New strategies in soft tissue sarcoma treatment.

Soft tissue sarcomas (STS) have long been a formidable challenge in oncology, partly because of their rarity and diversity, which complicates large-scale studies and slows the advent of new treatments. Traditionally anchored by anthracycline-based chemotherapy, the landscape of STS treatment hasn't shifted dramatically in the past twenty years. However, recent strides in research are starting to paint a more hopeful picture. Leveraging advanced molecular profiling, researchers are now tailoring treatments to the unique genetic makeup of tumors, with targeted therapies showing promise. Innovations such as NTRK inhibitors for NTRK-rearranged sarcomas and gamma-secretase inhibitors for desmoid tumors are changing clinical practices. The rise of immunotherapy, including novel agents like LAG-3 inhibitors and bifunctional proteins that target both TGF-ß and PD-L1, offers new avenues for treatment, particularly when combined with traditional therapies like chemotherapy. Meanwhile, the approval of epigenetic treatments for specific sarcoma subtypes heralds a new wave of strategy based on histological specificity, which could lead to more personalized and effective care. While challenges remain, the field of STS treatment is evolving, driven by a deeper understanding of the disease's biological underpinnings and a commitment to innovative research approaches.

Industry visions of technology for older adults: A futures anthropology perspective.

The negative portrayal of ageing as a human decline burdening society has prompted Ageing Technology industries (AgeTech) to foresee solutions rooted in the Ageing in Place paradigm. These ostensibly neutral future interventions are intertwined with socio-technical dynamics. While Science and Technology Studies (STS) and anthropology scholars have questioned these AgeTech practices, limited literature explores industry's predictions of future AgeTech. Drawing on STS and futures-anthropology literature, I interrogate AgeTech industry visions of future assemblages involving older people, smart home technology, and socio-material discourses rooted in their own discrepancies and dilemmas. To unpack AgeTech futures, my methods include a review of 49 industry reports and 29 interviews with industry experts. Based on the reports, I designed comics to be used in interviews with experts spanning CEOs and managers of companies designing technology for older people, consultants, and aged-care workers based in 12 countries. Ageing futures are far from being neutral or a chronological process, instead they are non-consensual and fragmented. In the review and interviews, I captured future assemblages of a fragmented AgeTech industry in relationships with governments and industry giants. The fragmentation continues unfolding in participants from diverse countries and professions contesting dominant AgeTech narratives. In dissecting future assemblages, I also unpack non-consensual futures based on diverging experts' values (e.g. safety versus activity) and humans' values like control and improvisation challenging predictive and surveillance technology. AgeTech Futures transcend physical matters or assemblages of technologies and humans. They encompass future normativities, tensions, divergent values, and ideological concepts. I propose not only alternatives to the visions found in industry narratives, but also encourage scholars to understand the AgeTech industry's dilemmas.

Successful pazopanib treatment of undifferentiated pleomorphic sarcoma with coamplification of PDGFRA, VEGFR2 and KIT: A case report.

Undifferentiated pleomorphic sarcoma (UPS) is a high-grade, aggressive soft tissue sarcoma (STS) with a poor prognosis, and no definitive or effective treatment is currently available for it. Pazopanib, an orally available multiple tyrosine kinase inhibitor, has been approved for the treatment of advanced STS. The present study documents the case of a 51-year-old man with advanced UPS with coamplification of platelet-derived growth factor receptor A (PDGFRA), vascular endothelial growth factor receptor 2 (VEGFR2) and stem cell factor receptor (KIT) genes. The patient exhibited a marked and sustained response to pazopanib. The patient presented with a retroperitoneal tumour with pancreatic head lymph node metastasis, and bone metastases in the second/fifth thoracic vertebrae and left femur. Based on the histological analysis of the retroperitoneal tumour and femoral mass, the patient was diagnosed with UPS. Palliative radiation therapy was administered to the left femur and second/fifth thoracic vertebrae to prevent fractures. After radiation therapy, the patient achieved a partial response after eight courses of doxorubicin. A comprehensive genomic profiling analysis (FoundationOne® CDx) revealed coamplification of PDGFRA, VEGFR2 and KIT genes. Hence, pazopanib was initiated as a second-line treatment. Notably, the retroperitoneal tumour shrank, and no new lesions developed for 3 years after the initiation of pazopanib treatment. This response suggests that the coamplification of PDGFRA, VEGFR2 and KIT may predict favourable outcomes in response to pazopanib.

