GRU-powered sleep stage classification with permutation-based EEG channel selection.

We present a new approach to classifying the sleep stage that incorporates a computationally inexpensive method based on permutations for channel selection and takes advantage of deep learning power, specifically the gated recurrent unit (GRU) model, along with other deep learning methods. By systematically permuting the electroencephalographic (EEG) channels, different combinations of EEG channels are evaluated to identify the most informative subset for the classification of the 5-class sleep stage. For analysis, we used an EEG dataset that was collected at the International Institute for Integrative Sleep Medicine (WPI-IIIS) at the University of Tsukuba in Japan. The results of these explorations provide many new insights such as the (1) drastic decrease in performance when channels are fewer than 3, (2) 3-random channels selected by permutation provide the same or better prediction than the 3 channels recommended by the American Academy of Sleep Medicine (AASM), (3) N1 class suffers the most in prediction accuracy as the channels drop from 128 to 3 random or 3 AASM, and (4) no single channel provides acceptable levels of accuracy in the prediction of 5 classes. The results obtained show the GRU's ability to retain essential temporal information from EEG data, which allows capturing the underlying patterns associated with each sleep stage effectively. Using permutation-based channel selection, we enhance or at least maintain as high model efficiency as when using high-density EEG, incorporating only the most informative EEG channels.

Molecular microbiological profiling of bottled unsweetened tea beverages: a screening experiment.

To explore the potential storage and safety of drinking leftover bottled tea beverages from various manufacturers after direct drinking from bottles, we conducted a screening experiment on the growth of salivary bacteria in plastic bottles of tea. The diluted saliva samples from 10 participants were inoculated into the test bottled beverages, which resulted in bacteria, particularly former members of the genus Lactobacillus, growing in some green tea beverages with a neutral pH. In contrast, tea beverages with less bacterial growth contained Streptococcus spp., and the leftovers may be safe to store and drink again.

Clinical Evaluation of the Accuracy of the Panbio™ COVID-19/Flu A&B Rapid Panel: A Combination Antigen Rapid Diagnostic Test for the Omicron Variant and Influenza A Virus.

It is difficult to differentiate between coronavirus disease 2019 (COVID-19) and influenza based on the symptoms. In the present study, a newly developed antigen rapid diagnostic test (Ag-RDT) called Panbio™ COVID-19/Flu A&B that can simultaneously detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A/B virus was evaluated. Its accuracy was evaluated using 235 pairs of nasopharyngeal samples collected from patients with respiratory symptoms and fever (>37.5°C). Reverse transcription polymerase chain reaction was used as a reference method to evaluate the accuracy of the SARS-CoV-2 detection. We confirmed the accuracy of the developed Ag-RDT against the Omicron variant where the sensitivity and specificity were 94.8% and 100%, respectively. In addition, to identify the influenza A virus, a noninferiority test was conducted using a commercial Ag-RDT, which has a sensitivity and specificity in comparison with viral culture of 94.8% and 98.4%, respectively. The positive and negative predictive values for influenza A virus were 98.5% and 98.1%, respectively, for the Panbio COVID-19/Flu A&B test. The evaluation of this newly developed Ag-RDT using clinical samples suggests that it has a high efficacy in clinical settings.

Structural-model-based genome mining can efficiently discover novel non-canonical terpene synthases hidden in genomes of diverse species.

