Young Onset Research Articles

Type 2 diabetes: a contemporary view from the Asian lens.

The aim of this article was to review the up-to-date evidence with regards to the unique features of the Type 2 diabetes (T2D) pathophysiology, complications, response to therapy with the possibility of precision medicine guiding therapeutic decision making in Asia. Asia is the epicenter of diabetes. There have been marked advances with genotyping and phenotyping of the Asian patient with T2D, particularly with young onset diabetes where early beta cell failure and rapid progression of complications are more frequent. As Asians have lower muscle mass and higher adiposity, sarcopenia is increasingly associated with diabetes. Response to lifestyle and pharmacotherapy are generally similar, but unique features exist with different populations. Across Asia, use of guideline directed medical therapy for cardio-renal protection are recommended, but uptake of these newer agents are suboptimal and barriers exist with regards to standardized care. Although many similarities have been observed across Asia, due to the heterogeneity of populations within Asia, further research is required to streamline and pave the way towards precision medicine. There is an urgent need for region wide consensus to minimize barriers to diabetes care and stigma in diabetes terminology across Asia.

Adjusting to dementia as part of life: an actantial analysis of agency reconstruction following diagnosis of young onset dementia

Adjusting to dementia as part of life: an actantial analysis of agency reconstruction following diagnosis of young onset dementia

Age at diagnosis of diabetes, obesity, and the risk of dementia among adult patients with type 2 diabetes.

While Type 2 Diabetes Mellitus (T2DM) prevalence is increasing among younger individuals, few studies have examined how age at T2DM diagnosis relates to dementia risk in diabetic populations. We aimed to investigate the association between age at T2DM diagnosis and subsequent dementia risk, and to determine whether obesity moderates this relationship. We conducted a prospective cohort study using data from the Health and Retirement Study (2002-2016) matched with its 2003 Diabetes Mail-Out Survey. The study included 1,213 dementia-free adults aged ≥50 with diagnosed T2DM. Primary exposures were age at T2DM diagnosis (categorized as <50, 50-59, 60-69, and ≥70 years) and obesity status (BMI ≥30 kg/m2). The outcome was incident dementia, assessed using the Telephone Interview for Cognitive Status. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for sociodemographic factors, health behaviors, health status, and diabetes medication use. Over a median follow-up of 10 (interquartile range, 6-14) years, 216 (17.8%) participants developed dementia. Compared to participants diagnosed with T2DM at age ≥70 years, those diagnosed at younger ages had increased dementia risk: HR 1.70 (95% CI, 1.03-2.80) for 60-69 years, 1.72 (95% CI, 1.06-2.79) for 50-59 years, and 1.90 (95% CI, 1.14-3.18) for <50 years. Obesity significantly moderated this relationship, with obese individuals diagnosed with T2DM before age 50 showing the highest dementia risk (HR 3.05; 95% CI 1.23-7.56) compared to non-obese individuals diagnosed at ≥50 years. Younger age at diagnosis of T2DM was significantly associated with a higher risk of dementia, particularly among individuals with obesity. Interventions specifically targeting obesity may be more effective in preventing dementia for adults with a younger onset of T2DM.

Type 2 diabetes pathway-specific polygenic risk scores elucidate heterogeneity in clinical presentation, disease progression and diabetic complications in 18,217 Chinese individuals with type 2 diabetes.

