Heterogeneous Group Research Articles

Detectable troponin below the 99th percentile predicts survival in patients undergoing coronary angiography

BackgroundCardiac troponin I (cTnI) above the 99th percentile is associated with an increased risk of major adverse events. Patients with detectable cTnI below the 99th percentile are a heterogeneous group with a less well-defined risk profile. The purpose of this study is to investigate the prognostic relevance of detectable cTnI below the 99th percentile in patients undergoing coronary angiography. MethodsThe study included 14,776 consecutive patients (mean age of 65.4 ± 12.7 years, 71.3 % male) from the Essen Coronary Artery Disease (ECAD) registry. Patients with cTnI levels above the 99th percentile and patients with ST-segment elevation acute myocardial infarction were excluded. All-cause mortality was defined as the primary endpoint. ResultsDetectable cTnI below the 99th percentile was present in 2811 (19.0 %) patients, while 11,965 (81.0 %) patients were below detection limit of the employed assay. The mean follow-up was 4.25 ± 3.76 years. All-cause mortality was 20.8 % for patients with detectable cTnI below the 99th percentile and 15.0 % for those without detectable cTnI. In a multivariable Cox regression analysis, detectable cTnI was independently associated with all-cause mortality with a hazard ratio of 1.60 (95 % CI 1.45–1.76; p < 0.001). There was a stepwise relationship with increasing all-cause mortality and tertiles of detectable cTnI levels with hazard ratios of 1.63 (95 % CI 1.39–1.90) for the first tertile to 2.02 (95 % CI 1.74–2.35) for the third tertile. ConclusionsDetectable cTnI below the 99th percentile is an independent predictor of mortality in patients undergoing coronary angiography with the risk of death growing progressively with increasing troponin levels.

Frequency of Hematologic and Nonhematologic Conditions in Pediatric Patients with Vascular Anomalies: A Pediatric Health Information System Database Study

Background: Vascular anomalies (VA) are a heterogeneous group of diseases which include vascular malformations and vascular tumors. In the pediatric population, there is a sparsity of data on the frequency of associated hematologic and nonhematologic conditions as well as overall outcomes for patients. Objectives: The objective of this study was to determine the rate of certain concurrent hematologic and nonhematologic conditions in patients with VA who underwent procedures and compare those to patients who did not undergo procedures. To examine the rates of intensive care unit admissions and discharge mortality in patients who had a vascular anomaly. Methods: This is a multicenter retrospective cohort study using data from the Pediatric Health Information System. The database was queried for children 0–18 years old with a diagnosis of a VA who had inpatient encounters between January 2016 and September 2021. Results: The most common hematologic conditions were thrombocytopenia, iron deficiency anemia, and venous thrombosis. The most common nonhematologic condition was electrolyte imbalances. Intensive care unit admissions were highest among patients with other congenital malformations of the peripheral vascular system, cerebral cavernous malformations, and sporadic arteriovenous malformations. Discharge mortality was highest in patients with lymphatic malformations and primary lymphedema. Conclusions: This is the largest database study of pediatric patients with VA and their concurrent medical conditions and outcomes to date. While our study could not prove associations, we hope that our results will serve as a foundation for more extensive research regarding the impact of these identified conditions and outcomes and contribute to improved management of patients with VA.

Suspected autoimmune encephalitis: A retrospective study of patients referred for therapeutic plasma exchange.

