Nevin Manimala

JAMA Otolaryngol Head Neck Surg. 2024 Dec 19. doi: 10.1001/jamaoto.2024.4373. Online ahead of print.

ABSTRACT

INTRODUCTION: Mild sleep-disordered breathing (mSDB) in children is associated with both neurobehavioral morbidity and reduced quality of life (QOL). However, the association between symptom burden and QOL with executive function is not well understood, and it is not known whether QOL and symptom burden may help identify children with neurocognitive dysfunction.

OBJECTIVE: To assess associations among executive function, QOL, and symptom burden in children with mSDB.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was a secondary analysis of the multicenter Pediatric Adenotonsillectomy Trial for Snoring, which included children aged 3 to 12 years randomized to watchful waiting or adenotonsillectomy for mSDB (snoring and an obstructive apnea-hypopnea index <3) between June 29, 2016, and February 1, 2021. The data for this report were analyzed between December 22, 2020, and October 3, 2024.

EXPOSURE: Pediatric mSDB.

MAIN OUTCOMES AND MEASURES: Quality of life was assessed using the Obstructive Sleep Apnea-18 (OSA-18), and symptom burden was assessed using the Pediatric Sleep Questionnaire-Sleep-Related Breathing Disorder Scale (PSQ-SRBD). Executive function, including self-control and working memory, was measured using the Behavior Rating Inventory of Executive Function Global Executive Composite (BRIEF GEC), and inhibitory control and sustained attention were measured by the GoNoGo vigilance test. Partial Pearson correlations and multiple linear regression models were used to assess the associations among QOL, symptoms, and executive function.

RESULTS: The sample included 459 children (mean [SD] age, 6.1 [2.3] years; 230 female [50.1%]). Moderate correlations were found between the BRIEF GEC and the PSQ-SRBD and OSA-18 (r = 0.58 [95% CI, 0.51-0.64] and 0.59 [95% CI, 0.52-0.64], respectively). After adjusting for age, sex, race and ethnicity, body mass index percentile, household income, maternal education, attention-deficit/hyperactivity disorder, test characteristics, and disease severity, both OSA-18 and PSQ-SRBD scores were associated with the BRIEF GEC (β = 0.41 [95% CI, 0.36-0.47] and 3.66 [95% CI, 3.17-4.15], respectively). In the fully adjusted model, PSQ-SRBD was also associated with GoNoGo inhibitory control (β = -0.04 [95% CI, -0.08 to -0.01]) and sustained attention (β = -0.05 [95% CI, -0.10 to -0.01]).

CONCLUSIONS AND RELEVANCE: In this study, disease-specific QOL and symptom burden were associated with executive function in children with mSDB. These findings may be useful in identifying those children who are at risk for neurocognitive dysfunction.

PMID:39699925 | DOI:10.1001/jamaoto.2024.4373

JAMA Oncol. 2024 Dec 19. doi: 10.1001/jamaoncol.2024.5403. Online ahead of print.

ABSTRACT

IMPORTANCE: Most patients with locally advanced hepatocellular carcinoma (HCC) recur within the liver following systemic therapy.

OBJECTIVE: To determine whether stereotactic body radiation therapy (SBRT) improves outcomes in patients with locally advanced HCC compared with sorafenib alone.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter phase 3 randomized clinical trial randomized patients with HCC 1:1 to sorafenib or SBRT followed by sorafenib, stratified by performance status, liver function, degree of metastases, and macrovascular invasion. Eligible patients had HCC unsuitable for or refractory to standard local-regional therapies and were candidates for first-line systemic therapy. Data were collected from April 2013 to March 2021, and data were analyzed from July 2022 to August 2023.

INTERVENTION: Personalized SBRT, 27.5 to 50 Gy in 5 fractions.

MAIN OUTCOMES AND MEASURES: The primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), adverse events, and quality of life.

