Glycan-Controlled Human PD-1 Variants Displaying Broad-Spectrum High Binding to PD-1 Ligands Potentiate T Cell.

Although therapeutic immunoglobulin G (IgG) antibodies that regulate the activity of immune checkpoints bring innovation to the field of immuno-oncology, they are still limited in their efficiency to infiltrate the tumor microenvironment due to their large molecular size (150 kDa) and the necessity of additional engineering works to ablate effector functions for antibodies targeting immune cells. To address these issues, the human PD-1 (hPD-1) ectodomain, a small protein moiety of 14-17 kDa, has been considered as a therapeutic agent. Here, we used bacterial display-based high-throughput directed evolution to successfully isolate glycan-controlled (aglycosylated or only single-N-linked glycosylated) human PD-1 variants exhibiting over 1000-fold increased hPD-L1 binding affinity compared to that of wild-type hPD-1. The resulting hPD-1 variants, aglycosylated JYQ12 and JYQ12-2 with a single-N-linked glycan chain, showed exceptionally high binding affinity to hPD-L1 and very high affinity to both hPD-L2 and mPD-L1. Moreover, the JYQ12-2 efficiently potentiated the proliferation of human T cells. hPD-1 variants with significantly improved binding affinities for hPD-1 ligands could be used as effective therapeutics or diagnostics that can be differentiated from large-sized IgG antibody-based molecules.

The 24-Hour Cardiac Autonomic Activity in Patients With Allergic Rhinitis.

BACKGROUND: Definitive knowledge of the 24-hour cardiac autonomic activity in patients with allergic rhinitis (AR) is lacking. Thus, we aimed to evaluate heart rate variability (HRV), which is used to measure cardiac autonomic activity by 24-hour Holter monitoring in patients with AR. METHODS: We enrolled 32 patients who visited our clinic and were diagnosed with AR. The control group was selected four-fold (n = 128) by matching (age, sex, hypertension, and diabetes) in the AR group from a Holter registry in the cardiology department. The HRV results, which were measured using 24-hour Holter monitoring, were compared between the AR and control groups. RESULTS: All time-domain parameters of HRV revealed no differences between the groups. However, among the frequency domain parameters of HRV, the low-frequency to high-frequency ratio and low-frequency power in normalized units were significantly lower in the AR group. Conversely, high-frequency power in normalized units was significantly higher in the AR group. In the multiple regression analysis, AR was independently associated with sympathetic withdrawal (adjusted odds ratio = 3.393, P = 0.020) after adjusting for age, sex, hypertension, diabetes mellitus, and hyperlipidemia. CONCLUSIONS: The present findings suggest differences in cardiac autonomic activity which are related with sympathetic withdrawal in patients with AR compared with that in the normal population over 24 hours.

Impact of Total Ischemic Time on the Recovery of Regional Wall Motion Abnormality after STEMI in the Modern Reperfusion Era.

BACKGROUND: Total ischemic time (TIT) is an important factor for predicting mortality among patients with ST-segment elevation myocardial infarction (STEMI). However, the correlation between TIT and the extent of wall motion abnormality has not been well studied. Therefore, we investigated changes in the wall motion score index (WMSI) value based on TIT in STEMI patients who underwent primary percutaneous coronary intervention (PCI) and subsequent transthoracic echocardiography. METHODS: STEMI patients who underwent primary PCI and follow-up coronary angiography were analyzed after the exclusion of cases of in-stent restenosis (ISR). WMSI values were calculated by dividing the sum of scores by the number of segments visualized. RESULTS: A total of 189 patients underwent primary PCI for STEMI, and 151 had no ISR with a median follow-up of 12.3 months. TIT was 180 (117-369) minutes in a subset of 151 patients (mean age of 62 years; 76% male). Among patients without ISR, 109 (72%) demonstrated a decrease in the WMSI value during the follow-up period. The WMSI values of patients with TITs of 180 minutes or less were significantly decreased relative to those among patients with TITs of greater than 180 minutes (p=0.020). Among patients with TITs of 180 minutes or less, the TIT was significantly shorter among those with a reduction in the WMSI value than among those with an increase in the WMSI value (106 [81-124] vs. 133 [100-151] minutes; p=0.018). TIT was an independent predictor for a reduction in the WMSI value among these patients (adjusted hazard ratio: 0.976 (0.957-0.995); p=0.016). CONCLUSIONS: In the modern reperfusion era of STEMI, patients with TITs of 180 minutes or less experienced a significant degree of recovery from regional wall motion abnormalities.