Autoimmune encephalitis (AE) comprises a heterogeneous group of autoantibody-mediated disorders targeting the brain parenchyma. Therapeutic plasma exchange (TPE), one of several first-line therapies for AE, is often initiated when AE is suspected, albeit prior to an established diagnosis. We sought to characterize the role of TPE in the treatment of suspected AE. A single-center, retrospective analysis was performed of adults (≥18 years) who underwent at least one TPE procedure for "suspected AE." The following parameters were extracted and evaluated descriptively: clinicopathologic characteristics, treatment course, TPE-related adverse events, outcomes (e.g., modified Rankin scale [mRS]), and diagnosis once investigation was complete. A total of 37 patients (median age 56 years, range 28-77 years, 62.2% male) were evaluated. Autoimmune antibody testing was positive in serum for 43.2% (n = 16) and cerebrospinal fluid for 29.7% (n = 11). Patients underwent a median of five TPE procedures (range 3-16), with 97.3% (n = 36) via a central line and 21.6% (n = 8) requiring at least one unit of plasma as replacement fluid. Fifteen patients (40.5%) experienced at least one TPE-related adverse event. Compared with mRS at admission, the mRS at discharge was improved in 21.6% (n = 8), unchanged in 59.5% (n = 22), or worse in 18.9% (n = 7). Final diagnosis of AE was determined to be definite in 48.6% (n = 18), probable in 8.1% (n = 3) and possible in 27.0% (n = 10). Six (16.2%) patients were ultimately determined to have an alternate etiology. Empiric TPE for suspected AE is generally well-tolerated. However, its efficacy remains uncertain in the absence of controlled trials, particularly in the setting of seronegative disease.

Antioxidants, Hormetic Nutrition, and Autism.

Autism spectrum disorder (ASD) includes a heterogeneous group of complex neurodevelopmental disorders characterized by atypical behaviors with two core pathological manifestations: deficits in social interaction/communication and repetitive behaviors, which are associated with disturbed redox homeostasis. Modulation of cellular resilience mechanisms induced by low levels of stressors represents a novel approach for the development of therapeutic strategies, and in this context, neuroprotective effects of a wide range of polyphenol compounds have been demonstrated in several in vitro and in vivo studies and thoroughly reviewed. Mushrooms have been used in traditional medicine for many years and have been associated with a long list of therapeutic properties, including antitumor, immunomodulatory, antioxidant, antiviral, antibacterial, and hepatoprotective effects. Our recent studies have strikingly indicated the presence of polyphenols in nutritional mushrooms and demonstrated their protective effects in different models of neurodegenerative disorders in humans and rats. Although their therapeutic effects are exerted through multiple mechanisms, increasing attention is focusing on their capacity to induce endogenous defense systems by modulating cellular signaling processes such as nuclear factor erythroid 2 related factor 2 (Nrf2) and nuclear factor-kappa B (NF-&#954;B) pathways. Here we discuss the protective role of hormesis and its modulation by hormetic nutrients in ASD.

MicroRNA-29-mediated cross-talk between metabolic organs in the pathogenesis of diabetes mellitus and its complications: A narrative review.

Diabetes mellitus (DM) is a heterogeneous group of disorders characterized by hyperglycemia. Microribonucleic acids (microRNAs) are noncoding RNA molecules synthesized in the nucleus, modified, and exported to the extracellular environment to bind to their complementary target sequences. It regulates protein synthesis in the targeted cells by inhibiting translation or triggering the degradation of the target messenger. MicroRNA-29 is one of noncoding RNA that can be secreted by adipose tissue, hepatocytes, islet cells, and brain cells. The expression level of the microRNA-29 family in several metabolic organs is regulated by body weight, blood concentrations of inflammatory mediators, serum glucose levels, and smoking habits. Several experimental studies have demonstrated the effect of microRNA-29 on the expression of target genes involved in glucose metabolism, insulin synthesis and secretion, islet cell survival, and proliferation. These findings shed new light on the role of microRNA-29 in the pathogenesis of diabetes and its complications, which plays a vital role in developing appropriate therapies. Different molecular pathways have been proposed to explain how microRNA-29 promotes the development of diabetes and its complications. However, to the best of our knowledge, no published review article has summarized the molecular mechanism of microRNA-29-mediated initiation of DM and its complications. Therefore, this narrative review aims to summarize the role of microRNA-29-mediated cross-talk between metabolic organs in the pathogenesis of diabetes and its complications.