Revisiting X-linked congenital ichthyosis.

X-linked recessive ichthyosis (XLI) is a hereditary skin disease characterized by generalized dryness and scaling of the skin, with frequent extracutaneous manifestations. It is the second most common type of ichthyosis, with a prevalence of 1/6,000 to 1/2,000 in males and without any racial or geographical differences. The causative gene for XLI is the steroid sulfatase gene (STS), located on Xp22.3. STS deficiency causes an abnormal cholesterol sulfate (CS) accumulation in the stratum corneum (SC). Excess CS induces epidermal permeability barrier dysfunction and scaling abnormalities. This review summarizes XLI's genetic, clinical, and pathological features, pathogenesis, diagnosis and differential diagnoses, and therapeutic perspectives. Further understanding the role of the STS gene pathogenic variants in XLI may contribute to a more accurate and efficient clinical diagnosis of XLI and provide novel strategies for its treatment and prenatal diagnosis.

Detection of trisomy 9 mosaicism in the second trimester screening by abnormal level of biochemical markers.

Trisomy 9 is a rare chromosomal abnormality that occurs in both mosaic and non-mosaic states. The present study reports a case of mosaic trisomy 9 detected during pregnancy in a 41-year-old woman in the second trimester screening. Maternal serum screening results were used to diagnose a chromosomal abnormality in utero. The results were validated by karyotyping. High levels of alpha-fetoprotein and low levels of unconjugated estriol (uE3), human chorionic gonadotropin (hCG), and inhibin A indicate a high risk for chromosomal abnormalities, including trisomy 18. Amniotic fluid karyotyping revealed 47, XX, +9 (30)/46, XX (20) in the fetus. Because a high level (60%) of mosaicism for trisomy 9 in the fetus can affect many parts of the body, the pregnancy was terminated. It seems that a significant reduction in the levels of hCG and uE3 is an informative marker for the detection of chromosomal abnormalities such as trisomy 9.

A Review on Canine and Human Soft Tissue Sarcomas: New Insights on Prognosis Factors and Treatment Measures.

Soft tissue sarcomas (STSs) represent a diverse group of tumors arising from mesenchymal cells, affecting both humans and animals, including dogs. Although STSs represent a class of rare tumors, especially in humans, they pose significant clinical challenges due to their potential for local recurrence and distant metastasis. Dogs, as a model for human STSs, offer several advantages, including exposure to similar environmental risk factors, genetic diversity among breeds, and the spontaneous development of tumors. Furthermore, canine tumors closely mimic the heterogeneity and complexity of human tumors, making them valuable for research into disease progression and treatment effectiveness. Current treatment approaches for STSs in both dogs and humans primarily involve surgery, radiation therapy, and chemotherapy, with treatment decisions based on tumor characteristics and patient factors. However, the development of novel therapeutic strategies is essential, given the high failure rate of new drugs in clinical trials. To better design new tailored treatments, comprehension of the tumor microenvironment (TME) is fundamental, since it plays a crucial role in STS initiation and progression by modulating tumor behavior, promoting angiogenesis, and suppressing immune responses. Notably, TME features include cancer-associated fibroblasts (CAFs), extracellular matrix (ECM) alterations, and tumor-associated macrophages (TAMs) that, depending on their polarization state, can affect immune responses and thus the patient's prognosis. In this review, new therapeutical approaches based on immunotherapy will be deeply explored as potential treatment options for both dogs and humans with STSs. In conclusion, this review provides an overview of the current understanding of STSs in dogs and humans, emphasizing the importance of the TME and potential treatment strategies.

Ethnographic Film, Fourth Cinema and Situated Knowledge Practices-from Colonial Film to Collaborative Research.