Does Surgical-site Multimodal Drug Injection After Palmar Plating of Distal Radius Fractures Improve Pain Scores?

BACKGROUND: Although palmar locked plating is a stable fixation method frequently used to treat unstable distal radius fractures (DRFs), surgical treatment may be painful, and so interventions to decrease that pain might improve our patients' experiences with surgery. Some surgeons use local multimodal drug injections to decrease postoperative pain after lower-extremity arthroplasty, but little is known about the effectiveness of a local multimodal drug injection in patients who undergo palmar plating for DRFs. QUESTIONS/PURPOSES: (1) Do patients who receive a local multimodal drug injection after palmar plating for unstable DRFs have better pain scores at 4, 8, 24, and 48 hours after surgery than patients who have not received such an injection? (2) Do patients who receive a local multimodal drug injection have lower fentanyl consumption and administration of anti-emetic drugs within the first 48 hours after surgery than patients who have not received such an injection? METHODS: A randomized controlled study was performed between August 2018 and August 2019 at a single tertiary care referral center. Patients who underwent palmar plating for DRFs under general anesthesia were eligible for inclusion. Patients were allocated into two groups: Those who received a local multimodal drug injection, and those who did not receive an injection. During the study period, 101 patients treated with palmar plating for DRFs met the inclusion criteria and were enrolled and randomized. Fifty-two patients were allocated to the multimodal injection group and 49 were allocated to the control group. Three patients (two in the multimodal injection group and one in the control group) were excluded after randomization because their pain level was not registered at any timepoint and so they could not be analyzed; our analysis was by intention to treat, and there was no crossover. After palmar plating, patients in the multimodal injection group received an injection of ropivacaine (10 mL), morphine (5 mL), ceftezole (5 mL) as well as normal saline (5 mL) to the periosteal area, pronator quadratus muscle, subcutaneous area, and skin. There were no differences between the groups in terms of age (62 years ± 13 years in the multimodal injection group versus 62 years ± 11 years in the control group; p = 0.93), gender (84% [42 of 50] women in the multimodal injection group versus 77% [37 of 48] women in the control group; p = 0.39), hand dominance (70% [35 of 50] dominant wrist in the multimodal injection group versus 60% [29 of 48] dominant wrist in the control group; p = 0.32) and AO/Orthopaedic Trauma Association (AO/OTA) classification (p = 0.57). All patients underwent treatment with the same perioperative protocol, and 25 µg of fentanyl was injected intravenously when a patient complained of pain and asked for additional pain control after surgery. In addition, when a patient complained of nausea or vomiting associated with fentanyl use, an anti-emetic drug was also injected. All nursing staff who administered the analgesics and anti-emetic drugs were blinded to treatment allocation. These two groups were compared regarding their pain level using a 100-mm VAS at 4, 8, 24, and 48 hours postoperatively. The minimum clinically important difference (MCID) for the VAS score was set to 20 mm. VAS scores were also collected by nursing staff who remained blinded to the treatment allocation. The total amount of fentanyl use and the number of patients who received anti-emetic drugs associated with administration of fentanyl within the first 48 hours were also recorded. RESULTS: With an MCID of 20 points, we found no clinically important reduction in VAS scores among patients who received a local multimodal injection compared with those who did not receive an injection at 4 hours (34 ± 15 versus 41 ± 20, mean difference -7.079 [95% CI -13.986 to -0.173]; p = 0.045), 8 hours (27 ± 16 versus 40 ± 19, mean difference -12.263 [95% CI -19.174 to -5.353]; p = 0.001), 24 hours (18 ± 12 versus 29 ± 20, mean difference -11.042 [95% CI -17.664 to -4.419]; p = 0.001), and 48 hours (9 ± 8 versus 10 ± 6, mean difference -1.318 [95% CI -4.000 to 1.365]; p = 0.33). Within the first 48 hours after surgery, fentanyl consumption was lower in patients receiving a local multimodal injection than in control patients (25 µg [range 0-100 µg] versus 37.5 µg [range 0-125 µg], difference of medians -12.5; p = 0.01). There was also a difference between the study groups in terms of the proportion of patients who received anti-emetic medications (16% [8 of 50] in the multimodal injection group versus 35% [17 of 48] in the control group, odds ratio = 2.879 [95% CI 1.102 to 7.519]; p = 0.03). CONCLUSIONS: Our data suggest that patients who received a surgical-site multimodal analgesic injection after palmar plating for a distal radius fracture had no clinically important reduction in pain scores, but they did consume lower doses of opioid analgesics and fewer of these patients received anti-emetic drugs within 2 days of surgery. The high-potency opioids or other analgesia usually used for postoperative pain management have many side effects. Thus, reducing additional analgesia is as important as postoperative pain management and a surgical-site multimodal analgesic injection is one of the methods to achieve this a goal. LEVEL OF EVIDENCE: Level I, therapeutic study.

