title
stringlengths 1
1.19k
| keywords
stringlengths 0
668
| concept
stringlengths 0
909
| paragraph
stringlengths 0
61.8k
| PMID
stringlengths 10
11
|
|---|---|---|---|---|
Procedures | tumor, death, toxicity, blood coagulation, Cancer | ADVERSE EVENT, TUMOR, DISEASE, ADVERSE EVENT, CPS, CANCER | This study enrolled 26 eligible patients with RM-NPC. The patients received 250 mg of apatinib orally once a day and camrelizumab 200 mg was injected intravenously once every two weeks until the disease progressed, intolerable toxicity appeared, the study was completed, or consent was withdrawn. Reduction of the dose of camrelizumab was not allowed. If the patient experienced a suspected immune related adverse event (AE), they could stop using camrelizumab temporarily or permanently, depending on the doctor’s judgment. Adjustments of the dose of apatinib were not permitted. Interruption of apatinib was allowed and was carried out according to the judgment of the therapist and local standard practice. If the dose of apatinib was interrupted, replenishment in subsequent cycles was not permitted, and if AEs greater than grade 3 occurred, treatment was discontinued.Each investigator (WJ, YFP, JZ, BZ, and YXS) assessed the tumor response in accordance with RECIST version 1.1. All patients underwent baseline examinations, including laboratory tests, magnetic resonance imaging (MRI), or computed tomography (CT), bone scan (bone scintigraphy), within 28 days after study inclusion. Laboratory tests were carried out every two weeks, which included renal function tests, liver function tests, and standard complete blood counts. Every 4 weeks, an electrocardiogram, routine stool and urine tests, blood coagulation tests, and thyroid function tests were reexamined. Imaging examination was performed every 6 weeks until the disease progressed or follow-up treatment began. According to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03), we recorded AEs during the trial, during treatment, and within 3 months after cessation of treatment. At the end of the study, patient follow-up was carried out every 4 weeks by telephone until death or the end of follow up. Efficacy analysis was performed in the intention-to-treat (ITT) population. Safety analyses were performed on all patients who received at least one dose of study treatment.Biomarker analyses employed blocks of paraffin-embedded tumor tissue taken from archival tumor tissue of the study participants. Immunohistochemical staining was performed after paraffin-embedded NPC tissue was cut into 5-µm-thick slides. The expression of PD-L1 was evaluated using a PD-L1 immunohistochemical kit (ab213524; Abcam, Cambridge, MA, USA) in the central laboratory. The comprehensive positive score (CPS) was used to report PD-L1 expression: CPS = (the number of PD-L1 positive tumor cells + the number of PD-L1 positive tumor associated immune cells)/the total number of tumor cells × 100. A CPS ≥ 1 indicated PD-L1 positivity. A primary antibody diluent was prepared using an antibody diluent (DAKO, Carpinteria, CA) containing background inducers and used for the following dilutions: anti-VEGFR-2 (ab115805, clone SP123,1:400; Abcam, Cambridge, UK); anti-CD4 (ab133616,1:800; Abcam); and anti-CD8 (ab245118,1:800; Abcam). Under light microscope, the whole section was randomly observed in 5 high power (10-40) visual fields, and the product of staining intensity and the percentage of positive cells was used as the judgment index. Finally, score of 0-7 was divided into low expression group, 8-12 was divided into high expression group. Real-time quantitative PCR was used to detect EBV DNA in plasma samples from patients. 400 copies/ml of plasma EBV DNA before treatment was taken as the critical value. A EBV DNA ≥ 400 copies/ml indicated EBV DNA positivity. | PMC10795162 |
Endpoints and assessment | death | DISEASE, DISEASE PROGRESSION, SECONDARY | The major endpoint was the objective response rate (ORR), which was determined by the investigators as the percentage of patients who had a complete response (CR) or a partial response (PR) according to RECIST version 1.1.The secondary endpoints were: Progression-free survival (PFS), defined as the interval between treatment initiation and the date of the disease progression or death from any cause); overall survival (OS), defined as the interval between treatment initiation and the date of death from any cause; the disease control rate (DCR), defined as the percentage of patients with stable disease, PR, or CR; and safety. | PMC10795162 |
Sample size calculation | This clinical trial was a single-arm study with ORR as the primary endpoint. In accordance with Simon’s optimal two-stage design (one-sided α 5% and power 80%), the intended sample size was 26 patients. The response rate (RR) of nivolumab in RM-NPC was 20.5%.( | PMC10795162 |
||
Statistical analysis | All analyses were performed for all patients who were administered with at least one dose of the research treatment. The Clopper-Pearson method was used to determine the 95% confidence interval (CI) for ORR and DCR. PFS and OS were determined using the Kaplan-Meier technique. Statistics provided clinical and demographic features, as well as AEs. We used the χ2 test or Fisher’s exact test to evaluate the relationship between ORR and exploratory subsets, and the log-rank test was employed to compare the relationships among them. SPSS software (version 25) was used to carry out the statistical analyses. All statistical tests were bilateral tests, and | PMC10795162 |
||
Study oversight | All participating centers’ institutional review committees gave their approval for the trial program, which was carried out in compliance with the Declaration of Helsinki and the guidelines for good clinical practice. Before participating in the trial, each patient gave their informed consent in Chinese. | PMC10795162 |
||
Role of the funding source | The funders of the study had no role in study design, data collection, data analysis, data interpretation, as well as writing the report. The corresponding author had the sole responsibility for choosing to submit the report for publication, and had complete access to all the data generated during the study. | PMC10795162 |
||
Results | PMC10795162 |
|||
Patient characteristics | Cancer | ONCOLOGY, VIRUS, EPSTEIN, CANCER | In stage 1 of the trial, among the seven participating patients, three patients achieved an OR. Therefore, another 16 patients were recruited in the second phase. According to the assumed 10% loss to follow-up, finally, 26 eligible patients were registered between 14 January 2021 and 15 September 2021 ((ITT and safety set; Trial profile.Baseline Characteristics of the patients (n = 26).Data are shown as the median (interquartile range (IQR)) or n (%). AJCC = American Joint Committee on Cancer. ECOG = Eastern Cooperative Oncology Group. EBV=Epstein–Barr virus. PD-L1= Program death-ligand 1. VEGFR-2=Vascular Endothelial Growth Factor Receptor-2. | PMC10795162 |
Antitumor activity | Tumor | TUMOR | All patients were subjected to efficacy analysis. Fifteen patients (57.7%) in the efficacy evaluable population had smaller target lesions than those at baseline. Among these 15 patients, 10 achieved an OR according to RESIST1.1.(Tumor responses as assessed by the investigators or independent reviewers.