Type 2 diabetes is a complex and heterogeneous disease and the aetiological components underlying the heterogeneity remain unclear in the Chinese and East Asian population. Therefore, we aimed to investigate whether specific pathophysiological pathways drive the clinical heterogeneity in type 2 diabetes. We employed newly developed type 2 diabetes hard-clustering and soft-clustering pathway-specific polygenic risk scores (psPRSs) to characterise individual genetic susceptibility to pathophysiological pathways implicated in type 2 diabetes in 18,217 Chinese patients from Hong Kong. The 'total' type 2 diabetes polygenic risk score (PRS) was summed by genome-wide significant type 2 diabetes signals (n=1289). We examined the associations between psPRSs and cardiometabolic profile, age of onset, two glycaemic deterioration outcomes (clinical requirement of insulin treatment, defined by two consecutive HbA1c values ≥69 mmol/mol [8.5%] more than 3 months apart during treatment with two or more oral glucose-lowering drugs, and insulin initiation), three renal (albuminuria, end-stage renal disease and chronic kidney disease) outcomes and five cardiovascular outcomes. Although most psPRSs and total type 2 diabetes PRS were associated with an earlier and younger onset of type 2 diabetes, the psPRSs showed distinct associations with clinical outcomes. In particular, individuals with normal weight showed higher psPRSs for beta cell dysfunction and lipodystrophy than those who were overweight. The psPRSs for obesity were associated with faster progression to clinical requirement of insulin treatment (adjusted HR [95% CI] 1.09 [1.05, 1.13], p<0.0001), end-stage renal disease (1.10 [1.04, 1.16], p=0.0007) and CVD (1.10 [1.05, 1.16], p<0.0001) while the psPRSs for beta cell dysfunction were associated with reduced incident end-stage renal disease (0.90 [0.85, 0.95], p=0.0001) and heart failure (0.83 [0.73, 0.93], p=0.0011). Major findings remained significant after adjusting for a set of clinical variables. Beta cell dysfunction and lipodystrophy could be the driving pathological pathways in type 2 diabetes in individuals with normal weight. Genetic risks of beta cell dysfunction and obesity represent two major genetic drivers of type 2 diabetes heterogeneity in disease progression and diabetic complications, which are shared across ancestry groups. Type 2 diabetes psPRSs may help inform patient stratification according to aetiology and guide precision diabetes care.

An Exploration of the Co-Occurrence of Hallucinations and Suicidal Mental Imagery Among Psychiatrically Hospitalised Adolescents at High Risk for Suicide.

Adolescents with psychosis-spectrum symptoms are at particularly high risk for suicide, however, little is known about how suicidal cognitions manifest in this population. Suicidal cognitions can occur as verbal thoughts and/or mental images of suicide, and mental images may be indicative of a higher risk for suicidal behaviours. Suicidal mental imagery could be a salient and important suicide-related risk factor for adolescents with hallucinations in particular, however, the co-occurrence of these phenomena has yet to be studied. In a sample of psychiatrically hospitalised adolescents, we hypothesize that hallucinations will be associated with increased suicidal mental imagery and suicide attempts. This chart review study included data from 219 adolescents admitted to a psychiatric inpatient unit. Adolescents completed an assessment battery probing hallucinations, suicidal cognitions, and suicide attempts. Adolescents with past-month hallucinations had higher rates of past-week suicidal verbal thoughts and suicidal mental imagery, but not suicide attempts, compared to those without hallucinations. Adolescents with hallucinations reported a younger onset of suicidal mental imagery, and they endorsed more frequent imagery. Past-month hallucinations were significantly and positively associated with suicidal mental imagery, beyond the effects of internalising symptoms. Suicidal mental imagery was positively associated with past-week suicide attempts, but past-month hallucinations were not. Our findings indicate that hallucinations are linked to suicidal mental imagery, an important yet under-studied risk factor for suicidal behaviour. These data highlight the need for more research exploring suicidal mental imagery among high-risk adolescents experiencing hallucinations to inform suicide risk assessment and intervention.

Changes in symptom pattern in Meniere's disease by duration: the need for comprehensive management.

