Heavy as a rock or light as dust: a comparison between the perceived workload for extracorporeal shockwave lithotripsy, ureterorenoscopy and percutaneous nephrolithotomy.

Introduction: There are three common treatment options for kidney stones: extracorporeal shockwave lithotripsy (ESWL), ureterorenoscopy (URS) and percutaneous nephrolithotomy (PNL). The choice of treatment is based on stone- and patient-related characteristics. However, some stones are eligible for several approaches and the decision is made based on patient and urologist's preferences. This study evaluates which approach has the highest workload. Material and methods: Between March and August 2022, five members of the Amsterdam Endourology Research Group collected data from 22 ESWL, 31 URS and 22 PNL procedures. After each procedure, the SURG-TLX questionnaire was completed by the surgeon to evaluate workload. Six dimensions were scored for each procedure, including: mental demands, physical demands, temporal demands, task complexity, situational stress, and distractions. The total workload, and the median for each dimension, was calculated and compared for the three treatments. Results: ESWL scored significantly lower than URS for mental demands, physical demands, temporal demands, situational stress, distraction and total workload. However, task complexity did not differ significantly between the two techniques. Compared with PNL, ESWL scored significantly lower for all dimensions. Finally, PNL received significantly higher scores for mental demands, physical demands, temporal demands, situational stress, distractions and total workload than URS. Only task complexity showed no significant difference between both groups. Conclusions: Urologists perceive the highest workload during PNL, followed by URS and finally ESWL. A follow-up study is needed to identify stressors that increase perceived workload with the purpose to address these variables and as final objective to improve urologists' workload, patient safety and treatment outcomes.

Autoimmune liver disease triggered by SARS-CoV-2: a case report and review of the literature.

BACKGROUND: An increasing number of coronavirus disease 2019 (COVID-19) related autoimmune hepatitis (AIH) and autoimmune liver disease (AILD) has been already described so far in the last three years. This rise has set up some diagnostic and therapeutic concerns, although steroid therapy has mostly been efficient, avoiding main significant side effects. CASE REPORT: We report the case of a 52-year-old subject displaying liver function impairment at the laboratory tests while positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) swab. Needle liver biopsy showed severe portal inflammation, interface hepatitis, lobular inflammation, abundant plasma cells, bridging necrosis, endothelialitis, bile duct vanishing disease, and ductular reaction. The diagnosis of autoimmune liver disease (AILD) was performed. After a month of steroid and ursodeoxycholic acid medications, liver function fully recovered. Azathioprine was introduced, and steroids were gradually reduced. CONCLUSIONS: Probably triggered by the SARS-CoV-2-induced cytokine storm, the association between COVID-19 and autoimmune-related inflammatory injury may display a particular paradigm of AILD pathogenesis.

Detection of PTCH1 Copy-Number Variants in Mosaic Basal Cell Nevus Syndrome.

Basal cell nevus syndrome (BCNS) is an inherited disorder characterized mainly by the development of basal cell carcinomas (BCCs) at an early age. BCNS is caused by heterozygous small-nucleotide variants (SNVs) and copy-number variants (CNVs) in the Patched1 (PTCH1) gene. Genetic diagnosis may be complicated in mosaic BCNS patients, as accurate SNV and CNV analysis requires high-sensitivity methods due to possible low variant allele frequencies. We compared test outcomes for PTCH1 CNV detection using multiplex ligation-probe amplification (MLPA) and digital droplet PCR (ddPCR) with samples from a BCNS patient heterozygous for a PTCH1 CNV duplication and the patient's father, suspected to have a mosaic form of BCNS. ddPCR detected a significantly increased PTCH1 copy-number ratio in the index patient's blood, and the father's blood and tissues, indicating that the father was postzygotic mosaic and the index patient inherited the CNV from him. MLPA only detected the PTCH1 duplication in the index patient's blood and in hair and saliva from the mosaic father. Our data indicate that ddPCR more accurately detects CNVs, even in low-grade mosaic BCNS patients, which may be missed by MLPA. In general, quantitative ddPCR can be of added value in the genetic diagnosis of mosaic BCNS patients and in estimating the recurrence risk for offspring.