Non-canonical terpene synthases (TPSs) with primary sequences that are unrecognizable as canonical TPSs have evaded detection by conventional genome mining. This study aimed to prove that novel non-canonical TPSs can be efficiently discovered from proteins, hidden in genome databases, predicted to have 3D structures similar to those of class I TPSs. Six types of non-canonical TPS candidates were detected using this search strategy from 268 genome sequences from actinomycetes. Functional analyses of these candidates revealed that at least three types were novel non-canonical TPSs. We propose classifying the non-canonical TPSs as classes ID, IE, and IF. A hypothetical protein MBB6373681 from Pseudonocardia eucalypti (PeuTPS) was selected as a representative example of class ID TPSs and characterized. PeuTPS was identified as a diterpene synthase that forms a 6/6/6-fused tricyclic gersemiane skeleton. Analyses of PeuTPS variants revealed that amino acid residues within new motifs [D(N/D), ND, and RXXKD] located close to the class I active site in the 3D structure were essential for enzymatic activity. The homologs of non-canonical TPSs found in this study exist in bacteria as well as in fungi, protists, and plants, and the PeuTPS gene is not located near terpene biosynthetic genes in the genome. Therefore, structural-model-based genome mining is an efficient strategy to search for novel non-canonical TPSs that are independent of biological species and biosynthetic gene clusters and will contribute to expanding the structural diversity of terpenoids.

Messenger RNA transcription levels of neuronal soluble N-ethylmaleimide-sensitive factor attachment protein receptor complex components in the olfactory nerve system of the anadromous Pacific salmon, masu salmon Oncorhynchus masou.

Anadromous Pacific salmon (genus Oncorhynchus) are known for homing behavior to their natal rivers based on olfactory imprinted memories during seaward migration. The SNARE complex is a regulator of vesicle exocytosis from the presynaptic membrane. Our previous study suggested that its component genes (Snap25, Stx1, and Vamp2) are more highly expressed in the olfactory nervous system (ONS) during the migration stages associated with olfactory imprinting in the evolutionary species of Pacific salmon, such as chum (O. keta) and pink (O. gorbuscha) salmon. Masu salmon (O. masou) has a significantly different life history from these species, living longer in rivers and being a more primitive Pacific salmon species. In this study, the transcription of snare mRNAs in the ONS was analyzed using mainly male wild masu salmon. Five cDNAs encoding masu salmon SNAREs, which are well conserved among vertebrates, were isolated and sequenced. Each snare mRNA was highly expressed in age 1+ (yearling) parr prior to smoltification, particularly in the olfactory bulb. Their transcription status was significantly different from that of chum and pink salmon, which showed high expression in earlier under-yearling juveniles. The present results and our previous studies indicate that snare mRNAs are highly transcripted until the seaward migration, reflecting neural development and neuroplasticity of the ONS for olfactory imprinting.

Tracking handgrip strength in Kendo athletes from university to middle and older adulthood.

OBJECTIVE: This study aimed to compare the current handgrip strength (HGS) of Kendo athletes with their HGS when they were in university (up to 50 years). METHODS: Eighty male graduates who were Kendo club members during their university days performed anthropometric and HGS measurements, and these HGS were compared with those measured during their university days (mean age of 19.5 years old). RESULTS: There was no evidence of a statistical difference in HGS between the current measurement and the measurement taken during university [-0.64 (-1.9, 0.67) kg, p = .336]. There was, however, evidence that the difference in HGS depended upon the current age of the individual (t = -6.43, p < .001). When probing the interaction, there were statistical differences between the ages of 24.6 and 38.2 years and between the ages of 47.4 and 69.9 years. Strength increased across time in the younger participants and decreased for those who were older. Between the ages of 38.9 and 46.1 years, there was no evidence of a statistical difference indicating a maintenance of strength. CONCLUSION: The HGS of Kendo club graduates, which they acquired during their formative years, continued to increase even after they graduated from university and entered their 30s. However, their HGS decreased from age 50, even though they practiced Kendo.

Molecular insights and the role of 18F-FDG-PET/CT in the diagnosis of spinal gliomas.

