Average Age Of Onset Research Articles

#4317 CLINICAL DIVERSITY OF STEROID-RESISTANT NEPHROTIC SYNDROME CAUSED BY TRPC6 MUTATIONS

Abstract Background and Aims Steroid-resistant nephrotic syndrome (SRNS) is a clinically and genetically heterogeneous disorder caused by either genetic or immunological factors or their combination. Approximately 30–40% of patients with SRNS make a fast progression to ESRD. SRNS represents the second leading cause of end-stage renal disease in individuals under the age of 25 years worldwide. More than 60 podocyte-related gene mutations have thus far been reported in monogenic SRNS. Recent studies indicate that almost 30% of patients with childhood-onset SRNS have monogenic causative variants in one of the 27 SRNS genes. Among these, a mutation in Transient Receptor Potential Canonical 6 (TRPC6) gene, encoding non-selective cation channel, accounts for 6% of familial SRNS and approximately 2% of sporadic cases. We recently detected eight patients with TRPC6 mutations in our SRNS cohort (n = 39, 21%) and found inter- and intra-familial heterogeneity of clinical phenotypes in terms of disease onset and progression. Method A total of 39 Japanese SRNS patients were studied according to the protocol approved by the institutional review board of each affiliation. Subjects who manifested SRNS at age one to 14-year-old with biopsy-proven FSGS were enrolled. A total of 39 SRNS patients, whose average onset of proteinuria at median age 4 (range 0.9 to 17 yr) and ESRD at median age 7 (49% of total n = 19, range 3.0 to 16.0 yr) were studied. Family history was found in 44% (n = 17), including 13 autosomal recessive, 3 dominant, and one X-linked transmission. Sixteen percent (n = 10) of the patients who underwent renal transplantation win no recurrence. Sequence analysis revealed the pathogenic variants in 62% (n = 24) of all cases. Library for whole-exome sequencing or targeted panel sequencing were prepared from genomic DNA by use of SureSelect Human All Exon V5 (Agilent) or a HaloPlex target enrichment system kit (Agilent Technologies), or Ampli-Seq (Thermo), Prepared samples were run on a HiSeq 2000, or MiSeq (Illumina), or Ion PGM (Thermo). The sequence reads with 101-bp paired-end reads and 7-bp index reads were mapped to the human reference sequence (hg19, GRCh38.p7). After filtering the superfluous begin variants, only variants that fulfill the “pathogenic” criteria of ACMG and/or ClinVar, Varsome were selected. Results Sequence analysis revealed the pathogenic variants in 62% (n = 24) of all cases. TRPC6 mutations were the most frequent cause of SRNS (n = 8), which was followed by NUP107 (n = 5), PLCE1 (n = 3), COL4A3 (n = 2), COL4A5 (n = 1), and others were identified in only single case. The eight TRPC6 mutations clustered into the two distinctive cytoplasmic domains; N-terminal ANK (Y173D, R175W, R175G) and C-terminal coiled-coil domain (p.E875V, p.867_868Del, p.S893N, p.R895C). The p.R895C is deposited as the pathogenic in ClinVar and may be a gain-of-function. The remaining 7 variants are of unknown functions: six have not yet been deposited in ClinVar, whereas one is VUS. Four patients were de novo occurrence, three followed the dominant transmission, and one arose from gonadal mosaicism. Two index patients exhibited SRNS in early childhood (< age 3), four manifested it in childhood (age 3–12), while the remaining two developed it in adolescence (age >12). In familial cases, for example, affected ones harboring R175W or p.E875V showed a remarkable discordant age onset and disease severity. Conclusion TRPC6 channelopathy was found to be the most frequent cause in our SRNS cohort, of which age onset ranges from age 0.9 to 17 year. Heterogeneity of disease severity may reflect that channel activity is regulated by the mode of action (gain- or loss-of-function), the combination of channel subunit assembly, and interaction with other modifying factors. Mutations in these TRPCs are associated with relatively common kidney diseases as well as other pathologies. Further expression studies will improve our mechanistic understanding of TRP channel pathology and may help the development of novel therapeutic targets.

Demographic changes in a large motor neuron disease cohort in Portugal: a 27 year experience

Objective Motor Neuron Diseases (MND) have a large clinical spectrum, being the most common amyotrophic lateral sclerosis (ALS) but there is significant clinical heterogeneity. Our goal was to investigate this heterogeneity and any potential changes during a long period. Methods We performed a retrospective cohort study among a large Portuguese cohort of MND patients (n = 1550) and investigated changing patterns in clinical and demographic characteristics over the 27-year period of our database. With that aim, patients were divided into three 9-year groups according to the date of their first visit to our unit: P1, 1994–2002; P2, 2003–2011; P3, 2012–2020. Results The overall cohort’s clinical and demographic characteristics are consistent with clinical experience, but our findings point to gradual changes over time. Time pattern analysis revealed statistically significant differences in the distribution of clinical phenotypes, the average age of onset, diagnostic delay, the proportin of patients using respiratory support with noninvasive ventilation (NIV), time to NIV, and survival. Across time, in the overall cohort, we found an increasing age at onset (p = 0.029), a decrease of two months in diagnostic delay (p < 0.001) and a higher relative frequency of progressive muscular atrophy patients. For ALS patients with spinal onset, from P1 to P2, there was a more widespread (54.8% vs 69.4%, p = 0.005) and earlier (36.9 vs 27.2 months, p = 0.05) use of NIV and a noteworthy 13-month increase in median survival (p = 0.041). Conclusions Our results probably reflect better comprehensive care, and they are relevant for future studies exploring the impact of new treatments on ALS patients.