Lower diastolic wall strain is associated with coronary revascularization in patients with stable angina.

BACKGROUND: Left ventricular (LV) diastolic dysfunction occurs earlier in the ischemic cascade than LV systolic dysfunction and electrocardiographic changes. Diastolic wall strain (DWS) has been proposed as a marker of LV diastolic stiffness. Therefore, the objectives of this study were to define the relationship between DWS and coronary revascularization and to evaluate other echocardiographic parameters in patients with stable angina who were undergoing coronary angiography (CAG). METHODS: Four hundred forty patients [mean age: 61 ± 10; 249 (57%) men] undergoing CAG and with normal left ventricular systolic function without regional wall motion abnormalities were enrolled. Among them, 128 (29%) patients underwent revascularization (percutaneous intervention: 117, bypass surgery: 11). All patients underwent echocardiography before CAG and the DWS was defined using posterior wall thickness (PWT) measurements from standard echocardiographic images [DWS = PWT(systole)-PWT(diastole)/PWT(systole)]. RESULTS: Patients who underwent revascularization had a significantly lower DWS than those who did not (0.26 ± 0.08 vs. 0.38 ± 0.09, p < 0.001). Age was comparable between the two groups (61 ± 9 vs. 60 ± 11, p = 0.337), but the proportion of males was significantly higher among patients who underwent revascularization (69 vs. 52%, p = 0.001). The LV ejection fraction was similar but slightly decreased (60.9 ± 5.7 vs. 62.4 ± 6.2%, p = 0.019) and the E/E' ratio was elevated (10.3 ± 4.0 vs. 9.0 ± 3.1, p < 0.001) among patients who underwent revascularization. In multiple regression analysis, lower DWS was an independent predictor of revascularization (cut-off value: 0.34; sensitivity: 89%; AUC: 0.870; SE: 0.025; p < 0.001). CONCLUSION: DWS, a simple parameter that can be calculated from routine 2D echocardiography, is inversely associated with the presence of coronary artery disease and the need for revascularization.

Asymptomatic ventricular premature depolarizations are not necessarily benign.

AIMS: Most patients with idiopathic ventricular premature depolarizations (VPDs) complain of symptoms related to this arrhythmia, but some patients are asymptomatic even with a high VPD burden. Our understanding of the relationship between symptoms and cardiomyopathy related to this arrhythmia remains limited. METHODS AND RESULTS: We evaluated 801 subjects (381 men; mean age, 55 ± 17 years) who visited our outpatient clinic. All subjects were diagnosed with frequent VPDs (1% or >1000 beats/day). The patients were divided into two groups according to the presence or absence of typical VPD symptoms (palpitations or skipped beats during VPDs): symptomatic patients (n = 455) and asymptomatic patients (n = 346). Clinical and electrocardiogram parameters were compared between these two groups. In the symptomatic group, palpitations were the most frequent symptom (91%). Daily VPD burden (P = 0.90) and electrocardiogram parameters (P>0.05) did not differ significantly between groups. The incidence of frequent VPDs with left ventricular dysfunction was significantly higher in the asymptomatic group (symptomatic patients, 3.0%; asymptomatic patients, 10.5%; P < 0.001). CONCLUSION: The absence of typical VPD-related symptoms may be a risk factor for cardiomyopathy and be associated with an adverse outcome.

Electrocardiogram PR Interval Is a Surrogate Marker to Predict New Occurrence of Atrial Fibrillation in Patients with Frequent Premature Atrial Contractions.

