Comparison of the Effects of Desflurane and Sevoflurane on Variations in Salivary Melatonin and Sleep Disturbance After Total Knee Arthroplasty: A Single-center, Prospective, Randomized, Controlled, Open-label Study.

PURPOSE: Anesthesia has been shown to disrupt the circadian rhythm. Recovery of the circadian rhythm after general anesthesia might help alleviate symptoms of insomnia and postoperative delirium. We hypothesized that recovery of the circadian rhythm is faster after total knee arthroplasty (TKA) with desflurane than with sevoflurane. This study compared the influence of sevoflurane versus desflurane anesthesia on the postoperative circadian rhythm of melatonin in adults undergoing TKA. DESIGN: Single-center, prospective, randomized, controlled, open-label study. METHODS: This study involved adult patients undergoing TKA at a university hospital in Japan from May 1, 2018 to December 31, 2019. The primary outcome of the study was the comparison of the effect of sevoflurane and desflurane on the circadian rhythm of salivary melatonin for 3 days postoperatively. The secondary outcomes were postoperative fatigue and sleep quality for 3 days postoperatively. FINDINGS: Twenty-eight patients (American Society of Anesthesiologists physical status of I or II) were scheduled for TKA and randomized to receive sevoflurane (n = 14) or desflurane (n = 14) anesthesia. There was no significant difference in the melatonin concentration between the sevoflurane and desflurane groups. The salivary melatonin concentration after sevoflurane or desflurane anesthesia was significantly higher at 9:00 p.m. on a postoperative day (POD)0 and POD1 than on POD3 (P < .05). Patients in the desflurane group had significantly greater fatigue than those in the sevoflurane group at 7:00 a.m. and 12:00 p.m. on POD3 (P < .05). Patients in the sevoflurane group had a deeper sleep than those in the desflurane group on POD0 (P < .05). In the sevoflurane group, the sleep time during the night of POD2 was longer than that on POD0 (6.1 vs 4.2 hours, P < .05). CONCLUSIONS: Under the current study conditions, desflurane was equivalent to sevoflurane in terms of the postoperative salivary melatonin concentration and sleep disturbance after TKA but not in terms of recovering the postoperative circadian rhythm.

Efficacy of antihyperglycemic therapies on cardiovascular and heart failure outcomes: an updated meta-analysis and meta-regression analysis of 35 randomized cardiovascular outcome trials.

BACKGROUND: Effects of antihyperglycemic therapies on cardiovascular and heart failure (HF) risks have varied widely across cardiovascular outcome trials (CVOTs), and underlying factors remain incompletely understood. We aimed to determine the relationships of glycated hemoglobin (HbA1c) or bodyweight changes with these outcomes in all CVOTs of antihyperglycemic therapies. METHODS: We searched PubMed and EMBASE up to 25 January 2023 for all randomized controlled CVOTs of antihyperglycemic therapies reporting both major adverse cardiovascular events (MACE) and HF outcomes in patients with type 2 diabetes or prediabetes. We performed meta-regression analyses following random-effects meta-analyses to evaluate the effects of HbA1c or bodyweight reductions on each outcome. RESULTS: Thirty-five trials comprising 256,524 patients were included. Overall, antihyperglycemic therapies reduced MACE by 9% [risk ratio (RR): 0.91; 95% confidence interval (CI) 0.88-0.94; P < 0.001; I2 = 36.5%]. In meta-regression, every 1% greater reduction in HbA1c was associated with a 14% reduction in the RR of MACE (95% CI 4-24; P = 0.010), whereas bodyweight change was not associated with the RR of MACE. The magnitude of the reduction in MACE risk associated with HbA1c reduction was greater in trials with a higher baseline prevalence of atherosclerotic cardiovascular disease. On the other hand, antihyperglycemic therapies showed no overall significant effect on HF (RR: 0.95; 95% CI 0.87-1.04; P = 0.28; I2 = 75.9%). In a subgroup analysis based on intervention type, sodium-glucose cotransporter-2 inhibitors (SGLT2i) conferred the greatest HF risk reduction (RR: 0.68; 95% CI 0.62-0.75; P < 0.001; I2 = 0.0%). In meta-regression, every 1 kg bodyweight reduction, but not HbA1c reduction, was found to reduce the RR of HF by 7% (95% CI 4-10; P < 0.001); however, significant residual heterogeneity (P < 0.001) was observed, and SGLT2i reduced HF more than could be explained by HbA1c or bodyweight reductions. CONCLUSIONS: Antihyperglycemic therapies reduce MACE in an HbA1c-dependent manner. These findings indicate that HbA1c can be a useful marker of MACE risk reduction across a wide range of antihyperglycemic therapies, including drugs with pleiotropic effects. In contrast, HF is reduced not in an HbA1c-dependent but in a bodyweight-dependent manner. Notably, SGLT2i have shown class-specific benefits for HF beyond HbA1c or bodyweight reductions.