Cystoid Macular Edema after Cataract Surgery in the United States: IRIS® Registry (Intelligent Research in Sight) Analysis

To determine the incidence, risk factors, and visual outcomes of cystoid macular edema (CME) after cataract surgery in the United States. Retrospective, longitudinal, case-control study. Patients aged ≥ 18 years who underwent phacoemulsification cataract surgery. The American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) was used to analyze patients who underwent cataract surgery between 2016 and 2019. Patients who received a diagnosis of CME within 90 days after cataract surgery were classified as cases, and the rest were classified as controls. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with the development of CME as well as poor visual outcome (defined as a best-recorded visual acuity worse than 20/40 Snellen equivalent at postoperative month 12). Incidence, demographics, baseline characteristics, and visual outcomes. Of 3.1 million cataract surgeries performed during the study period, CME was diagnosed in 25 595 eyes (0.8%), with an average onset of 6 weeks. Patients with CME were more likely to be male, to be aged < 65 years, to be Black, and to have preexisting diabetic retinopathy. Patients with CME were more likely to have a poor visual outcome (OR, 1.75; 95% CI, 1.66-1.84; P < 0.001), with a mean best-recorded visual acuity of 20/30 at postoperative month 12 (compared with 20/25 for those without CME; P < 0.001). Other factors associated with a poor visual outcome included smoking, Medicaid insurance, non-White race, and baseline ocular comorbidities such as macular degeneration and retinal vein occlusion. Although the incidence of CME after cataract surgery is low and most eyes achieve a visual acuity of 20/40 or better, there are significant outcome disparities that warrant further exploration. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

A Split-Mouth Clinical Comparative Evaluation of the Anesthetic Efficacy of Articaine and Lignocaine for Maxillary Bicuspids Extraction.

Aim The study compared the anesthetic effectiveness of articaine and lignocaine when premolars are extracted bilaterally for orthodontic purposes. Material and methods This prospective split-mouth study was performed on 30 cases selected from orthodontic referral patients reporting to the Oral and Maxillofacial Surgery Department at Maharaja Ganga Singh Dental College and Research Center, Rajasthan, India, for bilateral extraction of premolars under local anesthesia. We used 4% articaine hydrochloride and adrenaline 1:100000 (AH) as group A and 2% lignocaine hydrochloride with adrenaline 1:100000 (LH) on the control side as group B. For premolar anesthetization, 0.6-1.6 ml of AH and 1-2 ml of LH were injected submucosally in the buccal vestibular area. The extraction procedure was then carried out after achieving adequate anesthesia. The pain was assessed with Visual Analog Scale. The average onset time and duration of anesthesia were recorded. Data collected were summarized with descriptive statistics.The SPSSversion 23.0 (IBM Corp., Armonk, New York) was used for data entry, validation, and analysis. Means of continuous variables were compared using the student t-test. All tests were 2-tailed and significant at equal or less than 0.05. (p≤0.05). Results When comparing the overall anesthetic efficiency, Group A had a lower overall pain score of 0.43 while Group B had a higher overall pain score of 2.9. The average onset time of anesthesia in Group A was 1.2 minutes and 2.55 minutes in Group B. In Group A, the average duration of anesthesia was 70 minutes, and 46.5 minutes in Group B. These parameters were statistically significant with a p-value of <0.05. Conclusion The study concluded that as an alternative to lignocaine, articaine could be used effectively for maxillary premolar extractions for orthodontic reasons obviating palatal injection which is very painful to the patient.

Early systemic lupus erythematos: onset with thrombosis

Systemic lupus erythematosus (SLE) is a global pathology that can affect people of any age, with an average age of onset between 15 and 44 years. The female/male ratio is 13:1, while in children and the elderly it is only 2:1 [2, 5]. SLE can affect any organ and presents a wide spectrum of clinical and immunological manifestations, being one of the conditions with the highest mortality rates among systemic diseases [10]. This article presents the clinical case of patient X, aged 19 years, with subacute SLE, with involvement of the skin, vessels, mucous membranes, kidneys, muscles, hematopoietic system, immune system and secondary seronegative antiphospholipid syndrome. The diagnosis was established based on clinical and immunological SLICC criteria, laboratory tests, ECG, EcoCG, chest X-ray, ultrasonography of internal organs, Doppler ultrasonography of lower limb vessels and brain MRI. Against the background of immunosuppressive, anticoagulant, antiplatelet treatment, the patient’s condition improved and she was discharged with the recommendation to continue the basic and symptomatic treatment.