BACKGROUND: In recent years, molecular findings on spinal gliomas have become increasingly important. This study aimed to investigate the role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in the diagnosis of spinal glioma. METHODS: This study included patients diagnosed with spinal cord glioma who underwent 18F-FDG-PET examination at the Department of Neurosurgery, Nagoya University Hospital between January 2016 and November 2023. The gliomas were divided into two groups, high-grade and low-grade, based on pathological and molecular studies. The maximum standardized uptake values (SUVmax) of the tumors were quantified and subsequently represented using receiver operating characteristic (ROC) curves. RESULTS: Eighteen participants were included in this study. Of the participants, seven had high-grade glioma with an SUVmax of 6.76 ± 0.72, and eleven had low-grade glioma with an SUVmax of 4.02 ± 1.78, and a statistically significant difference between the two groups. The ROC curve delineated an SUVmax cutoff value of 5.650, with an area under the curve (AUC) of approximately 0.909. Based on the cutoff value, the results of the diagnostic performance rendered a sensitivity and negative predictive value of 1.0, whereas the specificity and positive predictive value were 0.909 and 0.875, respectively. CONCLUSIONS: The present study shows that 18F-FDG-PET exhibits a markedly sensitive and negative predictive value in the assessment of spinal gliomas. Additionally, these findings have potential implications for the qualitative assessment of spinal gliomas using 18F-FDG-PET/CT. This imaging modality may be useful for making timely treatment decisions in situations where a detailed diagnosis by molecular analysis is not possible.

Hyperglycemic Clamp and Hypoglycemic Clamp in Conscious Mice.

Diabetes mellitus (DM) is caused by insufficient insulin release from the pancreatic ß-cells (Type1 DM) and insulin sensitivity in muscles, liver, and adipose tissues (Type2 DM). Insulin injection treats DM patients but leads to hypoglycemia as a side effect. Cortisol and catecholamines are released to activate glucose production from the liver to recover hypoglycemia, called counter-regulatory responses (CRR). In DM research using rodent models, glucose tolerance tests and 2-deoxy-glucose injection are used to measure insulin release and CRR, respectively. However, blood glucose concentrations change persistently during experiments, causing difficulties in assessing net insulin release and CRR. This article describes a method in which blood glucose is kept at 250 mg/dL or 50 mg/dL in conscious mice to compare the release of insulin and CRR hormones, respectively. Polyethylene tubing is implanted in the mice's carotid artery and jugular vein, and the mice are allowed to recover from the surgery. The jugular vein tubing is connected to a Hamilton syringe with a syringe pump to enable insulin or glucose infusion at a constant and variable rate. The carotid artery tubing is for blood collection. For the hyperglycemic clamp, 30% glucose is infused into the vein, and blood glucose levels are measured from the arterial blood every 5 min or 10 min. The infusion rate of 30% glucose is increased until the blood glucose level becomes 250 mg/dL. Blood is collected to measure insulin concentrations. For hypoglycemic clamp, 10 mU/kg/min insulin is infused together with 30% glucose, whose infusion rate is variable to maintain 50 mg/dL of blood glucose level. Blood is collected to measure counter-regulatory hormones when both glucose infusion and blood glucose reach a steady state. Both hyperglycemic and hypoglycemic clamps have the same surgical procedure and experimental setups. Thus, this method is useful for researchers of systemic glucose metabolism.

Protective Mechanism of Stem Cells from Human Exfoliated Deciduous Teeth in Treating Spinal Cord Injury.

