title stringlengths 1 1.19k | keywords stringlengths 0 668 | concept stringlengths 0 909 | paragraph stringlengths 0 61.8k | PMID stringlengths 10 11 |
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Declarations | PMC10731819 | |||
Ethics approval and consent to participate | The study protocol was approved by the Service Provider for the Education Sector (SIKT, reference 305866). Study permission was obtained from the head of the nursing study program at the Department of Health and Nursing Sciences at the University of Agder, the Faculty Ethics Committee at the University of Agder, the he... | PMC10731819 | ||
Consent for publication | Not applicable. | PMC10731819 | ||
Competing interests | The authors declare no competing interests. | PMC10731819 | ||
References | PMC10731819 | |||
Subject terms | Parkinson’s disease, PD | NEURODEGENERATIVE DISORDERS | Nicotinamide adenine dinucleotide (NAD) replenishment therapy using nicotinamide riboside (NR) shows promise for Parkinson’s disease (PD) and other neurodegenerative disorders. However, the optimal dose of NR remains unknown, and doses exceeding 2000 mg daily have not been tested in humans. To evaluate the safety of hi... | PMC10684646 |
Introduction | Parkinson’s disease, PD, neurological disorders | ADVERSE EVENTS, ADVERSE EFFECTS, MOVEMENT DISORDER, DISEASES, NEUROLOGICAL DISORDERS | Parkinson’s disease (PD) affects 1–2% of the population over 65 years, and is one of the fastest growing neurological disorders worldwideIncreasing cellular levels of nicotinamide adenine dinucleotide (NAD) has been proposed as a potential neuroprotective therapeutic strategy for neurodegenerationNAD levels decline wit... | PMC10684646 |
Results | PMC10684646 | |||
Study population | PD | In total, 26 individuals with PD were screened, and 20 eligible participants were enrolled, all of whom completed the study (Fig. | PMC10684646 | |
High dose NR treatment augments the NAD metabolome | Next, we explored the effect of 3000 mg NR daily on the NAD metabolome in blood and urine. First, flash frozen whole blood samples were analyzed for NAD | PMC10684646 | ||
High dose NR treatment is not associated with depletion of the methyl group pool | One re-occurring concern in the literature is that NAD precursor supplementation may lead to methyl group depletion due to an increased elimination of Nam by methylation | PMC10684646 | ||
Discussion | toxicity, PD, neurological and non-neurological diseases | ADVERSE EVENTS | Our study met its primary outcome and established that orally administered NR at a dose of 3000 mg daily is well tolerated in PD over a course of 4 weeks. NR-recipients developed no moderate or severe adverse events. Furthermore, there were no mild adverse events likely attributed to NR, and no other clinical or bioche... | PMC10684646 |
Overview of NAD metabolism in interaction with methyl-group metabolism. | PD, SAH, SAH S-adenosyl homocysteine | The figure shows various routes of NAD biosynthesis, and examples of NAD degradation leading to Nam production. If not recycled, Nam is methylated to Me-Nam, in a reaction catalyzed by NNMT and requiring SAM as methyl-group donor. The other product of this reaction, SAH, is further converted to HCy, and subsequently re... | PMC10684646 | |
Methods | PMC10684646 | |||
Participants and study design | idiopathic PD | This study design was a phase I, single-center, randomized, double-blinded, placebo-controlled trial, aiming to provide initial evidence of safety and tolerability for NR at a dose of 3000 mg daily. The trial was conducted at the Department of Neurology, Haukeland University Hospital, Norway, from the 29.04.22 to the 0... | PMC10684646 | |
Randomization and masking | 20 participants (5 female and 15 male) were randomly allocated to receive either 1500 mg NR twice daily or placebo for 4 weeks (number of blocks: 2, block size 4, allocation: 1:1), using the electronic Case Report Form ( | PMC10684646 | ||
Primary outcome | ADVERSE EVENTS | The primary outcome was the safety of 3000 mg NR daily for 4 weeks, defined as the absence of clinically significant, NR-associated moderate or severe adverse events. | PMC10684646 | |
Secondary outcomes | PD | ADVERSE EVENTS, SECONDARY | The secondary outcomes were the incidence of treatment-associated mild adverse events, treatment-associated changes in the NAD metabolome in blood and urine, and the change in the overall clinical severity of PD, measured by total MDS-UPDRS. | PMC10684646 |