Characterizing the molecular landscape of early onset and average onset prostate cancer.

5059 Background: Prostate cancer (PC) has a median onset age of 66, however, recent evidence suggests an increase in incidence of PC diagnosis in males &lt;55 years of age. Family history and increased mutational burden has been associated with early onset PC (EOPC), nonetheless, comprehensive molecular and immune signatures that cluster in EOPC and average onset PC (AOPC) is poorly understood. Here, we characterized EOPC and AOPC, and their association with molecular and immune signature. Methods: 5,305 PC samples (&lt;55 yrs, n=575; ≥65 yrs, n=4730) were tested by NGS (592, NextSeq; WES, NovaSeq), WTS (NovaSeq) (Caris Life Sciences, Phoenix, AZ). PC Patients with age &lt;55 and ≥65 was classified as EOPC and AOPC, respectively. Microsatellite-instability (MSI) was tested by IHC and NGS. Tumor mutational burden (TMB) totaled somatic mutations per tumor (high≥10 mt/MB). Androgen receptor (AR) signature and Neuroendocrine Prostate Cancer (NEPC) score was calculated based on expression of a list of previously defined genes (Hieronymus et al. 2006, Beltran et al. 2016). Pathway enrichment determined by Gene Set Enrichment Analysis (Broad Inst). Immune cell fractions were calculated by deconvolution of WTS: Quantiseq. Statistical significance was determined using chi-square and Mann-Whitney U test (p &lt;0.05) along with FDR-corrected p-values (q)&lt;0.05. Results: EOPC had higher frequency of TMPRSS2 (35.8% vs 29.7%), ETV1 (5.2% vs 2.8%), ETV4 (3.4% vs 1.6%), and BRAF (1.9 vs 0.7%) fusions, but lower frequency of APC (4% vs 8%), CTNNB1 (2.4% vs 4.6%), RB1 (2.3% vs 4.7%) and AR (1% vs 4.9%) mutation, TMB high (2.1% vs 4.6%) and dMMR/MSI-H (2.1% vs 4%) compared to AOPC (all p&lt;0.05). EOPC had pathway enrichment of myogenesis (NES: 1.5, q&lt;0.01), but no difference in hedgehog signaling (NES:1.3, q=0.09) and epithelial mesenchymal transition (NES: 1.3, q=0.09) pathways compared to AOPC. EOPC had higher median NEPC score (0.359 vs 0.353, q=0.04), higher MAPK pathway activity score (MPAS) (3-fold, q=0.02) but no difference in median AR signature (q=0.39) compared to AOPC. In addition, EOPC had higher expression of PSA (1.2-fold, q&lt;0.01) and immunomodulatory genes ( IL12A, CTLA4, FC:1.2, q&lt;0.05) with reduced AR expression (1.3-fold, q&lt;0.01), however there was no difference in IHC-AR (q=1) and PD-L1 (q=0.57). Analysis of inferred immune cell infiltrates showed that EOPC had increased infiltration of NK cells (4.5% vs 4.1%, q&lt;0.01) and dendritic cells (1.9% vs 1.8% q&lt;0.05) compared to AOPC. Conclusions: Our data suggest that EOPC is enriched in fusion events including TMPRSS2, ETV1, ETV4 and BRAF. Distinct transcriptomic features seen in EOPC included neuroendocrine differentiation, MAPK activations, immunomodulatory gene expression, and increased infiltration of NK cells and dendritic cells, suggesting inherent molecular differences and differential tumor immune microenvironment in EOPC and AOPC.

Caracterización clínica, bioquímica e imagenológica en una cohorte de pacientes diagnosticados con hiperglicinemia no cetósica clásica: estudio ambispectivo 2000-2014, Medellín, Colombia

Introducción: La hiperglicinemia no cetósica (HGNC) es un error innato del metabolismo del grupo de las aminoacidopatías, de carácter autosómico recesivo, causado por un defecto en el sistema de clivaje de la glicina. Es una entidad rara y no se conoce su incidencia en Colombia.&#x0D; Objetivo:Describir características clínicas, bioquímica e imagenológicas en una cohorte de pacientes diagnosticados con hiperglicinemia no cetósica clásica&#x0D; Materiales y métodos: Estudio de tipo descriptivo, ambispectivo, en el periodo enero 2000-2014, en varios centros de Medellín.&#x0D; Resultados: Se incluyeron 20 pacientes que cumplían criterios de inclusión, de los 35 pacientes que cumplían con el criterio de búsqueda, en su mayoría de sexo femenino y con un Apgar adecuado al nacer. El promedio de inicio de los síntomas fue de 2,6 días; somnolencia, hipoactividad, apnea, convulsiones y singulto fueron los principales síntomas, y las convulsiones de tipo focal las más frecuentes. La relación glicina LCR/plasma en promedio fue 0,42. El patrón estallido-supresión en el electroencefalograma y la ausencia o retraso en la mielinización de la sustancia blanca supratentorial en la resonancia magnética fueron hallazgos comunes.&#x0D; Conclusión: La HGNC es frecuente en nuestro medio, por lo cual es necesario que se disponga de pruebas bioquímicas y moleculares necesarias para diagnóstico oportuno, manejo integral y asesoría genética.