The text attempts to understand the development of collaborative audiovisual knowledge practices in anthropology as situated and diffractive knowledge (Haraway, Barad, Smith). By considering specific stages in the history of collaborative and participatory projects, the article argues that collaborative filmmaking is not only a decentering of one-sided authorship and one-sided modes of representation, but also a media-specific form of knowledge that is bound to and embedded in social contexts. Through the example of colonial film, the article describes stations of demarcation and attempts to decolonize film. Current film experiments with marginalized groups have their origins in "shared anthropologies" (Rouch) and have further developed this approach through more consistent forms of Fourth Cinema and power sharing with Indigenous communities. Film is thus also able to depict amateur knowledge practices within collaborative research projects.

Systematic Review of the Gonadotoxicity and Risk of Infertility of Soft Tissue Sarcoma Chemotherapies in Pre- and Postpubertal Females and Males.

Increasing awareness of gonadotoxicity in cancer treatments and infertility risk is essential for counseling young cancer patients. While fertility preservation options are available in many countries, limited data on gonadotoxicity hinder recommendations, especially for soft tissue cancers. This review, part of the FertiTOX project (www.fertitox.com), organized by FertiPROTEKT (www.fertiprotekt.com), aims to address this knowledge gap to improve fertility preservation guidance. We performed a systematic literature search on gonadotoxicity in soft tissue sarcoma (STS) cancer treatments. Only patients without metastases or recurrent disease were considered. "Suspected infertility" was defined based on low ovarian reserve parameters, low inhibin B levels, high gonadotropin concentration, gonadal dysfunction, amenorrhea, oligomenorrhea, azoospermia, or oligozoospermia due to limited infertility data. The study quality was assessed using the Newcastle-Ottawa Scale. The search yielded 3309 abstracts, with 138 undergoing full-text analysis. Eight studies on STS were included. Suspected infertility was observed in 20 of 28 females (71.4%, range 0-100%) and 38 of 63 males (60.3%, range 34.8-100%) with STS. Six of the eight studies received high-quality scores on the NOS, while two received a fair score. Our data suggest a high risk of infertility from chemotherapy in pre- and postpubertal STS survivors. This underscores the importance of considering fertility preservation measures when counseling these patients.

Conceptualizing Automated Decision-Making in Organizational Contexts.

Despite growing interest in automated (or algorithmic) decision-making (ADM), little work has been done to conceptually clarify the term. This article aims to tackle this issue by developing a conceptualization of ADM specifically tailored to organizational contexts. It has two main goals: (1) to meaningfully demarcate ADM from similar, yet distinct algorithm-supported practices; and (2) to draw internal distinctions such that different ADM types can be meaningfully distinguished. The proposed conceptualization builds on three arguments: First, ADM primarily refers to the automation of practical decisions (decisions to φ) as opposed to cognitive decisions (decisions that p). Second, rather than referring to algorithms as literally making decisions, ADM refers to the use of algorithms to solve decision problems at an organizational level. Third, since algorithmic tools by nature primarily settle cognitive decision problems, their classification as ADM depends on whether and to what extent an algorithmically generated output p has an action triggering effect-i.e., translates into a consequential action φ. The examination of precisely this p-φ relationship, allows us to pinpoint different ADM types (suggesting, offloading, superseding). Taking these three arguments into account, we arrive at the following definition: ADM refers to the practice of using algorithms to solve decision problems, where these algorithms can play a suggesting, offloading, or superseding role relative to humans, and decisions are defined as action triggering choices.

Perioperative Marinobufagenin (MBG) Measurement May Improve Acute Kidney Injury Risk Assessment in Patients Undergoing Major Cardiac Surgery: A Proof-of-Concept Study.

