UNASSIGNED: Intrahepatic cholestasis of pregnancy (ICP) and gestational diabetes mellitus (GDM) are two common pregnancy complications that pose considerable health challenges. The interplay between these conditions is believed to significantly influence pregnancy outcomes, yet the nature of this relationship remains elusive. This study was designed to elucidate the connection between ICP and GDM.
UNASSIGNED: This retrospective cohort study included 742 singleton pregnancies delivered at the Shanghai Public Health Clinical Center from January 2015 to December 2023. We compared the incidence of GDM and pregnancy outcomes between multiple ICP subgroups and a control group of healthy pregnancies. A multivariate regression model was used to measure the independent association between ICP and propensity for GDM development, as well as to assess the impact of potential bidirectional effects between ICP and GDM.
UNASSIGNED: The results indicate that the incidence of GDM is highest in the early-onset ICP (diagnosed before the 24th week of gestation) group compared to the control group and other ICP subgroups. Early-onset ICP is an independent risk factor for the development of GDM, with other risk factors including age, history of abortion, family history of diabetes, and elevated ALT levels. Subgroup interaction analysis did not reveal heterogeneity in the influence of early-onset ICP on the development of GDM across different subgroups. Further analysis showed that GDM itself does not increase the risk of late-onset ICP. Additionally, when comparing pregnancy outcomes between GDM patients with or without ICP, those with both GDM and ICP had significantly higher rates of preterm birth, cesarean section, and small for gestational age (SGA) compared to patients with GDM alone. Furthermore, elevated TBA levels (first diagnosed) of early-onset ICP patients were associated with an increased risk of GDM in a nonlinear fashion.
UNASSIGNED: Our study indicated that early-onset ICP is significantly linked to an increased risk of GDM. Further research is warranted to explore the mechanisms behind this association and to develop strategies for early identification and intervention to mitigate GDM risk.

BACKGROUND: Colorectal cancer (CRC) is a major global health concern, with a rising incidence in young individuals. Early-onset CRC displays unique clinicopathological and molecular characteristics, necessitating a closer examination of prognosis, particularly in the context of adjuvant chemotherapy. This study aimed to investigate the prognosis of early-onset CRC patients (< 50 years) diagnosed at stage II/III compared to older counterparts, utilizing propensity score matching to minimize heterogeneity.
METHODS: A retrospective analysis of 3324 stage II/III CRC patients aged < 70 years was conducted, focusing on age-based subgroups (< 50 vs. ≥ 50 years). Propensity score matching balanced clinical characteristics. Relapse-free survival (RFS) and overall survival (OS) were analyzed.
RESULTS: In stage II CRC, age of onset did not impact prognosis after adjuvant chemotherapy, with no significant differences in RFS (5-year RFS rates: 80% in both groups, p = 0.98) and OS (5-year OS rates: 96% vs. 92%, p = 0.17). In stage III, a trend suggested slightly poorer OS in patients aged < 50 years than those ≥ 50 years (5-year OS rates: 85% vs. 88%, p = 0.077). However, in a propensity score-matched cohort, age-dependent differences were attenuated (5-year OS rates: 85% vs. 88%, p = 0.32).
CONCLUSIONS: In the context of stage II/III CRC patients receiving adjuvant chemotherapy, age was not an independent predictor of prognosis. Age alone should not be the sole factor guiding treatment decisions.