Survival outcomes of the patients with RM-NPC. Kaplan-Meier plots showing progression-free survival
| PMC10795162 |
Safety | fatigue, anemia | ADVERSE EVENT, ANEMIA | All 26 (100%) patients experienced treatment-related AEs of any grade. The most frequent AEs were anemia (57.7%), increased alkaline phosphatase (34.6%), and fatigue (30.8%) (Treatment-Related Adverse Events in Total Treated Patients (n = 26). | PMC10795162 |
EBV DNA, PD-L1, VEGFR-2, CD4 and CD8 expression | tumor, tumors, PD-L1-positive tumors | CPS, TUMOR, TUMORS | Plasma EBV DNA was detectable before treatment in 22 of the 26 patients, but not in 4 patients. Of the 22 detectable patients, 9 were positive and 13 were negative. Their ORRs were 55.6% (5/9) and 38.5% (5/13), respectively, and there was no significant difference (P=0.666).Among the 26 patients, 21(80.8%) had evaluable tumor biological samples to analyze the expression of PD-L1, VEGFR-2, CD4 and CD8 expression. Among these 21 patients, 16 (76.2%) had a PD-L1 CPS ≥ 1 and 14 (66.7%) patients had a PD-L1 CPS ≥ 10. In patients with a PD-L1 CPS ≥1, the ORR was 37.5% (6/16, 95% CI, 10.9–64.1) and the DCR was 56.3% (9/16, 95% CI, 28.9–83.6). The mPFS and mOS were 6 months and 13 months, respectively, in PD-L1-positive patients. PD-L1 negative patients had an mPFS of 14 months and mOS of 15 months. There is no significant difference in ORR was observed between patients with PD-L1-positive and PD-L1-negative tumors (37.5% vs 60.0%, P=0.611). In addition, patients with PD-L1-positive tumors had longer mPFS than patients with PD-L1-negative tumors.Among the 21 patients, 8(38.1%) had high expression of VEGFR-2 and 13(61.9%) had low expression. In the patients with high expression of VEGFR-2, no patient reached the objective response. In the patients with low expression of VEGFR-2, 9(69.2%) patients reached the objective response. Among the 21 patients, 8(38.1%) had high expression of CD4 and 13(61.9%) had low expression. In the patients with high expression of CD4, 4(50.0%) patients reached the objective response. In the patients with low expression of CD4, 5(38.5%) patients reached the objective response.Among the 21 patients, 2(9.5%) had high expression of CD8 and 19(90.5%) had low expression. In the patients with high expression of CD8, 1(50.0%) patient reached the objective response. In the patients with low expression of CD8, 8(42.1%) patients reached the objective response.There was a significant difference in the ORR between VEGFR-2 high expression group and VEGFR-2 low expression group (0.0% vs. 69.2%, P =0.002). There is no significant difference in ORR was observed between patients with CD4 high expression group and CD4 low expression group (50.0% vs 38.5%, P=0.673). There is no significant difference in ORR was observed between patients with CD8 high expression group and CD8 low expression group (50.0% vs 42.1%, P=0.686). | PMC10795162 |
Discussion | tumor, cancers, bleeding | ADVERSE REACTIONS, TUMOR, INFILTRATION, CANCERS, BLEEDING, ADVERSE EVENTS | In this multicenter, single-arm, phase II, prospective clinical trial, we reported the efficacy and safety of the VEGFR2-targeting apatinib combined with PD-1 inhibitor camrelizumab in patients with RM-NPC. Our findings revealed that the ORR of patients with RM-NPC treated with apatinib plus camrelizumab was 38.5% (10/26), the DCR was 61.5% (16/26), the mPFS was 6 months, and mOS was 14 months. Apatinib plus camrelizumab was well tolerated in patients with advanced NPC, regardless of their PD-L1 status, showing good ORR and PFS. Most treatment-related adverse events could be controlled by suspending apatinib and/or camrelizumab, or taking other drugs.After receiving first-line chemotherapy, patients with RM-NPC who progress have few treatment alternatives. In the previous phase 1b KEYNOTE-028((NCT02054806) trial,(Studies by Huang et al. found that the ORR of apatinib monotherapy in patients with RM-NPC was 31.4%, the mPFS was 3.9 months, and mOS was 5.8 months. (In our previous study (NCT03130270), apatinib at 500 mg/day was used as the initial dosage for all patients, as opposed to 250 mg/day in the current study.(Anti-angiogenic therapy can boost sensitivity to anti-PD-1/PD-L1 therapy by increasing PD-L1 expression and the infiltration of CD8+T cells into the tumor microenvironment, according to preclinical research.(Currently, scant investigations exist pertaining to the amalgamation of apatinib and camrelizumab in the therapeutic intervention of RM-NPC. A recent Phase II clinical study conducted by Ding et al. showed that the coadministration of apatinib and camrelizumab yielded an ORR of 65.5% and a DCR of 86.2% for RM-NPC.(In this study, the observed adverse reactions were generally mild (23.6% grade 3–4 adverse events), and was similar to the results for apatinib combined with camrelizumab in other cancers.(This study has a number of limitations. First, the small number of patients included made it less likely that the effectiveness observed was indeed successful, hence the results for anti-tumor activity were at the preliminary stage. Second, the patients had an ECOG performance status of 0-1 from southern China, which suggests that a selected population was enrolled in the study. Therefore, a further study would be needed to investigate the efficacy of this combination for non-Chiness patients with RM-NPC. Third, we excluded patients with tumor infiltration into major blood vessels from the study cohort to reduce the risk of bleeding during treatment. In subsequent studies, we will continue to focus on evaluating the post-treatment bleeding susceptibility of patients. Fourth, this was a single-arm study with no control group for comparison, and thus selection bias could not be ruled out. | PMC10795162 |
Conclusions | toxicity | Our findings indicated that in patients with RM-NPC, camrelizumab plus apatinib exhibited promising antitumor efficacy and acceptable toxicity. These results support the view that anti-angiogenic drugs combined with immunosuppressants represent a new and promising anti-tumor combination regimen for RM-NPC. To confirm our findings, larger randomized controlled trials are required. | PMC10795162 |
|
Data availability statement | The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author. | PMC10795162 |
||
Ethics statement | CROSS | The studies involving humans were approved by Affiliated Hospital of Guilin Medical University, Nanxishan Hospital of Guangxi Zhuang Autonomous Region, Wuzhou Red Cross Hospital, Laibin people’s Hospital, Lingshan County people’s Hospital. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study. | PMC10795162 |
|
Author contributions | HC | YM: Writing – original draft, Writing – review & editing. YufP: Writing – original draft. BZ: Writing – original draft, Writing – review & editing. JZ: Writing – original draft, Writing – review & editing. YS: Writing – original draft, Writing – review & editing. ZL: Writing – original draft, Writing – review & editing. ML: Writing – review & editing. GQ: Writing – review & editing. XK: Writing – review & editing. RZ: Writing – review & editing. YuP: Writing – review & editing. YL: Writing – review & editing. DW: Writing – review & editing. YW: Writing – review & editing. HC: Writing – review & editing. WJ: Writing – original draft, Writing – review & editing. | PMC10795162 |
|