RESULTS: Of 193 patients randomized, 177 were eligible. Accrual was stopped early due to a change in standard-of-care systemic therapy. Of 177 included patients, 150 (84.7%) were male, and the median (IQR) age was 66 (60-72) years. Macrovascular invasion was seen in 131 (74.0%). As of July 1, 2022, the median OS was 12.3 months (90% CI, 10.6-14.3) with sorafenib vs 15.8 months (90% CI, 11.4-19.2) following SBRT and sorafenib (hazard ratio [HR], 0.77; 90% CI, 0.59-1.01; 1-sided P = .06). Adjusting for stratification factors, OS was improved with SBRT (HR, 0.72; 95% CI, 0.52-0.99; 2-sided P = .04). Median PFS was improved from 5.5 months (95% CI, 3.4-6.3) with sorafenib to 9.2 months (95% CI, 7.5-11.9) with SBRT and sorafenib (HR, 0.55; 95% CI, 0.40-0.75; 2-sided P < .001). Treatment-related grade 3 or higher adverse events were seen in 37 of 88 (42%) and 39 of 83 (47%) of patients treated with sorafenib vs SBRT and sorafenib, respectively (P = .52). There were 2 treatment-related deaths in the sorafenib group (death not otherwise specified and liver failure) and 1 in the SBRT and sorafenib group (lung infection). At 6 months, improved quality of life was seen in 2 of 20 (10%) and 6 of 17 (35%) of patients treated with sorafenib and SBRT and sorafenib, respectively.

CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, among patients with locally advanced HCC, SBRT was associated with a clinically important but not statistically significant improved overall survival compared with sorafenib alone.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01730937.

PMID:39699905 | DOI:10.1001/jamaoncol.2024.5403

JAMA Netw Open. 2024 Dec 2;7(12):e2450489. doi: 10.1001/jamanetworkopen.2024.50489.

ABSTRACT

IMPORTANCE: Little is known about the nature of change in goals of care (GOC) over time among adolescents and younger adult (AYA) patients aged 12 to 39 years with cancer near the end of life. Understanding how GOC evolve may guide clinicians in supporting AYA patients in making end-of-life decisions.

OBJECTIVE: To assess frequency, timing, and evolution of documented GOC among AYA patients with cancer in the last 90 days of life.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included a retrospective review of medical records from the Dana-Farber Cancer Institute, Kaiser Permanente Northern California, and Kaiser Permanente Southern California of AYA patients with cancer who were 12 to 39 years of age at death and who died between January 1, 2003, and December 31, 2019. Data were analyzed from July 1, 2023, through April 30, 2024.

EXPOSURES: Stage IV cancer or stage I-III cancer with new metastasis or recurrence.

MAIN OUTCOME AND MEASURES: The primary outcome was documented GOC discussions, categorized by timing before death as initial (>60 days), middle (31-60 days), or late (≤30 days). Goals were classified as palliative, nonpalliative, undecided, or not discussed. Subgroup analysis according to race and ethnicity were also performed.

RESULTS: Among 1929 AYA patients with a mean (SD) age at cancer diagnosis of 28 (8) years, 1049 (54.5%) were female; 5 (0.3%) were American Indian or Alaska Native, 227 (11.8%) were Asian, 157 (8.1%) were Black or African American, 14 (0.7%) were Native Hawaiian or Other Pacific Islander, 1184 (61.4%) were White, 11 (0.6%) were of more than 1 race, 38 (2.0%) were categorized as other race, 293 (15.2%) were without documented race, 514 (26.6%) were Hispanic or Latino, 762 (39.5%) were not Hispanic or Latino, and 653 (33.9%) had no documented ethnicity. Few AYA patients had palliative goals documented in the initial period (139 [7.2%]), increasing to 331 (17.2%) in the middle period and 1113 (57.7%) in the late period. In total, 393 patients (20.4%) transitioned from documented nonpalliative goals in the initial or middle periods to palliative goals by the late period. Many patients had no documented GOC discussion until close to death (initial, 1364 [70.7%]; middle, 969 [50.2%]; and late, 322 [16.7%]). Among the 1929 patients, non-White patients were disproportionately represented among those not having documented GOC discussions (Black, 30 of 157 [19.1%]; Asian, 45 of 227 [19.8%]; and other or undocumented race, 80 of 361 [22.2%]) compared with White patients (167 of 1184 [14.1%]) (P < .001) as were Hispanic or Latino patients (116 of 514 [22.6%]) compared with non-Hispanic patients (93 of 762 [12.2%]) (P < .001) and individuals with no ethnicity documented (113 of 653 [17.3%]) (P < .001).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study of AYA patients who died of cancer, palliative goals were rarely documented before the last month of life, highlighting the need for timely and ongoing GOC discussions.