Experts' recommendations in laser use for the treatment of urolithiasis: a comprehensive guide by the European Section of Uro-Technology (ESUT) and Training-Research in Urological Surgery and Technology (T.R.U.S.T.)-Group.

PURPOSE: To identify laser lithotripsy settings used by experts for specific clinical scenarios and to identify preventive measures to reduce complications. METHODS: After literature research to identify relevant questions, a survey was conducted and sent to laser experts. Participants were asked for preferred laser settings during specific clinical lithotripsy scenarios. Different settings were compared for the reported laser types, and common settings and preventive measures were identified. RESULTS: Twenty-six laser experts fully returned the survey. Holmium-yttrium-aluminum-garnet (Ho:YAG) was the primary laser used (88%), followed by thulium fiber laser (TFL) (42%) and pulsed thulium-yttrium-aluminum-garnet (Tm:YAG) (23%). For most scenarios, we could not identify relevant differences among laser settings. However, the laser power was significantly different for middle-ureteral (p = 0.027), pelvic (p = 0.047), and lower pole stone (p = 0.018) lithotripsy. Fragmentation or a combined fragmentation with dusting was more common for Ho:YAG and pulsed Tm:YAG lasers, whereas dusting or a combination of dusting and fragmentation was more common for TFL lasers. Experts prefer long pulse modes for Ho:YAG lasers to short pulse modes for TFL lasers. Thermal injury due to temperature development during lithotripsy is seriously considered by experts, with preventive measures applied routinely. CONCLUSIONS: Laser settings do not vary significantly between commonly used lasers for lithotripsy. Lithotripsy techniques and settings mainly depend on the generated laser pulse's and generator settings' physical characteristics. Preventive measures such as maximum power limits, intermittent laser activation, and ureteral access sheaths are commonly used by experts to decrease thermal injury-caused complications.

Potentiality switches and epistemic uncertainty: the Argument from Potential in times of human embryo-like structures.

Recent advancements in developmental biology enable the creation of embryo-like structures from human stem cells, which we refer to as human embryo-like structures (hELS). These structures provide promising tools to complement-and perhaps ultimately replace-the use of human embryos in clinical and fundamental research. But what if these hELS-when further improved-also have a claim to moral status? What would that imply for their research use? In this paper, we explore these questions in relation to the traditional answer as to why human embryos should be given greater protection than other (non-)human cells: the so-called Argument from Potential (AfP). According to the AfP, human embryos deserve special moral status because they have the unique potential to develop into persons. While some take the development of hELS to challenge the very foundations of the AfP, the ongoing debate suggests that its dismissal would be premature. Since the AfP is a spectrum of views with different moral implications, it does not need to imply that research with human embryos or hELS that (may) have 'active' potential should be completely off-limits. However, the problem with determining active potential in hELS is that this depends on development passing through 'potentiality switches' about the precise coordinates of which we are still in the dark. As long as this epistemic uncertainty persists, extending embryo research regulations to research with specific types of hELS would amount to a form of regulative precaution that as such would require further justification.

Longer is Better for Endoscopic Follow-up of Upper Tract Urothelial Carcinoma After Ureteroscopic Treatment: An Evaluation Spanning 10 Years of Data.