This study aimed to explore the different characteristics between early-onset severe preeclampsia (ESPE) and late-onset severe preeclampsia (LSPE) to improve pregnancy outcomes. We performed a retrospective cohort study between January 2016 and December 2021. Eligible hospitalized pregnant women with severe preeclampsia were assigned into the early-onset or late-onset group, depending on the gestational age at the time of severe preeclampsia onset (< or ≥ 34 gestational weeks, respectively). The clinical characteristics, laboratory results, maternal complications, and fetal and neonatal outcomes were recorded and compared between the two groups. A total of 1,238 pregnant women were included, with 525 in the early-onset group and 713 in the late-onset group. The late-onset group had more cases of gestational diabetes, whereas the early-onset group had a higher blood pressure, showed more proteinuria, had more liver and renal damage, exhibited more serious adverse maternal, fetal, and neonatal outcomes, was more likely to be admitted to the intensive care unit, and required longer hospital stays (all P < 0.05). In addition, the early-onset group had fewer prenatal care appointments and was more often transferred from a primary or secondary care hospital. The logistic regression analysis showed that a weekly weight gain of > 100 g was a risk factor for ESPE and that fewer prenatal care appointments were a risk factor for ESPE in pregnant women with female fetuses. Moreover, logistic regression analysis indicated that nulliparity and gestational diabetes during the current pregnancy were risk factors for LSPE. In conclusion, compared with the women with LSPE, those with ESPE usually had worse maternal, fetal, and neonatal outcomes. More frequent prenatal screening and care should be provided for pregnant women with high-risk factors.

Small-Fiber Neuropathy (SFN) is a disorder of the peripheral nervous system, characterised by neuropathic pain; approximately 11% of cases are linked to variants in Voltage-Gated Sodium Channels (VGSCs). This study aims to broaden the genetic knowledge on painful SFN by applying Whole-Exome Sequencing (WES) in Early-Onset (EO) cases. A total of 88 patients from Italy (n = 52) and the Netherlands (n = 36), with a disease onset at age ≤ 45 years old and a Pain Numerical Rating Score ≥ 4, were recruited. After variant filtering and classification, WES analysis identified 142 potentially causative variants in 93 genes; 8 are Pathogenic, 15 are Likely Pathogenic, and 119 are Variants of Uncertain Significance. Notably, an enrichment of variants in transient receptor potential genes was observed, suggesting their role in pain modulation alongside VGSCs. A pathway analysis performed by comparing EO cases with 40 Italian healthy controls found enriched mutated genes in the \"Nicotinic acetylcholine receptor signaling pathway\". Targeting this pathway with non-opioid drugs could offer novel therapeutic avenues for painful SFN. Additionally, with this study we demonstrated that employing a gene panel of reported mutated genes could serve as an initial screening tool for SFN in genetic studies, enhancing clinical diagnostics.

BACKGROUND: Colorectal cancer (CRC) is estimated to be the fourth most common cancer diagnosis in Canada (except for nonmelanoma skin cancers) and the second and third leading cause of cancer-related death in male and female individuals, respectively.
OBJECTIVE: The rising incidence of early age-onset colorectal cancer (EAO-CRC; diagnosis at less than 50 years) calls for a better understanding of patients\' pathway to diagnosis. Therefore, we evaluated patterns of prescription medication use before EAO-CRC diagnosis.
METHODS: We used linked administrative health databases in British Columbia (BC), Canada, to identify individuals diagnosed with EAO-CRC between January 1, 2010, and December 31, 2016 (hereinafter referred to as \"cases\"), along with cancer-free controls (1:10), matched by age and sex. We identified all prescriptions dispensed from community pharmacies during the year prior to diagnosis and used the Anatomical Therapeutic Chemical Classification system Level 3 to group prescriptions according to the drug class. A parallel assessment was conducted for individuals diagnosed with average age-onset CRC (diagnosis at age 50 years and older).
RESULTS: We included 1001 EAO-CRC cases (n=450, 45% female participants; mean 41.0, SD 6.1 years), and 12,989 prescriptions were filled in the year before diagnosis by 797 (79.7%) individuals. Top-filled drugs were antidepressants (first; n=1698, 13.1%). Drugs for peptic ulcer disease and gastroesophageal reflux disease (third; n=795, 6.1%) were more likely filled by EAO-CRC cases than controls (odds ratio [OR] 1.4, 95% CI 1.2-1.7) and with more frequent fills (OR 1.8, 95% CI 1.7-1.9). We noted similar patterns for topical agents for hemorrhoids and anal fissures, which were more likely filled by EAO-CRC cases than controls (OR 7.4, 95% CI 5.8-9.4) and with more frequent fills (OR 15.6, 95% CI 13.1-18.6).
CONCLUSIONS: We observed frequent prescription medication use in the year before diagnosis of EAO-CRC, including for drugs to treat commonly reported symptoms of EAO-CRC.