Stabilization of kidney function and reduction in heart failure events with sodium-glucose co-transporter 2 inhibitors: A meta-analysis and meta-regression analysis.

AIMS: Sodium-glucose co-transporter 2 (SGLT2) inhibitors reduce the risk of heart failure (HF) events regardless of diabetes status. However, factors associated with their efficacy in HF reduction remain unknown. This study aims to identify clinically relevant markers for the efficacy of SGLT2 inhibitors in HF risk reduction. MATERIALS AND METHODS: We searched PubMed/MEDLINE and EMBASE for randomized placebo-controlled trials of SGLT2 inhibitors reporting a composite of HF hospitalization or cardiovascular death in participants with or without type 2 diabetes published until 28 February 2023. Random-effects meta-analysis and mixed-effects meta-regression were conducted to evaluate the association between the outcomes and clinical variables, including changes in glycated haemoglobin, body weight, systolic blood pressure, haematocrit and overall/chronic estimated glomerular filtration rate (eGFR) slope. RESULTS: Thirteen trials with 90 413 participants were included. SGLT2 inhibitors reduced the hazard ratio of the composite of HF hospitalization or cardiovascular death (hazard ratio 0.77; 95% confidence interval, 0.74-0.81; p < .0001). In meta-regression analysis, chronic eGFR slope (eGFR change after the initial dip) was significantly associated with the composite outcome (p = .017), and each 1 ml/min/1.73 m2 /year improvement in chronic eGFR slope led to a 14% reduction in the composite outcome. By contrast, changes in the other parameters showed no significant associations. CONCLUSIONS: Improvement in chronic eGFR slope, which reflects the stabilization of kidney function, is significantly associated with the efficacy of the SGLT2 inhibitor in HF, highlighting the cardiorenal axis role in the beneficial effects on HF. The chronic eGFR slope can be a surrogate marker of the effects of SGLT2 inhibitors on HF reduction.

Management of sarcopenia in patients with rheumatoid arthritis.

This review summarizes the evidence for the management of sarcopenia in patients with rheumatoid arthritis (RA) in terms of drugs, exercise, and nutrition. Sarcopenia is a decrease in skeletal muscle mass and muscle strength or physical function. The prevalence of sarcopenia in patients with RA is higher than that in the general population. The treatment and management of sarcopenia in patients with RA are clinically important for long-term prognosis. One of the mechanisms of muscle metabolism is the pro-inflammatory cytokine pathway, which involves tumour necrosis factor α and interleukin-6, and is a common pathway in the pathogenesis of RA. Thus, tumour necrosis factor α and interleukin-6 inhibitors may play a potential role in controlling sarcopenia. In exercise therapy, a combination of moderate resistance and aerobic exercise may be effective in improving muscle strength, muscle mass, and physical function; however, intense exercise may exacerbate the inflammatory response in RA. Regarding nutrition, protein intake is generally considered beneficial, but other nutrients such as vitamin D and carotenoids have also been studied. Overall, there remains a lack of concrete evidence on sarcopenia treatment and management in patients with RA from any perspective; more longitudinal and intervention studies are needed in the future.

High plasma homocysteine level is associated with increased prevalence of the non-remission state in rheumatoid arthritis: Findings from the KURAMA cohort.

