-
BMC Cancer Jun 2024The cardiotoxicity related to 5-Fluorouracil (5-FU) in cancer patients has garnered widespread attention. The systemic immune-inflammation index (SII) has recently been...
BACKGROUND AND AIMS
The cardiotoxicity related to 5-Fluorouracil (5-FU) in cancer patients has garnered widespread attention. The systemic immune-inflammation index (SII) has recently been identified as a novel predictive marker for the development of cardiovascular illnesses in individuals without pre-existing health conditions. However, it remains unclear whether the levels of SII are linked to cardiotoxicity related to 5-FU. This retrospective study aims to fill this knowledge gap by examining the correlation between SII and cardiotoxicity related to 5-FU in a colorectal cancer cohort.
METHODS
The study comprised colorectal cancer patients who received 5-FU-based chemotherapy at the affiliated cancer hospital of Guizhou Medical University between January 1, 2018 and December 31, 2020. After adjustment for confounders and stratification by tertiles of the interactive factor, linear regression analyses, curve fitting and threshold effect analyses were conducted.
RESULTS
Of the 754 patients included final analysis, approximately 21% (n = 156) of them ultimately experienced cardiotoxicity related to 5-FU. Monocytes (M) was found as an influential element in the interaction between SII and cardiotoxicity related to 5-FU. In the low tertile of M (T1: M ≤ 0.38 × 10/L), increasing log SII was positively correlated with cardiotoxicity related to 5-FU (Odds Ratio [OR], 8.04; 95% confidence interval [95%CI], 1.68 to 38.56). However, a curvilinear relationship between log SII and cardiotoxicity was observed in the middle tertile of M (T2: 0.38 < M ≤ 0.52 × 10/L). An increase in log SII above 1.37 was shown to be associated with a decreased risk of cardiotoxicity (OR, 0.14; 95%CI, 0.02 to 0.88), indicating a threshold effect. In the high tertile of M (T3: M > 0.52 × 10/L), there was a tendency towards a negative linear correlation between the log SII and cardiotoxicity was observed (OR, 0.85; 95%CI, 0.37 to 1.98).
CONCLUSION
Our findings suggest that SII may serve as a potential biomarker for predicting cardiotoxicity related to 5-FU in colorectal cancer patients. SII is an independent risk factor for cardiotoxicity related to 5-FU with low monocytes levels (T1). Conversely, in the middle monocytes levels (T2), SII is a protective factor for cardiotoxicity related to 5-FU but with a threshold effect.
Topics: Humans; Fluorouracil; Colorectal Neoplasms; Male; Female; Middle Aged; Cardiotoxicity; Retrospective Studies; Aged; Inflammation; Antimetabolites, Antineoplastic; Monocytes; Adult
PubMed: 38951749
DOI: 10.1186/s12885-024-12568-0 -
Cell Death and Differentiation Jun 2024Chronic kidney disease (CKD) is a major global health concern and the third leading cause of premature death. Renal fibrosis is the primary process driving the...
Chronic kidney disease (CKD) is a major global health concern and the third leading cause of premature death. Renal fibrosis is the primary process driving the progression of CKD, but the mechanisms behind it are not fully understood, making treatment options limited. Here, we find that the E3 ligase TRIM65 is a positive regulator of renal fibrosis. Deletion of TRIM65 results in a reduction of pathological lesions and renal fibrosis in mouse models of kidney fibrosis induced by unilateral ureteral obstruction (UUO)- and folic acid. Through screening with a yeast-hybrid system, we identify a new interactor of TRIM65, the mammalian cleavage factor I subunit CFIm25 (NUDT21), which plays a crucial role in fibrosis through alternative polyadenylation (APA). TRIM65 interacts with NUDT21 to induce K48-linked polyubiquitination of lysine 56 and proteasomal degradation, leading to the inhibition of TGF-β1-mediated SMAD and ERK1/2 signaling pathways. The degradation of NUDT21 subsequently altered the length and sequence content of the 3'UTR (3'UTR-APA) of several pro-fibrotic genes including Col1a1, Fn-1, Tgfbr1, Wnt5a, and Fzd2. Furthermore, reducing NUDT21 expression via hydrodynamic renal pelvis injection of adeno-associated virus 9 (AAV9) exacerbated UUO-induced renal fibrosis in the normal mouse kidneys and blocked the protective effect of TRIM65 deletion. These findings suggest that TRIM65 promotes renal fibrosis by regulating NUDT21-mediated APA and highlight TRIM65 as a potential target for reducing renal fibrosis in CKD patients.