Acknowledgments | The authors are grateful to all patients and their families who participated in the study. The authors appreciate the support from Jiangsu Hengrui Pharmaceuticals. | PMC10795162 |
||
Abbreviations | Epstein-Barr virus | NASOPHARYNGEAL CARCINOMA, ADVERSE EVENT, NASOPHARYNGEAL CARCINOMA, SOLID TUMOR, CPS, DISEASE | RM-NPC, Recurrent/metastatic nasopharyngeal carcinoma; ORR, Objective response rate; PFS, Progression-free survival; OS, Overall survival; DCR, Disease control rate; NPC, Nasopharyngeal carcinoma; EBV, Epstein-Barr virus; PD-L1, Programmed death-ligand 1; VEGF, Vascular endothelial growth factor; RECIST, Response Evaluation Criteria in Solid Tumor; AE, Adverse event; MRI, Magnetic resonance imaging; CT, Computed tomography; CPS, Comprehensive positive score; CR, Complete response; PR, Partial response; ITT, Intention-to-treat. | PMC10795162 |
Conflict of interest | The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. | PMC10795162 |
||
Publisher’s note | All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. | PMC10795162 |
||
References | PMC10795162 |
|||
ABSTRACT | Chagas disease | CHAGAS DISEASE | The authors declare a conflict of interest. J.A. acted as a consultant to Bayer for the design, conduct and review of the CHICO and CHICO SECURE studies. U.G. is an employee of Bayer AG (Berlin, Germany). E.H. is an employee of Bayer US LLC (Whippany, New Jersey, USA). G.M. received personal fees from Bayer during the conduct of the study. O.D. is an employee of Bayer Healthcare Co., Ltd. (Shanghai, China). V.S., T.R., and J.J.P.R. have no conflicts of interest to disclose.Nifurtimox is recommended for the treatment of Chagas disease; however, long-term follow-up data are scarce. This prolonged follow-up phase of the prospective, historically controlled, CHICO clinical trial evaluated seronegative conversion in pediatric patients aged <18 years with Chagas disease who were followed for 4 years after nifurtimox treatment. Patients were randomly assigned 2:1 to nifurtimox 60-day or 30-day regimens comprising 10 to 20 mg/kg/day for patients aged <12 years and body weight <40 kg, and 8 to 10 mg/kg/day for those aged ≥12 years and body weight ≥40 kg. Anti- | PMC10112190 |
KEYWORDS | PMC10112190 |
|||
INTRODUCTION | infection, Chagas disease, Chagasic cardiomyopathy | AMERICAN TRYPANOSOMIASIS, DISEASE, PARASITIC DISEASE, CHAGAS DISEASE, DISORDERS, CHRONIC CHAGAS DISEASE, INFECTION | Chagas disease (American trypanosomiasis) is a potentially life-threatening parasitic disease caused by the hemoflagellate protozoan Chagas disease has two phases: an initial acute phase of 6 to 8 weeks and then, if the patient is not treated, a chronic phase, which can be indeterminate, lasting years or decades, or symptomatic. About two-thirds of patients display the indeterminate chronic form without clinical signs or symptoms, but in up to 40% of patients, Chagas disease can progress to the symptomatic chronic form 10 to 30 years after the initial infection, with affected patients experiencing a range of clinical manifestations, including cardiac, digestive system, neurological, or combined disorders. The most serious manifestation of the disease is Chagasic cardiomyopathy (Two pharmacological agents have been available for the treatment of The current standard criterion for cure involves the conversion of serological response to negative as measured by at least two different types of conventional serological assay, such as enzyme-linked immunosorbent assay (ELISA), indirect hemagglutination assay (IHA), or indirect immunofluorescence assay (We evaluated the changes in serological profile in pediatric patients with acute or chronic Chagas disease following treatment with a new formulation of nifurtimox for 60 days. Patients were enrolled in a prospective, historically controlled, phase III clinical trial: the | PMC10112190 |
RESULTS | PMC10112190 |
|||
Patient demographics and characteristics. | Of the 330 pediatric patients randomized and treated with nifurtimox in CHICO study (Demographic and patient characteristics at baseline (full analysis set)Age was defined as the patient's age at the time of randomization in CHICO ( | PMC10112190 |
||
Duration of observation. | The median duration of observation, defined as the actual number of years an individual was at risk during the study, was 4.0 years for patients in both treatment groups (Duration of observation (full analysis set)Duration of observation was the actual number of years a patient was at risk in the study, i.e., the time from when a patient was randomized in the study until they were confirmed as having seroconversion, withdrawn from the study, used antitrypanosomal therapy, or completed the study, whichever was the earliest. The duration of observation has been rounded to the nearest integer.One patient initiated treatment with benznidazole <0.5 years after randomization.IQR, interquartile range. | PMC10112190 |
||
Seronegative conversion. | During the 4-year posttreatment follow-up, seronegative conversion was observed in a total of 16 (8.12%) and 8 (8.16%) patients in the 60-day and 30-day nifurtimox regimens, respectively (Number and incidence rate of seronegative conversion with nifurtimox treatment (full analysis set)Total duration of observation is the estimated actual number of years at risk for all patients who contributed to the study.The incidence rate was the number of new cases of seronegative conversion during the study period (i.e., 4 years after the end of nifurtimox treatment) divided by the patient-time at risk. It was modeled using a Poisson distribution with a two-sided 95% exact CI.CI, confidence interval.Overall, the number of new cases with seronegative conversion increased during the posttreatment follow-up. In the 60-day regimen, seronegative conversion, measured and confirmed by two types of assays (recombinant ELISA and IHA), was observed for the first time in 7 (3.55%), 3 (1.52%), 3 (1.52%), and 3 (1.52%) patients at the 1-, 2-, 3-, and 4-year posttreatment follow-up, respectively. The first observation of seronegative conversion in the 30-day nifurtimox regimen group at the corresponding follow-up time points was documented in 4 (4.08%), 1 (1.02%), 2 (2.04%), and 1 (1.02%) patients, respectively (Kaplan–Meier curves of seronegative conversion in patients receiving 60-day or 30-day nifurtimox treatment regimens (full analysis set, In an exploratory analysis of serological response by age group, the highest number of seronegative conversions occurred in those aged 2 years or younger. In this age group, seronegative conversion was observed in 13 of 30 patients (43.33%) in the 60-day regimen and 7 of 13 patients (53.85%) in the 30-day regimen, with corresponding incidence rates of 14.61 100 patients/year (95% CI: 7.78–24.98 100 patients/year) and 18.92 100 patients/year (95% CI: 7.61–38.98 100 patients/year), respectively (Seronegative conversion measured by two types of assay (recombinant ELISA and IHA) according to age 4 years after the end of nifurtimox treatment (full analysis set)Total duration of observation is the estimated actual number of years at risk for all patients who contributed to the study.The incidence rate was the number of new cases of seronegative conversion during the study period (i.e., 4 years after the end of nifurtimox treatment) divided by the patient-time at risk. It was modeled using a Poisson distribution with a two-sided 95% exact CI. Negative results for both recombinant enzyme-linked immunosorbent assay (ELISA) and indirect hemagglutination assay (IHA) were required for the patient to be considered to have achieved seronegative conversion. | PMC10112190 |
