Lymphangioleiomyomatosis as a potent lung cancer risk factor: Insights from a Japanese large cohort study.

BACKGROUND AND OBJECTIVE: Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease associated with the functional tumour suppressor genes TSC1 and TSC2 and causes structural destruction in the lungs, which could potentially increase the risk of lung cancer. However, this relationship remains unclear because of the rarity of the disease. METHODS: We investigated the relative risk of developing lung cancer among patients diagnosed with LAM between 2001 and 2022 at a single high-volume centre in Japan, using data from the Japanese Cancer Registry as the reference population. Next-generation sequencing (NGS) was performed in cases where tumour samples were available. RESULTS: Among 642 patients diagnosed with LAM (sporadic LAM, n = 557; tuberous sclerosis complex-LAM, n = 80; unclassified, n = 5), 13 (2.2%) were diagnosed with lung cancer during a median follow-up period of 5.13 years. All patients were female, 61.5% were never smokers, and the median age at lung cancer diagnosis was 53 years. Eight patients developed lung cancer after LAM diagnosis. The estimated incidence of lung cancer was 301.4 cases per 100,000 person-years, and the standardized incidence ratio was 13.6 (95% confidence interval, 6.2-21.0; p = 0.0008). Actionable genetic alterations were identified in 38.5% of the patients (EGFR: 3, ALK: 1 and ERBB2: 1). No findings suggested loss of TSC gene function in the two patients analysed by NGS. CONCLUSION: Our study revealed that patients diagnosed with LAM had a significantly increased risk of lung cancer. Further research is warranted to clarify the carcinogenesis of lung cancer in patients with LAM.

Antimicrobial therapy and outcome of methicillin-resistant Staphylococcus aureus endocarditis: A retrospective multicenter study in Japan.

BACKGROUND: MRSA (methicillin-resistant Staphylococcus aureus)-infective endocarditis (IE) is associated with high morbidity and mortality. This study aimed to assess data from patients with MRSA-IE across multiple facilities in Japan, with a specific focus on antimicrobial therapy and prognosis. METHODS: This retrospective study enrolled patients with a confirmed diagnosis of IE attributed to MRSA, spanning the period from January 2015 to April 2019. RESULTS: Sixty-four patients from 19 centers were included, with a median age of 67 years. The overall mortality rate was 28.1% at 30 days, with an in-hospital mortality of 45.3%. The most frequently chosen initial anti-MRSA agents were glycopeptide in 67.2% of cases. Daptomycin and linezolid were selected as initial therapy in 23.4% and 17.2% of cases, respectively. Approximately 40% of all patients underwent medication changes due to difficulty in controlling infection or drug-related side effects. Significant prognostic factors by multivariable analysis were DIC for 30-day mortality and surgical treatment for 30-day and in-hospital mortality. For vancomycin as initial monotherapy, there was a trend toward a worse prognosis for 30-day and in-hospital mortality (OR, 6.29; 95%CI, 1.00-39.65; p = 0.050, OR, 3.61; 95%CI, 0.93-14.00; p = 0.064). Regarding the choice of initial antibiotic therapy, statistical analysis did not show significant differences in prognosis. CONCLUSION: Glycopeptide and daptomycin were the preferred antibiotics for the initial therapy of MRSA-IE. Antimicrobial regimens were changed for various reasons. Prognosis was not significantly affected by choice of antibiotic therapy (glycopeptide, daptomycin, linezolid), but further studies are needed to determine which antimicrobials are optimal as first-line agents.

Physical Peculiarity of Two Sites in Human Promoters: Universality and Diverse Usage in Gene Function.

Since the discovery of physical peculiarities around transcription start sites (TSSs) and a site corresponding to the TATA box, research has revealed only the average features of these sites. Unsettled enigmas include the individual genes with these features and whether they relate to gene function. Herein, using 10 physical properties of DNA, including duplex DNA free energy, base stacking energy, protein-induced deformability, and stabilizing energy of Z-DNA, we clarified for the first time that approximately 97% of the promoters of 21,056 human protein-coding genes have distinctive physical properties around the TSS and/or position -27; of these, nearly 65% exhibited such properties at both sites. Furthermore, about 55% of the 21,056 genes had a minimum value of regional duplex DNA free energy within TSS-centered ±300 bp regions. Notably, distinctive physical properties within the promoters and free energies of the surrounding regions separated human protein-coding genes into five groups; each contained specific gene ontology (GO) terms. The group represented by immune response genes differed distinctly from the other four regarding the parameter of the free energies of the surrounding regions. A vital suggestion from this study is that physical-feature-based analyses of genomes may reveal new aspects of the organization and regulation of genes.