Progressive pulmonary fibrosis (PPF): Estimation of incidence and treatment rates in Japan using a claims database

BackgroundInterstitial lung diseases (ILDs) are a heterogeneous group of disorders, a subset of which develop progressive pulmonary fibrosis (PPF). There is little information on the epidemiology and treatment of PPFs in Japan. This retrospective cohort study estimated the incidence probability of progression to PPFs in patients with fibrosing ILDs other than idiopathic pulmonary fibrosis in a real-world Japanese setting. Management procedures and treatment patterns were also quantified. MethodsData were extracted from the Medical Data Vision database from 01-Jan-2012 to 28-May-2020, comprising a 6.91-year patient identification period, 1-year pre-index period, and post-index period. The primary outcome was the cumulative incidence probability of progression to PPF up to 24 months. Subgroup analyses were performed by the presence/absence of connective tissue disease-ILD and by pre-specified ILD clinical diagnosis. ResultsOf the 34,960 eligible patients (mean age: 71.1 years, males: 52.5%), 14,580 (41.7%) progressed to PPF. The 24-month incidence probability of progression to PPF was 39.5%. A relatively comparable percentage of patients progressed across all ILD subtypes. Oral corticosteroids and tacrolimus were the most common therapies during the pre- and post-index periods. Treatment rates were very low in the post-index period. ConclusionsThis is the first claims database study to estimate the incidence probability of progression to PPF in Japan. Progression appeared common in patients with chronic fibrosing ILDs, with comparable percentages of patients across all subtypes developing PPF at 2 years. Future studies should assess the impact of regular monitoring and early intervention on treating fibrotic ILDs and preventing progression.

Quality of life assessment among ethnically diverse Black prostate cancer survivors: a constructivist grounded theory approach.

Prostate cancer (CaP) is the most common cancer in Black men (BM), and the number of Black CaP survivors is rapidly increasing. Although Black immigrants are among the fastest-growing and most heterogeneous ethnic groups in the USA, limited data exist regarding their CaP experiences. Therefore, this study aimed to explore and model the experiences of ethnically diverse Black men with CaP. In-depth interviews were conducted with 34 participants: native-born BM (NBBM) (n = 17), African-born BM (ABBM) (n = 11), and Caribbean-born BM (CBBM) (n = 6) CaP survivors recruited through QR code-embedded flyers posted in Black businesses, clinics, social media platforms, and existing research networks within the USA. Guided by Charmaz's constructivist grounded theory methodology, the interviews were analyzed using constant comparison following key stages of initial, focused, and theoretical coding using Atlas.ti v23. Participants were thirty-four men aged 49-84years (mean ± SD, 66 ± 8). Most were married (77%), likely to be diagnosed at stage I (35%), and treated with radiotherapy (56%). Our study findings explored the complex trajectory of Black prostate cancer (CaP) survivors, unveiling a comprehensive model termed "Journeying through Unfamiliar Terrain." Comprising three phases and 11 sub-phases, this model uniquely captures the pre-diagnosis awareness and post-treatment adaptation among survivors. The resulting theoretical model delineates the entire CaP survivorship process among BM, providing contextual and conceptual understanding for developing interventions and enhancing patient-centered care for ethnically diverse CaP survivors, pivotal in bridging the gaps in survivorship research and healthcare practices. Black CAP survivors experience significant burdens and challenges that impact their overall quality of life.Understsnding the factors that impact the complex survivorship journey can inform design and implementation ofinterventions to address the multiple challenges and thus improve quality of life.

Analysis of Replication, Cell Division-Mediated Spread, and HBV Envelope Protein-Dependent Pseudotyping of Three Mammalian Delta-like Agents