Ultrasound Visualization and Recording of Transient Myocardial Vibrations

A new visualization and recording method used to assess and quantitate autogenic high-velocity motions in myocardial walls to provide a new description of cardiac function is described. The regional motion display (RMD) is based on high-speed difference ultrasound B-mode images and spatiotemporal processing to record propagating events (PEs). Sixteen normal participants and one patient with cardiac amyloidosis were imaged at rates of 500-1000/s using the Duke Phased Array Scanner, T5. RMDs were generated using difference images and spatially integrating these to display velocity as function of time along a cardiac wall. In normal participants, RMDs revealed four discrete PEs with average onset timing with respect to the QRS complex of -31.7, +46, +365 and +536 ms. The late diastolic PE propagated apex to base in all participants at an average velocity of 3.4 m/s by the RMD. The RMD of the amyloidosis patient revealed significant changes in the appearance of PEs compared with normal participants. The late diastolic PE propagated at 5.3 m/s from apex to base. All four PEs lagged the average timing of normal participants. The RMD method reliably reveals PEs as discrete events and successfully allows reproducible measurement of PE timing and the velocity of at least one PE. The RMD method is applicable to live, clinical high-speed studies and may offer a new approach to characterization of cardiac function.

Clinical features and therapeutic outcomes of GH/TSH cosecreting pituitary adenomas: experience of a single pituitary center.

Growth hormone (GH)/thyroid stimulating hormone (TSH) cosecreting pituitary adenoma (PA) is an exceedingly rare kind of bihormonal pituitary neuroendocrine tumors (PitNETs). Its clinical characteristics have rarely been reported. This study aimed to summarize the clinical characteristics and experience of diagnosis and treatment among patients with mixed GH/TSH PAs from a single center. We retrospectively reviewed GH/TSH cosecreting PAs from 2063 patients diagnosed with GH-secreting PAs admitted to Peking Union Medical College Hospital between January 1st, 2010, and August 30th, 2022, to investigate the clinical characteristics, hormone detection, imaging findings, treatment patterns and outcomes of follow-up. We further compared these mixed adenomas with age- and sex-matched cases of GH mono-secreting PAs (GHPAs). The data of the included subjects were collected using electronic records from the hospital's information system. Based on the inclusion and exclusion criteria, 21 GH/TSH cosecreting PAs were included. The average age of symptom onset was 41.6 ± 14.9 years old, and delayed diagnosis occurred in 57.1% (12/21) of patients. Thyrotoxicosis was the most common complaint (10/21, 47.6%). The median inhibition rates of GH and TSH in octreotide suppression tests were 79.1% [68.8%, 82.0%] and 94.7% [88.2%, 97.0%], respectively. All these mixed PAs were macroadenomas, and 23.8% (5/21) of them were giant adenomas. Comprehensive treatment strategies comprised of two or more therapy methods were applied in 66.7% (14/21) of patients. Complete remission of both GH and TSH was accomplished in one-third of cases. In the comparison with the matched GHPA subjects, the mixed GH/TSH group presented with a higher maximum diameter of the tumor (24.0 [15.0, 36.0] mm vs. 14.7 [10.8, 23.0] mm, P = 0.005), a greater incidence of cavernous sinus invasion (57.1% vs. 23.8%, P = 0.009) and a greater difficulty of long-term remission (28.6% vs. 71.4%, P <0.001). In addition, higher occurrence rates of arrhythmia (28.6% vs. 2.4%, P = 0.004), heart enlargement (33.3% vs. 4.8%, P = 0.005) and osteopenia/osteoporosis (33.3% vs. 2.4%, P = 0.001) were observed in the mixed PA group. There are great challenges in the treatment and management of GH/TSH cosecreting PA. Early diagnosis, multidisciplinary therapy and careful follow-up are required to improve the prognosis of this bihormonal PA.

Initial frontal lobe involvement in adult cerebral X-linked adrenoleukodystrophy.

Adult cerebral X-linked adrenoleukodystrophy (ACALD) with initial frontal lobe involvement is a rare genetic disease that is easily misdiagnosed and underdiagnosed. We sought to improve the early identification of such diseases. We present three cases of adult X-linked adrenoleukodystrophy (ALD) with initial frontal lobe involvement and identify an additional 13 cases from the database. The clinical and imaging characteristics of the overall sixteen cases were analyzed. The average age of onset was 37years, with 15 male and 1 female patient. A total of 12 patients (75%) developed a decline in cerebral executive and cognitive functions. Brain trauma is the possible trigger for the onset of ALD in five patients (31%). An elevated level of very-long-chain fatty acids (VLCFA) was observed in all 15 patients on whom a plasma VLCFA was performed.10 patients with gene tests showed different mutation sites in the ABCD1 gene. Brain MRI of six patients (46%) were characterized by frontal lobe "butterfly wings"-like lesions with peripheral rim enhancement. Four patients underwent brain biopsies (patients 1, 3, 15, and 13), and five patients (31%) were initially misdiagnosed (patients 1, 2, 3, 11, and 15). Nine of the patients with follow-up records experienced poor prognoses, and five of them, unfortunately, died (56%). ACALD patients with anterior patterns tend to be misdiagnosed. The early clinical manifestation is a decline in cerebral executive and cognitive function. Brain trauma may be a trigger for this pattern. Brain MRI findings are characterized by frontal lobe "butterfly wing"-like lesions with peripheral rim enhancement. The determination of the VLCFA levels and the genetic detection of the causative mutations are required to confirm the diagnosis.