This retrospective study aimed to analyze the symptom profile of Meniere's disease (MD) patients, particularly focusing on the cessation of episodic vertigo and the disease's longitudinal course and the impact of major symptoms on quality of life (QoL). The study employed a cross-sectional design and was conducted on 365 out of 560 individuals with definite MD from the Finnish Vestibular and Meniere Federation, utilizing an internet-based questionnaire. Participants were surveyed on vertigo attacks, vestibular drop attacks (VDA), balance issues, selective cognitive complaints, hearing loss, and their effects on overall quality of life (QoL). The study population comprised 79.5% females and 20.5% males, with a mean age of 63 years and an average disease duration of 15.2 years. The onset of MD was characterized by simultaneous hearing loss, vertigo, and tinnitus in 38% of participants. There was a significant delay in diagnosis for many, with 20% experiencing a delay of over 5 years. The frequency and duration of vertigo attacks generally decreased over time, with attacks becoming shorter and less severe as the disease progressed. Spontaneous remission from episodic vertigo occurred in 34% of participants variably throughout the course of MD. Of the participants 65.5% reported balance issues, and 34% experienced mild VDAs, with severe falls occurring in 10%. VDAs were more common with longer disease duration. Bilateral hearing loss developed in 34.5% of participants over the long term, with a higher risk associated with younger onset age, migraines, and family history of MD. Fatigue, anxiety, and depression were prevalent, particularly among younger participants. Cognitive impairments were linked to the severity of these symptoms and the presence of constant dizziness. QoL was significantly lower among participants with constant dizziness, with factors like fatigue, depression, VDA, and hearing loss contributing to this reduction. The study highlights the complexity of MD. While vertigo may spontaneously remit, other symptoms such as VDAs, balance issues, cognitive complaints, and hearing loss often persist and worsen over time. Assessing MD solely on primary symptoms like vertigo and hearing loss is insufficient; a comprehensive evaluation is necessary for effective management.

Exosomes derived from Umbilical cord mesenchymal stem cell promote hair regrowth in C57BL6 mice through upregulation of the RAS/ERK signaling pathway.

Androgenetic alopecia is one of the common types of hair loss and has become a medical and social problem due to its increasingly young onset. Existing therapies, although effective, have serious side effects and therefore better treatments need to be sought. The aim of this study was to evaluate the efficacy of umbilical cord mesenchymal stem cell-derived exosomes in the treatment of androgenetic alopecia and to investigate the mechanism of exosome regulation of hair growth. First, we randomly divided 20 C57BL/6J mice into blank group, model group, positive control group and exosomal hydrogel group, and mice were treated with hair removal on the back. The mice were injected intraperitoneally with dihydrotestosterone solution except for the blank group. At the end of the experiment, new hairs were collected and the differences in length, diameter and number of hair follicles were compared among the groups; the histopathological changes of hair follicles were observed by HE staining; the expression of androgen receptor mRNA and protein in skin tissues were compared; and the skin tissues were analyzed by real-time PCR, western blotting, immunofluorescence staining and transcriptome sequencing. Finally, the results of transcriptome sequencing experiments were verified by real-time PCR, western blotting and other techniques for the corresponding genes and proteins. Compared with the blank group, mice in the model group had shorter hair length and reduced hair diameter, and pathological observation showed that the total number of hair follicles was significantly reduced and the hair follicles were miniaturized; compared with the model group, mice in the positive control and exosome groups had longer hair length, larger hair diameter and more hair follicles; the androgen receptor mRNA content and protein expression in the skin tissue of mice in the model group were significantly higher than those in the blank group, and the protein expression in the exosome gel group was lower than that in the model group. Similarly, compared with the model group, the expression of stemness-related proteins K15 and CD200 in the skin tissues of mice in the exosome group increased, and the expression of PCNA, a protein related to cell proliferation, increased. The KEGG data showed that the differential genes were mainly enriched in the RAS/ERK pathway. In this study, we demonstrated the therapeutic effect of umbilical cord MSC-derived exosomes on androgenetic alopecia and verified that exosomes regulate hair follicle stem cell stemness through the RAS/ERK pathway to promote hair proliferation and thus hair growth in mice with androgenetic alopecia, providing a potential therapeutic strategy for androgenetic alopecia.