||
Seroreduction. | Optical density (OD) values measured by conventional ELISAs decreased over time in both treatment regimens during the study. At the 4-year posttreatment follow-up, the reduction in mean OD values from baseline was 23.72% and 18.68% by recombinant ELISA, and 23.81% and 19.08% by total purified antigen ELISA in the 60-day and 30-day treatment regimens, respectively. In Kaplan–Meier analyses that generated probability estimates for ≥20% to 100% seroreduction in OD values from baseline measured by two conventional ELISAs (recombinant ELISA and total purified antigen ELISA), a progressive reduction was seen in both treatment groups. At the 4-year follow-up, ≥20% to 100% seroreduction of around 50% and 40% was observed in the 60- and 30-day treatment regimen groups, respectively (Kaplan–Meier curves of ≥20% to 100% seroreduction in patients receiving 60-day or 30-day nifurtimox treatment regimens (full analysis set, Kaplan–Meier curves of ≥20% to 100% seroreduction by age in patients receiving (a) 60-day and (b) 30-day nifurtimox treatment regimens (full analysis set, | PMC10112190 |
||
Serological response and Chagas disease-related cardiomyopathy. | cardiomyopathy | CHAGAS, CARDIOMYOPATHY | More than 90% of patients in both treatment groups showed successive negative Parasitological response of patients according to follow-up visit (full analysis set), measured by quantitative PCRData shown are No patients showed signs of established Chagas disease-related cardiomyopathy as measured by electrocardiogram (ECG) in the 60- or 30-day treatment groups at any of the posttreatment follow-up visits. | PMC10112190 |
Safety. | The safety of the nifurtimox regimens during treatment and at the 1-year follow-up has been reported previously ( | PMC10112190 |
||
DISCUSSION | Chagas disease, chronic Chagas disease | CHAGAS DISEASE, CHRONIC INFECTION, CHRONIC CHAGAS DISEASE | Establishing the efficacy of antitrypanosomal therapy in patients with Chagas disease using the currently accepted criterion of treatment response is challenging. In Chagas disease, it is widely acknowledged that treatment success is difficult to measure with the current diagnostic tools because the parasites are highly antigenic and produce a strong antibody response that persists even after successful antiparasitic treatment (In this study, we evaluated seronegative conversion in pediatric patients with Chagas disease followed over a period of 4 years posttreatment. The results confirm the effectiveness and safety of nifurtimox administered over 60 days in pediatric patients, from newborn to 17 years of age, with Chagas disease. The superior seronegative conversion attributable to the 60-day nifurtimox treatment regimen compared with historical placebo control that was demonstrated at 12 months after the end of treatment (Conversion of serological response to negative measured by conventional serological testing remains the gold standard for monitoring the posttherapeutic response in Chagas disease (The previously reported results of the first year of posttreatment follow-up in this prospective trial (Up to two-thirds of people with Chagas disease never develop signs or symptoms, even during the chronic infection phase (No AEs considered at least possibly related to nifurtimox treatment or caused by procedures required by the protocol were reported during the further 3 years of observation that followed CHICO (The main limitation of this study is the lack of a prospective untreated control group, which would not have been ethical to include because the current standard of care is the treatment of all infected children. The primary outcomes of treatment were compared with an estimated 0% seronegative conversion rate from historical placebo data obtained from a previously published clinical trial in 6- to 12-year-old children with early chronic Chagas disease treated with benznidazole and followed for 4 years ( | PMC10112190 |
Conclusions. | Chagas disease | CHAGAS DISEASE | This study confirms the efficacy and safety of a pediatric formulation of nifurtimox administered in an age- and weight-adjusted regimen for 60 days to treat Chagas disease in pediatric patients with 4-year follow-up data. Children younger than 2 years treated with nifurtimox are more likely to show seronegative conversion than older children during a relatively short posttreatment follow-up observation. Reduction of ELISA OD values and consecutive negative | PMC10112190 |
MATERIALS AND METHODS | PMC10112190 |
|||
Ethics statement. | Approval from the ethics committee was obtained for all participating research sites, as described above ( | PMC10112190 |
||
Study design. | This was a prospective, randomized, blinded, historically controlled, parallel-group, long-term follow-up study (Study design and schedule of follow-up visits. The schedule of study visits V1 to V10 are as previously reported ( | PMC10112190 |
||
Study participants. | This study included patients who were randomized to treatment and received at least one dose of their assigned treatment with nifurtimox. Prior to enrollment, written informed consent was obtained from the patient and/or their parents or legally authorized representative(s) according to age and local regulations. Depending on their age, patient assent was also obtained if required by locally applicable laws and regulations in each country. Patients were considered to have completed the study if they completed the 4-year posttreatment follow-up ( | PMC10112190 |
||
Outcome measures. | cardiomyopathy | CHAGAS, CARDIOMYOPATHY | The primary outcome was the incidence rate of seronegative conversion measured and confirmed by recombinant ELISA (Secondary outcomes investigated included: the incidence rate of seronegative conversion confirmed by recombinant ELISA and IHA in patients who were randomized and received at least one dose of nifurtimox in the 30-day treatment regimen; the proportion of responders who showed seronegative conversion by two types of assay and no evidence of established Chagas disease-related cardiomyopathy measured by ECG; and seroreduction (as reduction of ELISA OD) measured by recombinant ELISA and total purified antigen ELISA.Exploratory analyses performed included the incidence rate of seroconversion by age at randomization according to the following age groups: ≤2 years, 3 to ≤6 years, 7 to ≤12 years, and 13 to <18 years.Safety evaluations included the occurrence of AEs considered possibly related to nifurtimox treatment, AEs caused by protocol-required procedures, physical examination abnormalities, cardiac assessment by 12-lead ECG, and assessment of vital signs. | PMC10112190 |
Follow-up assessments. | CHAGAS DISEASE | At annual follow-up visits, patients underwent a physical examination, including measurements of height, weight, and vital signs. Body mass index, treatment-related AEs, and AEs caused by procedures required by the protocol were also recorded. In addition, a standard 12-lead ECG was performed at the discretion of the investigator, and details of any concomitant medications were recorded. Intermediate follow-up visits were conducted by telephone approximately 6 months after the 2- and 3-year follow-up visits to identify any potential clinical symptoms of Chagas disease. During these two intermediate visits, qualified staff interviewed patients and/or their legally authorized parents or representatives. In case of suspected findings, an unscheduled visit to the research site was requested to initiate appropriate diagnostic evaluations. | PMC10112190 |