Effectiveness of tumor necrosis factor inhibitors in children with enthesitis-related arthritis: a single-center retrospective analysis.

In children with enthesitis-related arthritis (ERA), the hip and sacroiliac joint function might be impaired if not properly treated. We sought to evaluate the effectiveness of anti-tumor necrosis factor-α (TNF-α) therapy using the inflammatory indicators, Juvenile Arthritis Disease Activity Score 27 (JADAS27) and magnetic resonance imaging (MRI). We conducted a single-center retrospective study of 134 patients with ERA. We evaluated the effect of anti-TNF therapy on the inflammatory indicators, active joint count, MRI quantitative score, and JADAS27 over 18 months. We used the Spondyloarthritis Research Consortium of Canada (SPARCC) and the Hip Inflammation MRI Scoring System (HIMRISS) scoring systems for hip and sacroiliac joints scoring. The average age of onset of children with ERA was 11.62 ± 1.95 years, and they were treated with disease-modifying antirheumatic drugs (DMARDs) combined with biologics (n = 87, 64.93%). There were no differences in HLA-B27 positivity between the biologics and non-biologics treatment groups [66 (49.25%) vs. 68 (50.75%), P > 0.05]. Children who received anti-TNF (71 received etanercept, 13 adalimumab, 2 golimumab, and 1 infliximab) therapy improved significantly. Children with ERA used DMARDs and biologics at baseline (Group A) were followed up to 18 months, and their active joint count (4.29 ± 1.99 vs. 0.76 ± 1.33, P = 0.000), JADAS27 (13.70 ± 4.80 vs. 4.53 ± 4.52, P = 0.000) and MRI quantitative scores (P = 0.001) were significantly lower than those at baseline. Some of the patients (n = 13, 9.70%) were treated with DMARDs at the onset of the disease, but did not show significant improvement (Group B). After 6-18 months of switching to anti-TNF therapy, related indicators of the children were significantly lower than at baseline and 1 month (P < 0.013). At 18 months, a total of 33 patients (n = 74, 44.59%) in Group A and 7 (n = 13, 53.85%) in Group B reached inactive state. Eighteen months after diagnosis, anti-TNF therapy was found to be effective in children diagnosed with ERA. MRI is important for the early diagnosis of juvenile idiopathic arthritis. TNF-α inhibitors can significantly improve the clinical manifestations of sacroiliac joint and hip involvement in patients with ERA. Overall, the real-world study provides more evidence for precision diagnosis and treatment for other hospitals, families and patients.

(125) Sexual Pain Symptoms in 910 Premenopausal Women with Vulvar Lichen Sclerosus

Abstract Introduction Lichen sclerosus (LS) is an autoimmune inflammatory skin condition primarily affecting the vulva and perianal areas and leading to scarring that can affect sexual function. Most research on symptomatology of LS to date includes predominantly postmenopausal populations and focuses on pruritis, not sexual pain symptoms. Objective This study aims to characterize sexual pain symptoms associated vulvar LS among premenopausal women. Methods A cross-sectional web-based study was conducted in premenopausal women with clinical and/or biopsy-confirmed vulvar LS between the ages of 18-50 years. Participants completed a 28-question survey evaluating demographics, characteristics of symptoms, timing and accuracy of diagnosis, and concomitant autoimmune conditions. Numerical data were expressed as mean +/- standard deviation. Bivariate Pearson correlation was used to determine the relationship between age of symptom onset and time interval to diagnosis. Results Of the 956 responses received, 910 met inclusion criteria. Self-reported ethnicity of the study population was 87% White, 4% Latina or Hispanic, 3% Asian, and 1% Black. The mean age of the population was 36.5 years, ranging from 18-50 years. There was a 4.3-year mean delay in diagnosis, with average age of symptom onset of 27.7 years and average age of diagnosis of 33.2 years. There was an inverse correlation between the age at which symptoms began and the time interval to diagnosis with a Pearson correlation coefficient of -0.509 (t(805)=16.752, p&amp;lt;0.0001). Most prevalent symptoms were vulvar fissures (68%), dyspareunia (68%), tearing with intercourse or vaginal insertion (63%), and labial resorption (61%), with vulvar fissures (49%) and dyspareunia (46%). These symptoms were more common than introital stenosis (34%). Vulvar fissures (41%) and dyspareunia (35%) most often prompted medical attention. Thirty-six percent reported clitoral phimosis and 34% reported decreased clitoral sensation. Only 4% of respondents reported that decreased clitoral sensation prompted medical attention. Over 75% of respondents initially received an alternative diagnosis, most commonly vulvovaginal yeast infection (54%) or bacterial vaginosis (22%). Most common concomitant autoimmune condition reported was hypothyroidism (10%); which was significantly greater than the general population prevalence (2%) (p&amp;lt;0.0001). Post-hoc analysis indicated no statistical difference between biopsy-confirmed and clinically-diagnosed LS across all demographics and responses. Conclusions Vulvar LS affects sexual function in premenopausal women. LS symptoms in premenopausal women include vulvar fissures, dyspareunia, tearing with intercourse or vaginal insertion, and decreased clitoral sensation. Dyspareunia is present is over two-thirds of premenopausal women with vulvar LS, with vulvar fissures and tearing much more common and bothersome than introital stenosis. Patients are less likely to be affected by or seek medical attention for clitoral phimosis, even though it is present in over one-third of those with LS. Vulvar LS should be considered and evaluated in women of all ages presenting with vulvar symptoms. Sexual health and function should be a core outcome measure in LS research and addressed in the evaluation and treatment of this condition. Disclosure No