PMID:39699897 | DOI:10.1001/jamanetworkopen.2024.50489

JAMA Netw Open. 2024 Dec 2;7(12):e2450744. doi: 10.1001/jamanetworkopen.2024.50744.

ABSTRACT

IMPORTANCE: Post-COVID-19 condition (PCC) is emerging as a common and debilitating condition with few treatment options.

OBJECTIVE: To assess the effectiveness of a brief outpatient rehabilitation program based on a cognitive and behavioral approach for patients with PCC.

DESIGN, SETTING, AND PARTICIPANTS: Patients with mild to moderate PCC were randomized 1:1 to an established transdiagnostic rehabilitation program or care as usual at a single referral center recruiting from the region of the South-Eastern Norway Regional Health Authority. Participants were followed up after treatment completion and 12 months after enrollment using participant-reported outcome measures. Data were collected from February 22, 2022, until April 15, 2024. Intention-to-treat analysis was performed.

INTERVENTION: The program consisted of 2 to 8 outpatient encounters with approximately 2 to 6 weeks between each encounter. The intervention was theoretically grounded in the cognitive activation theory of stress, and physicians and physiotherapists were trained in cognitive and behavioral approaches with targeted negative stimuli and response outcome expectancies being particularly important.

MAIN OUTCOMES AND MEASURES: Participant-reported physical function assessed by the Short-Form Health Survey 36 Physical Function Subscale (SF-36-PFS) served as the primary outcome. Secondary outcome measures were the remaining subscales of the SF-36, return to work self-efficacy and symptom scores on fatigue, postexertional malaise, breathlessness, cognitive difficulties, sleep problems, anxiety and depression symptoms, and smell and taste abnormalities. Safety measures included primary health care contacts; hospital admissions; initiation of pharmacologic and/or nonpharmacologic therapy; occurrence of novel disease, illness, or other health problems; worsening of selected key symptoms; working abilities; and thoughts of suicide.

RESULTS: A total of 473 patients with mild to moderate PCC were assessed for eligibility (n = 364 physician referred; n = 109 self-referred); 314 were included (225 females [72%]; mean [SD] age, 43 [12] years) and 231 completed the primary end point evaluation. The SF-36-PFS scores improved statistically and clinically significantly in the intervention group (score difference between groups, 9.2; 95% CI, 4.3-14.2; P < .001; Cohen d = 0.43; intention-to-treat analysis). The effect was sustained over time. Most secondary and safety measures favored the intervention.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, a brief outpatient rehabilitation program with a cognitive and behavioral approach in patients with PCC was effective and safe. This trial adds to the evidence supporting such interventions in routine clinical care. Future research should investigate which elements of this approach are the most effective and identify subgroups for which the current treatment is most relevant.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05196451.

PMID:39699896 | DOI:10.1001/jamanetworkopen.2024.50744

JAMA Netw Open. 2024 Dec 2;7(12):e2451094. doi: 10.1001/jamanetworkopen.2024.51094.