|
Serological tests. | BLOOD | Blood samples for | PMC10112190 |
|
Parasitological tests. | BLOOD | Blood was also collected for qPCR tests to detect the presence of | PMC10112190 |
|
Statistical analyses. | cardiomyopathy | CARDIOMYOPATHY | In the primary outcome analysis, the difference in the incidence rate of patients treated with nifurtimox with seronegative conversion (60-day regimen) and the estimated seronegative rate from a historical placebo control group was tested using a Poisson two-sided 95% exact CI. The historical control group comprised children 6 to 12 years of age and seropositive for Recombinant ELISA OD values and total purified antigen ELISA were analyzed descriptively. The changes from baseline were summarized to show any serial reductions in OD values. Baseline was defined as the OD values of the same ELISAs measured at visit 1. The number of patients who showed seronegative conversion and no evidence of established cardiomyopathy was calculated overall and by treatment regimen. Baseline, efficacy, and safety analyses were performed using the full analysis set, based on patient randomization and treatment. | PMC10112190 |
Data availability. | The authors confirm that all data underlying the findings are fully available without restriction. All data files are available from the | PMC10112190 |
||
ACKNOWLEDGMENTS | We thank the study participants and their families. The CHICO SECURE Study Group members are listed in the supplemental material. We sincerely thank LAT Research, Buenos Aires, Argentina, for excellent support in conducting the study. We also wish to thank the laboratory of Stamboulian Health Services, Buenos Aires, Argentina, for technical assistance in the analyses of patient samples. We acknowledge Highfield Communication, Oxford, United Kingdom, funded by Bayer AG, for medical writing and editorial support.J.A. acted as a consultant to Bayer for the design, conduct and review of the CHICO and CHICO SECURE studies. U.G. is an employee of Bayer AG (Berlin, Germany). E.H. is an employee of Bayer US LLC (Whippany, New Jersey, USA). G.M. received personal fees from Bayer during the conduct of the study. O.D. is an employee of Bayer Healthcare Co., Ltd. (Shanghai, China).V.S., T.R., and J.J.P.R. have no conflicts of interest to disclose.Supplemental material is available online only.
Supplemental material. Download | PMC10112190 |
||
REFERENCES | PMC10112190 |
|||
Key Points | PMC10403785 |
|||
Question | depressive disorder, MDD | CORTEX | Is antidepressant treatment associated with volumetric and resting-state functional connectivity (rsFC) changes over time in the dorsolateral prefrontal cortex (DLPFC) in adolescents with major depressive disorder (MDD)? | PMC10403785 |
Findings | MDD, depressive | In this cohort study of 95 adolescents with MDD and 57 healthy control participants, responders with at least 40% depressive symptom improvement showed increased right DLPFC volume, decreased bilateral DLPFC rsFC with the superior frontal gyri, and decreased left DLPFC rsFC with the ventromedial PFC after treatment compared with before treatment. | PMC10403785 |
|
Meaning | depressive disorder, depressive | CORTEX | These findings suggest that DLPFC volumetric and rsFC changes after treatment may represent one set of potential neurobiological treatment markers that are associated with depressive symptom improvement in adolescents with MDD.This cohort study examines neurobiological changes associated with selective serotonin reuptake inhibitor treatment in adolescents in Korea with major depressive disorder by evaluating longitudinal changes in volume and resting-state functional connectivity in the dorsolateral prefrontal cortex. | PMC10403785 |
Importance | depression | Selective serotonin reuptake inhibitors (SSRIs) are considered a first-line pharmacological treatment for adolescent depression with moderate or higher levels of symptom severity. Thus, it is important to understand neurobiological changes related to SSRIs during the course of treatment for adolescents with depression. | PMC10403785 |
|
Objective | depressive disorder, MDD | CORTEX | To examine neurobiological changes associated with SSRI treatment in adolescents with major depressive disorder (MDD) by measuring longitudinal changes in volume and resting-state functional connectivity (rsFC) in the dorsolateral prefrontal cortex (DLPFC), a core region of cognitive control. | PMC10403785 |
Design, Setting, and Participants | MDD | This cohort study was conducted with an open-label design. Adolescents with MDD and healthy controls were recruited at the Seoul National University Hospital (Seoul, South Korea). Adolescents with MDD were treated with escitalopram for 8 weeks. Data analysis was conducted between April 2021 and February 2022. | PMC10403785 |
|
Main Outcomes and Measures | Depressive, Depression, depressive symptoms | Depressive symptoms were assessed using the Children’s Depression Rating Scale–Revised. The outcome measure was defined as the change in Children’s Depression Rating Scale–Revised scores from week 0 (before treatment) to week 8 (after treatment) or upon termination. Participants completed structural and resting-state functional magnetic resonance imaging (rsfMRI) assessments before (week 0) and after (week 8) SSRI treatment. Repeated measures analysis of variance and liner mixed model analyses were used to examine the longitudinal associations of SSRI treatment with DLPFC volume and rsFC between responders who showed at least a 40% decrease in depressive symptoms and nonresponders who did not. | PMC10403785 |
|
Results | MDD | Ninety-five adolescents with MDD and 57 healthy controls were initially recruited. The final analyses of volume included 36 responders (mean [SD] age, 15.0 [1.6] years; 25 girls [69.4%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). Analyses of rsFC included 33 responders (mean [SD] age, 15.2 [1.5] years; 21 girls [63.6%]) and 26 nonresponders (mean [SD] age, 15.3 [1.5] years; 19 girls [73.1%]). The longitudinal associations of SSRI treatment were more evident in responders than in nonresponders. Responders showed significantly increased right DLPFC volume, decreased bilateral DLPFC rsFC with the superior frontal gyri, and decreased left DLPFC rsFC with the ventromedial PFC after treatment compared with before treatment. Furthermore, increased right DLPFC volume was correlated with decreased rsFC between the right DLPFC and superior frontal gyri after SSRI treatment. | PMC10403785 |
|
Conclusions and Relevance | MDD | The preliminary results of this cohort study suggest that the DLPFC volumetric and rsFC changes may serve as potential neurobiological treatment markers that are associated with symptom improvement in adolescents with MDD. | PMC10403785 |
|