The clinical significance of prolonged PR interval has not been evaluated in patients with frequent premature atrial contractions (PACs). We investigated whether prolonged PR interval could predict new occurrence of atrial fibrillation (AF) in patients with frequent PACs. We retrospectively analyzed 684 patients with frequent PACs (> 100 PACs/day) who performed repeated 24-hour Holter monitoring. Prolonged PR interval was defined as longer than 200 msec. Among 684 patients, 626 patients had normal PR intervals (group A) and 58 patients had prolonged PR intervals (group B). After a mean follow-up of 59.3 months, 14 patients (24.1%) in group B developed AF compared to 50 patients (8.0%) in group A (P < 0.001). Cox regression analysis showed that prolonged PR interval (hazard ratio [HR], 1.950; 95% CI, 1.029-3.698; P = 0.041), age (HR, 1.033; 95% CI, 1.006-1.060; P = 0.015), and left atrial (LA) dimension (HR, 1.061; 95% CI, 1.012-1.112; P = 0.015) were associated with AF occurrence. Prolonged PR interval, advanced age, and enlarged LA dimension are independent risk factors of AF occurrence in patients with frequent PACs.

Cardiomyopathy With Frequent Ventricular Premature Depolarization ­ Predicting Irreversible Ventricular Dysfunction.

BACKGROUND: High ventricular premature depolarization (VPD) burden is associated with left ventricular (LV) dysfunction that typically resolves after successful ablation. Some patients, however, have persistent LV dysfunction, even after successful radiofrequency (RF) ablation. Identifying factors associated with irreversibility of LV cardiomyopathy (CMP) may help predict clinical outcome. METHODS AND RESULTS: Patients with frequent VPD (>10%/day) who underwent successful VPD suppression were divided into 2 groups according to transthoracic echocardiography (TTE) before and after suppression: group A (n=38) had depressed LV function that normalized after VPD suppression; group B (n=19) had depressed LV function before and after suppression. Of 57 patients (43 men; mean age, 54±15 years), RF ablation was performed in 39. Clinical, electrocardiographic, and TTE parameters were compared between groups. LV end-diastolic dimension (LVEDD; group A vs. B: 54±5 mm vs. 60±10 mm, P=0.01), end-systolic dimension (group A vs. B: 42±6 mm vs. 48±11 mm, P=0.01) before VPD suppression differed significantly between groups. Pre-suppression LVEDD was ≤66 mm in all reversible-CMP patients. LVEDD >66 mm predicted irreversible CMP with 50% sensitivity, 100% specificity, 100% positive predictive value, and 81% negative predictive value. CONCLUSIONS: LVEDD was a good predictor of irreversible LV CMP with frequent VPD, with 50% sensitivity and 100% specificity.

Long-term Prognosis of Paroxysmal Atrial Fibrillation and Predictors for Progression to Persistnt or Chronic Atrial Fibrillation in the Korean Population.

Little is known about the long-term prognosis of or predictors for the different clinical types of atrial fibrillation (AF) in Korean populations. The aim of this study was to validate a risk stratification to assess the probability of AF progression from paroxysmal AF (PAF) to persistent AF (PeAF) or permanent AF. A total of 434 patients with PAF were consecutively enrolled (mean age; 71.7 ± 10.7 yr, 60.6% male). PeAF was defined as episodes that are sustained > 7 days and not self-terminating, while permanent AF was defined as an ongoing long-term episode. Atrial arrhythmia during follow-up was defined as atrial premature complex, atrial tachycardia, and atrial flutter. During a mean follow-up of 72.7 ± 58.3 months, 168 patients (38.7%) with PAF progressed to PeAF or permanent AF. The mean annual AF progression was 10.7% per year. In univariate analysis, age at diagnosis, body mass index, atrial arrhythmia during follow-up, left ventricular ejection fraction, concentric left ventricular hypertrophy, left atrial diameter (LAD), and severe mitral regurgitation (MR) were significantly associated with AF progression. In multivariate analysis, age at diagnosis (P = 0.009), atrial arrhythmia during follow-up (P = 0.015), LAD (P = 0.002) and MR grade (P = 0.026) were independent risk factors for AF progression. Patients with younger age at diagnosis, atrial arrhythmia during follow-up, larger left atrial chamber size, and severe MR grade are more likely to progress to PeAF or permanent AF, suggesting more intensive medical therapy with close clinical follow-up would be required in those patients.

Analysis of Protrusio Acetabuli Using a CT-based Diagnostic Method in Korean Patients with Marfan Syndrome: Prevalence and Association with Other Manifestations.