Local Anesthesia Onset and Pain Perception in Hemophilic and Thalassemic Conditions.

The study aims to evaluate and compare the onset of local anesthesia (LA) and pain perception during endodontic treatment in hemophilic and thalassemic patients. Methods: The study included 90 patients with symptomatic irreversible pulpitis of the mandibular molars. Three groups (n = 30 in each group) were included. Group 1: hemophilic patients; group 2: thalassemic patients; and group 3: individuals without any systemic diseases. Onset of LA and visual analogue scale (VAS) scores was recorded immediately after the administration of local anesthesia, during the pulp exposure procedure, and during canal instrumentation, and were compared between the three groups. Frequency distribution, ANOVA, and linear regression analysis (p < 0.05) were applied. Results: The mean onset time was 46 ± 34 s in the hemophilic group, 42 ± 23 s in the thalassemic group, and 38 ± 12 s in controls, but the differences were statistically insignificant. After LA administration (LA-VAS), all three groups experienced a statistically significant reduction in pain (p = 0.048). On pulp exposure (PE-VAS) (p = 0.82) and during canal instrumentation (CI-VAS) (p = 0.55), there was no statistically significant difference in pain perception between the groups. The coefficients indicate a positive correlation between the VAS and onset time, indicating a positive reduction in the VAS following the administration of LA. Conclusions: Hemophilic patients exhibited a clinically longer average onset time for LA. However, the difference among the three groups with regard to the overall pain perception after LA administration, during and after pulp exposure, and during canal instrumentation was statistically insignificant.

Whole Exome Sequencing Reveals Clustering of Variants of Known Vitiligo Genes in Multiplex Consanguineous Pakistani Families.

Vitiligo is an autoimmune complex pigmentation disease characterized by non-pigmented patches on the surface of the skin that affect approximately 0.5-2% population worldwide. The exact etiology is still unknown; however, vitiligo is hypothesized to be a multifactorial and genetically heterogeneous condition. Therefore, the current study is designed to investigate the anthropometric presentation and genetic spectrum of vitiligo in fifteen consanguineous Pakistani families. The clinical evaluation of participating individuals revealed varying degrees of disease severity, with 23 years as the average age of disease onset. The majority of the affected individuals had non-segmental vitiligo (NSV). Whole exome sequencing analysis revealed clustering of rare variants of known vitiligo-associated genes. For instance, in the affected individuals of family VF-12, we identified three novel rare variants of PTPN22 (c.1108C>A), NRROS (c.197C>T) and HERC2 (c.10969G>A) genes. All three variants replaced evolutionarily conserved amino acid residues in encoded proteins, which are predicted to impact the ionic interactions in the secondary structure. Although various in silico algorithms predicted low effect sizes for these variants individually, the clustering of them in affected individuals increases the polygenic burden of risk alleles. To our knowledge, this is the first study that highlights the complex etiology of vitiligo and genetic heterogeneity in multiplex consanguineous Pakistani families.

Differences in sleep patterns between patients with anorexia nervosa and healthy controls: a cross-sectional study