BACKGROUND: Tumour recurrences are frequent among patients with upper tract urothelial carcinoma (UTUC) treated with ureteroscopy (URS). Therefore, guidelines recommend a strict follow-up regimen, but there is little evidence on how to do this. OBJECTIVE: To analyse outcomes during our follow-up regimen and the impact on treatment in terms of ipsilateral UTUC recurrence, treatment conversion, and tumour upgrading, and to evaluate potential prognostic factors, including second-look URS outcomes. A secondary objective was to evaluate survival outcomes. DESIGN, SETTING, AND PARTICIPANTS: The single-centre cohort included all adult patients with nonmetastatic UTUC treated with URS from January 2010 to December 2020. Follow-up involved endoscopy at 3-mo intervals in the first year, then at 6-mo intervals up to year 3, and yearly thereafter. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive analyses were performed for the follow-up outcomes. The Andersen-Gill model for recurrent event analysis was used to analyse tumour recurrences, and multivariable Cox regression to analyse for predictors for treatment conversion in low-grade tumours. RESULTS AND LIMITATIONS: We analysed 71 patients with median follow-up of 49.5 mo. The overall 2-yr recurrence-free survival (RFS) rate was 22%. In low-grade disease, the 1-yr RFS rate was 50% and the 2-yr RFS rate was 29%. Treatment was converted to radical nephroureterectomy for 23 patients, at a median time to conversion of 9.9 mo. Upgrading was seen in 13 patients, at a median time to upgrading of 21.9 mo. No factors were prognostic for either tumour recurrence or treatment conversion. The 5-yr OS, CSS, and MFS rates were 82%, 86%, and 84%, respectively. CONCLUSIONS: Our data show that it is rational to extend endoscopic follow-up for UTUC treated with URS, as clinically relevant events (treatment conversion and tumour upgrading) occur beyond the current 6-mo guideline recommendation. Second-look URS outcomes were not prognostic for tumour recurrence or treatment conversion during follow-up. PATIENT SUMMARY: Our study results show that for patients with cancer of the upper urinary tract treated with kidney-sparing surgery through a small telescope called a ureteroscope (URS), most of the clinically relevant events (treatment conversion and tumour upgrading) occur outside the current recommended follow-up of 6 months. Therefore, URS follow-up should be extended for these patients.

Late third trimester diagnosis of congenital giant hemangioma complicated by the Kasabach-Merritt phenomen: a case report and literature review.

Objective. To describe the case of a large cervical mass diagnosed in the late third trimester with development of Kasabach-Merritt phenomenon (KMP) in the immediate postnatal period, along with a literature review.Methods. Description of case-report and literature search through Medline/Pubmed, performed from inception to December 2022 for articles relating to the pre and postnatal diagnosis of KMP.Results. A 36-year-old multiparous woman was admitted to hospital for contractions at 40 weeks of gestation, in an otherwise uneventful pregnancy. Admission's ultrasound showed the presence of a voluminous mass of 14x15 cm of the posterior side of the neck, highly vascularized, and no signs of hemodynamic imbalance. Postnatally, blood tests showed the presence of severe anemia and thrombocytopenia requiring several transfusions of blood, plasma, platelets and clotting factors. Due to the association of congenital hemangioma and thrombocytopenia a diagnosis of KMP was made. After attempts of conservative treatment, surgical removal was needed to stop the hematological cascade with regression of symptoms. The review of the literature identified 14 articles including 9 cases of prenatally suspected KMP and 6 diagnosed in the immediate postnatal period and without signs of fetal hydrops. Adverse perinatal outcome, in terms of postnatal death/termination of pregnancy, was observed in 67% of cases (6/9) in the prenatally suspected group and 33% of cases in those with a postnatal diagnosis of KMP. Fetal hydrops was present in 83% of cases with adverse perinatal outcome.Conclusions. The Kasabach-Merrit syndrome is a rare condition, which can have a dangerous evolution when it develops in utero or in the immediate postnatal period carrying a risk of perinatal mortality of approximately 50%. Even if the fetus shows no signs of anemia or heart failure, the risk of developing it in the immediate postnatal period is high and should be mentioned to the couple.

Obesity and glomerular filtration rate.