Clinical progression of Parkinson's disease in the early 21st century: Insights from the accelerating medicine partnership (AMP-PD) data

BackgroundParkinson's disease (PD) therapeutic strategies have evolved since levodopa introduction in mid 1900s. To understand their impact and research gaps, this study delineated the clinical progression of PD in recent years. MethodsUsing Accelerating Medicine Partnership-PD (AMP-PD) data harmonized from seven biomarker discovery studies (2010–2020), we extracted: overall [Schwab and England (S&E), PD Questionnaire (PDQ-39)]; motor [Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS)-II and -III and Hoehn & Yahr (HY)]; and non-motor [MDS-UPDRS-I, University of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), and Epworth Sleepiness Scale (ESS)] scores. Age at diagnosis was set as 0 years, and data were tracked for 15 subsequent years. ResultsAmong 3001 PD cases identified to be suitable for this study, 2838 are white, 1843 are males, with a mean age at diagnosis was 60.2 ± 10.3 years. At baseline evaluation, the disease duration was 9.9 ± 6.0 years overall, 1915 within 0–5, 541 with 6–10, 254 within 11–15, and 163 greater than 15 years. Participants largely reported independence (S&E, 5y: 86.6 ± 12.3; 10y: 78.9 ± 19.3; 15y: 78.5 ± 17.0) and good quality of life (PDQ-39, 5y: 15.5 ± 12.3; 10y: 22.1 ± 15.8; 15y: 24.3 ± 14.4). Motor scores displayed a linear progression, whereas non-motor scores plateaued ∼10–15 years. Younger onset age and female correlated with slower progression. ConclusionsTwenty-first century PD patients remain largely independent in the first decade of disease at tertiary subspecialty care and research centers. There are data gaps for those who are non-whites or longer PD duration, and sensible metrics that can gauge non-motor progression when PD is beyond 10 years.

Young onset coronary artery disease in India: A descriptive observational study

Young onset coronary artery disease in India: A descriptive observational study

Polysomnographic Findings into Sleep Disorders in Essential Tremor and Essential Tremor Plus: A Comparison with Healthy Controls.

To explore sleep patterns in individuals with Essential Tremor (ET) and Essential Tremor Plus (ET-Plus), compared to healthy controls, and assess differences between ET and ET-Plus, given the lack of established polysomnography (PSG) data on these groups and the potential for sleep disturbances to serve as clinical markers. We conducted a prospective cross-sectional study at NIMHANS, Bengaluru, from November 2021 to August 2023 on 45 patients (26 ET, 19 ET-Plus) and 45 controls. Tremor severity was assessed using TETRAS and FTMTRS, and sleep symptoms with ESS, PSQI, Mayo Sleep Questionnaire, RLS-Q, BQ, GAD-7 and PHQ-9. All cases and controls underwent overnight video PSG. Sleep scoring was manually done by a technically adequate sleep researcher and the first author following AASM (2022) guidelines with data analysed using R studio. ET patients exhibited younger onset age (30.8 ± 16.7 years) compared to ET-Plus patients (46.8 ± 11.1 years). ET-Plus had higher TETRAS and FTMRS scores (P < 0.001) than ET. Both ET and ET-Plus patients exhibited poorer sleep quality, excessive daytime sleepiness, REM sleep behavior disorder (RBD), and Restless Legs Syndrome (RLS) symptoms compared to controls. PSG findings supported these clinical observations, showing elevated Apnea-Hypopnea Index (AHI), reduced Total Sleep Time (TST), prolonged REM latency, decreased sleep efficiency, increased N1 stage duration, and reduced N2/N3 durations and percentages in patients versus controls. The study highlights significant sleep architecture abnormalities in both ET and ET-Plus patients as compared to healthy controls, with no differences between the ET groups.

Effect of C-to-T transition at CpG sites on tumor suppressor genes in tumor development in cattle evaluated by somatic mutation analysis in enzootic bovine leukosis.