OBJECTIVES: We aimed to determine the clinical impact of plasma homocysteine levels on disease activity and clinical remission in patients with rheumatoid arthritis (RA). METHODS: A cross-sectional study was conducted using KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. We enrolled 291 female patients, who were treated in a treat-to-target manner. We measured plasma total homocysteine using a liquid chromatography-tandem mass spectrometry system and collected clinical data including a 28-joint RA disease activity score-erythrocyte sedimentation rate (DAS28-ESR). Clinical remission of disease activity was defined as a DAS28-ESR < 2.6. RESULTS: In a univariable analysis, the plasma homocysteine concentration was significantly and positively associated with DAS-28-ESR and was higher in the non-remission group than in the remission group. The cutoff value of the plasma homocysteine level was calculated to be 7.9 nmol/mL by the test of the receiver operating characteristic curve analysis. In a multivariable analysis, after adjusting for clinically relevant variables, the high homocysteine level remained a significant positive association for DAS28-ESR (estimate 0.27, P = .0019) and a positive factor for the presence of RA non-remission (odds ratio 2.39, P = .0071). CONCLUSIONS: Increased plasma homocysteine levels showed a significant positive association with current disease activity and the non-remission state in female patients with RA under treat-to-target treatment. The findings suggest the potential utility of plasma homocysteine as a disease state marker reflecting conditions that are treatment failure and difficult to remission and may provide clinical evidence on the interplay between homocysteine and inflammatory activation in RA.

Metformin: New Preparations and Nonglycemic Benefits.

Metformin has been widely used for over 5 decades. New preparations have been developed for possible enhancement of efficiency, tolerability, and pleiotropic nonglycemic effects. Extended-release metformin has contributed to adherence and improved gastrointestinal tolerability. Delayed-release metformin acts in the lower gastrointestinal tract and exerts glucose-lowering effects at lower plasma metformin levels, which might suggest use of this biguanide in patients with chronic kidney disease. Metformin is also known to have numerous nonglycemic effects. Results of the UK Prospective Diabetes Study indicate improvements in cardiovascular outcome and reduced total mortality independent of glycemic control. Anticancer effects of metformin have been discussed and many clinical trials are on-going. Metformin is noted for its beneficial effects on lifespan extension and on disorders due to increased insulin resistance. Further investigations, including randomized control trials in nondiabetic individuals, are required to demonstrate the nonglycemic effects of metformin.

Effects of landiolol on refractory tachyarrhythmia after total cavopulmonary connection: a retrospective, observational, cohort study.

The onset of tachyarrhythmia after the Fontan procedure (total cavopulmonary connection; TCPC) should be considered a medical emergency. Landiolol is an ultra-short-acting ß1-selective blocker whose effect on tachyarrhythmia after TCPC is unclear. We evaluated the efficacy and safety of landiolol for tachyarrhythmia after TCPC. Consecutive patients undergoing TCPC were enrolled from January 2007 to December 2011. Of 435 pediatric open heart surgeries, 28 patients underwent TCPC. Of the 28 patients, 13 were treated with landiolol for critical tachyarrhythmia. Excluding three patients who received landiolol during surgery, we investigated the remaining 10 patients and statistical analysis was performed without a 10-year-old patient as outlier. The median age was 4.08 years. The subjects comprised five patients with sinus tachycardia, four with junctional ectopic tachycardia and one with paroxysmal supraventricular tachycardia. The initial dose was 4.7 ± 2.3 µg/kg/min, without a loading dose. Landiolol reduced the heart rate from 151.8 ± 23.2 at the start to 132.9 ± 20.0 at 1 h and 126.1 ± 24.9 at 2 h (P < 0.01 and P < 0.01, respectively), without blood pressure decrease (P = 0.235). Landiolol was effective in treating critical tachyarrhythmia without hemodynamic deterioration. We believe that landiolol is a promising option for postoperative tachyarrhythmia after the Fontan procedure.

DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells.

Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy.

A short period of fasting before surgery conserves basal metabolism and suppresses catabolism according to indirect calorimetry performed under general anesthesia.