BackgroundSleep difficulties are common in patients with anorexia nervosa (AN), but objective assessments have mostly been performed in hospital and laboratory settings. We aimed to identify differences in sleep patterns between patients with AN and healthy controls (HC) in their free-living environments, and potential associations between sleep patterns and clinical symptoms in patients with AN.MethodsThis cross-sectional study analyzed 20 patients with AN prior to them starting outpatient treatment and 23 HC. Sleep patterns were measured objectively using an accelerometer (Philips Actiwatch 2) for 7 consecutive days. Average sleep onset, sleep offset, total sleep time, sleep efficiency, wake after sleep onset (WASO) and mid-sleep awakenings lasting ≥ 5 min were compared between patients with AN and HC using nonparametric statistical analyses. Associations of sleep patterns with body mass index, eating-disorder symptoms, eating-disorder-associated impairment, and symptoms of depression were assessed in the patient group.ResultsCompared with HC, patients with AN had shorter WASO [median (interquartile range(IQR)): 33 vs. 42 min], but a longer average duration of mid-sleep awakenings lasting ≥ 5 min [median (IQR): 9 vs. 6 min, p = 0.006] and had more nights with no sleep (six nights in four patients with AN vs. zero nights in HC). There were no differences between patients with AN and HC regarding other sleep parameters and no significant correlations between sleep patterns and clinical parameters in patients with AN. However, HC presented a Intraindividual variability pattern that was closer to a normal distribution, whereas patients with AN tended to either have very regular or large variability in sleep onset time (AN; n = 7 < 25th percentile and n = 8 > 75th percentile vs. HC; n = 4 < 25 percentile and n = 3 > 75th percentile) during the week of sleep recordings.ConclusionPatients with AN seem to spend more time awake during the night and have more nights without sleep than do HC, even though their average weekly sleep duration did not differ from that in HC. The intraindividual variability in sleep pattern seems to be an important parameter that should be assessed when studying sleep in patients with AN.Trial registration ClinicalTroals.gov. Identifier: NCT02745067. Registered: April 20, 2016.

Evaluation of the relationship between values and psychological resilience of individuals diagnosed with substance use disorder: A cross-sectional study

The purpose of this study was to determine the relationship between values and psychological resilience in individuals with substance use disorder. This descriptive and correlational study was conducted with 70 individuals diagnosed with substance use disorder who had applied to the Alcohol and Drug Addiction Treatment and Research Center between February and April 2022 and volunteered to participate in the study. The data were collected using the Personal Information Form, Values Scale, and Brief Resilience Scale (BRS). All participants were male, the average age of substance use onset was 17.67 ± 5.95 years, and they had been receiving addiction treatment for 1.97 ± 2.30 years on average. The average total score of the individuals on the BRS scale was 17.18 ± 1.45. A significant positive correlation was found between the social values, intellectual values, spiritual values, materialistic values, human dignity, and freedom sub-dimensions of the Values Scale and psychological resilience (p < .001). Additionally, spiritual values were found to have the highest positive effect on the psychological resilience levels of individuals (B = 0.185; p < .05). Individuals with higher levels of social values, intellectual values, spiritual values, materialistic values, human dignity, and freedom were found to have higher psychological resilience. Nursing care provided by taking into account the values of the individual and strengthening their values may contribute to the psychological resilience of the patient.

Frailty transitions and prevalence in an ageing population: longitudinal analysis of primary care data from an open cohort of adults aged 50 and over in England, 2006-2017.

frailty is common in older adults and is associated with increased health and social care use. Longitudinal information is needed on population-level incidence, prevalence and frailty progression to plan services to meet future population needs. retrospective open cohort study using electronic health records of adults aged ≥50 from primary care in England, 2006-2017. Frailty was calculated annually using the electronic Frailty Index (eFI). Multistate models estimated transition rates between each frailty category, adjusting for sociodemographic characteristics. Prevalence overall for each eFI category (fit, mild, moderate and severe) was calculated. the cohort included 2,171,497 patients and 15,514,734 person-years. Frailty prevalence increased from 26.5 (2006) to 38.9% (2017). The average age of frailty onset was 69; however, 10.8% of people aged 50-64 were already frail in 2006. Estimated transitions from fit to any level of frailty were 48/1,000 person-years aged 50-64, 130/1,000 person-years aged 65-74, 214/1,000 person-years aged 75-84 and 380/1,000 person-years aged ≥ 85. Transitions were independently associated with older age, higher deprivation, female sex, Asian ethnicity and urban dwelling. Mean time spent in each frailty category decreased with age, with the longest period spent in severe frailty at all ages. frailty is prevalent in adults aged ≥50 and time spent in successive frailty states is longer as frailty progresses, resulting in extended healthcare burden. Larger population numbers and fewer transitions in adults aged 50-64 present an opportunity for earlier identification and intervention. A large increase in frailty over 12years highlights the urgency of informed service planning in ageing populations.

PO-02-200 CIRCADIAN OCCURENCE PATTERNS OF ATRIAL FIBRILLATION AFTER CARDIAC SURGERY DURING 2.5 YEARS OF CONTINUOUS RHYTHM MONITORING