A new CT-based diagnostic method of protrusio acetabuli (PA) was introduced. However, prevalence of PA by this method and correlation between PA and other manifestations of Marfan syndrome (MFS) is unknown in Korean MFS patients. This study aimed to investigate the prevalence of PA diagnosed by a CT-based method in Korean patients with MFS, the association of PA with other manifestations of MFS, and the contribution of PA to MFS diagnosis. We retrospectively reviewed the records of 146 MFS patients with the presence of a causative FBN1 mutation and 146 age- and sex-matched controls from a single tertiary care center. All MFS patients underwent a complete assessment of criteria based on the revised Ghent nosology. PA was assessed quantitatively using a CT-based circle-wall distance (CWD) method. PA was diagnosed in 77.4% of patients in the MFS group and in 11.0% of the control group. CWD was significantly different between the two groups (1.50 mm vs. -0.64 mm, P<0.001). The presence of PA did not correlate with the presence of ectopia lentis, aortic root diameter, or history of aortic dissection. The presence of PA did not have a significant impact on the final diagnosis of MFS. Even though the presence of PA does not related to the cardinal clinical features of MFS or influence MFS diagnosis, its presence may be helpful for the suspicion of MFS when aortic dissection or aneurysm is found on CT angiography of the aorta because of the high frequency of PA in MFS patients.

The Effect of Sodium-Glucose Cotransporter-2 Inhibitors on COVID-19 Patients with Type 2 Diabetes Mellitus: A Retrospective Cohort Study Using the Common Data Model.

BACKGROUND: There is no clinical evidence about the effect of sodium-glucose cotransporter-2 (SGLT2) inhibitors on diabetic patients who have been diagnosed with coronavirus disease 19 (COVID-19). METHODS: The dataset is based on insurance benefit claims sent to the Health Insurance Review and Assessment Service of Korea from January, 2018 to April, 2022. Among 9,822,577 patients who were involved in the claims, diabetic patients were divided into two groups based on whether they had a prescription for an SGLT2 inhibitor. The primary outcome was major adverse cardiac and cerebrovascular events (MACCEs), which were a composite of all-cause mortality, myocardial infarction, stroke, and revascularization over 90 days. RESULTS: A total of 172,682 patients was analyzed. In the propensity score-matched analysis, the rate of MACCE was lower in the SGLT2 inhibitor group compared to the non-SGLT2 inhibitor group (0.89% vs. 1.31%; hazard ratio, 0.71; 95% confidence interval, 0.53-0.94; p =0.020). Each of the MACCEs showed no differences between the two groups. The rate of pneumonia was similar between the two groups (4.45% vs. 4.39%; hazard ratio, 1.06; 95% confidence interval, 0.91-1.16; p = 0.620). CONCLUSIONS: In the diabetic patients who were diagnosed with COVID-19, SGLT2 inhibitors were associated with improved clinical outcomes in terms of MACCEs. SGLT2 inhibitors might be considered for prescription to diabetic patients in the current context of long COVID-19.

Long-Term Clinical Implications of Atrial Fibrillation on Mortality in Patients Hospitalized with COVID-19: A Nationwide Cohort Study.

BACKGROUND: Atrial fibrillation (AF) increases the risk of long-term mortality in patients hospitalized with Coronavirus Disease 2019 (COVID-19), but the evidence is limited. METHODS: This study used data from the Common Data Model of the Health Insurance Review and Assessment Service of Korea collected between 1 January 2020 and 30 April 2022. A total of 107,247 patients hospitalized with COVID-19 were included in this study. They were divided into two groups according to a history of AF. The primary outcome was all-cause mortality. RESULTS: After propensity score stratification, 1919 patients with a history of AF and 105,328 patients without a history of AF who were hospitalized with COVID-19 were analyzed to determine long-term mortality. The primary outcome occurred in 99 of 1919 patients (5.2%) with a history of AF and in 1397 of 105,328 patients (1.3%) without a history of AF (hazard ratio, 1.49; 95% confidence interval 1.20-1.82; p < 0.01). A history of AF was also associated with an increased risk of within 30-day mortality. CONCLUSION: A history of AF was associated with an increased risk of long-term mortality in patients hospitalized with COVID-19. Our findings indicate the necessity for physicians to reevaluate the optimal management of patients with AF following discharge.

How can progression be predicted in patients with mild to moderate aortic valve stenosis?