ABSTRACT

IMPORTANCE: Anorexia nervosa (AN) is commonly associated with cardiovascular complications.

OBJECTIVE: To investigate the trajectories of the risk of cardiovascular conditions in a nationwide cohort of patients with AN in Taiwan.

DESIGN, SETTING, AND PARTICIPANTS: From a population-based health insurance database from January 1, 2011, to December 31, 2021, this longitudinal cohort study identified patients with AN and controls through propensity score matching at a 1:10 ratio according to sex, age, urbanization level of residence, socioeconomic status, and year of diagnosis. Data were analyzed from June 27, 2023, to February 23, 2024.

EXPOSURE: First-time diagnosis of AN by psychiatrists during the study period.

MAIN OUTCOMES AND MEASURES: Incidence and risk of composite cardiovascular conditions. Kaplan-Meier curves were used to estimate the cumulative incidence of major adverse cardiovascular events (MACE) and any cardiovascular condition. With adjustment for psychiatric comorbidities, conditional Cox proportional hazards regression analyses were performed to estimate the risk of cardiovascular events, which were presented as hazard ratios (HRs) and 95% CIs, relative to the comparison group. Risks of individual cardiovascular conditions were calculated during 3 follow-up periods after AN diagnosis.

RESULTS: The study population included 2081 patients with AN and 20 810 matched controls, for a total of 22 891 participants (mean [SD] age, 24.9 [9.9] years; 91.3% female). In total, 99 patients with AN (4.8%) had MACE vs 175 (0.8%) in controls, and 124 patients with AN (6.0%) had any cardiovascular condition vs 483 controls (2.3%). At the 5-year follow-up, the cumulative incidence rate of MACE was 4.82% (95% CI, 3.85%-6.02%) and of any cardiovascular condition was 6.19% (95% CI, 5.19%-7.53%). Compared with the control group, the AN group had significantly higher risks of MACE (adjusted HR [AHR], 3.78; 95% CI, 2.83-5.05) and any cardiovascular condition (AHR, 1.93; 95% CI, 1.54-2.41). The significantly increased risks of congestive heart failure, conduction disorder, and structural heart disease occurred in the initial follow-up period and disappeared after 60 months of follow-up. Notably, patients with AN did not have an increased risk of ischemic heart disease until after 60 months of follow-up (AHR, 3.01; 95% CI, 1.48-6.13).

CONCLUSIONS AND RELEVANCE: In this national matched cohort study, increased risk of cardiovascular conditions was found in different periods after AN diagnosis. Clinicians should monitor comorbid cardiovascular conditions among patients with AN at initial presentation, during treatment, and at follow-up.

PMID:39699895 | DOI:10.1001/jamanetworkopen.2024.51094

JAMA Netw Open. 2024 Dec 2;7(12):e2451707. doi: 10.1001/jamanetworkopen.2024.51707.

ABSTRACT

IMPORTANCE: Previous research has examined outcomes among very preterm newborns by the birthing parent’s race and ethnicity, but knowledge about these trends during the COVID-19 pandemic is limited.

OBJECTIVE: To examine trends in outcomes among Black, Hispanic, and Asian preterm newborns compared with White preterm newborns.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study (2018-2022) took place at 774 neonatal intensive care units in the Vermont Oxford Network. Participants were newborns born at 22 to 29 weeks’ gestation.

EXPOSURE: Race and ethnicity.

MAIN OUTCOMES AND MEASURES: The primary outcomes were mortality and complications, including respiratory distress syndrome, necrotizing enterocolitis (NEC), early-onset sepsis, late-onset sepsis (LOS), severe intraventricular hemorrhage (sIVH), severe retinopathy of prematurity, chronic lung disease, pneumothorax, and complication-free survival.