It is recommended that the period of fasting before elective surgery should be shortened to facilitate a rapid recovery by preventing catabolism. We examined the effects of a short period of fasting on metabolism by performing indirect calorimetry (IC) under general anesthesia. A prospective observational study involving 26 consecutive patients who underwent elective surgery and whose metabolism was evaluated using IC during anesthesia was conducted. The patients were divided into two groups, those who fasted for <8 h (group S) and those who fasted for >10 h (group L). Oxygen consumption, the volume of carbon dioxide emissions (VCO2), the respiratory quotient (RQ), resting energy expenditure (REE), and basal energy expenditure (BEE) were compared. The REE, VCO2, and RQ of group L (17.7 ± 2.3 kcal/kg/day, 118.5 ± 20.8 ml/min, and 0.71 ± 0.12, respectively) were significantly lower than those of group S (19.7 ± 2.3 kcal/kg/day, 143.6 ± 30.9 ml/min, and 0.81 ± 0.09, respectively) (P < 0.05). In group L, the relationship between REE and BEE was weaker (r(2) = 0.501) and the BEE-REE slope was less steep (REE = 0.419BEE + 509.477) than those seen in group S (r(2) = 0.749 and REE = 1.113BEE - 376.111, respectively). Our findings suggest that a short period of fasting (<8 h) before surgery is more strongly associated with the conservation of basal metabolism.

Estimation of the success rate of anesthetic management for thymectomy in patients with myasthenia gravis treated without muscle relaxants: a retrospective observational cohort study.

Although maintaining anesthesia for myasthenia gravis (MG) with minimal muscle relaxants (MR) is common, the success rate of anesthetic management for MG without MR is not clear. We therefore retrospectively examined the success rate of anesthetic management for MG without MR among 66 consecutive cases of thymectomy for MG performed at our hospital between January 2004 and April 2010, before approval of using sugammadex. A total of 60 patients (90.9 %) were treated without MR (N group). Among the 60 cases, 17 (28.3 %) patients were not extubated in the operating room due to postoperative respiratory depression or other reasons. Therefore, the success rate of anesthetic management for thymectomy in patients with MG without treating MR was 71.7 % (43/60) [95 % confident interval (CI): 65.9-77.5 %]. The reasons for using MR included coughing at intubation in one case, bucking during surgery in two cases, and MR was considered to be safer by the attending anesthesiologist in three cases. The number of cases of impossible extubation requiring ventilation on that day was three in the N group and none in the R group. Finally, the success rate of anesthetic management for MG without MR was estimated to be 71.1 % (95 % CI: 65.9-77.5 %).

Tidal volume and airway pressure under percutaneous transtracheal ventilation without a jet ventilator: comparison of high-flow oxygen ventilation and manual ventilation in complete and incomplete upper airway obstruction models.

PURPOSE: Percutaneous transtracheal ventilation (PTV) can be life-saving in a cannot ventilate, cannot intubate situation. The aim of this study was to investigate the efficacy of PTV by measuring tidal volumes (VTs) and airway pressure (Paw) in high-flow oxygen ventilation and manual ventilation using a model lung. METHODS: We examined 14G, 16G, 18G, and 20G intravenous catheters and minitracheotomy catheters. In high-flow oxygen ventilation, the flow was set to 10 L/min, while the inspiratory:expiratory phases (I:E) were 1 s:4 s in the complete upper airway obstruction model and 1 s:1 s in the incomplete obstruction model. In manual ventilation, I:E were 2 s:4 s in the complete obstruction model and 2 s:3 s in the incomplete obstruction model. We ventilated through each catheter for 2 min and measured VT and Paw. RESULTS: In high-flow ventilation, the average VTs were approximately 150 ml and <100 ml with 14G catheters in complete and incomplete upper airway obstruction, respectively. The VTs obtained were reduced when the bore size was decreased. In manual ventilation, the average VTs were over 300 ml and approximately 260 ml with 14G catheters in complete and incomplete upper airway obstruction, respectively. In high-flow ventilation, the airway pressure tended to be higher. The minitracheotomy catheters produced over 800 ml of VT and created almost no positive end-expiratory pressure. CONCLUSIONS: High-flow ventilation tends to result in higher airway pressure despite a smaller VT, which is probably due to a PEEP effect caused by high flow.

No improvement in mortality among critically ill patients with carbapenems as initial empirical therapy and more detection of multi-drug resistant pathogens associated with longer use: a post hoc analysis of a prospective cohort study.