PubMed: 38951701
DOI: 10.1038/s41418-024-01336-z -
Neurocritical Care Jul 2024The apnea test (AT) is an important component in the determination of brain death/death by neurologic criteria (BD/DNC) and often entails disconnecting the patient from...
BACKGROUND
The apnea test (AT) is an important component in the determination of brain death/death by neurologic criteria (BD/DNC) and often entails disconnecting the patient from the ventilator followed by tracheal oxygen insufflation to ensure adequate oxygenation. To rate the test as positive, most international guidelines state that a lack of spontaneous breathing must be demonstrated when the arterial partial pressure of carbon dioxide (PaCO) ≥ 60 mm Hg. However, the loss of positive end-expiratory pressure that is associated with disconnection from the ventilator may cause rapid desaturation. This, in turn, can lead to cardiopulmonary instability (especially in patients with pulmonary impairment and diseases such as acute respiratory distress syndrome), putting patients at increased risk. Therefore, this prospective study aimed to investigate whether a modified version of the AT (mAT), in which the patient remains connected to the ventilator, is a safer yet still valid alternative.
METHODS
The mAT was performed in all 140 BD/DNC candidates registered between January 2019 and December 2022: after 10 min of preoxygenation, (1) positive end-expiratory pressure was increased by 2 mbar (1.5 mm Hg), (2) ventilation mode was switched to continuous positive airway pressure, and (3) apnea back-up mode was turned off (flow trigger 10 L/min). The mAT was considered positive when spontaneous breathing did not occur upon PaCO increase to ≥ 60 mm Hg (baseline 35-45 mm Hg). Clinical complications during/after mAT were documented.
RESULTS
The mAT was possible in 139/140 patients and had a median duration of 15 min (interquartile range 13-19 min). Severe complications were not evident. In 51 patients, the post-mAT arterial partial pressure of oxygen (PaO) was lower than the pre-mAT PaO, whereas it was the same or higher in 88 cases. In patients with pulmonary impairment, apneic oxygenation during the mAT improved PaO. In 123 cases, there was a transient drop in blood pressure at the end of or after the mAT, whereas in 12 cases, the mean arterial pressure dropped below 60 mm Hg.
CONCLUSIONS
The mAT is a safe and protective means of identifying patients who no longer have an intact central respiratory drive, which is a critical factor in the diagnosis of BD/DNC. Clinical trial registration DRKS, DRKS00017803, retrospectively registered 23.11.2020, https://drks.de/search/de/trial/DRKS00017803.
PubMed: 38951444
DOI: 10.1007/s12028-024-02035-w -
Journal of Neurology Jul 2024Cognitive reserve (CR) is considered a protective factor for cognitive function and may explain interindividual differences of cognitive performance given similar levels...
Mid- and late-life lifestyle activities as main drivers of general and domain-specific cognitive reserve in individuals with Parkinson's disease: cross-sectional and longitudinal evidence from the LANDSCAPE study.
BACKGROUND
Cognitive reserve (CR) is considered a protective factor for cognitive function and may explain interindividual differences of cognitive performance given similar levels of neurodegeneration, e.g., in Alzheimer´s disease. Recent evidence suggests that CR is also relevant in Parkinson's disease (PD).
OBJECTIVE
We aimed to explore the role of life-stage specific CR for overall cognition and specific cognitive domains cross-sectionally and longitudinally in PD.
METHODS
The cross-sectional analysis with data from the DEMPARK/LANDSCAPE study included 81 individuals without cognitive impairment (PD-N) and 87 individuals with mild cognitive impairment (PD-MCI). Longitudinal data covered 4 years with over 500 observations. CR was operationalized with the Lifetime of Experiences Questionnaire (LEQ), capturing the complexity of lifestyle activities across distinct life-stages. Cognition was assessed using a comprehensive neuropsychological test battery.
RESULTS
Higher LEQ scores, particularly from mid- and late-life, were observed in PD-N compared to PD-MCI [F(1,153) = 4.609, p = .033, η = 0.029]. They were significantly associated with better cognitive performance (0.200 ≤ β ≤ 0.292). Longitudinally, linear mixed effect models (0.236 ≤ marginal R ≤ 0.441) revealed that LEQ scores were positively related to cognitive performance independent of time. However, the decline in overall cognition and memory over time was slightly more pronounced with higher LEQ scores.