The human hepatitis delta virus (HDV) is a satellite RNA virus that depends on hepatitis B virus (HBV) surface proteins (HBsAg) to assemble into infectious virions targeting the same organ (liver) as HBV. Until recently, the evolutionary origin of HDV remained largely unknown. The application of bioinformatics on whole sequence databases lead to discoveries of HDV-like agents (DLA) and shed light on HDV’s evolution, expanding our understanding of HDV biology. DLA were identified in heterogeneous groups of vertebrates and invertebrates, highlighting that the evolution of HDV, represented by eight distinct genotypes, is broader and more complex than previously foreseen. In this study, we focused on the characterization of three mammalian DLA discovered in woodchuck (Marmota monax), white-tailed deer (Odocoileus virginianus), and lesser dog-like bat (Peropteryx macrotis) in terms of replication, cell-type permissiveness, and spreading pathways. We generated replication-competent constructs expressing 1.1-fold over-length antigenomic RNA of each DLA. Replication was initiated by transfecting the cDNAs into human (HuH7, HeLa, HEK293T, A549) and non-human (Vero E6, CHO, PaKi, LMH) cell lines. Upon transfection and replication establishment, none of the DLA expressed a large delta antigen. A cell division-mediated viral amplification assay demonstrated the capability of non-human DLA to replicate and propagate in hepatic and non-hepatic tissues, without the requirement of envelope proteins from a helper virus. Remarkably L-HDAg but not S-HDAg from HDV can artificially mediate envelopment of WoDV and DeDV ribonucleoproteins (RNPs) by HBsAg to form infectious particles, as demonstrated by co-transfection of HuH7 cells with the respective DLA expression constructs and a plasmid encoding HBV envelope proteins. These chimeric viruses are sensitive to HDV entry inhibitors and allow synchronized infections for comparative replication studies. Our results provide a more detailed understanding of the molecular biology, evolution, and virus–host interaction of this unique group of animal viroid-like agents in relation to HDV.

Climate change and healthy ageing: An assessment of the impact of climate hazards on older people.

Climate change not only directly impacts older people's longevity but also healthy ageing, which is the process of maintaining physical and mental capacities while optimising functional abilities. The urgency to address both population ageing and climate change necessitates a rethink and assessment of the impact of climate change on older people. This includes identifying what can be done to anticipate, mitigate and adapt to climate change and engage older persons. A review of climate change and healthy ageing forms the basis of evidence in this report. We developed a comprehensive search to assess current literature, combining terms related to ageing and climate change across four major data sets and assessing articles published up to the end of 2021. We summarised the current and future impact of climate change on older people and developed a framework identifying climate change impacts on older persons, recognising social and environmental determinants of healthy ageing. Major hazards and some key exposure pathways include extreme temperatures, wildfire, drought, flooding, storm and sea level rise, air quality, climate-sensitive infectious diseases, food and water insecurities, health and social care system displacement, migration, and relocation. Strategies to address climate change require interventions to improve systems and infrastructure to reduce vulnerability and increase resilience. As a heterogeneous group, older people's perceptions of climate change should be integrated into climate activism. Increasing climate change literacy among older people and enabling them to promote intergenerational dialogue will drive the development and implementation of equitable solutions. Pathways may operate via direct or indirect exposures, requiring longitudinal studies that enable assessment of exposures and outcomes at multiple time points, and analyses of cumulative impacts of hazards across the life course. The lack of systematic reviews and primary research on the impact of most climate hazards, except for heat, on older people is apparent. Future research should include outcomes beyond mortality and morbidity and assess how older people interact with their environment by focusing on their capacities and optimising abilities for being and doing what they value.

P.047 Survey of caregivers of individuals with NBIAs to identify relevant quality of life outcomes

Background: Neurodegeneration with Brain Iron Accumulation (NBIA) is a heterogenous group of disorders with the common theme of iron accumulation in the basal ganglia. These disorders typically present in childhood with progressive neurodegeneration and neuropsychiatric symptoms. Caring for an individual with NBIAs is intensive, however it is unknown what factors impact caregiver well-being and quality of life. Methods: Common themes were obtained via literature review of quality of life surveys in children with neurological and chronic illnesses. Five domains were addressed: Diagnosis, Communication, Symptom Management, Clinical Experience and Resources/Support. The survey was approved by the Family Advisory Committee at the CHEO Research Institute and the CHEO REB. The survey was distributed via the Rare Connect Platform to Canadian caregivers. Results: Survey responses are being analyzed and will be presented at the CNSF. Within each domain, Likert scales will be analyzed. Domains will be ranked according to the caregiver responses. Conclusions: Results of this survey will assist in developing care management guidelines, resources for families and help with future advocacy for patients and families affected by NBIAs. The results will also help guide future NBIA Canada Family Conferences.

