage of PAs displayed heterogeneous enhancement texture compared to WTs. Contrarily, the enhanced lesion size, the enhancement margin, and the presence of the enhancement rim did not differ significantly between the entities. Significantly longer normalized mean transit time (nMTT) and time to peak (TTP) were observed in PAs. Contrarily, the mean values of area under the curve (AUC) and time from peak to one half (TPH) were significantly higher for WTs. Due to the considerable overlap among the qualitative CEUS characteristics of PAs and WTs, the reproducible, investigator-independent quantitative CEUS measurements have a greater potential to distinguish PAs from WTs, which might influence the selection of an appropriate management strategy.

The purpose of this study was to evaluate the reliability of motor evoked potentials (MEP), somatosensory evoked potentials (SSEP), and D-wave monitoring as predictors of postoperative neurological deficits in pediatric patients undergoing resection of intramedullary spinal cord tumors (IMSCTs). Additionally, we aimed to determine whether alerts in the intraoperative neurophysiological monitoring (IONM) influenced the extent of resection (EOR). A retrospective analysis of the pediatric patients who underwent resection of IMSCT between March 2010 and April 2021 with an IONM guidance was performed. IONM alerts were recorded and correlated with patients' clinical status at discharge. Twenty three pediatric patients were included. MEP and SSEP were successfully elicited in all patients, while D-wave monitoring was feasible for 14 of them (60.9%). Significant IONM alerts occurred in 6 individuals (26.1%) with monitorable MEP and SSEP and 2 patients with monitorable D-waves (14.3%). The sensitivity, specificity, positive predictive value, and negative predictive value accounted for 100%, 81.8%, 20%, 100% for MEP, 100%, 92.3%, 50%, 100% for D-wave, and 50%, 81%, 20%, 94.44% for SSEP, respectively. Both MEP (p < 0.001) and D-wave monitoring (p < 0.001) accurately predicted postoperative motor deficits, while SSEP failed to provide significant accuracy regarding sensory deficits (p = 0.491). Gross-total tumor resection was performed in 29.4% of patients without IONM alerts and 33.3% of patients with IONM alerts, indicating that IONM alerts did not limit the EOR (p = 0.0857). MEP and D-wave monitoring can be perceived as reliable IONM modalities in pediatric IMSCTs surgery. Caution is needed with the implementation of SSEP to guide surgical decisions., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