Spinal cord injury (SCI) induces devastating permanent deficits. Recently, cell transplantation therapy has become a notable treatment for SCI. Although stem cells from human exfoliated deciduous teeth (SHED) are an attractive therapy, their precise mechanism of action remains to be elucidated. In this study, we explored one of the neuroprotective mechanisms of SHED treatment at the subacute stage after SCI. We used a rat clip compression SCI model. The animals were randomly divided into three groups: SCI, SCI + phosphate-buffered saline (PBS), and SCI + SHED. The SHED or PBS intramedullary injection was administered immediately after SCI. After SCI, we explored the effects of SHED on motor function, as assessed by the Basso-Beattie-Bresnahan score and the inclined plane method, the signal transduction pathway, especially the Janus kinase (JAK) and the signal transducer and activator of transcription 3 (STAT3) pathway, the apoptotic pathway, and the expression of neurocan, one of the chondroitin sulfate proteoglycans. SHED treatment significantly improved functional recovery from Day 14 relative to the controls. Western blot analysis showed that SHED significantly reduced the expression of glial fibrillary acidic protein (GFAP) and phosphorylated STAT3 (p-STAT3) at Tyr705 on Day 10 but not on Day 5. However, SHED had no effect on the expression levels of Iba-1 on Days 5 or 10. Immunohistochemistry revealed that p-STAT3 at Tyr705 was mainly expressed in GFAP-positive astrocytes on Day 10 after SCI, and its expression was reduced by administration of SHED. Moreover, SHED treatment significantly induced expression of cleaved caspase 3 in GFAP-positive astrocytes only in the epicenter lesions on Day 10 after SCI but not on Day 5. The expression of neurocan was also significantly reduced by SHED injection on Day 10 after SCI. Our results show that SHED plays an important role in reducing astrogliosis and glial scar formation between Days 5 and 10 after SCI, possibly via apoptosis of astrocytes, ultimately resulting in improvement in neurological functions thereafter. Our data revealed one of the neuroprotective mechanisms of SHED at the subacute stage after SCI, which improved functional recovery after SCI, a serious condition.

Skeletal muscle mass in competitive physique-based athletes (bodybuilding, 212 bodybuilding, bikini, and physique divisions): A case series.

OBJECTIVES: (1) To examine the muscle thickness of various muscle groups of the body to estimate the absolute and relative skeletal muscle mass (SM) in competitive physique-based athletes (Bodybuilding, 212 Bodybuilding, Bikini, and Physique divisions) and (2) to compare values across various divisions of competition and to resistance trained and non-resistance trained individuals. METHODS: Eight competitive physique-based athletes (2 M and 6 F), two recreationally resistance trained (1 M and 1 F) and two non-resistance trained (1 M and 1 F) participants had muscle thickness measured by ultrasound at nine sites on the anterior and posterior aspects of the body. SM was estimated from an ultrasound-derived prediction equation and SM index was used to adjust for the influence of standing height (i.e., divided by height squared). RESULTS: SM values ranged from 19.6 to 60.4 kg in the eight competitive physique-based athletes and 16.1 to 32.6 kg in the four recreationally resistance trained and non-resistance trained participants. SM index ranged from 7.2 to 17.9 kg/m2 in the eight competitive physique-based athletes and 5.8 to 9.3 kg/m2 in the four recreationally resistance trained and non-resistance trained participants. CONCLUSION: Overall, varying magnitudes of SM and SM index were present across competitors and their respective divisions of bodybuilding. The Men's Open Bodybuilder in the present study had greater values of total SM and SM index compared to previously published values in the literature. Our data provides insight into the extent of SM present in this population and further extends the discussion regarding SM accumulation in humans.

Handgrip strength of young athletes differs based on the type of sport played and age.

OBJECTIVE: Handgrip strength may differ depending on the type of sport played during the developmental period. Youth sports in which athletes hold equipment in their hands may be the most effective for improving handgrip strength. This study aimed to examine the age at which differences in handgrip strength appear by comparing sports that involve gripping (kendo) with those that do not involve gripping (soccer) in young athletes. METHODS: Two hundred and twenty-two male athletes (115 kendo and 107 soccer) between 6 and 15 years old participated in this study. Handgrip strength was measured using a dynamometer, and the average value of both hands was used for analysis. Sports experience was determined when they started practicing each sport. Handgrip strength was compared between sports. Statistical moderation was used to determine if the relationship between sport and handgrip strength depended upon the age of the athlete. RESULTS: Kendo athletes had significantly higher handgrip strength than soccer athletes (4.77 kg [95% CI: 2.34, 7.19]) in the overall sample. We found that the relationship between sport and handgrip strength depended upon the age of the child (sport*age t = -3.6, p = .004). Using the Johnson-Neyman procedure, we found statistically significant differences between sports from 8.48 years and older. CONCLUSIONS: Our results suggest that the type of sport played, that is, whether or not an athlete plays with sports equipment in their hands, may influence the development of handgrip strength during the period of growth, and these sports may contribute to a higher level of handgrip strength in adulthood.