P.106 Using optic nerve sheath diameter over ventricular size to assess elevated intracranial pressure in pediatric patients with pineal region tumors

Background: Pineal region tumors are a heterogenous group of pathologies often symptomatic due to occlusive hydrocephalus leading to elevated intracranial pressure (ICP). High ICP may not always be associated with clinical signs. A non-invasive technique for assessment of ICP is measuring the optic nerve sheath diameter (ONSD). The goal of this study was to determine the utility of preoperative and postoperative ONSD measurements for assessment of elevated ICP in children with pineal region tumors. Methods: Retrospective data analysis was performed in patients operated for pineal region tumors at our tertiary care center between 2003 and 2022. Preoperative and postoperative MRI scans were reviewed. Clinical data and ONSD at multiple time points were analyzed and correlated. Results: Thirty-four patients with forty operative cases met the inclusion criteria. Hydrocephalus was seen in 80% of patients preoperatively (n=32/40). Presence of hydrocephalus was associated with significantly elevated ONSD preoperatively (p=0.006) and postoperatively (p=0.017). There was significant decrease in ONSD immediately postoperatively (p&lt;0.001), at 3 months (p&lt;0.001) and 12 months (p&lt;0.001). In patients without hydrocephalus, no significant changes in ONSD were observed (p=0.369). Conclusions: ONSD is a useful adjunct for the identification of high ICP preoperatively and evaluation of treatment response postoperatively in patients presenting with pineal region tumors.

#1713 Blood pressure goals in kidney transplant recipients: an analysis of the collaborative transplant study

Abstract Background and Aims Hypertension is an independent risk factor for cardiovascular disease, the leading cause of death in kidney transplant recipients. Because there is no “one size fits all” approach to blood pressure targets, particularly in the heterogenous group of kidney transplant recipients, identification of subgroup-specific targets, considering factors like age and sex, may be appropriate. However, currently available studies are limited because of sample sizes, and no subgroup analyses have been performed examining the effects of different blood pressure targets on allograft and patient survival. The aim of our study was to investigate the impact of different ACC/AHA blood pressure categories on graft survival and patient mortality and to identify subgroup-specific targets. Method This large-scale retrospective study included 1-year blood pressure data from 62, 556 kidney transplant recipients reported to the Collaborative Transplant Study from 209 centers in 39 countries. Hypertension was categorized according to 2017 ACC/AHA guidelines. The primary outcomes were death-censored graft failure and patient mortality during post-transplant year 1 to 6. Multivariable Cox regression analysis was performed to control for immunologic and nonimmunologic confounders. Results One year after transplantation, 77% of kidney transplant recipients had hypertension. Hypertension stages 1 (130–139/80–89 mmHg), 2a (140–159/90–99 mmHg), and 2b (≥160/≥100 mmHg) were associated with an 8%, 34%, and 102% increased risk of death-censored graft failure, respectively, whereas elevated blood pressure levels (120–129/&amp;lt;80 mmHg) did not significantly increase the risk. Patient mortality was only significantly higher in those with hypertension stage 2b with a Hazard Ratio of 1.21 (95% CI, 1.08–1.36; P &amp;lt; .001). In addition, the impact of hypertension stages on death-censored graft failure varied in different subpopulations (Fig. 1). Female recipients, younger recipients, recipients who received kidneys from donors younger than 60 years, re-transplanted recipients, and recipients with pre-transplant HLA antibodies had a significantly increased risk of death-censored graft failure associated with higher blood pressure levels (Fig. 1). Kidney transplant recipients with hypertension stage 2 continued to have an increased risk of graft failure one year after transplantation, even when they achieved normal blood pressure in the second year. Conclusion This study highlights the importance of treating hypertension early after kidney transplantation to improve long-term graft and patient survival. Attention should be paid to female, younger, and sensitized recipients, who may particularly benefit from optimal blood pressure control.

Resistance to immune checkpoint inhibitors in colorectal cancer with deficient mismatch repair/microsatellite instability: misdiagnosis, pseudoprogression and/or tumor heterogeneity?