This study aimed to systematically review the literature to determine the clinical utility and perspectives of diffusion tensor imaging (DTI) in the management of patients with brainstem cavernous malformations (BSCMs). PubMed, Embase, and Cochrane were searched for English-language articles published until May 10, 2021. Clinical studies and case series describing DTI-based evaluation of patients with BSCMs were included. Fourteen articles were included. Preoperative DTI enabled to adjust the surgical approach and choose a brainstem safe entry zone in deep-seated BSCMs. Preoperatively lower fractional anisotropy (FA) of the corticospinal tract (CST) correlated with the severity of CST injury and motor deficits. Postoperatively increased FA and decreased apparent diffusion coefficient (ADC) corresponded with the normalization of the perilesional CST, indicating motor improvement. The positive (PPV) and negative predictive value (NPV) of qualitative DTI ranged from 20 to 75% and from 66.6 to 100%, respectively. The presence of preoperative and postoperative motor deficits was associated with a higher preoperative resting motor threshold (RMT) and lower FA. A higher preoperative CST score was indicative of a lower preoperative and follow-up Medical Research Council (MRC) grade. DTI facilitated the determination of a surgical trajectory with minimized risk of WMTs' damage. Preoperative FA and RMT might indicate the severity of preoperative and postoperative motor deficits. Preoperative CST score can reliably reflect patients' preoperative and follow-up motor status. Due to high NPV, normal CST morphology might predict intact neurological outcomes. Contrarily, sparse and relatively low PPV limits the reliable prediction of neurological deficits., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Spontaneous intracranial hypotension (SIH) can be effectively treated by epidural blood patch (EBP) following the primary unsuccessful conservative therapy. Nevertheless, multi-site cerebrospinal fluid (CSF) leaks or those originating at the cervical or thoracic spine remain therapeutically challenging. Therefore, this study aimed to present our experience in the treatment of thoracic CSF leaks using epidural catheters for the EBP infusion., Methods: Three patients presenting with typical orthostatic headaches were qualified for an EBP procedure. Preoperative MRI scans, myelography, and CT myelography were performed. Additionally, delayed CT myelography was repeated after 3 h to identify the CSF leakage site. Patients were followed-up clinically and radiologically for three months., Results: The CT myelography identified CSF leak at the T2-3 (case 1), T5-12 (case 2), and T3-7 level (Case 3). A 0.06" diameter lumbar drainage catheter (Case 1 and 2) or Abbot's spinal cord stimulation (SCS) catheter (Case 3) was inserted epidurally through the lower thoracic/lumbar single-entry point and advanced into the identified thoracic leak site. The average volume of injected blood was 15.7 ml. No procedure-related complications were observed, and all patients improved clinically., Conclusions: Epidural catheters remain safe and effective in treating thoracic and multi-site CSF leaks. In addition, Abbot's SCS catheter was found superior to the lumbar drainage catheter due to higher rigidity and bigger diameter despite being shorter than the lumbar drainage catheter., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: For the majority of patients, the Internet constitutes the first source of health information influencing their medical decision-making. We aimed to assess the quality of the online videos regarding anterior lumbar interbody fusion (ALIF)., Methods: YouTube database was searched using 3 different phrases: "anterior lumbar interbody fusion", "ALIF", and "ALIF surgery". The first 50 videos for each phrase were selected. Video content was evaluated by 3 independent researchers using the DISCERN instrument. Qualitative data, quantitative data, and the source of upload were analyzed., Results: A total of 24 videos were included. The mean DISCERN score was 38.21, indicating the poor quality of ALIF videos on YouTube. Video duration was positively correlated with DISCERN score (r = 0.71, P < 0.001) but not with the video power index (VPI). A negative correlation between time since upload and DISCERN score (r = -0.8 P < 0.001) was found. Furthermore, videos containing surgical complications, risk factors, and postoperative prognosis had a significantly higher DISCERN score. Neither DISCERN score nor a VPI correlated with the presence of intraoperative recordings. Videos including the explanation of the spine anatomy had a significantly higher number of likes (P = 0.018)., Conclusions: Despite the increasing educational value of ALIF videos over time, the overall quality of YouTube videos on ALIF remains poor. However, the majority of videos can be recommended to the patient as an informative source of basic knowledge on the surgical details of the ALIF procedure. Longer video duration increases its quality without simultaneous negative influence on its popularity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: This study aimed to compare the effectiveness of posterior fossa decompression (PFD), posterior fossa decompression with duraplasty (PFDD), and posterior fossa decompression with resection of tonsils (PFDRT) in Chiari malformation type I (CMI). Furthermore, we aimed to evaluate the evidence supporting the efficacy of filum terminale sectioning (FTS), syringosubarachnoid shunting (SSS), and syringoperitoneal shunting (SPS) in CMI., Methods: PubMed, Cochrane, and Embase databases were screened for English-language studies published from inception until August 11, 2020. A total of 3593 studies were identified through the searching process. Fifteen cohort studies were included in the systematic review and network meta-analysis., Results: No studies concerning FTS, SSS, and SPS were found eligible. Therefore, only PFD, PFDD, and PFDRT were compared. PFDD showed significantly higher incidence of complications (relative risk [RR], 3.79; 95% confidence interval [CI], 2.54-5.64) cerebrospinal fluid leak (RR, 9.74; 95% CI, 2.33-40.78) and neurologic deficit (RR, 8.76; 95% CI, 2.08-36.90) than did PFD. Both PFDD and PFDRT achieved higher syringomyelia improvement (RR, 1.23, 95% CI, 1.09-1.39 and RR, 1.32, 95% CI, 1.15-1.51, respectively) and greater clinical improvement (RR, 1.24, 95% CI, 1.10-1.39 and RR, 1.24, 95% CI, 1.08-1.44, respectively) than did PFD. No differences were found between PFDD and PFDRT., Conclusions: PFDD and PFDRT are superior to PFD, especially in patients with syringomyelia-Chiari complex, because of greater syringomyelia reduction and better clinical improvement. However, PFDD and PFDRT can be considered equally efficient. There is no evidence pleading in favor of SFT, SSS, and SPS over any PFD technique., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Diffusion tensor imaging (DTI) application in Chiari malformation type I (CMI) is still poorly defined. This study aimed to systematically review the literature and propose perspectives toward the clinical application of DTI in CMI., Methods: PubMed and Embase were searched for English-language articles published until October 20, 2020. Clinical studies and case series, evaluating fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), or radial diffusivity values in patients with CMI, were included., Results: Eight articles were included. Lower FA values were found at the syrinx level, which decreased with syrinx extent and intensity of symptoms, reflecting myelopathy severity. Decreased AD and MD in the middle cerebellar peduncles in symptomatic patients with CMI might explain the presence of cerebellar signs. Increased FA in various supratentorial structures positively correlated with pain severity. Worse performance in neuropsychological tests correlated with decreased FA, increased MD, and radial diffusivity, reflecting axonal degeneration. Postoperative FA decrease in the brainstem compression area reflects successful decompression. A positive correlation was found between the extent of tonsillar ectopia and increased FA, MD, and AD values, which could act as an early indicator of acute brainstem compression., Conclusions: DTI might provide a valuable insight into the neurobiological foundation of symptomatic CMI presentation. The severity of white matter injury evident on DTI could serve as a reliable predictor of postoperative outcomes, therefore facilitating selection of appropriate surgical candidates. Postinterventional DTI reassessment might enable differentiation between unsuccessful surgical technique and irreversible myelopathy. The extent of tonsillar ectopia reflects the severity of microstructural brainstem injury., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