Procedures | Parkinson’s disease, movement disorder | ADVERSE EVENT, ADVERSE EVENTS, ADVERSE EVENT, MOVEMENT DISORDER, MOVEMENT DISORDER | At screening for trial entry, candidates underwent physical and neurological examination. Enrolled participants were assessed by physical visits by a movement disorder specialist at baseline (visit 1, V1), day 7 (V4), day 14 (V5), day 21 (V6) and day 28 (V7). At baseline and day 28 participants underwent additional ass... | PMC10684646 |
Clinical laboratory values | Analysis of clinical laboratory values from blood samples was performed by the Department of Medical Biochemistry and Pharmacology (MBF) at Haukeland University Hospital, Bergen, Norway. | PMC10684646 | ||
NAD and glutathione metabolite analysis from frozen blood | Analysis was carried out by NADMed (Helsinki, Finland; | PMC10684646 | ||
LC-MS analysis from whole blood and urine | Sample analysis was carried out by MS-Omics (Vedbæk, Denmark).Blood sample extraction was carried out by combining 100 µl whole blood with 900 µl ice-cold extraction solvent (Methanol/Acetonitrile/MQW – 10:6:4 fortified with stable isotope internal standards (Supplementary Data Urine sample extraction was carried out b... | PMC10684646 | ||
Statistical analysis | Data normality was tested by the Shapiro–Wilk test. The majority of variables in the dataset were normally distributed (Supplementary Data | PMC10684646 | ||
Reporting summary | Further information on research design is available in the | PMC10684646 | ||
Supplementary information |
Peer Review FileDescription of Additional Supplementary FilesSupplementary Data 1Supplementary Data 2Supplementary Data 3Supplementary Data 4Supplementary Data 5Supplementary Data 6Supplementary Data 7Reporting Summary | PMC10684646 | ||
Supplementary information | The online version contains supplementary material available at 10.1038/s41467-023-43514-6. | PMC10684646 | ||
Acknowledgements | We are deeply grateful to the patients involved in the study. We are grateful to study coordinator Ingunn Anundskås, and thank our technical laboratory staff, Martina Castelli, Sepideh Mostafavi, Yana Mikhaleva, Hanne Linda Nakkestad, and Gry Hilde Nilsen, for excellent technical assistance. We thank Prof Mathias Ziegl... | PMC10684646 | ||
Author contributions | H.B.: participated in the study conception and design, recruited and assessed study participants, collected, analyzed and interpreted data, and drafted the manuscript. S.K., G.O.S., K.H., E.S., M.S., S.A.G.: recruited and assessed study participants, and collected and interpreted data. C.D.: participated in study conce... | PMC10684646 | ||
Peer review | PMC10684646 | |||
Funding | Open access funding provided by University of Bergen. | PMC10684646 | ||
Data availability | NADMed | The vital signs, MDS-UPDRS and NADMed analysis data required to reproduce the results presented in this manuscript have been deposited in the Neuromics Group repository | PMC10684646 | |
Code availability | The code required to reproduce the results presented in this manuscript have been deposited in the Neuromics Group repository | PMC10684646 | ||
Competing interests | Parkinson’s disease | International patent applications relating to the use of nicotinamide riboside as a treatment for Parkinson’s disease have been filed by the Technology Transfer Office “Vestlandets Innovasjonsselskap As (VIS)” on behalf of Haukeland University Hospital, Bergen, Norway, with publication authors C.T. and C.D. as inventor... | PMC10684646 | |
References | PMC10684646 | |||
1. Introduction | Diabetes, vascular complications, diabetes | VASCULAR COMPLICATIONS, METABOLIC DISORDER, DISORDERS, DIABETES, OXIDATIVE STRESS, PATHOGENESIS, DIABETES | Reactive α-dicarbonyls (α-DCs), such as methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG), are potent precursors in the formation of advanced glycation end products (AGEs). In particular, MGO and MGO-derived AGEs are thought to be involved in the development of vascular complications in diabetes. Experimen... | PMC10488144 |
3. Materials and Methods | PMC10488144 | |||
3.1. Study Population and Design | The study was conducted from June 2018 to January 2019 and was approved by the local Medical Ethics Committee of the Maastricht University Medical Centre + and performed in accordance with the Declaration of Helsinki of 1975, as amended in 2013, and with the Dutch Regulations on Medical Research involving Human Subject... | PMC10488144 | ||