Introduction | MDD, depression, depressive, adolescence | PATHOPHYSIOLOGY | Antidepressants are widely used to treat depression in adolescents. Selective serotonin reuptake inhibitors (SSRIs) are known to be the most frequently prescribed antidepressantsThe literature suggests that neurobiological markers associated with the pathophysiology of depression can be targets for depression treatment.Previous studies have demonstrated that SSRI treatment is associated with structural and functional changes in the DLPFC, in adults with MDD. For example, after a 12-week SSRI treatment, adults with depression showed increases in the DLPFC gray matter volume, which, in turn, were associated with greater depressive symptom improvement.Despite such supportive findings, more research is needed to improve our understanding of the role of changes in DLPFC volume and activity as potential biomarkers for SSRI treatment. There are several reasons for further research. First, relatively little is known about neurobiological changes following SSRI treatment in adolescents with MDD. Given that adolescence is a developmental period with great importance of cognitive control and emotion regulation development and the protracted prefrontal development,Thus, we aimed to examine longitudinal DLPFC volume and rsFC changes associated with SSRI treatment in adolescents with MDD. Given the possibility of a bidirectional association between structural and functional alterations in depression, | PMC10403785 |
Methods | PMC10403785 |
|||
Participants | MDD | Adolescents aged 12 to 17 years were recruited by the Seoul National University Hospital. Adolescents with MDD were included if they had a current diagnosis of MDD according to the | PMC10403785 |
|
SSRI Treatment Procedures | MDD | All adolescents with MDD were treated with escitalopram in an 8-week, open-label trial. | PMC10403785 |
|
Depressive Symptom Assessment | depression, Depressive, Depression | Depressive symptoms were assessed using the Children’s Depression Rating Scale–Revised (CDRS-R), which is used to evaluate depression severity in children and adolescents. | PMC10403785 |
|
Structural MRI and rsfMRI Acquisition | T1-weighted structural MRI (sMRI) and rsfMRI data were collected using a 3-T scanner (Trio; Siemens Healthineers). T1-weighted images were obtained using a T1-weighted, 3-dimensional gradient-echo pulse sequence with magnetization-prepared rapid gradient-echo sequencing. The rsfMRI data were acquired with interleaved T2*-weighted echo planar imaging. Details of sMRI and rsfMRI data acquisition are described in eAppendix 1 in | PMC10403785 |
||
sMRI and rsfMRI Preprocessing | T1 and rsfMRI data were preprocessed using FreeSurfer imaging software version 6.0 (Harvard University) and Analysis of Functional NeuroImages imaging software version 21.3.09 (National Institute of Mental Health), respectively. Details of sMRI and rsfMRI data preprocessing and all analytical methods are described in eAppendix 1 in | PMC10403785 |
||
Examples of Dorsolateral Prefrontal Cortex (DLPFC) Seed Regions Segmented by FreeSurfer | Images show segmented DLPFC seed regions of 3 separate patients. | PMC10403785 |
||
Statistical Analysis | We calculated the volumes of the DLPFC seed regions. The extracted DLPFC volumes were exported to SPSS software version 25.0 (SPSS, Inc). We examined whether DLPFC volumes would differ between responders and nonresponders over time (week 0 vs week 8). We also extracted the average time series from the DLPFC seed region and used it to conduct seed-based voxelwise connectivity analyses. Seed-based voxelwise connectivity analyses created each individual’s whole brain correlation map, which contains | PMC10403785 |
||
Results | PMC10403785 |
|||
Demographic and Clinical Characteristics | MDD | A total of 152 adolescents, including 95 adolescents with MDD and 57 healthy controls, were initially recruited (eTable 1 in | PMC10403785 |
|
Longitudinal Changes (Before vs After Treatment) by SSRI Treatment in Adolescents With MDD | PMC10403785 |
|||
DLPFC Volumes | We found a significant group (responders vs nonresponders) by time (week 0 vs week 8) interaction in the right DLPFC volume, controlling for intracranial volume ( | PMC10403785 |
||
rsFC: DLPFC Seed-Based Analysis | Group by time interactions were found on the right DLPFC rsFC with the left superior frontal gyrus (SFG) and left middle frontal gyrus (MFG) (eTable 3 in | PMC10403785 |
||
Correlations Between DLPFC Volumetric Changes and DLPFC rsFC Changes After vs Before SSRI Treatment | Given the significant longitudinal associations of SSRI treatment with volume and rsFC in the right DLPFC, we investigated how volumetric changes (week 8 minus week 0) in the right DLPFC were associated with changes in DLPFC rsFC, with 6 regions reported in eTable 3 in | PMC10403785 |
||
Correlation Between the Right Dorsolateral Prefrontal Cortex (DLPFC) Volume Change and DLPFC–Left Superior Frontal Gyrus (SFG) Resting-State Functional Connectivity (rsFC) Change in Adolescents With Major Depressive Disorder | A greater increase in the right DLPFC volume was significantly correlated with a greater reduction in rsFC between the right DLPFC and left SFG. | PMC10403785 |
||
Discussion | MDD, depression | PATHOPHYSIOLOGY | To the best of our knowledge, this cohort study is one of the first to investigate neurobiological treatment markers after SSRI treatment that are associated with clinical symptom improvement in adolescents with MDD. We also examined the associations between neurobiological treatment markers, such as DLPFC volume and DLPFC rsFC. First, we found significant longitudinal associations of SSRI treatment with DLPFC volume and rsFC. Compared with nonresponders, responders showed increases in the gray matter volume of the right DLPFC, decreases in DLPFC rsFC with the prefrontal regions involved in cognitive control (eg, the left SFG and MFG), and decreases in rsFC between the left DLPFC and prefrontal regions involved in self-referential processing (eg, the VMPFC). Furthermore, increased right DLPFC volume after treatment was associated with decreased rsFC between the right DLPFC and left SFG.As hypothesized, the longitudinal associations of SSRI treatment with both DLPFC volume and rsFC were more pronounced in responders than nonresponders. First, the right DLPFC volume increased after SSRI treatment in responders, but not in nonresponders. This result is in line with a previous longitudinal studySecond, compared with nonresponders, responders showed significantly reduced rsFC between the right DLPFC and left prefrontal regions (ie, the left SFG and MFG) and between the left DLPFC and right prefrontal regions (ie, the right SFG) over the course of treatment. Elevated rsFCs within the prefrontal regions of cognitive control have been found in adults with MDD.Responders also showed greater reductions in rsFC between the left DLPFC and VMPFC, and between the left DLPFC and anterior temporal regions, compared with nonresponders over time. The VMPFC and anterior temporal regions are known to be responsible for self-referential processing. Therefore, reduced rsFC in the left DLPFC with the VMPFC and anterior temporal regions after SSRI treatment may indicate decreased communications between these regions in responders. Hyperconnectivity between the cognitive control regions and self-referential regions of the brain has been shown in depressionWe found some novel results. There was a significant negative correlation between right DLPFC volume change and right DLPFC–left SFG rsFC change after SSRI treatment. Although structural and functional alterations are known to be associated with the pathophysiology and recovery of depression, the association of structural with functional changes in depression remains largely unknown. Structural alterations could lead to altered functional connectivity or vice versa in depression. | PMC10403785 |