Usefulness of AI-Equipped Endoscopy for Detecting Colorectal Adenoma during Colonoscopy Screening: Confirm That Colon Neoplasm Finely Can Be Identified by AI without Overlooking Study (Confidential Study).

In the present prospective case series study, we investigated the lesion-detection ability of an AI-equipped colonoscopy as an addition to colonoscopy (CS) screening. Participants were 100 patients aged ≥20 years who had not undergone CS at the study site in the last 3 years and passed the exclusion criteria. CS procedures were conducted using conventional white light imaging and computer-aided detection (CADe). Adenoma detection rate (ADR; number of individuals with at least one adenoma detected) was compared between the conventional group and the CADe group. Of the 170 lesions identified, the ADR of the CADe group was significantly higher than the ADR of the conventional group (69% vs. 61%, p = 0.008). For the expert endoscopists, although ADR did not differ significantly, the mean number of detected adenomas per procedure (MAP) was significantly higher in the CADe group than in the conventional group (1.7 vs. 1.45, p = 0.034). For non-expert endoscopists, ADR and MAP were significantly higher in the CADe group than in the conventional group (ADR 69.5% vs. 56.6%, p = 0.016; MAP 1.66 vs. 1.11, p < 0.001). These results indicate that the CADe function in CS screening has a positive effect on adenoma detection, especially for non-experts.

SARS-CoV-2 HaploGraph: visualization of SARS-CoV-2 haplotype spread in Japan.

Since the early phase of the coronavirus disease 2019 (COVID-19) pandemic, a number of research institutes have been sequencing and sharing high-quality severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes to trace the route of infection in Japan. To provide insight into the spread of COVID-19, we developed a web platform named SARS-CoV-2 HaploGraph to visualize the emergence timing and geographical transmission of SARS-CoV-2 haplotypes. Using data from the GISAID EpiCoV database as of June 4, 2022, we created a haplotype naming system by determining the ancestral haplotype for each epidemic wave and showed prefecture- or region-specific haplotypes in each of four waves in Japan. The SARS-CoV-2 HaploGraph allows for interactive tracking of virus evolution and of geographical prevalence of haplotypes, and aids in developing effective public health control strategies during the global pandemic. The code and the data used for this study are publicly available at: https://github.com/ktym/covid19/.

Efficacy of Spinal Cord Stimulation Using Differential Target Multiplexed Stimulation for Intractable Pain of Hereditary Neuropathy with Liability to Pressure Palsies: A Case Report.

Hereditary neuropathy with liability to pressure palsies is an extremely rare genetic disorder; it is an autosomal dominant disorder with a high incidence of neuropathic and/or musculoskeletal pain. A case of achieving pain relief by spinal cord stimulation using differential target multiplexed stimulation for a 44-year-old female patient with hereditary neuropathy with liability to pressure palsies who was experiencing severe pain in her back, face, and all four limbs is presented. In her early teens, the initial symptoms were numbness and weakness of a limb after movement, which improved spontaneously. Transient pain in her back followed by systemic and persistent muscle weakness and pain developed. Deletion of the gene for peripheral myelin protein 22 was detected by peripheral nerve biopsy. The diagnosis of hereditary neuropathy with liability to pressure palsies was made in her early thirties. A spinal cord stimulation trial was performed because her severe pain continued despite administering many medications. Therefore, two spinal cord stimulation systems were implanted at the C3-5 and Th8-9 levels by two procedures. Pain in her back, arms, and legs decreased from 8 to 1, 5 to 1, and 6 to 2 on the numerical rating scale, respectively. Furthermore, opioid usage was tapered. The pain of hereditary neuropathy with liability to pressure palsies has a complicated pathogenesis and is resistant to pharmacological treatment. Spinal cord stimulation using differential target multiplexed stimulation may be a viable treatment option.