Obesity has received considerable attention in general medicine and nephrology over the last few years. This condition increases the risk of metabolic syndrome, diabetes mellitus, hypertension, and dyslipidemia, which are the main risk factors for developing chronic kidney disease (CKD). Kidney damage caused by obesity can be explained by many mechanisms, such as sympathetic nervous and renin-angiotensin-aldosterone systems activation, mechanical stress, hormonal unbalance, as well as inflammatory cytokines production. Even though creatinine-based glomerular filtration rate (GFR) equations in obese individuals have been validated (Salazar-Corcoran and CKD-MCQ), changes in body weight after bariatric surgery (BS) leads to changes in creatininemia, affecting its reliability. Thus, an average between creatine and cystatin-based GFR equations would be more appropriate in this setting. Bariatric surgery can reverse diabetes mellitus and improve hypertension, which are the main causes of CKD. Conclusion: GFR can be affected by obesity and BS, and its value should be cautiously evaluated in this setting.

Positioning the role of urine cytology within the diagnostic pathway for UTUC: supportive but inconclusive.

PURPOSE: With the introduction of kidney-sparing surgery (KSS) for low-risk Upper Tract Urothelial Carcinoma (UTUC), correct risk-stratification has become crucial. High-grade cytology is one of the decisive variables to stratify a tumor as high-risk. To position the role of urine cytology in the diagnostic pathway of UTUC patients, we evaluated the accuracy of urine cytology by comparing the outcomes with histopathology. METHOD: Patients with UTUC evaluated between 2010 and 2020, and diagnosed by imaging, cytology and histopathology were selected. Descriptive statistics were used to compare cytology with histopathological outcomes using crosstabs. Clinical performance characteristics of cytology were determined for the presence of a malignancy. RESULTS: This study included 176 patients with confirmed histopathological UTUC. Concordance between cytology and biopsy results was found in 14.8% of low-grade tumors and 16.8% of high-grade tumors. Comparing cytology with radical nephroureterectomy (RNU) specimens revealed concordance rates of 1.6% for low-grade tumors and 22.9% for high-grade tumors. Notably, 51.1% of urine cytology results were false negative. Sensitivity for detecting high-grade and low-grade tumors with a positive urine cytology was 56.6% and 52.6%, respectively, with specificities of 54.8% and 37.2%. CONCLUSION: In the current study, cytology appears to exhibit limited reliability when used as a sole diagnostic tool for assessing tumor grade and consequently risk stratification. It is imperative to recognize these limitations, optimize urine sampling techniques, and leverage a combination of diverse diagnostic methods for the most effective and individualized treatment decision-making.

Lingualyzer: A computational linguistic tool for multilingual and multidimensional text analysis.

Most natural language models and tools are restricted to one language, typically English. For researchers in the behavioral sciences investigating languages other than English, and for those researchers who would like to make cross-linguistic comparisons, hardly any computational linguistic tools exist, particularly none for those researchers who lack deep computational linguistic knowledge or programming skills. Yet, for interdisciplinary researchers in a variety of fields, ranging from psycholinguistics, social psychology, cognitive psychology, education, to literary studies, there certainly is a need for such a cross-linguistic tool. In the current paper, we present Lingualyzer ( https://lingualyzer.com ), an easily accessible tool that analyzes text at three different text levels (sentence, paragraph, document), which includes 351 multidimensional linguistic measures that are available in 41 different languages. This paper gives an overview of Lingualyzer, categorizes its hundreds of measures, demonstrates how it distinguishes itself from other text quantification tools, explains how it can be used, and provides validations. Lingualyzer is freely accessible for scientific purposes using an intuitive and easy-to-use interface.

Surface and Contextual Linguistic Cues in Dialog Act Classification: A Cognitive Science View.