3.2. Treatment and Placebo | The treatment was 500 mg | PMC10488144 | ||
3.3. Measurement of α-Dicarbonyls in Plasma | Fasting blood samples were collected into Heparin S-Monovette tubes (Sarstedt, Nümbrecht, Germany). Before analysis, all plasma samples stored at −80 °C were thawed and mixed thoroughly. The concentration of α-dicarbonyls in plasma samples was measured with ultra-performance liquid chromatography tandem mass spectromet... | PMC10488144 | ||
3.4. Instrumentation | A Waters Acquity I-class system combined with a Xevo TQ-XS mass spectrometer (Waters, Milford, MA, USA) equipped with a reversed-phase C18 column (Acquity UPLC HSS T3, 50 × 2.1 mm, 1.8 μm) was employed for the determination of α-dicarbonyl concentrations. | PMC10488144 | ||
3.5. Statistical Analysis | Statistical analyses were carried out according to a method previously described by Dower et al. [ | PMC10488144 | ||
Author Contributions | Conceptualization, C.G.S.; data curation, J.L.J.M.S. and K.B.; formal analysis, J.L.J.M.S. and K.B.; methodology, C.G.S. and S.A.; supervision, C.G.S., J.L.J.M.S. and I.F.; visualization, K.B., J.L.J.M.S. and I.F.; writing—original draft, K.B.; writing—review and editing, J.L.J.M.S., C.G.S., P.V., S.A. and I.F. All aut... | PMC10488144 | ||
Institutional Review Board Statement | The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of the Maastricht University Medical Centre+ (protocol code NCT03781999 approved by EC on 14 February 2018). | PMC10488144 | ||
Informed Consent Statement | Informed consent was obtained from all subjects involved in the study. | PMC10488144 | ||
Data Availability Statement | The data presented in this study are available on request from the corresponding author. | PMC10488144 | ||
Conflicts of Interest | S.A. receives a salary from BioActor BV. The other authors declare no conflict of interest. | PMC10488144 | ||
Abbreviations | PMC10488144 | |||
1. Introduction | brachial plexus block, nausea and vomiting, postoperative pain | ADVERSE EFFECTS, MINOR, POSTOPERATIVE COMPLICATIONS | To explore the early clinical value of enhanced recovery after surgery (ERAS) with interscalene brachial plexus block (ISB) for arthroscopic rotator cuff repair (ARCR). We enrolled 240 patients who underwent arthroscopic rotator cuff repair, randomly divided into 3 groups (n = 80 each). Groups A, B, and C underwent onl... | PMC10637507 |
2. Materials and methods | PMC10637507 | |||
2.1. Patient selection and general information | epilepsy, shoulder fracture, peripheral neurological diseases | GROUP B, EPILEPSY | This study enrolled patients with rotor cuff repair, treated in our joint and sports medicine department between April 2022 and April 2023. The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Li Huili Hospital affiliated with Ningbo University (KY2023... | PMC10637507 |
2.2. Treatment modalities | PMC10637507 | |||
2.2.1. Surgery. | All ARCR surgeries were performed by a senior chief physician. After achieving anesthesia, thorough disinfection, and draping, the affected limb was abducted and flexed in the anterior direction in preparation for suspension traction using the standard posterior approach for routine repair. | PMC10637507 | ||
2.2.2. Routine perioperative management. | pain | Before the operation, patients were routinely instructed not to take pain medications, to fast for 8 hours, and to not drink water for 6 hours prior to surgery in order to ensure accuracy of the experimental study. The lavage fluid was maintained at room temperature, and the volume was not controlled. Interventions wer... | PMC10637507 | |
2.2.3. ERAS perioperative management. | diabetes, blood glucose, insomnia, anxiety, pain | HYPERTENSION, CAVITY, COLD, POSTOPERATIVE COMPLICATIONS | Prior to the operation, the attending physician, anesthesiologist, rehabilitation physician, and the nurse-in-charge communicated with each patient in detail. This team comprehensively assessed physiological, psychological, mental, and nutritional status, and informed the patient about measures specific to ERAS, postop... | PMC10637507 |