CONCLUSIONS
This study emphasizes the association between complex lifestyle activities and cognition in PD. Data indicate that while CR might be related to a delay of cognitive decline, individuals with high CR may experience a more pronounced drop in overall cognition and memory. Future studies will have to replicate these findings, particularly regarding domain-specific effects and considering reverse causal mechanisms.
PubMed: 38951175
DOI: 10.1007/s00415-024-12484-0 -
Zhonghua Nei Ke Za Zhi Jul 2024To investigate the clinical and electrophysiological characteristics of patients with amyotrophic lateral sclerosis (ALS) with positive repetitive nerve stimulation...
To investigate the clinical and electrophysiological characteristics of patients with amyotrophic lateral sclerosis (ALS) with positive repetitive nerve stimulation (RNS) test results on the accessory nerve and negative needle electromyography (EMG) test results on the sternocleidomastoid with the goal to enrich the knowledge of disease progression in patients with ALS. The clinical data of 612 patients diagnosed with ALS at the Neurology Department of the First Medical Center, Chinese PLA General Hospital from June 2016 to August 2022 were collected. In total, 267 cases had undergone EMG tests on the sternocleidomastoid following a positive 3 Hz RNS test result on the accessory nerve, who were selected as the study subjects. The differences in clinical indicators were compared between RNS (+)/EMG (-) group and RNS (+)/EMG (+) group. A binomial distribution model with multiple variables was built to quantitatively analyze the major factors and their effects. At the initial visit, 15.8% of patients with ALS were 3 Hz RNS (+) on the accessory nerve and EMG (-) on the ipsilateral sternocleidomastoid, accounting for 36.3% of RNS (+) patients. The decremental range of the 3 Hz RNS test delivered to the accessory nerve in these patients [-14% (-19%, -12%)] was lower than that in patients with RNS (+)/EMG (+) [-17% (-23%, -13%)] (<0.05), while the ratio of upper limb onset (64.9%) and non-definite diagnosis (28.9%) were higher [54.7% and 13.5% for patients with RNS (+)/EMG (+), <0.05]. Furthermore, the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score [40 (37, 42)], body mass index (BMI) [23.8 (22.0, 25.4) kg/m] and forced vital capacity (FVC) [92.8% (76.6%, 103.8%)] were higher in patients with RNS(+)/EMG(+) (<0.05). The multivariate model suggested that, in patients with RNS (+)/EMG (-), the ratio of upper limb onset to lower limb onset was 1.04, while that of upper limb onset to bulbar onset was 2.02, and that of lower limb onset to bulbar onset was 1.94. The ratio of non-definite ALS to definite ALS was 1.13. The ALSFRS-R score, BMI, and FVC had a protective contribution to the electrophysiological function of the motor neurons. The ratio of the effect size of the ALSFRS-R or BMI to that of FVC was 3.37 and 1.14, respectively. Patients with ALS that were 3 Hz RNS (+) on the accessory nerve and EMG (-) on the ipsilateral sternocleidomastoid had a smaller decremental range of the compound muscle action potential amplitude, and a higher proportion of upper limb onset and non-definite ALS. A higher ALSFRS-R score, BMI, and FVC have a protective effect to the electrophysiological function of motor neurons. The effect size of the ALSFRS-R score is the largest, followed by BMI and FVC.
Topics: Humans; Amyotrophic Lateral Sclerosis; Electromyography; Motor Neurons; Neuromuscular Junction; Electric Stimulation; Accessory Nerve; Male; Female; Middle Aged
PubMed: 38951089
DOI: 10.3760/cma.j.cn112138-20230811-00049 -
Journal of Affective Disorders Jun 2024Loneliness is a pressing public mental health issue. So far, there has been a paucity of investigations focused on the individual differences modulating this subjective...
INTRODUCTION
Loneliness is a pressing public mental health issue. So far, there has been a paucity of investigations focused on the individual differences modulating this subjective feeling in the face of difficult circumstances, e.g., the COVID-19 pandemic. As such, the present study aimed to investigate the role of mentalization; given that the construct comprises reflection abilities that might be particularly relevant to the pandemic's interpersonal challenges.
METHODS
A survey representative of the German population was conducted from May to June 2020 (N = 2503). We examined mentalization, operationalized as reflective functioning (RF) and measured using the Mentalization Questionnaire (MZQ), both as a protective factor against loneliness on its own and as a moderator of the association of social isolation with loneliness.