Background and Objectives: Acute kidney injury (AKI) remains a significant complication following major cardiac surgery. Marinobufagenin (MBG), a cardiotonic steroid involved in sodium balance and blood pressure regulation, has been linked to organ damage after ischemia-reperfusion events. This pilot, prospective study investigates the utility of circulating MBG to improve AKI risk assessment in cardiac surgery patients as a stand-alone biomarker and after inclusion in a validated risk model (STS-AKI score). Materials and Methods: We included 45 patients undergoing elective cardiac surgery. The MBG levels were measured preoperatively and at 4, 8, and 12 h post-surgery. The AKI was defined according to the KDIGO guidelines. Statistical analyses assessed the diagnostic and prognostic utility of MBG and its integration with the STS-AKI score. Results: An AKI occurred in 26.7% of the patients. The STS-AKI score performed well in this cohort (AUC: 0.736). The MBG levels displayed a decreasing trend in the whole population after surgery (p = 0.02). However, in the AKI patients, MBG increased at 4 and 8 h before decreasing at 12 h post-surgery. The MBG changes from the baseline to 8 h and from 8 to 12 h post-surgery showed a remarkable diagnostic accuracy for an AKI (AUCs: 0.917 and 0.843, respectively). Integrating these MBG changes with the STS-AKI score significantly improved the model performance, including discrimination, calibration, and risk reclassification. Conclusions: The MBG measurement, particularly any dynamic changes post-surgery, enhances AKI risk stratification in cardiac surgery patients. Integrating MBG with the STS-AKI score offers more accurate risk predictions, potentially leading to better patient management and outcomes.

Genetic Variation among the Partial Gene Sequences of the Ribosomal Protein Large-Two, the Internal Transcribed Spacer, and the Small Ribosomal Subunit of Blastocystis sp. from Human Fecal Samples.

In the present study, we compared the genetic variability of fragments from the internal transcribed spacer region (ITS) and the small subunit ribosomal DNA (SSUrDNA) as nuclear markers, in contrast with the ribosomal protein large two (rpl2) loci, placed in the mitochondrion-related organelles (MROs) within and among human fecal samples with Blastocystis. Samples were analyzed using polymerase chain reaction (PCR)-sequencing, phylogenies, and genetics of population structure analyses were performed. In total, 96 sequences were analyzed, i.e., 33 of SSUrDNA, 35 of rpl2, and 28 of ITS. Only three subtypes (STs) were identified, i.e., ST1 (11.4%), ST2 (28.6%), and ST3 (60%); in all cases, kappa indexes were 1, meaning a perfect agreement among ST assignations. The topologies of phylogenetic inferences were similar among them, clustering to each ST in its specific cluster; discrepancies between phylogeny and assignment of STs were not observed. The STRUCTURE v2.3.4 software assigned three subpopulations corresponding to the STs 1-3, respectively. The population indices were consistent with those previously reported by other groups. Our results suggest the potential use of the ITS and rpl2 genes as molecular markers for Blastocystis subtyping as an alternative approach for the study of the genetic diversity observed within and between human isolates of this microorganism.

Cortical Face-Selective Responses Emerge Early in Human Infancy.

In human adults, multiple cortical regions respond robustly to faces, including the occipital face area (OFA) and fusiform face area (FFA), implicated in face perception, and the superior temporal sulcus (STS) and medial prefrontal cortex (MPFC), implicated in higher-level social functions. When in development, does face selectivity arise in each of these regions? Here, we combined two awake infant functional magnetic resonance imaging (fMRI) datasets to create a sample size twice the size of previous reports (n = 65 infants; 2.6-9.6 months). Infants watched movies of faces, bodies, objects, and scenes, while fMRI data were collected. Despite variable amounts of data from each infant, individual subject whole-brain activation maps revealed responses to faces compared to nonface visual categories in the approximate location of OFA, FFA, STS, and MPFC. To determine the strength and nature of face selectivity in these regions, we used cross-validated functional region of interest analyses. Across this larger sample size, face responses in OFA, FFA, STS, and MPFC were significantly greater than responses to bodies, objects, and scenes. Even the youngest infants (2-5 months) showed significantly face-selective responses in FFA, STS, and MPFC, but not OFA. These results demonstrate that face selectivity is present in multiple cortical regions within months of birth, providing powerful constraints on theories of cortical development.

Identification of tritium-contaminated areas using a tritium survey on the snow cover, the case of Semipalatinsk test site.