Oncogenic transformation of normal cells is caused by mutations and chromosomal abnormalities in cancer-related genes. Enzootic bovine leukosis (EBL) is a malignant B-cell lymphoma caused by bovine leukemia virus (BLV) infection in cattle. Although a small fraction of BLV-infected cattle develops EBL after a long latent period, the mechanisms for oncogenesis in EBL cattle remain largely unknown. In this study, we analyzed the types and patterns of somatic mutations in cancer cells from 36 EBL cases, targeting 21 cancer-related genes. Various somatic mutations were identified in eight genes, TP53, KMT2D, CREBBP, KRAS, PTEN, NOTCH1, MYD88, and CARD11. In addition, TP53 gene was found to be mutated in 69.4% of EBL cases, with most being biallelic mutations. In some cases, associations were observed between the ages at which cattle had developed EBL and somatic mutation patterns; young onset of EBL possibly occurs due to high impact mutations affecting protein translation and biallelic mutations. Furthermore, nucleotide substitution patterns indicated that cytosine at CpG sites tended to be converted to thymine in many EBL cases, which was considered to be the result of spontaneous deamination of 5-methylcytosine. These results demonstrate how somatic mutations have occurred in cancer cells leading to EBL development, thereby explaining its pathogenic mechanism. These findings will contribute to a better understanding and future elucidation of disease progression in BLV infection.IMPORTANCEEnzootic bovine leukosis (EBL) is a malignant and lethal disease in cattle. Currently, there are no effective vaccines or therapeutic methods against bovine leukemia virus (BLV) infection, resulting in severe economic losses in livestock industry. This study provides a renewed hypothesis to explain the general mechanisms of EBL onset by combining the previous finding that several integration sites of BLV provirus can affect the increase in survival and proliferation of infected cells. We demonstrate that two additional random events are necessary for oncogenic transformation in infected cell clones, elucidating the reason why only few infected cattle develop EBL. Further exploration of somatic mutation and BLV integration sites could support this hypothesis more firmly, potentially contributing to the development of novel control methods for EBL onset.

Stakeholder Consultation to Establish Research Priorities for Specialist Dementia Nursing in the United Kingdom.

In the United Kingdom, there are a growing number of specialist dementia nurses called Admiral Nurses. Admiral Nurses, supported in their professional development and clinical supervision by the charity Dementia UK, work with families affected by dementia using a relationship-centred approach. Given the growing need for this type of support, Dementia UK is committed to research that will expand the evidence base for Admiral Nursing. This article describes a stakeholder consultation to identify research priorities for Admiral Nursing for the next 3 years (2023-2026). We adopted a participatory approach using an adapted Nominal Group Technique and priority-setting workshop. All elements of the process were designed in consultation with a steering group comprising a range of stakeholders, including people with dementia, carers, Admiral Nurses, Dementia UK staff and researchers. Stakeholders were identified as those who were likely to be affected by or interested in the emerging research priorities. Nominal groups were held both face-to-face and online. A total of 144 people shared their research priorities. Data generated through each nominal group were thematically analysed and then ranked in order of priority. Four themes reflecting research priority areas were taken to a priority-setting workshop for consideration. This resulted in three research priorities for Admiral Nursing: (1) people with dementia who live alone and carers who provide support from a distance; (2) people living with young onset and rarer dementia and their families; and (3) people living with multiple health conditions alongside dementia, including mental health problems. Risk, diversity and the effectiveness of Admiral Nursing were strands that ran throughout these themes. We identified shared research priorities for Admiral Nursing using a rigorous, consensus-driven approach involving key stakeholders. These priorities reflect a desire to ensure that Admiral Nursing services reach the most vulnerable people living with dementia and their families and respond to the widening health and social care inequalities faced by this group. People with dementia and carers were involved in the design of this process as members of our steering group and through consultation on our initial plans with Dementia UK's Lived Experience Advisory Panel (LEAP). People living with dementia and carers also participated in consultation groups to share their views on research priorities. All stakeholders were invited to share feedback on the themes as part of the analysis and interpretation of the priorities, and a meeting was held with LEAP to discuss the emerging priorities.

S2344 Young Versus Older Onset Gastric Adenocarcinoma at a Safety Net Hospital

S2344 Young Versus Older Onset Gastric Adenocarcinoma at a Safety Net Hospital

S415 Time is “TikToking:” Missed Opportunities in Educating Millions About Young Onset Colorectal Cancer in the Era of Misinformation

S415 Time is “TikToking:” Missed Opportunities in Educating Millions About Young Onset Colorectal Cancer in the Era of Misinformation

S135 Survival Analysis and Associated Factors in Metastatic Young Onset Cholangiocarcinoma vs Metastatic Average Onset Cholangiocarcinoma

S135 Survival Analysis and Associated Factors in Metastatic Young Onset Cholangiocarcinoma vs Metastatic Average Onset Cholangiocarcinoma

Exploring the incidence of dysplasia or adenocarcinoma in early onset Barrett's esophagus.