In recent years, organ-on-chip (OoC) systems have provoked increasing interest among researchers from different disciplines. OoCs enable the recreation of in vivo -like microenvironments and the generation of a wide range of different tissues or organs in a miniaturized way. Most commonly, OoC platforms are based on microfluidic modules made of polydimethylsiloxane (PDMS). While advantageous in terms of biocompatibility, oxygen permeability, and fast prototyping amenability, PDMS features a major limitation as it absorbs small hydrophobic molecules, including many types of test compounds, hormones, and cytokines. Another common feature of OoC systems is the integration of membranes (i) to separate different tissue compartments, (ii) to confine convective perfusion to media channels, and/or (iii) to provide mechanical support for cell monolayers. Typically, porous polymer membranes are microstructured using track-etching (e.g., polyethylene terephthalate; PET) or lithography (e.g., PDMS). Although membranes of different biomechanical properties (rigid PET to elastic PDMS) have been utilized, the membrane structure and material remain mostly artificial and do not resemble in vivo conditions (extracellular matrix). Here, we report a method for the reliable fabrication and integration of electrospun membranes in OoC modules, which are made of laser-structured poly(methyl methacrylate) (PMMA). The choice of PMMA as base material provides optical parameters and biocompatibility similar to PDMS while avoiding the absorption problem. Using electrospinning for the generation of 3D membranes, microenvironments resembling the native extracellular matrix (ECM) can be generated. We tested two different kinds of electrospun membranes and established processes for a tight integration into PMMA modules. Human (microvasculature) endothelial as well as (retinal pigment) epithelial cell layers could be successfully cultured inside the systems for up to 7 days, while being either directly exposed to (endothelial cells) or protected (epithelial cells) from the shear flow. Our novel method enables the versatile fabrication of OoC platforms that can be tailored to the native environment of tissues of interest and at the same time are applicable for the testing of compounds or chemicals without constraints.