The article presents research findings on the content of tritium in the snow cover of test locations 'Balapan' and 'Sary-Uzen' in the territory of the Semipalatinsk Test Site. Based upon results, a number of tritium-contaminated areas were revealed. At the 'Balapan' site, elevated tritium concentrations in the snow were revealed in the vicinity of the 'Atomic lake' close to the 'Karazhyra' deposit and at the location of Lake 'Kishkensor'. At the 'Sary-Uzen' site, elevated tritium concentrations in the snow were discovered near borehole 101, at object 'Lazurite' and at an unnamed creek outflowing from the mountain range. Maximal of tritium activity concentration in the snow were 45 Bq/kg and 36 Bq/kg at the 'Balapan' and 'Sary-Uzen' sites, respectively. Background tritium concentrations in the snow cover of the STS territory were found to be 4.6-12 Bq/kg.

Bridging technology and care: integrating web-based PROMs in mental health services for refugees: a study on clinician training and technology adoption.

This study explores the integration of a web-based electronic database technology containing patient-reported outcome measures (PROMs) with electronic health records for refugees with PTSD, emphasizing the systematic inclusion of patient perspectives in clinical decision-making. Our research addresses the notable gap in literature regarding training clinicians for the competent integration of health information technology in healthcare. The training program developed aimed at equipping clinicians, particularly inexperienced with technology, to effectively utilize an electronic PROM system for collecting systematic patient information. Our study is set in the context of the Mental Health Services (MHS) in Denmark, focusing on a specialized clinic for treating trauma-affected refugees. The multidisciplinary team involved in this project reflects a wide range of healthcare professionals. The training program employed a variety of activities over nearly 2 years, adapting to feedback and aiming to engage clinicians in continuous improvement processes. Analyzing qualitative data with thematic analysis we interpreted that the training's extended focus on discussion of the implementation process, with limited hands-on experience, potentially reinforced clinicians' hesitations toward new technology, rather than reducing them. Clinicians prioritized immediate concerns over potential long-term benefits. Despite this, their approach reflects a strong commitment to patient welfare and careful evaluation of new practices. Notably, there were also positive engagements with the technology, highlighting its potential in patient care. This study concludes that the successful integration of technology in clinical settings hinges on its alignment with clinicians' workflows, respect for their professional judgment, and clear benefits to patient care.

Short-Term Outcomes of Transcatheter Aortic Valve Replacement in Low-Risk Patients With Pure Severe Aortic Regurgitation.

Transcatheter aortic valve replacement (TAVR) has emerged as an alternative treatment for patients with pure severe aortic regurgitation (PSAR) who are contraindicated for surgery or have a high surgical risk. However, the therapeutic efficacy and safety of TAVR in low Society of Thoracic Surgeons (STS) score risk patients remain to be clarified. This study aimed to explore the feasibility of TAVR treatment in different STS-risk patients and to compare the adverse events between the groups. In this study, patients with PSAR who underwent TAVR at Zhongshan Hospital, Fudan University, China, during the inclusion period were included and categorized into 3 groups based on STS scores. The baseline data, imaging results, and follow-up data of the patients were documented. Therefore, of 75 TAVR patients, 38 (50.7%) were categorized as low risk (STS <4), and 37 (49.3%) patients were categorized as intermediate and high risk (STS ≥4). Compared with patients at intermediate and high risk, those in the low-risk group were younger, had a lower body mass index, had a lower prevalence of hypertension, chronic obstructive pulmonary disease, and previous percutaneous coronary intervention, and had better cardiac function (p all <0.05). In the hospital and at the 1-month follow-up, the degree of aortic regurgitation and cardiac function were significantly improved. No significant difference was found between the 2 groups in the hospital or during the 30-day follow-up. In conclusion, TAVR for PSAR in low-STS-risk patients is safe and efficient during 30 days of follow-up compared with intermediate- and high-STS-risk groups. TAVR for PSAR should not be limited to inoperable or STS-defined high-risk patients. Long-term follow-up is needed for further investigation.

Exposure to secondary traumatic stress and its related factors among emergency nurses in Saudi Arabia: a mixed method study.