Currently data on the risk of progression to and lifetime risk of cancer are not available for patients with young onset Barrett's esophagus (BE). Our aim was to obtain epidemiologic data on the incidence of dysplasia or adenocarcinoma in young onset BE in the Netherlands by collecting data on all histologically confirmed cases over a prolonged period of 25 years between January 1, 1991 and December 31, 2015. Data were obtained from the Dutch National Pathology Registry. Patients were included if there was a suspicion of BE visualized in the esophagus during the endoscopic examination in combination with a concordant histologic diagnosis of intestinal metaplasia. 231 patients with early onset BE were identified (median age 26 years [range 0-29 years]), with 17 progressing to dysplasia (6 prevalent and 11 incident). For the patients with incident dysplasia, the median surveillance time between the diagnosis of early onset BE and diagnosis of dysplasia was 5 years (range 0-16 years). The incidence rate of dysplasia was 7.3 per 1000 person-years. There were three patients who developed adenocarcinoma (1 prevalent and 2 incident), who were diagnosed at ages 28, 35, and 36 years. The incidence rate of adenocarcinoma was 1.3 per 1000 person-years. In this 25-year period, 231 patients were diagnosed with early onset BE in the Netherlands, with 17 patients progressing to dysplasia and three developing adenocarcinoma. This corresponded to incidence rates of 7.3 per 1000 person-years for dysplasia and 1.3 per 1000 person-years for adenocarcinoma.

The phenotype of the pediatric patient with Cushing syndrome but without obesity.

Cushing syndrome (CS) often presents with obesity that is not as severe in children as it is in adults. The role of obesity in the severity of metabolic syndrome in children with CS has not been studied. This study evaluates whether pediatric patients with CS have obesity-specific differences in their demographic, biochemical, and presenting findings. Cohort study. We analyzed 273 patients with young onset of CS at ≤18 years old and who were classified as patients with or without obesity based on their BMI z scores. Patients without obesity (n = 84, 31%) were more frequently females with an older age of onset compared with patients with obesity (n = 189, 69%). Consistent with their older age, patients without obesity were also more likely to have advanced Tanner stages. Patients with and without obesity had a similar duration of disease, but patients with obesity showed higher markers of hypercortisolemia (urinary free cortisol, UFC). A higher prevalence of hypertension and insulin resistance was seen in patients with obesity than those without obesity, adjusting for UFC (P < .05 for all comparisons). While fatty liver disease was not statistically different among the entire cohort, elevated alanine transaminase and metabolic dysfunction-associated steatotic liver disease scores were more common in ACTH-dependent CS patients with obesity (P < .05). Weight gain appears to mediate some but not all the cortisol-associated complications in pediatric CS. Therefore, obesity may be a modifiable risk factor among these patients.

Transitions of care for people living with dementia – insights using linked data

Objective People living with dementia have increasing care needs as their condition progresses, and tend to be high users of health and aged care. Linked data provide an opportunity to better understand transitions between services, to enable quality and timely care. Approach The pilot study used a new multi-source enduring linked dataset to analyse the use of health and residential aged care by Australians living with younger onset dementia between 2011–2016. The subsequent study focused on movements between hospital and residential aged care for older Australians who were hospitalised in 2017. ResultsThe younger onset dementia cohort comprised 5,400 Australians aged 30–69. More than half (58%) the cohort had moved from the community into residential aged care by the end of the study period. Of these, 21% had a hospital stay while living in the community that ended with entry to residential aged care. This important transition point was analysed further using a dementia cohort of 79,000 people aged 65 and over. One in 4 people (23%) with dementia who were living in the community moved into residential aged care within 7 days of a hospital stay. This group spent 20 days longer in hospital than other older people. People living in aged care were less likely than those in the community to return to hospital during the following year. ConclusionsThese results can help inform planning of community-based dementia support services, improve coordination of care, and investigate sources of delay for people awaiting entry to aged care.