2.2.4. Interscalene brachial plexus block. | ISB was performed under ultrasound guidance. After the puncture needle reached the target location under ultrasound guidance, 0.5 µg/kg dexmedetomidine compounded with 0.5% ropivacaine 15 to 20 mL was injected. The efficacy of the block was tested, and general anesthesia was induced after successful completion of the b... | PMC10637507 | ||
2.3. Outcome indicators | postoperative joint stiffness, pain | SECONDARY, HAND SWELLING | The primary outcome was pain intensity, measured using the VAS score, measured at 0–6, 6–24, and 24–48 hours postoperatively. LOS, 1- and 3-month Constant-Murley shoulder scores (CMS), University of California-Los Angeles (UCLA) shoulder scores, and incidence of postoperative joint stiffness and swelling in the 3 group... | PMC10637507 |
2.4. Statistical analysis | Data were analyzed using SPSS v. 25.0 (IBM, Armonk, NY). Continuous variables were expressed as the mean ± standard deviation and categorical variables were expressed as number of cases. After determining whether the data conformed to a normal distribution, normally distributed continuous variables were analyzed by one... | PMC10637507 | ||
3. Results | PMC10637507 | |||
3.1. Primary outcome | VAS scores were compared as the primary outcome. Results at 0–6 and 6–24 hours postoperatively exhibited differences between the 3 groups (Comparison of VAS scores among the 3 groups at different time points. VAS = Visual Analog Scale. | PMC10637507 | ||
3.2. Secondary outcomes | PMC10637507 | |||
3.2.1. Length of hospital stay. | A significant difference in the LOS was found among the 3 groups (Comparison of LOS among the 3 groups. LOS = length of hospital stay. | PMC10637507 | ||
3.2.2. CMS and UCLA scores. | The preoperative shoulder function scores did not significantly differ among the 3 groups. However, at 6 weeks and 3 months postoperatively, the scores of Groups B and C were better than those of Group A (Comparison of CMS among the 3 groups at different time points. CMS = Constant-Murley shoulder score.Comparison of U... | PMC10637507 | ||
3.2.3. Postoperative complications. | postoperative stiffness | POSTOPERATIVE COMPLICATIONS | The incidence of postoperative stiffness did not significantly differ among the 3 groups (Comparison of incidence of postoperative complications among the 3 groups. | PMC10637507 |
4. Discussion | Postoperative pain, shoulder stiffness, Shoulder swelling, pain | COMPLICATIONS | Shoulder surgery involves multiple muscles and ligaments. Patients undergoing ARCR experience more pain after surgery than those who undergo other shoulder arthroscopy procedures.The concept of perioperative ERAS was introduced by Danish surgeon Henrik Kehlet in 1990.Nerve block techniques modify the generation of resp... | PMC10637507 |
5. Conclusion | postoperative shoulder swelling, pain | We found that the combination of ERAS and ISB eliminates pain in the early postoperative period following ARCR, reduces LOS, and decreases the incidence of postoperative shoulder swelling. However, the effect on early postoperative functional recovery is similar. | PMC10637507 | |
Acknowledgments | We would like to thank Editage ( | PMC10637507 | ||
Abbreviations: | arthroscopic rotator cuff repairConstant-Murley shoulder scoreenhanced recovery after surgerygeneral anesthesiainterscalene brachial plexus blocklength of hospital stayUniversity of California-Los Angeles scoresVisual Analog ScaleThe study was conducted in accordance with the Declaration of Helsinki, and approved by th... | PMC10637507 | ||
References | PMC10637507 | |||
Abstract | PMC10626224 | |||
Background | As the outcome of immunotherapy can be improved when concurrently or sequentially combined with cytotoxic chemotherapy or radiotherapy, we investigated the efficacy of immunotherapy maintenance following platinum‐based chemotherapy in epidermal growth factor receptor ( | PMC10626224 | ||
Methods | In this prospective, open‐label, single arm phase 2 trial, we enrolled patients aged 18 years or older with | PMC10626224 | ||
Results | tumor | MAY, DISEASE, TUMOR | We enrolled 26 patients between May 2020 and July 2021. The median PFS was 1.7 months (95% CI: 0.401–2.999 months). The median OS was 21.4 months (95% CI: 18.790–24.010 months) with 6‐ and 12‐month OS rates of 96.2% and 76.9%, respectively. The objective response rate was 7.7% (2/26) and disease control rate, 11.5% (3/... | PMC10626224 |