Limitations | MDD, trauma | This study has some limitations. First, this study was conducted with an open-label design, which made it difficult to disentangle the effects of SSRI treatment from the effects of nonspecific factors (eg, expectation of improvement or knowledge of treatment). Second, this study treated all adolescents with MDD with 1 SSRI, escitalopram, which further limited the generalizability of our findings across different classes of SSRIs. However, using 1 SSRI for treatment may also have some benefits by excluding possible confounding effects, which may be caused by different SSRIs. Third, given that several factors, including specific symptoms and abuse or trauma history, could alter the effects of SSRI treatment, we did not test the potential moderation because of the lack of available data. Fourth, given the significant baseline difference in right DLPFC–left SFG rsFC between responders and nonresponders, the significant change of this rsFC in responders may be associated with the baseline difference, indicating the potential role of baseline differences in examining longitudinal associations of treatment with rsFC. Fifth, for rsFC analysis, we applied a seed-based approach, which has some advantages, such as a straightforward interpretation of the findings. However, this approach has some limitations, and future research should use a large-scale network analysis approach. | PMC10403785 |
|
Conclusions | MDD | This study found longitudinal associations of SSRI treatments with both volume and rsFC in the DLPFC of adolescents with MDD using a relatively large sample. More significant longitudinal changes in the DLPFC volume and rsFC in responders may be potential treatment markers of neural plasticity that can mediate the effects of SSRI treatment or be modulated by the beneficial effects of SSRI treatment. Therefore, our findings, while preliminary, underscored the importance of the DLPFC volumetric and rsFC changes as potential neurobiological treatment markers that are associated with symptom improvement in adolescents with MDD. | PMC10403785 |
|
Background | SECONDARY | Serum albumin concentrations are frequently used to monitor nutritional therapy in the hospital setting but supporting studies are largely lacking. Within this secondary analysis of a randomized nutritional trial (EFFORT), we assessed whether nutritional support affects short-term changes in serum albumin concentrations and whether an increase in albumin concentration has prognostic implications regarding clinical outcome and response to treatment. | PMC10564620 |
|
Methods | We analyzed patients with available serum albumin concentrations at baseline and day 7 included in EFFORT, a Swiss-wide multicenter randomized clinical trial that compared individualized nutritional therapy with usual hospital food (control group). | PMC10564620 |
||
Results | SD | Albumin concentrations increased in 320 of 763 (41.9%) included patients (mean age 73.3 years (SD ± 12.9), 53.6% males) with no difference between patients receiving nutritional support and controls. Compared with patients that showed a decrease in albumin concentrations over 7 days, those with an increase had a lower 180-day mortality [74/320 (23.1%) | PMC10564620 |
|
Conclusion | inflammation | INFLAMMATION, SECONDARY | Results from this secondary analysis indicate that nutritional support did not increase short-term concentrations of albumin over 7 days, and changes in albumin did not correlate with response to nutritional interventions. However, an increase in albumin concentrations possibly mirroring resolution of inflammation was associated with better clinical outcomes. Repeated in-hospital albumin measurements in the short-term is, thus, not indicated for monitoring of patients receiving nutritional support but provides prognostic information. | PMC10564620 |
Trail Registration | ClinicalTrials.gov Identifier: NCT02517476. | PMC10564620 |
||
Subject terms | PMC10564620 |
|||
Introduction | Malnutrition, Frailty | MALNOURISHED, MALNUTRITION, NUTRITIONAL DEFICIENCIES | Historically, serum albumin concentration was considered to be a marker of nutritional status and physicians monitored albumin concentrations in patients during their hospital stay. This assumption was based on the pathophysiological grounds that albumin concentration reflects circulating proteins in plasma, with lower concentrations indicating nutritional deficiencies [Malnutrition is a common condition among medical inpatients, with a prevalence of about 30%, and is associated with increased mortality, morbidity, disability, and higher health care costs [Herein, we tested the hypothesis that nutritional support influences short-term changes in serum albumin concentrations in medical inpatients and that these changes would correlate with medical outcomes and response to nutritional support in patients included in the Effect of early nutritional therapy on Frailty, Functional Outcomes, and Recovery on malnourished medical inpatients Trial (EFFORT) [ | PMC10564620 |
Material & Methods | PMC10564620 |
|||
Study design and setting | SECONDARY | This is a secondary analysis of EFFORT [ | PMC10564620 |
|
Patient population and management | NRS | DISEASE | EFFORT enrolled adult ( ≥ 18 years of age) medical inpatients at nutritional risk with an anticipated hospital stay of at least 5 days who were willing to give informed consent within the first 48 hours after admission. Nutritional risk was defined as a Nutritional Risk Screening (NRS 2002) score of 3 points or more. The NRS 2002 consists of two parts: the patient’s current nutritional status and the severity of the underlying disease. Both parts score from 0 (absent) to 3 (severe) with an extra point for age ≥ 70 years. An total score of 3 or more points indicates “nutritionally at risk” and additional nutritional support should be considered [ | PMC10564620 |
Research objective and outcomes | gastrointestinal failure | GASTROINTESTINAL FAILURE, RESPIRATORY FAILURE, EVENT, ACUTE RENAL FAILURE, NOSOCOMIAL INFECTION, COMPLICATIONS | We had three main goals for this analysis: first, to investigate how nutritional therapy impacts on the short-term changes in serum albumin concentrations from baseline to 7 days in the overall population and within subgroups of patients with high and low baseline albumin concentrations ( < 30 g/L or ≥ 30 g/L) [Our primary endpoint for the prognostic analyses was long-term all-cause mortality measured over 180 days, while for the response to nutritional support we focused on short-term 30-day mortality. Secondary endpoints where adverse outcome within 30 days (composite endpoint consisting of all-cause mortality, admission to the intensive care unit from medical ward, major complications (nosocomial infection, respiratory failure, major cardiovascular event, acute renal failure, gastrointestinal failure), nonelective hospital readmission after discharge, decline in functional status ≥10% measured by Barthel’s index), length of hospital stay, loss of function according to Barthel’s index (score ranging from 0 to 100 with lower scores indicating worse functional status) and quality of life measured by 5-level European Quality of life 5 Dimensions index (EQ5D) including the self-assessment visual analogue scale (VAS). Detailed information for the single endpoints and their composites is summarized in the Supplement. We defined treatment response as the difference in outcomes among control group and intervention group patients, similar to the initial EFFORT trial. | PMC10564620 |