P2: Analysis of resilience levels in caregivers of patients with young and late onset Alzheimer’s disease

Introduction: Resilience is a dynamic process involving the interaction between risk and protective factors that act to modify the effects of adverse life events. Understanding the resilience of caregivers of patients with AD and its predictors is essential for the development of intervention strategies aimed at solutions that can contribute to the improvement of their emotional disorders, such as anxiety, stress, anddepression.Methods: 93 dyads of patients diagnosed with AD, where 60 (64.5%) dyads had Late-onset AD (LOAD) and 33 (35.5%) dyads had Young-onset AD (YOAD). Patients were assessed for: quality of life (QoL), disease awareness, and depression. Caregivers were assessed for: resilience, depression, anxiety, burden, and QoL. Additionally, caregivers provided information about mood, neuropsychiatric symptoms, dementia severity, and patients’ activities of daily living.Results: Caregivers showed moderate levels of resilience, with an average score of 140 (SD = 13.20), moderate level of burden 28.94 (SD = 14.74), low level of anxiety 7.56 (SD = 7.44), and low level of depressive symptoms 8.17 (SD = 6.34). Patients had an average cognition score of 18.81, 63.4% had mild dementia, low depression index .2 (SD = 5.78), low index of neuropsychiatric symptoms 16.11 (SD = 14.47), and partially compromised disease awareness 9.06 (SD = 5.12).Conclusions: No relationship was found between caregivers’ resilience and patients’ clinical condition, indicating that resilience seems to be associated with caregivers’ individual characteristics. Interventions such as psychoeducational groups, behavioral or religious counseling, may stimulate or develop resilience characteristics in caregivers who exhibit avoidance or denial behaviors regarding the patient’s diagnosis.

Germline AIP variants in sporadic young acromegaly and pituitary gigantism: clinical and genetic insights from a Han Chinese cohort.

Variants in the Aryl hydrocarbon receptor-interacting protein (AIP) gene have been identified in sporadic acromegaly and pituitary gigantism, especially in young patients, with a predisposition to aggressive clinical phenotype and poor treatment efficacy. The clinical characteristics of patients with sporadic acromegaly and pituitary gigantism as well as AIP variants in Han Chinese have been rarely reported. We aimed to identify AIP gene variants and analyze the clinical characteristics of patients with sporadic acromegaly and pituitary gigantism in Han Chinese. The study included 181 sporadic acromegaly (N = 163) and pituitary gigantism (N = 18) patients with an onset age of no more than 45 years old, who were diagnosed, treated, and followed up in Huashan Hospital. All 6 exons and their flanking regions of the AIP gene were analyzed with Sanger sequencing or NGS. The clinical characteristics were compared between groups with and without AIP variants. Germline AIP variants were found in 15/181 (8.29%) cases. In patients with an onset age ≤30 years old, AIP variants were identified in 12/133 (9.02%). Overall, 13 variants were detected. The pathogenic (P) variants p.R304X and p.R81X were identified in four cases, with two instances of each variant. Six exon variants (p.C254R, p.K103fs, p.Q228fs, p.Y38X, p.Q213*, and p.1115 fs) have not been reported before, which were likely pathogenic (LP). Patients with P/LP variants had younger onset ages, a higher prevalence of pituitary gigantism, larger tumor volumes, and a higher percentage of Ki-67-positive cells in tumors. In addition, the group with P/LP variants showed a less significant reduction of GH levels in an acute octreotide suppression test (OST) [17.7% (0, 65.0%) vs. 80.5% (63.9%, 90.2%), P = 0.001], and a trend of less GH decrease after the 3-month treatment with long-acting somatostatin analogs (SSAs). Germline AIP variants existed in sporadic Chinese Han acromegaly and pituitary gigantism patients and were more likely to be detected in young patients. AIP variants were associated with more aggressive tumor phenotypes and less response to SSA treatment.