Atrial fibrillation (AF) is a frequent complication after cardiac surgery and current theories suggest that autonomic nervous system plays a major role in early-POAF development, but its role in late-recurrences is still unknown. Previous studies in non-surgical patients have shown distinct preferential AF-occurrence patterns, such as adrenergic/daytime AF, or nocturnal AF. However, the circadian onset patterns for POAF episodes have never been studied before. To investigate POAF circadian onset patterns after cardiac surgery during 2.5 years of continuous rhythm monitoring. Patients with and without history of AF undergoing cardiac surgery were included. Continuous rhythm monitoring was performed over a period of 2.5 years. Circadian distribution of AF-episodes onset was presented in radial histograms for the whole FU period, early postoperative phase (first 90 days), and late postoperative phase (after first 90 days). In addition, Bayesian circular regression was performed to calculate the average episode onset, along with 95% credibility intervals, for different classes of episode duration. The study population consisted of 134 patients with a median follow-up of 2.7 years (IQR: 2.2-2.9 years). Eighty-one (60.4%) patients developed AF during the follow-up period. Early-POAF (first 90 days) occurred in 75 patients (56.0%) and late-POAF (after first 90 days) in 47 patients (35.1%). In patients without history of AF, there was a heterogenuous POAF-episode onset pattern with peak incidence at 4:18pm (95%CI: 6:53am to 2:16am) (Figure 1). Paroxysmal AF and persistent AF patients showed more homogenuous occurrence patterns with peak incidence at 10:07am (95%CI: 9:29am to 10:51am) for paroxysmal AF, and 9:16am (95%CI: 8:42am till 9:50am) for persistent AF (Figure 1). Peak incidence of early-POAF was at night and in the morning for all rhythm groups (Figure 1), whearas late-POAF also started during the afternoon in patients without history of AF (Figure 1). In patients without history of AF, shorter AF episodes started predominantly during the afternoon whereas longer episodes started at night and in the morning (Table 1). In paroxysmal and persistent AF patients, most episodes started in the morning hours (Table 1). In patients with history of AF, POAF starts mostly during the night and in the morning, wheras patients with new-onset AF show a more heterogeneuous daytime occurrence pattern.

Frontal Fibrosing Alopecia: A prospective observational study

Introduction: Frontal fibrosing alopecia (FFA) is a scarring alopecia of unknown etiology that affects mainly postmenopausal women. It is responsible for progressive recession of the frontotemporal hairline and sometimes occipital hairline with inconsistent eyebrow hair loss. We aimed to investigate the demographics, clinical and trichoscopic features of FFA in the Moroccan population. Patients and methods: We conducted a prospective study over a period of 2 years and 1/2, from January 2020 to July 2022. We enrolled twenty four patients, with clinical and/or histopathological diagnosis of FFA, seen at the dermatology department of Ibn Rochd University Hospital in Casablanca, Morocco. Data regarding demographics, clinical and trichoscopic findings were collected. Results: Twenty Four patients with FFA met the inclusion criteria. There were all women and half of them were postmenopausal (50%). The average age of disease onset was 46,95 years old. Pruritus was the most reported symptom (80%). An emotional factor was found in 40% of the cases and 45% of the patients reported the use of traditional products to their hairs. All patients presented with frontotemporal hairline recession with parietal or occipital involvement in 70% and 50% of the cases respectively, and 16 patients experienced eyebrow loss. Facial micropapules were found in 9 patients (45%), followed by patchy hyperpigmentation in 6 patients (30%) and follicular hyperpigmentation in 4 patients (20%). The majority of patients presented mild FFA (grades I and II), with a recession of less than 3 cm of the frontotemporal hairline (85%). The most frequent trichoscopic findings were perifollicular erythema (80%) and follicular hyperkeratosis (70%), followed by decreased or absence of vellus hairs (60%), lonely hairs (45%), perifollicular blue-gray pigmentation (35%), perifollicular brownish pigmentation (30%) and loss or absence of follicular openings (30%). Tufted hairs and white patches of scarring alopecia were found in 25% and 20% patients, respectively. Conclusion: Our study supports the role of cosmetic products or emotional factors in the physiopathology of FFA. Trichoscopy seems a valuable tool in the diagnosis of AFF. Perifollicular erythema, follicular hyperkeratosis and decreased of absence of vellus hairs are easily identified and are very suggestive of the diagnosis.

Sequential onset of bilateral trigeminal neuralgia: clinical presentation and outcomes

PurposeSequential onset of bilateral trigeminal neuralgia (TN) is rare and not well-described in the literature. The objective of this study was to characterize demographic, clinical, and procedural characteristics of patients with sequential onset bilateral TN. MethodsWe retrospectively reviewed patients presenting with sequential onset bilateral TN at our institution from 2007 to 2020. Patient demographics, clinical diagnoses, pain outcomes, and procedural characteristics were recorded and compared. Factors associated with pain recurrence were assessed using survival analyses and multivariate regressions. ResultsWe identified 34 patients who presented with sequential onset bilateral TN. The average age of onset for the index case was 49.9 ± 15.5 years, and 58.0 ± 16.8 years for the contralateral case. In total for our cohort, 91 surgical procedures were performed for the index case, and 70 for the contralateral case. With each additional surgical intervention, pain-free survival was more likely to decrease, p = 0.05. When controlled for order of intervention, glycerin rhizotomy (p = 0.01) and glycerin-radiofrequency rhizotomy (p = 0.05) were more likely associated with pain recurrence compared to microvascular decompression. While pain outcomes were significantly decreased in our cohort at final follow-up, 82.4% of patients were still dependent on medication for pain management after an average of 5.03 ± 7.74 years. ConclusionOur results represent one of the largest series of sequential onset bilateral TN in North America. Our study demonstrates the high treatment burden and chronicity of pain encountered in this population.