Bleeding from ruptured brain arteriovenous malformations (bAVMs) represents the most prevalent cause of pediatric intracranial hemorrhage, being also the most common initial bAVM manifestation. A therapeutic approach in these patients should aim at preventing rebleeding and associated significant morbidity and mortality. The purpose of this study was to determine the clinical outcomes of pediatric patients who initially presented at our institution with ruptured bAVMs and to review our experience with a multimodality approach in the management of pediatric ruptured bAVMs. We retrospectively reviewed pediatric patients' medical records with ruptured bAVMs who underwent interventional treatment (microsurgery, embolization, or radiosurgery; solely or in combination) at our institution between 2011 and 2020. We identified 22 patients. There was no intraoperative and postoperative intervention-related mortality. Neither procedure-related complications nor rebleeding were observed after interventional treatment. Modified Rankin Scale (mRS) assessment at discharge revealed 19 patients (86.4%) with favorable outcomes (mRS 0-2) and 3 patients (13.6%) classified as disabled (mRS 3). Microsurgery ensured the complete obliteration in all patients whose postoperative digital subtraction angiography (DSA) was available. Management of high-grade bAVMs with radiosurgery or embolization can provide satisfactory outcomes without a high disability risk.

Children who travel internationally to visit friends and relatives (VFRs) are at risk for travel-related illness, but underuse pretravel health services. Although primary care clinics can identify travelers and address pretravel health needs, to date, there are few published reports on effective primary care-based pretravel interventions. We developed a quality improvement initiative to increase traveler identification at a primary care clinic serving families that frequently travel to VFRs. Interventions included a screening question asked at all clinic visits, provider and staff training, travel fliers, and health recommendation sheets for families. Interventions were implemented during 2017 and 2018 peak travel seasons. Travel visit rates and characteristics during the intervention period were compared with pre-intervention baseline periods (April-August, 2015-16). Surveys with providers were conducted to assess disruptiveness of the interventions, and rates of duplicate travel visits were assessed. A total of 738 unique travel events were identified during peak travel seasons from 2015 to 2018, encompassing travel to 29 countries across five continents. Overall, there were 428 unique travel events (3.0% of all clinic visits) during peak seasons 2017-18, compared with 310 unique travel events (2.2% of all clinic visits) during peak seasons 2015-16 (rate ratio 1.34 [95% CI: 1.16-1.56], P < 0.001). None of the 18 healthcare providers or staff surveyed found new travel screening processes to be disruptive or bothersome. Implementation of a primary care-based multimodal travel screening and education initiative was associated with a significantly increased rate of travel visits.

Mutations in more than 200 retina-specific genes have been associated with inherited retinal diseases. Genome editing represents a promising emerging field in the treatment of monogenic disorders, as it aims to correct disease-causing mutations within the genome. Genome editing relies on highly specific endonucleases and the capacity of the cells to repair double-strand breaks (DSBs). As DSB pathways are cell-cycle dependent, their activity in postmitotic retinal neurons, with a focus on photoreceptors, needs to be assessed in order to develop therapeutic in vivo genome editing. Three DSB-repair pathways are found in mammalian cells: Non-homologous end joining (NHEJ); microhomology-mediated end joining (MMEJ); and homology-directed repair (HDR). While NHEJ can be used to knock out mutant alleles in dominant disorders, HDR and MMEJ are better suited for precise genome editing, or for replacing entire mutation hotspots in genomic regions. Here, we analyzed transcriptomic in vivo and in vitro data and revealed that HDR is indeed downregulated in postmitotic neurons, whereas MMEJ and NHEJ are active. Using single-cell RNA sequencing analysis, we characterized the dynamics of DSB repair pathways in the transition from dividing cells to postmitotic retinal cells. Time-course bulk RNA-seq data confirmed DSB repair gene expression in both in vivo and in vitro samples. Transcriptomic DSB repair pathway profiles are very similar in adult human, macaque, and mouse retinas, but not in ground squirrel retinas. Moreover, human-induced pluripotent stem-cell-derived neurons and retinal organoids can serve as well suited in vitro testbeds for developing genomic engineering approaches in photoreceptors. Our study provides additional support for designing precise in vivo genome-editing approaches via MMEJ, which is active in mature photoreceptors., Competing Interests: The authors declare no conflict of interest.