BACKGROUND: Emergency department (ED) nurses are exposed to the risk of secondary traumatic stress (STS), which poses a threat not only to nurses' health and psychological well-being but also adversely affects the execution of their professional duties. The quality and outcome of their nursing services are negatively affected by STS. PURPOSE: The purpose of this study is to comprehensively investigate the prevalence and intensity of Secondary Traumatic Stress (STS) among Emergency Department (ED) nurses. It aims to identify and analyze the socio-demographic, occupational, and psychological factors that influence the severity and variation of STS experienced by these nurses. METHODS: The study utilized a sequential explanatory mixed methods approach, including two phases. Phase 1 employed a cross-sectional study design, utilizing a convenience sample of 181 nurses to explore the levels of STS and the factors associated with it. Following this, Phase 2 was structured as a qualitative descriptive study, which involved conducting semi-structured interviews with a purposefully selected group of ten ED nurses. Data collection took place at three major hospitals in Saudi Arabia during the period from January to June 2022. RESULTS: A total of 181 participants were included in the study. The mean STSS score reported by the nurses was 51 (SD = 13.23) out of the maximum possible score of 85, indicating severe STS among ED nurses. Factors associated with an increase in the levels of STS among ED nurses included being female, older in age, married, possessing higher education and experience, having a positive relationship with colleagues, receiving organisational support, and dealing with a higher number of trauma cases. Several themes emerged from the qualitative interviews including: ED Characteristics: Dual Impact on STS, Emotional Resonance and Vulnerability, Personal Life Stressors, The Ability to Cope, and Social Support. CONCLUSION AND IMPLICATIONS FOR PRACTICE: Future strategies and interventions targeting STS should be prioritized to effectively manage its impact on ED nurses. It is crucial to develop targeted interventions that address the specific factors contributing to STS, as identified in this study. Additionally, these findings aim to enhance awareness among nursing administrators, managers, and supervisors about the critical factors associated with STS. This awareness is essential for accurately assessing and developing interventions that mitigate STS among nursing staff.

Optimization of Multiplex-PCR Technique To Determine Azf Deletions in infertility Male Patients.

Background: To optimize the multiplex polymerase chain reaction (M-PCR) technique to diagnose microdeletions of azoospermia factors (AZF) on the Y chromosome and initially apply the technique to diagnose male patients with sperm density less than 5×106 million sperm/mL was assigned to do a test to check for AZF microdeletions on the Y chromosome. Methods: Based on the positive control samples which belong to male subjects who have had 2 healthy children without any assisted reproductive technologies, the M-PCR method was developed to detect simultaneously and accurately AZF microdeletions on 32 male patients with sperm densities below 5×106 million sperm/mL of semen at the Department of Biology and Medical Genetics - Vietnam Military Medical University. Results: Successful optimization of the M-PCR technique including 7 reactions arranged according to each AZFabc region using 24 STS/gene on the Y chromosome. Initial application to diagnose AZF deletion on 32 azoospermic and oligospermic men reveals that AZFa deletion accounts for 6.25% (2/32); deletion of all 3 regions AZFa,b,c with 18.75% (6/32 cases); The combined deletion rate of AZFb,c is highest, accounting for 56.24% (18/32 patients). Conclusion: Successfully optimized the M-PCR technique in identifying AZF microdeletions using 24 sequence tagged sites (STS)/gene for azoospermic and oligozoospermic men. The M-PCR technique has great potential in the application of AZF deletion diagnosis.

Human immunodeficiency virus infection is associated with greater risk of pneumonia and readmission after cardiac surgery.