Statistical analyses | Continuous variables are shown as means and standard deviation. Categorical and binary data are expressed as counts and percentages. Baseline characteristics were compared between patients with an increase in albumin and without an increase in albumin after 7 days using Pearson’s χ | PMC10564620 |
||
Results | PMC10564620 |
|||
Patient population | From the 2088 participants of the initial trial, we had complete data on 763 patients regarding baseline and day 7 albumin concentration and all clinical outcomes (Fig. | PMC10564620 |
||
Survival of patients according to increase or decrease in albumin levels over 7 days. | Kaplan–Meier estimate for 180-days mortality for increase and decrease in serum albumin from baseline to day 7. | PMC10564620 |
||
Effect of nutritional intervention in association with kinetics of serum albumin levels | Last, we evaluated whether the effectiveness of nutritional support concerning 30-day mortality in the intervention group and control group would differ according to changes in albumin concentrations. The mortality benefit of nutritional support was independent of changes in albumin concentrations in the overall population (p interaction 0.327), and also when stratified by albumin concentrations (Fig. | PMC10564620 |
||
Forest plot for 30-days mortality, Effect of nutritional intervention depending on kinetics of serum albumin concentrations. | OR Odds ratio, 95% CI Confidence interval. | PMC10564620 |
||
Discussion | ACUTE DISEASE, SECONDARY, DISEASE | In this secondary post-hoc analysis of a randomized clinical trial, we investigated first whether nutritional support affects short-term changes in serum albumin concentrations among medical inpatients at nutritional risk, and second, whether an increase in albumin concentrations has prognostic implications regarding clinical outcome and treatment response. We found that 42% of patients in our study population had an increase in albumin concentrations from baseline to day 7 and, compared with usual hospital food, nutritional support was not associated with a more pronounced increase in albumin concentrations. The changes in serum albumin concentrations, however, provided prognostic information, and mortality and length of hospital stay were significantly lower in patients with an increase in albumin concentration compared with those with decrease. Finally, patients with and without increase in albumin concentrations had a similar treatment response to the nutritional intervention and monitoring of albumin from baseline to day 7 was, thus, not helpful for predicting response to nutritional support.These findings are largely in line with a recent statement by the American Society for Parenteral and Enteral Nutrition (ASPEN) stating that “visceral proteins have not been shown to be sensitive markers of energy and protein intake adequacy and therefore should not be a guide for therapeutic changes.” [While nutritional intervention did not show differences in albumin concentrations in the overall population suggesting that nutritional support had little effect on the short-term changes in serum albumin concentrations over one week, there were some significant effects in the subgroup of patients in participants with a high Interestingly, most patients in our study showed an absolute decrease in serum albumin concentrations in the short-term follow-up over 7 days. We assume that this was due to the acute disease of our patients with an increase in catabolism and the fact that human serum albumin has a half-life of about 19 days [We are aware of several strengths and limitations. To our knowledge, this analysis is among the first and maybe the most comprehensive study to look at changes in serum albumin concentrations in a large population of medical patients from a previous randomized trial with detailed information about nutritional intake and the resolution of the disease. In the 1980s Winkler et al. [ | PMC10564620 |
|
Conclusion | inflammation | INFLAMMATION, SECONDARY | Results from this secondary analysis including medical inpatients at nutritional risk indicate that nutritional support did not increase concentrations of albumin within 7 days, and changes in serum albumin concentrations did not correlate with treatment response to nutritional interventions. However, an increase in albumin concentrations possibly mirroring resolution of inflammation was associated with better clinical outcomes. Repeated in-hospital albumin measurements in the short-term is, thus, not indicated for monitoring of patients receiving nutritional support but provides prognostic information. | PMC10564620 |
Supplementary information | The online version contains supplementary material available at 10.1038/s41430-023-01303-w. | PMC10564620 |
||
Acknowledgements | We thank all patients and hospital staff for their support of our trial. | PMC10564620 |
||
Author contributions | SECONDARY | FB and PS were responsible for the data analysis and interpretation of the present secondary analysis. FB, DNL, and PS drafted the final manuscript and all authors contributed to the critical revision of the manuscript. PS was responsible for obtaining funding. PS, ZS, and BM were involved in obtaining funding, drafting the trial protocol, supervising study sites, drafting the final manuscript of the original EFFORT trial and approving the final version of the current manuscript. The corresponding authors had full access to all the data used and shared the final responsibility for the accuracy of the analyzed data. All authors were involved in data collection and/or interpretation and approved the final version of the manuscript. | PMC10564620 |
|
Funding | The initial trial was supported by grants from the Swiss National Science Foundation to PS and the Research Council of Kantonsspital Aarau, Switzerland. Unrelated to this trial, Nestlé Health Science and Abbott Nutrition previously provided unrestricted grant money to the institution of PS; The institution of ZS received speaking honorariums and research support from Nestlé Health Science, Abbott Nutrition, and Fresenius Kabi. All other authors report no conflicts of interest. Open access funding provided by University of Basel. | PMC10564620 |
||
Data availability | SECONDARY | We intend to make data collected for the study, including anonymized individual participant data and a data dictionary defining each field in the set, available to others. Related documents will be available, including the trial protocol and the statistical analysis plan. These data will be available with the publication of our main manuscript and all secondary projects as outlined in our trial protocol on receipt of a letter of intention detailing the study hypothesis and statistical analysis plan. The steering committee of this trial will discuss all requests and decide on the basis of the scientific rigor of the proposal whether data sharing is appropriate. All applicants are asked to sign a data access agreement. Please send any request to the principal investigator of this trial. | PMC10564620 |
|
Competing interests | The authors declare no competing interests. | PMC10564620 |
||
References | PMC10564620 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.