Colorectal carcinoma (CRC) with deficiency of the deficient mismatch repair (dMMR) pathway/ microsatellite instability (MSI) is characterized by a high mutation load and infiltration of immune cells in the tumor microenvironment. In agreement with these findings, clinical trials have demonstrated a significant activity of immune checkpoint inhibitors (ICIs) in dMMR/MSI metastatic CRC (mCRC) patients and, more recently, in CRC patients with early disease undergoing neoadjuvant therapy. However, despite high response rates and durable clinical benefits, a fraction of mCRC patients, up to 30%, showed progressive disease when treated with single agent anti-programmed cell death 1 (PD-1) antibody. This article discusses the three main causes that have been associated with early progression of dMMR/MSI mCRC patients while on treatment with ICIs, i.e., misdiagnosis, pseudoprogression and tumor heterogeneity. While pseudoprogression probably does not play a relevant role, data from clinical studies demonstrate that some dMMR/MSI CRC cases with rapid progression on ICIs may be misdiagnosed, underlining the importance of correct diagnostics. More importantly, evidence suggests that dMMR/MSI mCRC is a heterogeneous group of tumors with different sensitivity to ICIs. Therefore, we propose novel diagnostic and therapeutic strategies to improve the outcome of dMMR/MSI CRC patients.

#2438 ADPKD and collagen genes (COL4A3, COL4A4, COL4A5)

Abstract Background and Aims Familial hematuria diseases are a heterogeneous group of monogenic conditions caused by mutations in one of the collagen IV genes: COL4A3 (2q36.3), COL4A4 (2q36.3), and COL4A5 (Xq22.3) that are expressed in the glomerular basement membranes (GBM) and are responsible for the most frequent forms of microscopic hematuria (MH), Alport syndrome, and thin basement membrane nephropathy (TBMN). Recent data suggest that about 1% (1 in 106 individuals) of the world population may have heterozygous predicted pathogenic COL4A3 or COL4A4 variants, a frequency that leads to the occasional superimposition of TBMN with other glomerulopathies. Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a major genetic disorder affecting up to 12.5 million individuals worldwide and it is the fourth most common global cause of renal replacement therapy. Two are the principal causative genes: PKD1(16p13.3) and PKD2 (4q22.1). The aim of the study was to describe a cohort of clinically ADPKD patients studying collagen IV genes COL4A3, COL4A4, and COL4A5. Method We performed NGS with Sophia Genetic “Nephropathies Solution” Panel on clinically ADPKD patients (pts). This panel includes 44 genes (target region 105.8 kb) involved in different types of nephropathies. We considered variants that are categorized as Variant of Uncertain Significance (Vus), likely pathogenic, or pathogenic (Class 3,4, or 5 of American College of Medical Genetics (ACMG)) in COL4A3, COL4A4, and COL4A5 genes. Results We analyzed 250 consecutive clinically ADPKD pts (consecutive in the outpatient clinic). We found 13 (6.3%) clinically potentially interesting (Class 3,4 or 5 of ACMG) variants in collagen genes. We found 2 pts that were negative for PKD1, PKD2, PKHD1 analysis: 1 pt carrier COL4A4 NM_000092.5: c.2908C&amp;gt;T (p.Gln970Ter), Pathogenic and c.2756A&amp;gt;G (p.Glu919Gly) Vus; 1 male pt carrier COL4A3 NM_000091.5: c.609+3_609+6del, Vus and COL4A5 NM_000495:c.169G&amp;gt;A p.(Gly57Arg), likely pathogenic. We also found 4 pts with 4 Vus variants in collagens genes combined with at least 1 pathogenic or likely pathogenic variant in PKD1 or PKD2 genes. We found 3 pts with likely pathogenic variants in COL4A4 or COL4A3 genes combined with Vus or likely benign variants in PKD1 or PKD2 genes and 1 patient with 1 likely pathogenic variant in COL4A3 and 1 likely pathogenic variant in PKD1. Conclusion Variants in collagen genes are very frequent and the associated phenotype is varied, sometimes very mild such as microhematuria. Furthermore, penetrance has to be considered. The study outlines the importance of considering also collagen genes, even if we have a clear clinical manifestation of ADPKD. An additional variant in a kidney already compromised can have an impact on the phenotype. Analysis of genes involved in these 2 pathologies could lead to a better understanding of the phenotype-genotype correlation at least in patients with both conditions.