OBJECTIVE: Adults with early-onset diabetes (age < 40 years) have an increased risk of complications, and it is unclear whether they are receiving guideline recommended care. We compared the frequency and results of haemoglobin A1c (HbA1c) testing in adults with early-onset and usual-onset diabetes and assessed factors related to guideline concordance.
METHODS: Population-level databases from Alberta, Canada (∼4.5 million) were used to identify adults with incident diabetes. The cohort was stratified by age at diagnosis (< 40 vs. ≥ 40 years) and then followed for 365 days for HbA1c testing. Adjusted multivariable analyses were used to identify clinical and sociodemographic factors associated with guideline concordance.
RESULTS: Among 23,643 adults with incident diabetes (mean age 54.1 ± 15.4 years; 42.1 % female), 18.9 % had early-onset diabetes. Early-onset diabetes was associated with lower frequency of testing (adjusted odds ratio (aOR), 0.80; 95 % CI 0.70-0.90) and above target glycaemic levels compared to usual-onset diabetes (aOR, 1.45; 95 % CI 1.29-1.64). Factors associated with guideline concordant frequency of HbA1c testing were rural residence and insulin use.
CONCLUSIONS: In our universal care setting with premium-free health care, early-onset diabetes was associated with lower rates of HbA1c testing and sub-optimal glycaemic control compared to those with usual-onset diabetes.

UNASSIGNED: Rising trends in early-onset colorectal cancer (CRC) burden have been observed, but the distribution and temporal patterns of early-onset CRC attributable to dietary risks remain unclear.
UNASSIGNED: This study aimed to estimate the burden of early-onset CRC attributable to dietary risk factors globally, regionally, and nationally, by age and sex, from 1990 to 2019.
UNASSIGNED: The absolute number and age-specific rates (ASR) of diet-related early-onset CRC burden, as well as summary exposure value (SEV) of attributable dietary risk factors, were extracted from the Global Burden of Disease (GBD) Study 2019. The temporal changes in the burden between 1990 and 2019 were analyzed by calculating the percentage change in the absolute number of burden and the estimated annual percentage change (EAPC) in ASR of burden. The annualized rates of change (ARC) were calculated to evaluate the variation trend of SEV.
UNASSIGNED: In 2019, diet-related early-onset CRC caused 30,096 (95% UI: 23,148 to 36,091) death cases and 1,465,755 (95% UI: 1,126,489 to 1,761,661) DALYs worldwide, accounting for 34.8% deaths and 34.4% DALYs of overall early-onset CRC, respectively. Moreover, a diet low in milk (responsible for 16.5% [95% UI: 11.1 to 21.9%] of DALYs in 2019), low in whole grains (15.2% [95% UI: 5.9 to 19.9%]), low in calcium (14.3% [95% UI: 10.7 to 18.9%]), high in red meat (5.3% [95% UI: 1.7 to 9.5%]), high in processed meat (2.5% [95% UI: 0.9 to 4.0%]), and low in fiber (2.3% [95% UI: 0.9 to 4.2%]) were early-onset CRC attributable dietary risk factors. The age-specific DALYs rate of early-onset CRC attributable to each dietary risk factor generally showed an increasing trend globally between 1990 and 2019, except for low intake of fiber (EAPC = -0.57, 95% CI: -0.76 to -0.38). In addition, from 1990 to 2019, males have a higher burden than females and this gap may continue to widen due to the increasing difference between the sexes in most dietary risk factors. Furthermore, dietary risks-attributable early-onset CRC burden has shifted from regions with high socio-demographic index (SDI) to high-middle and middle SDI quintiles with uncontrolled dietary risks.
UNASSIGNED: Early-onset CRC remains a concerning issue globally, and effective prevention and modification of dietary risk factors holds great promise to reduce early-onset CRC-related burden. Prioritizing diet improvement for males is critical and urgent for CRC control efforts, particularly for those living in developing countries with ongoing dietary pattern transition.