RESULTS: Among 90 336 newborns (47 215 male [52.3%]; 43 121 female [47.7%]; mean [SD] gestational age, 26.4 [2.1] weeks), 4734 (5.2%) were born to Asian, 20 345 (22.3%) to Hispanic, 31 264 (34.3%) to non-Hispanic Black, and 33 993 (37.3%) to non-Hispanic White birthing individuals. Rates of in-hospital mortality (4831 Black newborns [15.6%]; 3009 Hispanic newborns [14.9%]; and 4886 White newborns [14.4%]), NEC (2374 Black newborns [7.8%]; 1359 Hispanic newborns [6.9%]; and 2137 White newborns [6.5%]), LOS (3846 Black newborns [13.5%]; 2258 Hispanic newborns [12.3%]; and 3575 White newborns [11.5%]), and sIVH (2919 Black newborns [10.3%]; 1673 Hispanic newborns [9.2%]; and 2800 White newborns [9.1%]) were highest among Black and lowest among White newborns. Chronic lung disease and pneumothorax rates were lowest among Black and highest among White newborns. Over the study period, mortality rate differences were slightly higher for Black than White newborns, with no differences by 2022. NEC and LOS rates were consistently higher among Black than White newborns. By 2022, Black newborns had higher rates of NEC (rate difference, 1.3 percentage points; 95% CI, 0.46-2.2 percentage points) and LOS (rate difference, 2.7 percentage points; 95% CI, 1.4-4.0 percentage points). sIVH rates were higher for Black newborns in some years, whereas severe retinopathy of prematurity rates were lower. Hispanic newborns had mortality and complication rates similar to those of White newborns. Black and Hispanic newborns had lower respiratory complication rates and higher complication-free survival than White newborns.

CONCLUSIONS AND RELEVANCE: In this cohort study, there were no differences in mortality rates between Black and White newborns, but Black newborns had higher rates of NEC and LOS. Continued quality improvement and addressing social determinants of health are critical for promoting health equity in hospital outcomes and beyond.

PMID:39699894 | DOI:10.1001/jamanetworkopen.2024.51707

JAMA Netw Open. 2024 Dec 2;7(12):e2451715. doi: 10.1001/jamanetworkopen.2024.51715.

ABSTRACT

IMPORTANCE: Prior studies have shown that the benefits, harms, and costs of colorectal cancer (CRC) screening at older ages are associated with a patient’s sex, health, and screening history. However, these studies were hypothetical exercises and not directly informed by data on CRC risk.

OBJECTIVE: To identify the optimal stopping ages for CRC screening by sex, comorbidity, and screening history from a cost-effectiveness perspective.

DESIGN, SETTING, AND PARTICIPANTS: This economic evaluation first validated the MISCAN-Colon (Microsimulation Screening Analysis-Colon) model against community-based CRC incidence and mortality rates for 2 subcohorts of the PRECISE (Optimizing Colorectal Cancer Screening Precision and Outcomes in Community-Based Populations) cohort. Subsequently, different CRC screening scenarios were simulated in older individuals. Cohorts of US adults aged 76 to 90 years varied by sex and comorbidity status (none, low, moderate, or severe). Statistical and sensitivity analyses were performed from March 2023 to May 2024.

EXPOSURES: CRC screening histories including fecal immunochemical test (FIT) or colonoscopy, such as a negative colonoscopy result from 10, 15, 20, 25, or 30 years before the index age; 1 to 5 negative FIT results within 5 years of the index age, with different patterns of recency; or a combination of negative colonoscopy and negative FIT results.

MAIN OUTCOMES AND MEASURES: The main outcomes included estimated lifetime clinical outcomes, incremental costs, and quality-adjusted life-years gained (QALYG) associated with 1 additional FIT or colonoscopy. Optimal stopping age for screening, defined as the oldest age for which the incremental cost-effectiveness ratio was still below the willingness-to-pay threshold of $100 000 per QALYG, was evaluated.