AIMS: The pressure increase per time unit (dP/dt) in aortic stenosis (AS) jet velocity is assumed to have inter-individual variability in the progressive AS stage. We sought to examine the association of aortic valve (AoV) Doppler-derived dP/dt in patients with mild to moderate AS with risk of progression to severe disease. METHODS AND RESULTS: A total of 481 patients diagnosed with mild or moderate AS [peak aortic jet velocity (Vmax) between 2 and 4 m/s] according to echocardiographic criteria were included. AoV Doppler-derived dP/dt was determined by measuring the time needed for the pressure to increase at a velocity of the AoV jet from 1 m/s to 2 m/s. During a median follow-up period of 2.7 years, 12 of 404 (3%) patients progressed from mild to severe AS and 31 of 77 (40%) patients progressed from moderate to severe AS. AoV Doppler-derived dP/dt had a good ability to predict risk of progression to severe AS (area under the curve = 0.868) and the cut-off value was 600 mmHg/s. In multivariable logistic regression, initial AoV calcium score (adjusted odds ratio [aOR], 1.79; 95% confidence interval [CI], 1.18-2.73; P = 0.006) and AoV Doppler-derived dP/dt (aOR, 1.52/100 mmHg/s higher dP/dt; 95% CI, 1.10-2.05; P = 0.012) were associated with progression to severe AS. CONCLUSION: AoV Doppler-derived dP/dt above 600 mmHg/s was associated with risk of AS progression to the severe stage in patients with mild to moderate AS. This may be useful in individualized surveillance strategies for AS progression.

Impact of low-density lipoprotein cholesterol on progression of aortic valve sclerosis and stenosis.

Background: Little research has been assessed atherosclerotic risk factors at various stages of calcific aortic valve disease. This study sought to determine risk factors of patients with aortic valve sclerosis (AVS) and mild to moderate aortic stenosis (AS). Methods: The study included 1,007 patients diagnosed with AVS or mild to moderate AS according to echocardiographic criteria. Patients were identified as a rapid progression group if the annualized difference in peak aortic jet velocity (Vmax) between two echocardiographic examinations was >0.08 m/s/yr in AVS and >0.3 m/s/yr in AS, respectively. We used multivariable logistic regression analyses to assess the factors associated with rapid disease progression or progression to severe AS. Results: Among 526 AVS patients, higher LDL-C level (odds ratio [OR] 1.22/per 25 mg/dl higher LDL-C, 95% confidence interval [CI] 1.05-1.43) was significantly associated with rapid disease progression. Compared to patients with LDL-C level <70 mg/dl, the adjusted OR for rapid progression were 1.32, 2.15, and 2.98 for those with LDL-C level of 70-95 mg/dl, 95-120 mg/dl, and ≥120 mg/dl, respectively. Among 481 mild to moderate AS patients, the baseline Vmax (OR 1.79/per 0.5 m/s higher Vmax, 95% CI 1.18-2.70) was associated with rapid progression. Compared to patients with Vmax 2.0-2.5 m/s, the adjusted OR for rapid progression were 2.47, 2.78, and 3.49 for those with Vmax of 2.5-3.0 m/s, 3.0-3.5 m/s, and 3.5-4.0 m/s, respectively. LDL-C and baseline Vmax values were independently associated with progression to severe AS. Conclusion: Atherosclerotic risk factors such as LDL-C were significantly associated with the rapid progression in AVS and baseline Vmax was important in the stage of mild to moderate AS.

The differences between daytime and nighttime heart rate variability may usefully predict the apnea-hypopnea index in patients with obstructive sleep apnea.