One-Year Handgrip Strength Change in Kindergarteners Depends upon Physical Activity Status.

Free play in kindergarten can be roughly divided into fine and gross motor activities, but the effects of these activities on improving handgrip strength are unknown. Therefore, we aimed to compare one-year changes in handgrip strength and forearm flexor muscle size in children separated by preferred play in a kindergarten. One hundred and eleven children were recruited from a local kindergarten. They underwent handgrip strength and forearm muscle thickness measurements, and 95 (49 boys and 46 girls) underwent a second measurement one year after the first measurement. Class teachers assessed the physical activity of everyone in their class after the second measurement. Using three evaluation scores by the class teachers, we divided children into three groups based on the children's preference to play in kindergarten (fine movement vs. gross motor movement). Handgrip strength did not change differently between groups across one year. However, children who liked active playing outside (i.e., gross motor activity) were stronger than others. Furthermore, children who like playing outside observed greater changes than the other groups in the ulna (right hand) and radius muscle thickness (left hand), suggesting that changes in forearm muscle size might be incongruent with changes in handgrip strength among the three activity groups.

Unilateral high-load resistance training influences strength changes in the contralateral arm undergoing low-load training.

OBJECTIVES: Within-subject training models have become common within the exercise literature. However, it is currently unknown if training one arm with a high load would impact muscle size and strength of the opposing arm training with a low load. DESIGN: Parallel group. METHODS: 116 participants were randomized to one of three groups that completed 6-weeks (18 sessions) of elbow flexion exercise. Group 1 trained their dominant arm only, beginning with a one-repetition maximum test (≤5 attempts), followed by four sets of exercise using a weight equivalent to 8-12 repetition maximum. Group 2 completed the same training as Group 1 in their dominant arm, while the non-dominant arm completed four sets of low-load exercise (30-40 repetition maximum). Group 3 trained their non-dominant arm only, performing the same low-load exercise as Group 2. Participants were compared for changes in muscle thickness and elbow flexion one-repetition maximum. RESULTS: The greatest changes in non-dominant strength were present in Groups 1 (Δ 1.5 kg; untrained arm) and 2 (Δ1.1 kg; low-load arm with high load on opposite arm), compared to Group 3 (Δ 0.3 kg; low-load only). Only the arms being directly trained observed changes in muscle thickness (≈Δ 0.25 cm depending on site). CONCLUSIONS: Within-subject training models are potentially problematic when investigating changes in strength (though not muscle growth). This is based on the finding that the untrained limb of Group 1 saw similar changes in strength as the non-dominant limb of Group 2 which were both greater than the low-load training limb of Group 3.

Improved interference control after exercise with blood flow restriction and cooling is associated with but not mediated by increased lactate.

BACKGROUND: To evaluate the effects of recumbent sprint interval exercise with and without blood flow restriction and body cooling on interference control and whether the changes in interference control can be explained by the changes in blood lactate. METHODS: 85 participants (22 SD 3 years old) completed 1 familiarization visit and then 5 experimental visits in a randomized order: exercise only (Ex), exercise with blood flow restriction (ExB), exercise with cooling (ExC), and exercise with blood flow restriction and cooling (ExBC), and non-exercise control (Con). Measurements of blood lactate and the Stroop Color Word Test were performed before and after exercise. Each bout began with a 15-minute low-moderate intensity warm-up, followed by five 20-second "all out" sprints separated by 40 s of active recovery. Bayes Factors (BF10) quantified evidence for or against the null hypothesis. Within-subject mediation analysis quantified the indirect effect of changes in blood lactate (mediator) on the change in interference control (each exercise condition vs. Con). RESULTS: Bayesian pairwise comparisons found that only ExC [σ: -0.37 (-0.59, -0.15)] and ExBC [σ: -0.3 (-0.53, -0.09)] produced changes in incongruent reaction time different from that of Con. There was also evidence that all exercise conditions increased blood lactate (BF10 = 8.65e+29 - 1.9e+32) and improved congruent reaction time (BF10 = 4.01 - 15.371) compared to that of Con. There was no evidence to show that changes in lactate mediated the change in incongruent reaction time. CONCLUSIONS: Both exercise with body cooling and when body cooling was combined with blood flow restriction presented favorable changes in incongruent reaction time (a marker of interference control), which might not be explained by the changes in systemic blood lactate concentration.