Vertical Mesh-Mediated Fascial Traction and Negative Pressure Wound Therapy: A Case Series of Nine Patients in General and Vascular Surgery.

Two patients in a vascular surgery unit and seven patients in an abdominal surgery unit with an OA were treated with VMMFT in combination with NPWT between September 2019 and June 2023. A DFC was achieved in seven of nine cases. The mean duration of OA was 9.6 ± 3.8 days, and fascial dehiscence at the beginning of OA was 14.2 ± 4.0 cm on average. Time to DFC after VMMFT was established was 6.2 ± 3.5 days (mean). No method-related complications occurred. The standardized combination of VMMFT and NPWT gave positive results in achieving DFC in our heterogenic patient group. Following a strict treatment pathway as shown here seems to improve OA outcome. It represents a promising further development of mesh-mediated fascial traction for OA treatment.

THE PREVALENCE OF SARCOMA IN LATVIA DEPENDING ON GENDER AND AGE OVER A 10-YEAR PERIOD

Sarcomas are a heterogeneous group of malignant neoplasms that arise from the mesenchymal tissues, including bone, cartilage, fat, muscle, blood vessels, nerves, and deep skin tissues. The World Health Organization (WHO) Classification of Tumors of Soft Tissue and Bone encompasses over 80 distinct histologic subtypes of sarcomas, each with unique morphologic and molecular features. The high degree of histologic diversity among sarcomas underlies their capacity to arise in virtually any anatomic site. Sarcomas represent a relatively uncommon form of cancer, accounting for less than 1% of all new cancer diagnoses in adults and approximately 15% in children. The global incidence of sarcomas is estimated to be approximately 8 cases per million per year for bone sarcomas and 30 cases per million per year for soft tissue sarcomas. The objectives of the study to provide a comprehensive overview of the gender and age differences in the epidemiology of sarcomas in Latvia across 10 years. This retrospective population-based study draws on epidemiological data regarding cases of bone sarcomas and soft tissue sarcomas collected by the pathological registry of the hospital of Traumatology and Orthopaedics. From 2012 to 2022, 146 new cases of sarcoma were diagnosed in Latvia. Of these, 74 (50.7%) were men and 72 (49.3%) were women. The average annual number of new cases was 6.73 for men and 6.55 for women. The age-standardized incidence rate per 100,000 people per year was 0.8 for men and 0.5 for women. The youngest patient was 14 years old and the oldest was 87 years old. The most common age group for the sarcomas was between 61-70 years old (19.2%). The study found that the incidence of sarcomas in Latvia was higher in males than in females, and that the incidence was highest in 2020 and lowest in 2016.

Clinical and genetic investigation of 14 families with various forms of short stature syndromes.

Skeletal dysplasias are a heterogeneous group of disorders presenting mild to lethal defects. Several factors, such as genetic, prenatal, and postnatal environmental may contribute to reduced growth. Fourteen families of Pakistani origin, presenting the syndromic form of short stature either in the autosomal recessive or autosomal dominant manner were clinically and genetically investigated to uncover the underlying genetic etiology. Homozygosity mapping, whole exome sequencing, and Sanger sequencing were used to search for the disease-causing gene variants. In total, we have identified 13 sequence variants in 10 different genes. The variants in the HSPG2 and XRCC4 genes were not reported previously in the Pakistani population. This study will expand the mutation spectrum of the identified genes and will help in improved diagnosis of the syndromic form of short stature in the local population.