STUDY OBJECTIVES: The association between daytime/nighttime heart rate variability (HRV) and the apnea-hypopnea index (AHI) remains unclear. We sought a relationship between AHI and the daytime-to-nighttime HRV ratio as measured by 24-hour Holter monitoring in patients with obstructive sleep apnea. METHODS: We prospectively enrolled 66 patients who visited our sleep clinic complaining of habitual snoring or sleep apnea. All underwent 24-hour Holter monitoring (to measure HRV) combined with full-night polysomnography. Sixty-two met our enrollment criteria. We evaluated the associations between HRV frequency domains and the polysomnography indices. We also considered medical histories and anthropometric data. RESULTS: The nighttime very-low-frequency (VLF), low-frequency (LF), and high-frequency HRVs were significantly higher than the daytime values. On correlation analysis, the day/night VLF (r = .550, P < .001), LF (r = .556, P < .001), and high-frequency (r = .303, P = .017) HRVs were significantly related to the AHI. Of the day/night HRV ratios, the VLF (P for trend = .003) and LF (P for trend = .013) ratios decreased significantly by obstructive sleep apnea severity. Multivariable analysis showed that the day/night VLF (ß = 16.387, P < .001) and day/night LF (ß = 25.248, P < .001) were independently (and significantly) associated with the AHI. CONCLUSIONS: Twenty-four-hour Holter monitoring may usefully predict AHI. The day/night VLF and day/night LF ratios tended to decrease by obstructive sleep apnea severity and were independently associated with the AHI. CITATION: Nam E-C, Chun KJ, Won JY, Kim J-W, Lee WH. The differences between daytime and nighttime heart rate variability may usefully predict the apnea-hypopnea index in patients with obstructive sleep apnea. J Clin Sleep Med. 2022;18(6):1557-1563.

Higher heart rate variability as a predictor of atrial fibrillation in patients with hypertension.

The autonomic nervous system (ANS) plays an important role in the initiation and maintenance of atrial fibrillation (AF). However, the meaning of higher heart rate variability (HRV) in predicting AF remains unclear. Among 2100 patients in the Holter registry, a total of 782 hypertensive patients were included in this study. Baseline HRV was measured by time domain and frequency domain methods using 24-h Holter monitoring. The primary outcome was the development of AF. During an average follow-up of 1.1 years, 44 patients developed AF. Higher HRV parameters including high-frequency (P < 0.001), the square root of the mean squared differences of successive NN intervals (P < 0.001), and the percentage of NN intervals that are more than 50 ms different from the previous interval (P < 0.001) were associated with the occurrence of AF in univariate analysis. Premature atrial contractions burden, lower baseline heart rate, age, hemodialysis, coronary artery disease, and chronic heart failure were also associated with AF. In Cox regression analysis, higher HRV (representing excessive autonomic fluctuation) was an independent risk factor for AF. Excessive autonomic fluctuation represented by higher HRV in patients with hypertension was associated with an increased risk of AF.

SGLT2 Inhibitors and Kidney and Cardiac Outcomes According to Estimated GFR and Albuminuria Levels: A Meta-analysis of Randomized Controlled Trials.

RATIONALE & OBJECTIVE: There are few data on the absolute effects of sodium/glucose cotransporter 2 (SGLT2) inhibitors, despite their importance in treatment decision making. We investigated absolute treatment effects according to baseline kidney disease status. STUDY DESIGN: Meta-analysis. STUDY POPULATIONS: Adults with type 2 diabetes, chronic kidney disease, or heart failure. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials of SGLT2 inhibitors (10 trials to November 20, 2020) for clinical outcomes of kidney disease progression, heart failure events, and major cardiovascular events. DATA EXTRACTION: Publications of 10 trials to November 20, 2020. ANALYTICAL APPROACH: The incidence rate difference (IRD) between SGLT2 inhibitor and placebo was compared across estimated glomerular filtration rate (eGFR) or urinary albumin-creatinine ratio (UACR) subgroups. RESULTS: Subgroup analyses included data from seven trials (61,821 participants with diabetes or chronic kidney disease). SGLT2 inhibitor treatment, in eGFR subgroups of <45, 45 to <60, and ≥60 mL/min/1.73 m2, reduced 16.0, 9.5, and 1.9 heart failure events per 1,000 patient-year, respectively (P < 0.001 for heterogeneity). In urine UACR subgroups of >300, 30 to 300, and <30 mg/g, SGLT2 inhibitors reduced 17.3, 1.4, and 2.2 kidney disease events per 1,000 patient-year, respectively (P < 0.001 for heterogeneity), and 14.8, 8.7, and 2.1 heart failure events per 1,000 patient-year, respectively (P = 0.006 for heterogeneity). The pooled IRDs for major cardiovascular events were also greater in lower eGFR or overt albuminuria subgroups. In secondary analyses, risk differences calculated using pooled baseline and relative risks were comparable to the pooled IRDs, while the relative risk reductions for kidney and heart failure outcomes were consistent across the subgroups. For treatment-related harms, IRDs were similar between eGFR subgroups. LIMITATIONS: Study-level data rather than individual patient data were used. CONCLUSIONS: SGLT2 inhibitor treatment resulted in greater reductions of cardiovascular events in patients with lower eGFR and higher albuminuria and had substantially greater absolute benefits of renoprotection in patients with overt albuminuria than in their counterparts.