Longitudinal changes of grip strength and forearm muscle thickness in young children.

Background: Grip strength is a marker of future health conditions and is mainly generated by the extrinsic flexor muscles of the fingers. Therefore, whether or not there is a relationship between grip strength and forearm muscle size is vital in considering strategies for grip strength development during growth. Thus, this study aimed to examine the association between changes in grip strength and forearm muscle thickness in young children. Methods: Two hundred eighteen young children (104 boys and 114 girls) performed maximum voluntary grip strength and ultrasound-measured muscle thickness measurements in the right hand. Two muscle thicknesses were measured as the perpendicular distance between the adipose tissue-muscle interface and muscle-bone interface of the radius (MT-radius) and ulna (MT-ulna). All participants completed the first measurement and underwent a second measurement one year after the first one. Results: There were significant (P < 0.001) within-subject correlations between MT-ulna and grip strength [r = 0.50 (0.40, 0.60)] and MT-radius and grip strength [r = 0.59 (0.49, 0.67)]. There was no significant between-subject correlation between MT-ulna and grip strength [r = 0.07 (-0.05, 0.20)], but there was a statistically significant (P < 0.001) between-subject relationship between MT-radius and grip strength [r = 0.27 (0.14, 0.39)]. Conclusion: Although we cannot infer causation from the present study, our findings suggest that as muscle size increases within a child, so does muscle strength. Our between-subject analysis, however, suggests that those who observed the greatest change in muscle size did not necessarily get the strongest.

Adjustment of creatinine clearance for carboplatin dosing in Calvert's formula and clinical efficacy for lung cancer.

BACKGROUND: The Cockcroft-Gault formula is commonly used as a substitute for glomerular filtration rate (GFR) in Calvert's formula for carboplatin dosing, where adjusting serum creatinine measured using the enzymatic method with 0.2 mg/dL has been suggested in Japan. However, the effects of these adjustments on efficacy in patients with non-small-cell lung cancer remain unknown. METHODS: We conducted a post hoc analysis of the PREDICT1 study (CJLSG1201), a multicenter prospective observational trial of carboplatin-pemetrexed. Glomerular filtration rate values in Calvert's formula were back-calculated from the administered dosages of carboplatin and the reported value of the target area under the curve. We estimated the serum creatinine adjustments and divided the patients into crude and adjusted groups. RESULTS: Patients in the crude group (N = 169) demonstrated similar efficacy to those in the adjusted group (N = 104) in progression-free survival (PFS) and overall survival (OS) (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.76-1.35; p = 0.916 vs. HR, 0.87; 95% CI, 0.65-1.17; p = 0.363), with higher grade 3-4 hematologic toxicity. Among patients aged ≥75 years, the crude group (N = 47) showed superior efficacy compared with the adjusted group (N = 17) in PFS and OS (HR, 0.37; 95% CI, 0.20-0.69; p = 0.002 vs. HR, 0.43; 95% CI, 0.23-0.82; p = 0.010). CONCLUSIONS: Serum creatinine adjustment may be associated with similar efficacy compared to the crude serum creatinine value. In older patients, the adjustment should be cautiously applied owing to the potential for reduced efficacy.