What role do linguistic cues on a surface and contextual level have in identifying the intention behind an utterance? Drawing on the wealth of studies and corpora from the computational task of dialog act classification, we studied this question from a cognitive science perspective. We first reviewed the role of linguistic cues in dialog act classification studies that evaluated model performance on three of the most commonly used English dialog act corpora. Findings show that frequency-based, machine learning, and deep learning methods all yield similar performance. Classification accuracies, moreover, generally do not explain which specific cues yield high performance. Using a cognitive science approach, in two analyses, we systematically investigated the role of cues in the surface structure of the utterance and cues of the surrounding context individually and combined. By comparing the explained variance, rather than the prediction accuracy of these cues in a logistic regression model, we found that (1) while surface and contextual linguistic cues can complement each other, surface linguistic cues form the backbone in human dialog act identification, (2) with word frequency statistics being particularly important for the dialog act, and (3) the similar trends across corpora, despite differences in the type of dialog, corpus setup, and dialog act tagset. The importance of surface linguistic cues in dialog act classification sheds light on how both computers and humans take advantage of these cues in speech act recognition.

Experts' recommendations in laser use for the treatment of upper tract urothelial carcinoma: a comprehensive guide by the European Section of Uro-Technology (ESUT) and Training Research in Urological Surgery and Technology (T.R.U.S.T.) group.

PURPOSE: To highlight and compare experts' laser settings during endoscopic laser treatment of upper tract urothelial carcinoma (UTUC), to identify measures to reduce complications, and to propose guidance for endourologists. METHODS: Following a focused literature search to identify relevant questions, a survey was sent to laser experts. We asked participants for typical settings during specific scenarios (ureteroscopy (URS), retrograde intrarenal surgery (RIRS), and percutaneous treatment). These settings were compared among the reported laser types to find common settings and limits. Additionally, we identified preventive measures commonly applied during surgery. RESULTS: Twenty experts completed the survey, needing a mean time of 12.7 min. Overall, most common laser type was Holmium-Yttrium-Aluminum-Garnet (Ho:YAG) (70%, 14/20) followed by Thulium fiber laser (TFL) (45%, 9/20), pulsed Thulium-Yttrium-Aluminum-Garnet (Tm:YAG) (3/20, 15%), and continuous wave (cw)Tm:YAG (1/20, 5%). Pulse energy for the treatment of distal ureteral tumors was significantly different with median settings of 0.9 J, 1 J and 0.45 J for Ho:YAG, TFL and pulsed Tm:YAG, respectively (p = 0.048). During URS and RIRS, pulse shapes were significantly different, with Ho:YAG being used in long pulse and TFL in short pulse mode (all p < 0.05). We did not find further disparities. CONCLUSION: Ho:YAG is used by most experts, while TFL is the most promising alternative. Laser settings largely do not vary significantly. However, further research with novel lasers is necessary to define the optimal approach. With the recent introduction of small caliber and more flexible scopes, minimal-invasive UTUC treatment is further undergoing an extension of applicability in appropriately selected patients.

Aptamer-enriched scaffolds for tissue regeneration: a systematic review of the literature.

Introduction: Aptamers are a brand-new class of receptors that can be exploited to improve the bioactivity of tissue engineering grafts. The aim of this work was to revise the current literature on in vitro and in vivo studies in order to i) identify current strategies adopted to improve scaffold bioactivity by aptamers; ii) assess effects of aptamer functionalization on cell behavior and iii) on tissue regeneration. Methods: Using a systematic search approach original research articles published up to 30 April 2022, were considered and screened. Results: In total, 131 records were identified and 18 were included in the final analysis. Included studies showed that aptamers can improve the bioactivity of biomaterials by specific adsorption of adhesive molecules or growth factors from the surrounding environment, or by capturing specific cell types. All the studies showed that aptamers ameliorate scaffold colonization by cells without modifying the physicochemical characteristics of the bare scaffold. Additionally, aptamers seem to promote the early stages of tissue healing and to promote anatomical and functional regeneration. Discussion: Although a metanalysis could not be performed due to the limited number of studies, we believe these findings provide solid evidence supporting the use of aptamers as a suitable modification to improve the bioactivity of tissue engineering constructs.