Early-onset colorectal cancer emerges as a distinctive clinical and biological entity and is generally defined as the onset of colon or rectal neoplasia before the age of 50. Several reports describe an increasing incidence worldwide of colorectal cancers occurring in individuals younger than 50 years, along with particular histologic and molecular features. Although heredity may be an explanation in some cases with young-onset colorectal cancer, other driving factors remain partially unknown. The present study explores demographic, clinical, and pathological features within a group of patients diagnosed with colorectal cancer before the age of 50. It is a retrospective survey based on data collected between 2017 and 2023 within three surgical departments from a tertiary Romanian hospital. The clinical and pathological features we identified (later-stage disease, distal colon tumor localization, mucinous histology) are mainly superimposed with the existing data in the literature regarding this pathology. In order to lower the burden that colorectal neoplasia diagnosed in the young implies, a change of paradigm should be made in terms of establishing effective and targeted screening programs but also in the direction of enhancing complex clinical, pathological, and molecular diagnosis.

OBJECTIVE: This study aimed to investigate the impact of tumor size on survival in early-onset colon and rectal cancer.
METHODS: Early-onset colon and rectal cancer patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Tumor size was analyzed as both continuous and categorical variables. Several statistical techniques, including restricted cubic spline (RCS), Cox proportional hazard model, subgroup analysis, propensity score matching (PSM), and Kaplan-Meier survival analysis, were employed to demonstrate the association between tumor size and overall survival (OS) and cancer-specific survival (CSS) of early-onset colon and rectal cancer.
RESULTS: Seventeen thousand five hundred fifty-one (76.7%) early-onset colon and 5323 (23.3%) rectal cancer patients were included. RCS analysis confirmed a linear association between tumor size and survival. Patients with a tumor size > 5 cm had worse OS and CSS, compared to those with a tumor size ≤ 5 cm for both early-onset colon and rectal cancer. Notably, subgroup analysis showed that a smaller tumor size (≤ 50 mm) was associated with worse survival in stage II early-onset colon cancer, although not statistically significant. After PSM, Kaplan-Meier survival curves showed that the survival of patients with tumor size ≤ 50 mm was better than that of patients with tumor size > 50 mm.
CONCLUSIONS: Patients with tumors larger than 5 cm were associated with worse survival in early-onset colon and rectal cancer. However, smaller tumor size may indicate a more biologically aggressive phenotype, correlating with poorer survival in stage II early-onset colon cancer.

Hope is an important but overlooked phenomenon in dementia studies. Few studies have examined how people with dementia experience or perceive hope, possibly because it is seen as a diagnosis without hope. In this article, we report on a doctoral study, the aim of which was to examine the phenomenon of hope from the perspective of younger people with dementia to generate new understanding and enable community-based healthcare professionals to support well-being. The study was conducted in the Midlands, England, and used a modified diary-interview method. Six participants were given a camera and asked to take pictures of whatever made them feel hopeful. During a post-diary semi-structured interview, a conversation about hope took place. Interviews were transcribed and interpreted using the \'Voice-Centred Relational Method\'. Findings show that hope is important to younger people with dementia. Sources of hope were the surrounding environment, keeping connected, taking action, and drawing on internal resources. An over-arching theme was \'defying dementia\' and participants demonstrated resistance to negative stereotypes. Living with dementia did not curtail hope, although it could be weakened when participants felt \'cast adrift\' by services. The In vivo codes generated were fear of dementia, threats to identity, disconnection from others, and frustrations and restrictions. It is concluded that hope should be a more central part of practice-based conversations with people with dementia.