The devastating effects and incurable nature of hereditary and sporadic retinal diseases such as Stargardt disease, age-related macular degeneration or retinitis pigmentosa urgently require the development of new therapeutic strategies. Additionally, a high prevalence of retinal toxicities is becoming more and more an issue of novel targeted therapeutic agents. Ophthalmologic drug development, to date, largely relies on animal models, which often do not provide results that are translatable to human patients. Hence, the establishment of sophisticated human tissue-based in vitro models is of upmost importance. The discovery of self-forming retinal organoids (ROs) derived from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) is a promising approach to model the complex stratified retinal tissue. Yet, ROs lack vascularization and cannot recapitulate the important physiological interactions of matured photoreceptors and the retinal pigment epithelium (RPE). In this study, we present the retina-on-a-chip (RoC), a novel microphysiological model of the human retina integrating more than seven different essential retinal cell types derived from hiPSCs. It provides vasculature-like perfusion and enables, for the first time, the recapitulation of the interaction of mature photoreceptor segments with RPE in vitro. We show that this interaction enhances the formation of outer segment-like structures and the establishment of in vivo-like physiological processes such as outer segment phagocytosis and calcium dynamics. In addition, we demonstrate the applicability of the RoC for drug testing, by reproducing the retinopathic side-effects of the anti-malaria drug chloroquine and the antibiotic gentamicin. The developed hiPSC-based RoC has the potential to promote drug development and provide new insights into the underlying pathology of retinal diseases., Competing Interests: KA, CP, JH, SB, JR, JC, MN, VC, LA, WH, NS, KS, MU, SL, PL No competing interests declared, (© 2019, Achberger et al.)

Pseudomonas aeruginosa is an opportunistic pathogen infecting human population. The pathogen is becoming a serious health problem due to its ability to evade normal immune response of the host and multiple drug resistance to many antibiotics. The pathogen has 2 major virulence systems of which the type III secretion system (T3SS) is of major concern to humans. A third system, type 2 secretion system (T2SS), is common to bacteria and used to secrete exotoxin A (ExoA) responsible for human cell destruction. To help bypass the drug resistance, a strategy to block the T2SS based on a low similarity between human ATPases and the essential ATPases of the T3SS and T2SS of P. aeruginosa, was used. An in silico-optimized inhibitor of T3SS, made directly from the computer-optimized of previously published compounds and their combinatorial libraries, showed IC 50  = 1.3 ± 0.2 μM in the T2SS ExoA secretion blocking test. The compound was non-toxic to human lung epithelial cell line A549 and could block cellular destruction of those cells in a cell infection model at 200 μM for at least 24 h. The compound could be a lead candidate for the development of T2SS virulence blockers of Pseudomonas aeruginosa., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Human induced pluripotent stem cell (hiPSC)-derived organoids mimicking tissues and organs in vitro have advanced medical research, as they opened up new possibilities for in-depth basic research on human organ development as well as providing a human in vitro model for personalized therapeutic approaches. hiPSC-derived retinal organoids have proven to be of great value for modeling the human retina featuring a very similar cellular composition, layering, and functionality. The technically challenging imaging of three-dimensional structures such as retinal organoids has, however, raised the need for robust whole-organoid imaging techniques. To improve imaging of retinal organoids we optimized a passive clearing technique (PACT), which enables high-resolution visualization of fragile intra-tissue structures. Using cleared retinal organoids, we could greatly enhance the antibody labeling efficiency and depth of imaging at high resolution, thereby improving the three-dimensional microscopy output. In that course, we were able to identify the spatial morphological shape and organization of, e.g., photoreceptor cells and bipolar cell layers. Moreover, we used the synaptic protein CtBP2/Ribeye to visualize the interconnection points of photoreceptor and bipolar cells forming the retinal-specific ribbon synapses.

Bolivian sex workers were more likely than other employed women to report tuberculosis screening only if they reported HIV screening. Of all women with household tuberculosis exposure, <40% reported screening for themselves or their children. Coupling tuberculosis screening with sex workers' mandatory HIV screenings may be a cost-efficient disease-control strategy., (Copyright © 2014 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.)