Whether empirical therapy with carbapenems positively affects the outcomes of critically ill patients with bacterial infections remains unclear. This study aimed to investigate whether the use of carbapenems as the initial antimicrobial administration reduces mortality and whether the duration of carbapenem use affects the detection of multidrug-resistant (MDR) pathogens. This was a post hoc analysis of data acquired from Japanese participating sites from a multicenter, prospective observational study [Determinants of Antimicrobial Use and De-escalation in Critical Care (DIANA study)]. A total of 268 adult patients with clinically suspected or confirmed bacterial infections from 31 Japanese intensive care units (ICUs) were analyzed. The patients were divided into two groups: patients who were administered carbapenems as initial antimicrobials (initial carbapenem group, n = 99) and those who were not administered carbapenems (initial non-carbapenem group, n = 169). The primary outcomes were mortality at day 28 and detection of MDR pathogens. Multivariate logistic regression analysis revealed that mortality at day 28 did not differ between the two groups [18 (18%) vs 27 (16%), respectively; odds ratio: 1.25 (95% confidence interval (CI): 0.59-2.65), P = 0.564]. The subdistribution hazard ratio for detecting MDR pathogens on day 28 per additional day of carbapenem use is 1.08 (95% CI: 1.05-1.13, P < 0.001 using the Fine-Gray model with death regarded as a competing event). In conclusion, in-hospital mortality was similar between the groups, and a longer duration of carbapenem use as the initial antimicrobial therapy resulted in a higher risk of detection of new MDR pathogens.IMPORTANCEWe found no statistical difference in mortality with the empirical use of carbapenems as initial antimicrobial therapy among critically ill patients with bacterial infections. Our study revealed a lower proportion of inappropriate initial antimicrobial administrations than those reported in previous studies. This result suggests the importance of appropriate risk assessment for the involvement of multidrug-resistant (MDR) pathogens and the selection of suitable antibiotics based on risk. To the best of our knowledge, this study is the first to demonstrate that a longer duration of carbapenem use as initial therapy is associated with a higher risk of subsequent detection of MDR pathogens. This finding underscores the importance of efforts to minimize the duration of carbapenem use as initial antimicrobial therapy when it is necessary.

Development of a stable isotope dilution UPLC-MS/MS method for quantification of dexmedetomidine in a small amount of human plasma.

Dexmedetomidine (Dex) is a selective central α2-agonist with anesthetic properties and has been used in clinical practice for sedation in the intensive care unit (ICU) after operations. In this study, an analytical assay for the determination of Dex in a small amount of plasma was developed for the application to pediatric ICU trials. The quantification of Dex was constructed using the original stable isotope Dex-d3 for electrospray ionization-tandem mass spectrometry (ESI-MS/MS) in the selected reaction monitoring mode. A rapid ultra-performance liquid chromatography technique was adopted using ESI-MS/MS with a runtime of 3 min. Efficacious concentration levels (50 pg/mL to 5 ng/mL) could be evaluated using a very small amount of plasma (10 µL) from patients. The lower limit of the quantification was 5 pg/mL in the plasma (100 µL). For sample preparation, a solid-phase extraction was used along with the OASIS-HLB cartridge type. Recovery values ranged from 98.8 to 100.3% for the intra- [relative standard deviation (RSD), 0.9-1.3%] and inter- (RSD, 0.9-1.5%) day assays. A stable test had recovery values that ranged from 97.8 to 99.7% with an RSD of 1.0-1.9% for the process/wet extract, bench-top, freeze-thaw and long-term tests. This method was used to measure the Dex levels in plasma from pediatric ICU patients. In the clinical ICU trial, the small amount of blood (approximate plasma volume, 200 µL) remaining from blood gas analysis was reused and targeted for the clinical analysis of Dex in plasma.

Effect of intraoperative systemic magnesium sulphate on postoperative Richmond Agitation-Sedation Scale score after endovascular repair of aortic aneurysm under general anesthesia: A double-blind, randomized, controlled trial.