RESULTS
Of the overall sample, 822 (32.8 %) individuals reported social isolation. Worse RF was moderately associated with higher levels of loneliness (r = 0.433, p < .001). A linear regression model (controlling for sociodemographic characteristics and general personality pathology) confirmed this positive association, but also indicated an interaction effect of RF and social isolation in the statistical prediction of loneliness. Stratified models showed that RF was a comparatively weaker statistical predictor of loneliness among the socially isolated.
DISCUSSION
This representative population study expanded our knowledge about the factors shaping loneliness in the population. RF emerged as a potentially modifiable protective influence. Further research needs to clarify the mechanisms through which it mitigates loneliness.
LIMITATIONS
The cross-sectional design does not give insight into the temporal association of RF and loneliness.
PubMed: 38950870
DOI: 10.1016/j.jad.2024.06.109 -
Journal of Psychosomatic Obstetrics and... Dec 2024In the Netherlands adverse perinatal outcomes are also associated with non-medical factors which vary across geographical locations. This study analyses the presence of...
In the Netherlands adverse perinatal outcomes are also associated with non-medical factors which vary across geographical locations. This study analyses the presence of non-medical vulnerabilities in pregnant women in two regions with high numbers of psychosocial adversity using the same definition for vulnerability in both regions. A register study was performed in 2 regions. Files from women in midwife-led care were analyzed using a standardized case report form addressing non-medical vulnerability based on the Rotterdam definition for vulnerability: measurement A in Groningen (n = 500), measurement B in South-Limburg (n = 538). Only in South-Limburg a second measurement was done after implementing an identification tool for vulnerability (C (n = 375)). In both regions about 10% of pregnant women had one or more urgent vulnerabilities and almost all of these women had an accumulation of several urgent and non-urgent vulnerabilities. Another 10% of women had an accumulation of three or more non-urgent vulnerabilities. This study showed that by using the Rotterdam definition of vulnerability in both regions about 20% of pregnant women seem to live in such a vulnerable situation that they may need psychosocial support. The definition seems a good tool to determine vulnerability. However, without considering protective factors it is difficult to establish precisely women's vulnerability. Research should reveal whether relevant women receive support and whether this approach contributes to better perinatal and child outcomes.
Topics: Humans; Female; Pregnancy; Netherlands; Adult; Registries; Vulnerable Populations; Pregnant Women
PubMed: 38950574
DOI: 10.1080/0167482X.2024.2362653 -
European Journal of Oncology Nursing :... Jun 2024Fear of cancer recurrence (FCR) is a psychological problem often faced by breast cancer patients in the rehabilitation period. The aim of this study was to identify FCR...
PURPOSE
Fear of cancer recurrence (FCR) is a psychological problem often faced by breast cancer patients in the rehabilitation period. The aim of this study was to identify FCR subgroups of Chinese breast cancer patients in rehabilitation and to analysis the factors affecting each subgroup. The effects of the subgroups on quality of life (QoL) were also explored.
METHODS
Cross-sectional data were collected from 300 breast cancer patients in a rehabilitation setting. The researchers invited the subjects to complete questionnaires on FCR, fatigue, anxiety depression, perception of illness and QoL. The researchers conducted a latent profile analysis. The factors influencing the subgroups of FCR were identified using ANOVA and multinomial logistic regression analyses. Linear regression analyses were used to explore the effect of subgroups on QoL.
RESULTS
There were three subgroups of FCR: profile 1 'Low FCR Group' (42.3%), profile 2 'Moderate FCR Group' (45.6%), and profile 3 'High FCR Group' (12.1%). Cancer stage II was a protective factor for FCR patients (OR = 0.107, P < 0.01) and was more likely to be categorized among the low FCR group. Anxiety depression was a risk factor for FCR patients and was more likely to be categorized in the medium FCR group (OR = 1.764, P < 0.001) and in the high FCR group (OR = 2.911, P < 0.001). In addition, patients subjected to a high perception of illness were more likely to be considered in the medium FCR group (OR = 1.041, P < 0.05), a risk factor affecting patients with FCR. Linear regression analysis showed that subgroups with higher FCR had a stronger negative predictive effect on their QoL (all P < 0.001).
CONCLUSIONS
The FCR was identified as three subgroups among breast cancer patients in rehabilitation, which suggests that healthcare professionals should give full consideration to the impact of cancer stage, anxiety and depression, and illness perceptions on the FCR subgroups in order to improve their QoL.
PubMed: 38950499
DOI: 10.1016/j.ejon.2024.102651 -
Neurosurgical Focus Jul 2024Few large studies have investigated the factors and outcomes related to concomitant injuries occurring alongside mild traumatic brain injury (mTBI) after motor vehicle...