RESULTS: The first of the 2 PRECISE subcohorts used in validating the simulation model included 25 974 adults (15 060 females [58.0%]; 54.7% aged 76 to 80 years) with a negative colonoscopy result 10 years before the index date. The second subcohort consisted of 118 269 adults (67 058 females [56.7%]; 90.5% aged 76 to 80 years) with a negative FIT result 1 year before the index date. Older age, male sex, higher comorbidity levels, and recent CRC screenings were associated with reduced incremental benefit and cost-effectiveness of additional screening. For the reference cohort of 76-year-old females without comorbidities and a negative colonoscopy result 10 years before the index age, 1 additional colonoscopy cost $38 226 per QALYG. For cohorts with otherwise equivalent characteristics, associated costs increased to $1 689 945 per QALYG for females at age 90 years without comorbidities and a negative colonoscopy results 10 years before the index age, $51 604 per QALYG for males at age 76 years without comorbidities and a negative colonoscopy result 10 years before the index age, and $108 480 per QALYG for females at age 76 years with severe comorbidities and a negative colonoscopy result 10 years before the index age and decreased to $16 870 per QALYG for females without comorbidities and a negative colonoscopy result 30 years before the index age. The optimal stopping ages across different cohorts ranged from younger than 76 to 86 years for colonoscopy and younger than 76 to 88 years for FIT.

CONCLUSIONS AND RELEVANCE: In this economic evaluation, age, sex, screening history, comorbidity, and future screening modality were associated with the clinical outcomes, cost-effectiveness, and optimal stopping age for CRC screening. These results can inform guideline development and patient-directed informed decision-making.

PMID:39699893 | DOI:10.1001/jamanetworkopen.2024.51715

JAMA Netw Open. 2024 Dec 2;7(12):e2451799. doi: 10.1001/jamanetworkopen.2024.51799.

ABSTRACT

IMPORTANCE: Physical activity, as a modifiable factor, emerges as a primary intervention strategy for the prevention and management of gestational diabetes (GD). Among women with GD, the association of physical activity during pregnancy with preterm birth remains unclear.

OBJECTIVE: To examine the association of accelerometer-derived physical activity metrics and patterns with preterm birth among women with GD.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study recruited pregnant women with GD in Hangzhou, China, from August 2019 to August 2023 as part of the Westlake Precision Birth Cohort study. Statistical analysis was performed between August and November 2023.

EXPOSURES: Wearable accelerometer-derived physical activity metrics and patterns. Measurements of physical activity via wearable accelerometer were performed at a median (IQR) of 25.4 (24.6-26.6) weeks’ gestation.

MAIN OUTCOMES AND MEASURES: Preterm birth was determined through the examination of delivery records. Incident preterm birth was defined as the delivery of infants before completing 37 weeks of gestation.

RESULTS: Among the 1427 women meeting the inclusion criteria, the mean (SD) age was 31.3 (3.8) years, and there were 80 cases of preterm birth. An increase in moderate-to-vigorous intensity physical activity (MVPA) and the fraction of physical activity energy expenditure derived from MVPA exhibited an inverse association with preterm birth, with an odds ratio per 30 minutes of 0.64 (95% CI, 0.42-0.98) and an odds ratio per SD of 0.69 (95% CI, 0.55-0.88). In the dose-response analysis, there was a progressive decrease in the odds of preterm birth with increasing duration of MVPA per day, reaching a plateau at approximately 74 minutes per day. Furthermore, the findings indicated that active MVPA (MVPA ≥30 minutes per day), whether it was concentrated into a few days or followed a more regular pattern, had similar beneficial association with preterm birth.

CONCLUSIONS AND RELEVANCE: In this prospective cohort study, MVPA during pregnancy exhibited an inverse association with preterm birth among women with GD. Concentrated physical activity was associated with similar benefits in reducing preterm birth risk as regular physical activity.

PMID:39699891 | DOI:10.1001/jamanetworkopen.2024.51799

Transl Vis Sci Technol. 2024 Dec 2;13(12):33. doi: 10.1167/tvst.13.12.33.