Intraoperative magnesium has the effect of reducing postoperative opiate requirement, pain, and agitation. However, its effect on postoperative sedation and delirium is unclear. This study investigated the effect of magnesium on the postoperative Richmond Agitation-Sedation Scale (RASS) score and delirium following endovascular repair of aortic aneurysm (EVAR). Sixty-three consecutive patients diagnosed with abdominal (45) and thoracic (18) aortic aneurysm who underwent EVAR under general anesthesia were eligible. Patients were allocated randomly to the magnesium group (infusion of 30 mg•kg-1 magnesium in the first hour followed by 10 mg•kg-1 h-1 until the end of surgical procedure, targeting total 60 mg•kg-1) or the control group (0.9% saline at the same volume and rate). The primary outcome was whether magnesium had an effect on RASS score of patients at postoperative ICU admission. Secondary outcomes were effects on RASS score, numerical rating scale (NRS) score, Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) until 24 h after postoperative ICU transfer, and length of ICU stay. At postoperative ICU admission, magnesium had no significant effect on the RASS score (0[-0.5 to 0] vs 0[0 to 0]; P = 0.114), but at 1 h the NRS score was statistically different, 2[0 to 4] vs 4[0 to 5] (P = 0.0406). However, other data (RASS score, NRS score, CAM-ICU and length of ICU stay) did not show a significant difference. Our results did not show that intraoperative magnesium of target total 60 mg•kg-1 affected postoperative RASS score for undergoing EVAR. Trial registration: The current study was registered according to WHO and ICMJE standards on 4 July 2018, under registration number the Japan Registry of Clinical Trials, iRCTs041190013.

Mevalonate biosynthesis pathway regulates the development and survival of brown adipocytes.

The high thermogenic activity of brown adipose tissue (BAT) has received considerable attention. Here, we demonstrated the role of the mevalonate (MVA) biosynthesis pathway in the regulation of brown adipocyte development and survival. The inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the rate-limiting enzyme in the MVA pathway and the molecular target of statins, suppressed brown adipocyte differentiation by suppressing protein geranylgeranylation-mediated mitotic clonal expansion. The development of BAT in neonatal mice exposed to statins during the fetal period was severely impaired. Moreover, statin-induced geranylgeranyl pyrophosphate (GGPP) deficiency led to the apoptosis of mature brown adipocytes. Brown adipocyte-specific Hmgcr knockout induced BAT atrophy and disrupted thermogenesis. Importantly, both genetic and pharmacological inhibition of HMGCR in adult mice induced morphological changes in BAT accompanied by an increase in apoptosis, and statin-treated diabetic mice showed worsened hyperglycemia. These findings revealed that MVA pathway-generated GGPP is indispensable for BAT development and survival.

Comment on "The effect of disease-modifying anti-rheumatic drugs on skeletal muscle mass in rheumatoid arthritis patients: a systematic review with meta-analysis".

We read with great interest the article by Hein et al., which described the meta-analysis study on the impact of disease-modifying anti-rheumatic drugs (DMARDs) therapy on skeletal muscle mass in rheumatoid arthritis (RA) patients. While the data presented are impressive, we add some remarks about methodological issues that should be considered. First, this meta-analysis does not include several necessary studies that have provided data on the relationship between anti-tumor necrosis factor (anti-TNF) therapy and body composition. To make the meta-analysis more comprehensive, it could be necessary to incorporate these studies into this analysis. Second, this study did not employ a representative measure of skeletal muscle mass that was adjusted for body size, such as skeletal muscle mass index (SMI). It is well recognized that skeletal muscle mass varies with body size, particularly height and body mass index. Given the heterogeneity background of body size in the studies included in this meta-analysis, it may be worthwhile to conduct an additional analysis regarding the associations between DMARDs and the adjusted measure of skeletal muscle mass such as SMI, which is recommended in several guidelines when determining and contrasting the quantity of skeletal muscle mass. Third, when determining body composition, several reports show variances between bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DEXA) in RA as well as in general. In this regard, it may not be appropriate to simultaneously perform a meta-analysis of skeletal muscle mass determined by DEXA and BIA. With the issues described above, we conclude by recommending additional investigations to strengthen the arguments presented by this valuable meta-analysis.

Year-long effects of COVID-19 restrictions on glycemic control and body composition in patients with glucose intolerance in Japan: A single-center retrospective study.