Conclusion | Nivolumab maintenance following platinum‐based chemotherapy did not show clinical benefits after EGFR‐TKI failure in patients with Immunotherapy in patients with
| PMC10626224 | ||
INTRODUCTION | cancer death, Lung cancer | LUNG CANCER | Lung cancer is the leading cause of cancer death worldwide,Several studies have shown that the response rate can be improved when immunotherapy is administered concurrently or sequentially with cytotoxic chemotherapy or radiotherapy.Recently, we encountered some
| PMC10626224 |
METHODS | PMC10626224 | |||
Study design and participants | This was a prospective, open‐label, single center, single‐arm, phase 2 trial performed at Asan Medical Center, Seoul, Republic of Korea. Eligible patients were aged at least 18 years with a pathologically proven diagnosis of The study was conducted in accordance with the principles of the Declaration of Helsinki and th... | PMC10626224 | ||
Procedures | EGFR‐TKI failure, tumor, Tumor, Cancer | DISEASE PROGRESSION, ADVERSE EVENT, TUMOR, TUMOR, BLOOD, CANCER | The patients received platinum‐based chemotherapy followed by nivolumab maintenance therapy after EGFR‐TKI failure (Figure Imaging assessments, including computed tomography or magnetic resonance imaging, of the brain were performed every 6 weeks (±7 days) for 6 months, and then every 12 weeks (±14 days) until disease ... | PMC10626224 |
Outcomes | death | TUMOR PROGRESSION | The primary endpoint was progression‐free survival (PFS), which was defined as the time from the day nivolumab was initiated until objective tumor progression or death. Secondary endpoints were the objective response rate (ORR) and overall survival (OS), which were also calculated from the initiation of nivolumab. The ... | PMC10626224 |
Statistical analysis | tumor | DISEASE, TUMOR | Continuous variables are described in mean (standard deviation) and median (IQR) values. Categorical variables are described as frequencies using counts and percentages. We used the Kaplan–Meier method to estimate PFS and OS and corresponding 95% CIs. For PFS, patients whose disease condition did not progress were cens... | PMC10626224 |
RESULTS | PMC10626224 | |||
Patient characteristics | death, tumor | ONCOLOGY, TUMOR, DISEASE CHARACTERISTIC | We enrolled 26 patients between January 2020 and December 2021, of whom one withdrew their consent during the study. The patient demographics and characteristics are shown in Table Baseline patient demographics and disease characteristics.Abbreviations: CCRT, concurrent chemoradiation therapy; ECOG PS, Eastern Cooperat... | PMC10626224 |
Efficacy | death, SD, tumor | LUNG CANCER, DISEASE, SOLID TUMORS, TUMOR | The median follow‐up duration was 1.9 months (range, 1.3–4.3 months). According to the investigator assessment, partial response (PR) was achieved in two patients (7.7%), and stable disease (SD) was exhibited in one (3.8%), with no complete response (Table Overall efficacy of nivolumab maintenance therapy following pla... | PMC10626224 |
Safety | ADVERSE EVENTS | AEs were reported by 13 (50.0%) patients. Treatment‐related AEs were mainly grade 1 or 2. Five (19.2%) patients had grade 3–4 AEs and two (7.7%), serious AEs (SAEs). The most common grade 3–4 AEs were laboratory abnormalities, especially increased alanine aminotransferase (7.7%) (Table Treatment‐related adverse events ... | PMC10626224 | |
DISCUSSION | nonsquamous NSCLC | ADVERSE EVENTS | It is well‐known that immunotherapy in Despite the negative impact of However, this phase 2 study failed to show any improvement in outcomes compared with previous studies on second‐line cytotoxic chemotherapy following EGFR‐TKI. In an open‐label phase 3 study called CheckMate‐057, patients with nonsquamous NSCLC that ... | PMC10626224 |
AUTHOR CONTRIBUTIONS | Conceptualization: Chang‐Min Choi, Wonjun Ji, Jae Cheol Lee. Data curation: Jiwon Kim, Chang‐Min Choi, Wonjun Ji, Jae Cheol Lee. Formal analysis: Jiwon Kim, Wonjun Ji. Funding acquisition: Jae Cheol Lee. Investigation: Chang‐Min Choi, Wonjun Ji, Jae Cheol Lee. Methodology: Wonjun Ji, Jae Cheol Lee. Validation: Chang‐Mi... | PMC10626224 | ||
CONFLICT OF INTEREST STATEMENT | The authors have no conflicts of interest to declare. The funders had no role in the design of this study, data collection, data analyses, data interpretation, writing of the manuscript, or the decision to publish the results. | PMC10626224 | ||
Supporting information |
Click here for additional data file.