Objective: Human immunodeficiency virus infection (HIV+) is associated with a 2-fold increased risk of cardiovascular disease. Increasingly, patients who are HIV + are being evaluated to undergo cardiac surgery. Current risk-adjusted scoring systems, including the Society of Thoracic Surgeons Predicted Risk of Mortality score, fail to stratify HIV + risk. Unfortunately, there exists a paucity of cardiac surgery outcomes data in modern patients who are HIV+. Methods: We conducted a retrospective review of PearlDiver, an all-payer claims administrative database. In total, 14,714,743 patients were captured between 2010 and 2020. Of these, 59,695 (0.4%) of patients had a history of HIV+, and 1759 (2.95%) of these patients underwent cardiac surgery. Patients who were HIV+ were younger, more often male, and had greater comorbidity, history of hypertension, chronic obstructive pulmonary disease, chronic liver disease, chronic kidney disease, chronic lung disease, and heart failure. Results: Postoperatively, patients who were HIV + had significantly greater rates of pneumonia (relative risk, 1.70; P = .0003) and 30-day all-cause readmission (relative risk, 1.28, P < .0001). After linear regression analysis, these results remained significant. Data also show that a lesser proportion of patients with HIV + underwent coronary artery bypass grafting, aortic valve replacement, and any cardiac surgery compared with controls. Conclusions: Patients who are HIV + undergoing cardiac surgery are at greater risk of pneumonia and readmission. Moreover, we discovered lower rates of cardiac surgery in patients who are HIV+, which may reflect limited access to surgery when indicated. Today's risk-adjusted scoring systems in cardiac surgery need to better account for the modern patient who is HIV+.

Genetic analysis of seven patients with inherited ichthyosis and Nagashima­type palmoplantar keratoderma.

Inherited ichthyosis comprises a series of heterogeneous dermal conditions; it mainly manifests as widespread hyperkeratosis, xerosis and scaling of the skin. At times, overlapping symptoms require differential diagnosis between ichthyosis and several other similar disorders. The present study reports seven patients with confirmed or suspected to be associated with ichthyosis by conducting a thorough clinical and genetic investigation. Genetic testing was conducted using whole­exome sequencing, with Sanger sequencing as the validation method. The MEGA7 program was used to analyze the conservation of amino acid residues affected by the detected missense variants. The enrolled patients exhibited ichthyosis­like but distinct clinical manifestations. Genetic analysis identified diagnostic variations in the FLG, STS, KRT10 and SERPINB7 genes and clarified the carrying status of each variant in the respective family members. The two residues affected by the detected missense variants remained conserved across multiple species. Of note, the two variants, namely STS: c.452C>T(p.P151L) and c.647_650del(p.L216fs) are novel. In conclusion, a clear genetic differential diagnosis was made for the enrolled ichthyosis­associated patients; the study findings also extended the mutation spectrum of ichthyosis and provided solid evidence for the counseling of the affected families.

Result of the left bundle branch area pacing data collection registry, an international multicenter study of conduction system pacing with a Tendril STS 2088 stylet-driven lead.

INTRODUCTION: Left bundle branch area (LBBA) pacing (LBBAP) has been proposed as an alternative therapy option in patients indicated for cardiac pacing to treat bradycardia or heart failure. The aim of the study was to evaluate the safety and effectiveness of LBBAP in patients implanted with a Tendril 2088 stylet-driven lead. METHODS: The international retrospective data collection registry included 11 sites from 5 countries globally. Patients with attempted implants of the Tendril lead in the LBBA were followed for at least 6 months post the implant attempt. The primary safety and efficacy endpoints were freedom from LBBAP lead-related serious adverse events and the composite of LBBA capture threshold of ≤2.0 V and R-wave amplitudes ≥5 mV (or ≥value at implant), respectively. RESULTS: Of 221 patients with attempted implants of the Tendril 2088 lead in the LBBA, 91.4% (202/221) had successful implants for LBBAP. Regardless of the LBBAP implant success, all patients were followed for at least 6 months (8.7 ± 7.3 months). Baseline characteristics: 44% female, 84% ≥65 years old, 34% coronary artery disease, and 86% of primary indications for pacemaker implant. Both primary safety and effectiveness endpoints were met (freedom from LBBAP lead-related serious adverse device effects of 99.5% and electrical performance composite success rate of 93%). The capture thresholds in LBBAP at implant and 6 months were 0.8 ± 0.3 V@0.4 ± 0.1 ms and 0.8 ± 0.3 V@0.4 ± 0.1 ms. The rate of patients with capture threshold rise ≥1 V was 1.5% through 6 months. The R-wave amplitudes in LBBAP at implant and 6 months were 9.3 ± 3.2 mV and 10.6 ± 3.0 mV. CONCLUSIONS: This large multicenter study demonstrates that the stylet-driven Tendril™ STS 2088 lead is safe and effective for LBBAP with high success and low complication rates.