AIMS/INSTRUCTION: During the coronavirus disease 2019 (COVID-19) pandemic, the lockdowns in Europe raised concerns about negative effects on glycemic control and body composition in patients with diabetes. In Japan, voluntary-based restrictions were imposed as the declaration of a state of emergency (DSE), whose metabolic consequences have not been fully investigated. We carried out a single-center retrospective study to evaluate changes in glycemic control and body composition in outpatients with glucose intolerance after the DSE. MATERIALS AND METHODS: We enrolled outpatients with glucose intolerance: (i) for whom longitudinal data about body composition were available; (ii) who participated in dietary follow up with nutritionists; and (iii) whose laboratory data included glycated hemoglobin (HbA1c) levels before and after the DSE. RESULTS: Among 415 patients, we found no significant changes in HbA1c overall after the DSE. Bodyweight and fat mass increased significantly, whereas skeletal mass decreased significantly. HbA1c changes after the DSE were significantly correlated with changes in bodyweight and fat mass. In 128 patients whose HbA1c levels increased ≥0.3%, changes in bodyweight and fat mass were significantly larger than those in the other 287 patients. With regard to lifestyle changes, increased snacking was likely to worsen glycemic control (odds ratio 1.76, P = 0.036). CONCLUSIONS: COVID-19 restrictions in Japan had unfavorable metabolic consequences for patients with glucose intolerance, highlighted by increased bodyweight and body fat, and decreased skeletal muscle. In addition, lifestyle changes, such as increased snacking, might worsen glycemic control. Clinical attention and interventions are required to prevent such metabolic changes.

Effect of intensive care provided by nurse practitioners for postoperative patients: A retrospective observational before-and-after study.

Nurse practitioners are increasingly now members of intensive care teams in Japan, but no data exist about their effect on the outcomes for critically ill patients. This study aimed to compare the outcomes of postoperative patients on mechanical ventilators before and after the participation of nurse practitioners in intensive care teams. We retrospectively identified 387 patients who underwent postoperative mechanical ventilation at a University Hospital in Japan, using data from medical records from 1 April 2015 to 31 March 2017. We extracted data and compared patients' length of stay in the intensive care unit and the hospital, mechanical ventilation days, postoperative rehabilitation start date, rehabilitation prescription, intensive care unit and hospital mortality, and intensive care unit readmission. Multiple regression analysis was used to analyze the factors affecting length of stay in the intensive care unit. Patients who received care from nurse practitioners and physicians had significantly shorter stays in intensive care (4.8 ± 4.8 days versus 6.7 ± 10.3 days, p < 0.021). Mechanical ventilation days, total length of hospital stay, rehabilitation prescription, mortality in intensive care and hospital, and readmission to intensive care were all similar to those who received care only from physicians. The multiple regression analysis suggests that participation of nurse practitioners in intensive care reduced the length of stay in the unit by 2.6 days (p = 0.003). These findings could help to increase use of non-physician healthcare providers in intensive care. Our results demonstrated that it is both effective and safe for nurse practitioners to participate in intensive care teams that provide care for postoperative patients receiving mechanical ventilation.

Causal associations between body fat accumulation and COVID-19 severity: A Mendelian randomization study.

Previous studies reported associations between obesity measured by body mass index (BMI) and coronavirus disease 2019 (COVID-19). However, BMI is calculated only with height and weight and cannot distinguish between body fat mass and fat-free mass. Thus, it is not clear if one or both of these measures are mediating the relationship between obesity and COVID-19. Here, we used Mendelian randomization (MR) to compare the independent causal relationships of body fat mass and fat-free mass with COVID-19 severity. We identified single nucleotide polymorphisms associated with body fat mass and fat-free mass in 454,137 and 454,850 individuals of European ancestry from the UK Biobank, respectively. We then performed two-sample MR to ascertain their effects on severe COVID-19 (cases: 4,792; controls: 1,054,664) from the COVID-19 Host Genetics Initiative. We found that an increase in body fat mass by one standard deviation was associated with severe COVID-19 (odds ratio (OR)body fat mass = 1.61, 95% confidence interval [CI]: 1.28-2.04, P = 5.51 × 10-5; ORbody fat-free mass = 1.31, 95% CI: 0.99-1.74, P = 5.77 × 10-2). Considering that body fat mass and fat-free mass were genetically correlated with each other (r = 0.64), we further evaluated independent causal effects of body fat mass and fat-free mass using multivariable MR and revealed that only body fat mass was independently associated with severe COVID-19 (ORbody fat mass = 2.91, 95% CI: 1.71-4.96, P = 8.85 × 10-5 and ORbody fat-free mass = 1.02, 95%CI: 0.61-1.67, P = 0.945). In summary, this study demonstrates the causal effects of body fat accumulation on COVID-19 severity and indicates that the biological pathways influencing the relationship between COVID-19 and obesity are likely mediated through body fat mass.