Click here for additional data file.
Click here for additional data file. | PMC10626224 | ||
ACKNOWLEDGMENTS | This research was supported by the Ono pharmaceutical company. | PMC10626224 | ||
REFERENCES | PMC10626224 | |||
1. Introduction | oral cancer, Cancer | CANCER, ORAL CANCER, ORAL SQUAMOUS CELL CARCINOMA | Background: Areca nut and betel quid (ANBQ) chewing is a widespread carcinogenic habit. The BENIT (ClinicalTrials—NCT02942745) is the first known randomized trial designed for ANBQ chewers. Methods: We compared the intensive behavioral treatment intervention condition (IC) with the control condition (CC) in the BENIT a... | PMC10454381 |
2. Materials and Methods | PMC10454381 | |||
2.1. Study Design | The study design of BENIT was described in detail previously [ | PMC10454381 | ||
2.2. Target Population, Inclusion/Exclusion Criteria, and Recruitment | Cancer | EVENTS, RECRUITMENT, CANCER | BENIT was conducted exclusively with Class 2 chewers residing in Guam and Saipan. Thus, all participants added tobacco to their BQ. This inclusion criterion was due to: (1) previous research that revealed a preponderance of Class 2 chewers in these locations [Inclusion criteria were: (1) self-identified chewer of ANBQ ... | PMC10454381 |
2.3. Sample Size and Early Termination Plan | The target sample size for BENIT was 324, which was based on a difference of 13 percentage points between intervention and control for ANBQ chewing cessation prevalence at 22 days with α = 0.05 (2-sided) and β = 0.20. However, an early termination plan was developed to accommodate the possibility of stronger-than-expec... | PMC10454381 | ||
2.4. Randomization | BENIT participants were randomized to each treatment condition within each island [ | PMC10454381 | ||
2.5. Control Condition Procedures | Participants in the control condition received a single booklet created specifically for BENIT and designed to encourage and facilitate ANBQ cessation. The booklet, entitled “Quitting Betel Nut”, included information about the health risks associated with ANBQ chewing as well as advice and strategies for quitting and m... | PMC10454381 | ||
2.6. Intervention Condition Procedures | SESSION | The BENIT intervention followed the general framework of intensive cognitive-behavioral therapy [The intervention was comprised of five in-person sessions over a 22-day period. The BENIT program’s structure was such that participants were expected to attempt to quit chewing ANBQ at Session 3 (Day 15). Thus, Sessions 1 ... | PMC10454381 | |
2.7. Baseline Assessments | Baseline survey assessments included questions on demographics, current chewing behavior, chewing history, ANBQ dependence measured by the Betel Quid Dependence Scale (BQDS) [ | PMC10454381 | ||
2.8. Follow-Up Assessments | Betel quid chewer” | SESSION | The first follow-up assessment was administered at the final intervention session (Session 5). This assessment was scheduled for approximately 22 days after the first intervention session. Participants in this assessment provided data regarding their experience with the BENIT program and their chewing and quitting beha... | PMC10454381 |
2.9. Statistical Analysis | REGRESSION | Participant characteristics were compared between randomization groups. A proportional hazards regression model of the time until cessation was fit using the randomization group as the independent variable, with and without adjustment for factors found to be out of balance between groups. The Wald test using a robust v... | PMC10454381 |
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