Juvenile dermatomyositis with Anti-SAE antibodies in a Moroccan child associated with pseudo-angioedema: a case report

BackgroundJuvenile Dermatomyositis (JDM) is the leading cause of non-infectious inflammatory myopathy in children. It is a heterogeneous group of autoimmune diseases characterized by a variable combination of muscular, dermatological, and visceral involvement. Myositis-specific autoantibodies help define homogeneous subgroups with common clinical characteristics and prognoses. Anti-SAE (small ubiquitin-like modifier 1 (SUMO-1) activating enzyme) antibodies are among the most recently discovered specific autoantibodies. The presence of these antibodies is very rare, making it challenging to define clinical features and prognosis in the juvenile form. We report the first case of an African patient with juvenile dermatomyositis and positive anti-SAE antibodies.Case ReportA 5-year-3-month-old Moroccan boy presented to the pediatric emergency department with dysphagia that had been evolving for two days, preceded two months earlier by facial erythema associated with fatigue, lower limb pain, difficulty walking, and progressive inflammatory polyarthralgia. On admission, the child had a heliotrope rash with predominant pseudo-angioedema on the lips, periungual telangiectasia, and Gottron’s papules over the bilateral interphalangeal and metatarsophalangeal joints. The patient had a more pronounced proximal muscle weakness in the lower limbs. He had no urticaria, fever, arthritis, calcinosis, cutaneous ulcers, or lipodystrophy. The Joint examination was normal, as was the pleuropulmonary examination. The electroneuromyography showed myogenic changes in all four limbs. Laboratory findings showed elevated levels of creatine phosphokinase and lactate dehydrogenase and a mild inflammatory syndrome. The electrocardiogram was normal. The anti-SAE antibodies were positive. The boy was diagnosed with juvenile dermatomyositis. He received methylprednisolone bolus therapy followed by oral prednisone. The latter was gradually tapered in combination with weekly intramuscular methotrexate. As a result, dysphagia disappeared within 48 h. After two weeks, there was an improvement in the muscular score and a significant regression of facial pseudo-angioedema.ConclusionWe report the first African patient with anti-SAE autoantibody-positive JDM. He had a typical dermatological manifestation of JDM associated with pseudo-angioedema predominant on the lips; a rarely reported sign in DM and JDM patients. The patient responded well to corticosteroid therapy and methotrexate.

A novel homozygous CLN6 Tyr142Cys variant in a nonconsanguineous family with Kufs disease.

Neuronal ceroid lipofuscinoses are a genetically heterogeneous group of inherited lysosomal storage disorders. Kufs disease is the predominant form of neuronal ceroid lipofuscinosis in adults, but it's rare and challenging to diagnose. The proband initially presented with cognitive deterioration and parkinsonian traits. At 35, he was admitted to hospital following a tonic-clonic seizure. Brain magnetic resonance imaging showed atrophy of the cerebral cortex and cerebellum, enlarged ventricles, and thinned corpus callosum. The proband's younger brother and sister were also affected, and the clinical phenotype within the family was consistent. Whole-exome Sequencing of the proband revealed a novel homozygous mutation in CLN6 (NM_017882: c.425A > G, p. Tyr142Cys). Co-segregation analysis revealed that two other affected individuals carried a homozygous mutation at the same locus, with both parents exhibiting heterozygous mutations of c.425A > G. Our study not only provides insights into the clinical presentation and development of the disease within the affected family but also expanded the mutational and phenotypical spectrum of the CLN6 gene.

The dark triad, dating app use and online disinhibition positively predict technology-facilitated sexual violence perpetration

Technology-facilitated sexual violence (TFSV) describes the perpetration of a variety of sexual offences committed through digital communication technologies. The current study aims to investigate the similarity of risk factors between TFSV and in-person sexual offending. The sample consisted of 105 young adult, Australian males who responded to measures of sexual violence acceptance, dating app usage, online disinhibition, and the dark triad. Overall, 45.3% of the sample reported at least one instance of TFSV perpetration in the past 5 years. Standard and hierarchical linear regressions revealed dating app usage, the dark triad, and online disinhibition positively predicted TFSV perpetration. Neither measure of attitudes accepting of sexual violence predicted TFSV perpetration, but their positive correlation is indicative of cultural norms enabling sexual violence against women. As illuminated here, the congruence between TFSV and in-person violence extends beyond conceptual and prevalence trends to predictive risk factors. Recommendations for interventions and prevention include raising awareness of risk-generating app features that create vulnerability to sexual harm and identifying heterogenous groups of TFSV offenders based on key characteristics to develop optimal intervention strategies.