OBJECTIVE
Few large studies have investigated the factors and outcomes related to concomitant injuries occurring alongside mild traumatic brain injury (mTBI) after motor vehicle collisions (MVCs). Thus, the objective of this study was to assess whether MVC characteristics predict which patients with mTBI will have concomitant whiplash injury, and whether concomitant whiplash injury affects care utilization for these patients.
METHODS
This retrospective cohort study included 22,213 patients with mTBI after MVC identified from the American College of Surgeons Trauma Quality Programs dataset. A hierarchical logistic regression model was constructed to investigate patient and MVC factors associated with concomitant whiplash injury. Propensity score matching on whiplash status, in conjunction with a multivariable logistic regression model, assessed if concomitant whiplash affected odds of hospitalization. In the subgroup of patients who were hospitalized, associations with hospital length of stay (LOS) and discharge disposition were investigated.
RESULTS
The median (IQR) age was 34 (24-51) years, with a median Glasgow Coma Scale score at presentation of 15 (15-15). Patients with concomitant whiplash were older (median 36 years vs 34 years, p = 0.03) and had higher rates of hospitalization (75% vs 64%, p < 0.001). In the hierarchical model for associations with concomitant whiplash injury, patients with blood alcohol content (BAC) greater than the federal driving limit had lower odds of concomitant whiplash (OR 0.63, 95% CI 0.49-0.81) along with those who had airbag deployment (OR 0.80, 95% CI 0.68-0.95), but seatbelt use was associated with greater odds (OR 1.41, 95% CI 1.16-1.71). After matching, concomitant whiplash was independently associated with increased odds of hospitalization (OR 1.67, 95% CI 1.40-1.99) while seatbelt use was associated with decreased odds (OR 0.88, 95% CI 0.81-0.95). Among hospitalized patients, concomitant whiplash was not associated with hospital LOS or discharge disposition.
CONCLUSIONS
MVC characteristics such as alcohol consumption and airbag deployment were protective toward development of concomitant whiplash for mTBI patients, while seatbelt use was associated with higher risk. Concomitant whiplash increases the odds of hospitalization for mTBI patients but does not affect hospital LOS or discharge disposition, while seatbelt use is associated with lower rates of hospitalization and a more favorable hospital course. These findings provide context to injury patterns and care provision after a common mechanism of injury.
Topics: Humans; Accidents, Traffic; Male; Female; Adult; Whiplash Injuries; Hospitalization; Middle Aged; Retrospective Studies; Young Adult; Brain Concussion; Cohort Studies; Length of Stay; Glasgow Coma Scale
PubMed: 38950447
DOI: 10.3171/2024.4.FOCUS24146 -
Circulation. Genomic and Precision... Jul 2024Chronic kidney disease (CKD) is highly prevalent in Central America, and genetic factors may contribute to CKD risk. To understand the influences of genetic admixture on...
BACKGROUND
Chronic kidney disease (CKD) is highly prevalent in Central America, and genetic factors may contribute to CKD risk. To understand the influences of genetic admixture on CKD susceptibility, we conducted an admixture mapping screening of CKD traits and risk factors in US Hispanic and Latino individuals from Central America country of origin.
METHODS
We analyzed 1023 participants of HCHS/SOL (Hispanic Community Health Study/Study of Latinos) who reported 4 grandparents originating from the same Central America country. Ancestry admixture findings were validated on 8191 African Americans from WHI (Women's Health Initiative), 3141 American Indians from SHS (Strong Heart Study), and over 1.1 million European individuals from a multistudy meta-analysis.
RESULTS
We identified 3 novel genomic regions for albuminuria (chromosome 14q24.2), CKD (chromosome 6q25.3), and type 2 diabetes (chromosome 3q22.2). The 14q24.2 locus driven by a Native American ancestry had a protective effect on albuminuria and consisted of 2 nearby regions spanning the gene. Variants at this locus were validated in American Indians. The 6q25.3 African ancestry-derived locus, encompassing the gene, was associated with increased risk for CKD and replicated in African Americans through admixture mapping. The European ancestry type 2 diabetes locus at 3q22.2, encompassing the and genes, was validated in European individuals through variant association.
CONCLUSIONS
US Hispanic/Latino populations are culturally and genetically diverse. This study focusing on Central America grandparent country of origin provides new loci discovery and insights into the ancestry-of-origin influences on CKD and risk factors in US Hispanic and Latino individuals.
PubMed: 38950085
DOI: 10.1161/CIRCGEN.123.004314