ABSTRACT

PURPOSE: Mutations affecting the CRB1 gene can result in a range of retinal phenotypes, including early onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA), retinitis pigmentosa, cone-rod dystrophy (CORD), and macular dystrophy (MD). As research into treatment strategies advances towards clinical translation, there is a need to establish reliable outcome metrics. This study explores the contrast sensitivity function (CSF) across different spatial frequencies in individuals with CRB1-retinopathies using the child-friendly PopCSF test, an iPad-based “gamified” assessment.

METHODS: Prospective cross-sectional study of 20 patients with molecularly confirmed biallelic CRB1 pathogenic variants from Moorfields Eye Hospital, London, UK, was conducted. Best-corrected visual acuity (BCVA), contrast sensitivity using the Pelli-Robson chart, and the PopCSF test were performed.

RESULTS: Of the 20 CRB1 patients, seven had EOSRD/LCA, three had CORD, and 10 had MD. There was no statistically significant difference between the mean BCVA between phenotypes (P = 0.066). However, a significant difference was found between groups in the mean letter log contrast sensitivity (logCS) and area under the contrast sensitivity function (AUCSF) with P = 0.047 and P < 0.001, respectively. A moderate positive correlation was observed between Pelli-Robson and PopCSF (r = 0.53, P = 0.020). The CRB1 cohort had significantly lower CSF at both low and high spatial frequencies compared to controls. Among the CRB1 phenotypes, patients with EOSRD/LCA, exhibited the lowest CSF.

CONCLUSIONS: This study is the first to examine CSF across spatial frequencies in patients with CRB1-retinopathies using the novel PopCSF test.

TRANSLATIONAL RELEVANCE: The CSF holds promise as a potential functional vision trial endpoint.

PMID:39699888 | DOI:10.1167/tvst.13.12.33

Clin Exp Rheumatol. 2024 Dec;42(12):2420-2426. doi: 10.55563/clinexprheumatol/ku7y1q. Epub 2024 Dec 19.

ABSTRACT

OBJECTIVES: In primary Sjögren’s disease (pSjD), in addition to glandular inflammation and atrophy, functional secretion impairment may contribute to dryness. Altered protein distribution and antibodies against aquaporin-5 (anti-AQP5) and poly-U-binding factor 60kDa protein (anti-PUF60) have been reported in pSjD and may be specifically implicated in the glandular secretive processes. This study aimed to assess the occurrence of serum anti-AQP5 and anti-PUF60 antibodies and their correlations with clinical and laboratory features of pSjD.

METHODS: Blood samples from pSjD patients and healthy donors (HD) were collected, and anti-AQP5 and anti-PUF60 antibodies were detected using an enzyme-linked immunosorbent assay. Differences between groups were evaluated using appropriate statistical tests, and odds ratios (OR) of high disease activity were assessed by multivariate stepwise backward multiple regression and adjusted for clinical covariates.

RESULTS: Serum samples from 36 pSjD patients and 8 HD were analysed, and anti-AQP5 and anti-PUF60 antibody levels were not significantly different between groups. However, pSjD patients with high disease activity (n. 10) had significantly higher levels of anti-AQP5 antibodies compared to those with low-moderate disease activity (p<0.001). At logistic regression analysis, variables associated with high disease activity were anti-AQP5 (OR 128.9, 95% CI 2.7-615), C-reactive protein (OR 12.9, 95% CI 1.2-137.2), and C4 <10 mg/dl (OR 60, 95% CI 1.1-318.9).

CONCLUSIONS: Our pilot study confirms that anti-AQP5 antibodies may discriminate pSjD patients with high disease activity. These findings offer valuable clinical implications for managing pSjD patients, potentially identifying patients at high risk of glandular deterioration.

PMID:39699867 | DOI:10.55563/clinexprheumatol/ku7y1q