Necessity of acceptable radiologic alignment by preoperative closed reduction for unstable distal radius fractures treated with volar locking plates.

PURPOSE: The purpose of this study was to demonstrate the necessity of achieving acceptable radiographic alignment by preoperative closed reduction in unstable distal radius fractures (DRFs) to improve preoperative pain and obtain satisfactory outcomes after surgery. METHODS: From 2013 to 2016, patients who received volar locking plates for DRFs were retrospectively reviewed. Patients were classified into acceptable and non-acceptable reduction groups based on immediate post-reduction radiographs. To avoid potential bias, a matched-pair analysis was performed, and paired patients were categorized into non-acceptable reduction (group A) and acceptable reduction (group B) groups. Preoperative pain level, mean length of stay, operation time, postoperative complications, and surgical outcomes were analysed. The preoperative pain level and functional results were assessed by the visual analogue scale (VAS) and Disabilities of the Arm, Shoulder and Hand (DASH) scores. RESULTS: Of the 239 patients, 80 had non-acceptable and 159 had acceptable reductions. Among these patients, 201 (66 in group A vs. 135 in group B) were matched in a 1:2 matched ratio. Although the radiological parameters after closed reduction were better in group B, there were no significant differences in the preoperative pain VAS score, mean length of stay, operation time, and postoperative complications between the groups. In addition, radiologic parameters and the DASH score at a 1-year follow-up were also not significantly different between the groups. CONCLUSION: Our results suggest that obtaining acceptable radiologic alignment by closed reduction is not necessary for patients who make an informed decision to undergo volar plating for unstable DRFs.

Diagnostic Accuracy of Magnetic Resonance Imaging in the Detection of Type and Location of Meniscus Tears: Comparison with Arthroscopic Findings.

Magnetic resonance imaging (MRI) has been widely used for the diagnosis of meniscal tears, but its diagnostic accuracy, depending on the type and location, has not been well investigated. We aimed to evaluate the diagnostic accuracy of MRI by comparing MRI and arthroscopic findings. Preoperative 3.0-T MRI and arthroscopic findings from 2005 to 2018 were reviewed to determine the presence, type, and location of meniscus tears. In addition, subgroup analysis was performed according to anterior cruciate ligament (ACL) injury. The exclusion criteria were as follows: (1) Inflammatory arthritis, (2) other ligament injuries, (3) inability to classify meniscal tears due to degenerative arthritis, (4) over 90 days from MRI to surgery, and (5) incomplete data. Of the 2998 eligible patients, 544 were finally included. The sensitivity and specificity of MRI in determining medial and lateral meniscus tears were 91.8% and 79.9%, and 80.8% and 85.4%, respectively. The accuracy of MRI in the ACL-injured group was lower than that in the ACL-intact group (medial meniscus: 81.7% vs. 88.1%, p = 0.041; 72.9% vs. lateral meniscus: 88.0%, p < 0.001). MRI accuracy was low for the longitudinal tears of the posterior horn of the medial meniscus in the ACL-injured group. MRI could be a diagnostic tool for meniscus tears, but has limited accuracy in their classification of the type and location. Hence, care should be taken during arthroscopic assessment of ACL-injured patients due to low diagnostic accuracy of preoperative MRI.

Angiotensin converting enzyme inhibitors and incidence of lung cancer in a population based cohort of common data model in Korea.

Contradictory findings exist about association of angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) with lung cancer development. This was a retrospective observational cohort study that used data from 7 hospitals in Korea, converted to the Observational Medical Outcomes Partnership Common Data Model. The primary outcome was occurrence of lung cancer. A total of 207,794 patients across the 7 databases was included in the final analysis; 33,230 (16%) were prescribed ACEi and 174,564 (84%) were prescribed ARB. Crude analysis adjusted for sex and age showed higher incidence of lung cancer in the ACEi group compared to the ARB group (hazard ratio [HR], 1.46; 95% confidence rate [CI], 1.08-1.97). After propensity-score matching, 30,445 pairs were generated, and there was no difference in incidence of lung cancer between the two groups (HR, 0.93; 95% CI, 0.64-1.35). Patients prescribed ACEi showed no difference in incidence of lung cancer development compared to those using ARB. This finding provides evidence on the association between ACEi and occurrence of lung cancer.