Conservative treatment of cervical cancer: A single center experience over a two-decade period.

Objective: To report the surgical, oncological, and obstetrical outcomes of the different surgical techniques used for the fertility-sparing treatment of patients with early-stage cervical cancer. Methods: We retrospectively analyzed all fertility-sparing procedures performed between 2004 and 2020. The study included patients desiring to preserve fertility who had squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma histology, all grades, and FIGO 2009 stage IA2-IB1 tumors. Results: 48 patients met the inclusion criteria. Eight patients (16.7%) had stage IA2, and 40 (83.3%) had stage IB1 tumors. Conization with pelvic lymph node assessment was performed in 5 (10.4%) patients, an open radical trachelectomy in 21 (43.8%), and a laparoscopic radical trachelectomy in 22 (45.8%). No major intraoperative complications were registered. Two patients required surgery due to an early postoperative complication. Late postoperative complications were seen in 15 patients (31.2%), with cervical stenosis being the most frequent (60%). The rate of DFS at 2 and 5 years was 89% (95% CI, 76-95%), and the 5- year OS was 96% (95% CI, 83-98%). Univariate analysis demonstrated a relationship between tumor size and recurrence, but not for other prognostic tumor factors or surgical approach. One patient (4.8%) developed recurrent disease in the open radical trachelectomy group, and five (22.7%) in the laparoscopic radical trachelectomy group. The pregnancy rate was 41.4%, and the live birth rate 88.2%. Conclusion: Fertility-sparing treatment for patients with early-stage cervical cancer is ever-evolving. This study adds information to the literature about the outcomes of these quite uncommon procedures, and allows a critical analysis of many of the topics which are under discussion.

Association of RANKL and EGFR gene expression with bone metastases in patients with metastatic non-small cell lung cancer.

Introduction: Bone metastases are frequent in patients with non-small cell lung cancer (NSCLC). The receptor activator of Nuclear Factor κB (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) pathway is important in bone metastases development. Furthermore, epidermal growth factor receptor (EGFR) signaling promotes osteoclast formation and stimulation. The understanding of the biological mechanism of bone metastases development might have implications for treatment strategies. Therefore, we studied whether there is an association between EGFR, RANKL, RANK and OPG gene expression in the tumor and presence of bone metastases in patients with NSCLC. Methods: From an updated multicenter study, including patients with EGFR mutated (EGFR+), Kirsten rat sarcoma (KRAS+) and EGFR/KRAS wildtype metastatic NSCLC, all patients with available formalin-fixed paraffin-embedded (FFPE) tumor samples were selected. Ribonucleic Acid (RNA) was isolated from these samples and gene expressions of EGFR, RANKL, OPG and RANKL were determined via quantitative Polymerase Chain Reaction (qPCR). Data on demographics, histology and molecular subtyping, sample origin, presence of bone metastasis, SREs and bone progression were collected. Primary endpoint was relation between EGFR, RANK, RANKL, OPG gene expression, RANKL: OPG ratio and bone metastases. Results: In 73/335 (32% EGFR+, 49% KRAS+, 19% EGFR/KRAS wildtype) samples from unique patients, gene expression analysis could be performed. Of these 73 patients, 46 (63%) had bone metastases at diagnosis or developed bone metastases during the disease course. No association was found between EGFR expression and presence of bone metastases. Patients with bone metastases had a significantly higher RANKL expression and RANKL: OPG ratio compared to those without. An increased RANKL: OPG ratio resulted in a 1.65x increased risk to develop bone metastases, especially in the first 450 days after diagnosis of metastatic NSCLC. Conclusion: Increased RANKL gene expression and RANKL: OPG ratio, but not EGFR expression, was associated with presence of bone metastases. Additionally, an increased RANKL: OPG gene ratio was associated with a higher incidence of bone metastases development.