Association between the antiadhesion membrane and small bowel obstruction after open gastrectomy: A supplemental analysis of the randomized controlled JCOG1001 trial.

Aim: Postoperative small bowel obstruction (SBO) is one of the major complications that is mainly caused by postoperative adhesion. Recently, the antiadhesion membrane has become popular for postoperative SBO prevention. However, its efficacy is yet to be confirmed in the gastric cancer surgery field. Here, we conducted the supplemental analysis of the randomized controlled trial JCOG1001 to investigate the efficacy of the antiadhesion membrane on SBO prevention in patients with open gastrectomy for gastric cancer. Methods: Of the 1204 patients enrolled in JCOG1001, 1200 patients were included. The development of SBO of Grade ≥ IIIa according to the Clavien-Dindo classification was recorded. Univariable and multivariable analyses were performed using the Fine and Gray model to determine the risk factors for SBO. Results: Fifty-one patients developed SBO (median follow-up duration: 5.6 years). Total gastrectomy, combined resection, and blood loss significantly increased the risk for SBO development in the univariable analysis. Large amount of blood loss was independently associated with SBO development in the multivariable analysis (hazard ratio [HR], 3.089; 95% confidence interval [CI], 1.562-6.109, p = 0.0012). Antiadhesion membrane did not reduce the risk for SBO (HR, 1.299; 95% CI 0.683-2.470; p = 0.4246). In the patients belonging to subgroup analyses who received distal and total gastrectomy, the antiadhesion membrane was not associated with the incidence of SBO. Conclusions: Antiadhesion membrane did not decrease SBO occurrence rate after open gastrectomy. Therefore, the use of antiadhesion membrane would not be effective for preventing SBO in gastric cancer surgery.

Distinctive physical properties of DNA shared by RNA polymerase II gene promoters and 5'-flanking regions of tRNA genes.

Numerous noncoding (nc)RNAs have been identified. Similar to the transcription of protein-coding (mRNA) genes, long noncoding (lnc)RNA genes and most of micro (mi)RNA genes are transcribed by RNA polymerase II (Pol II). In the transcription of mRNA genes, core promoters play an indispensable role; they support the assembly of the preinitiation complex (PIC). However, the structural and/or physical properties of the core promoters of lncRNA and miRNA genes remain largely unexplored, in contrast with those of mRNA genes. Using the core promoters of human genes, we analyzed the repertoire and population ratios of residing core promoter elements (CPEs) and calculated the following five DNA physical properties (DPPs): duplex DNA free energy, base stacking energy, protein-induced deformability, rigidity and stabilizing energy of Z-DNA. Here, we show that their CPE and DPP profiles are similar to those of mRNA gene promoters. Importantly, the core promoters of these three classes of genes have two highly distinctive sites in their DPP profiles around the TSS and position -27. Similar characteristics in DPPs are also found in the 5'-flanking regions of tRNA genes, indicating their common essential roles in transcription initiation over the kingdom of RNA polymerases.

Ocular Adverse Events After Influenza Vaccination in Older Adults: Self-Controlled Case Series Using a Large Database in Japan.

BACKGROUND: To clarify the risk of adverse ocular events following influenza vaccination. METHODS: This self-controlled case series study used a claims database linked to vaccination records of a large city in Japan between April 2014 and September 2021. Individuals aged ≥ 65 years who developed adverse ocular events during the follow-up period were included. The exposure was influenza vaccination. The primary outcome was defined as the occurrence of at least one of the following five eye diseases: uveitis, scleritis, retinal vein occlusion, retinal artery occlusion, or optic neuritis. Conditional Poisson regression was used to estimate the within-subject incidence rate ratio of ocular adverse events during the risk period (0-56 days after vaccination) compared to the control period. RESULTS: A total of 4,527 cases were eligible for the study (median age, 74 years; male, 42%). The incidence rate ratio for the outcome during the risk period was 0.99 (95% confidence interval, 0.87 to 1.14). No increased risk was observed for individual components of the outcome either; the incidence rate ratio was 0.94 (0.78 to 1.13) for uveitis, 1.17 (0.86 to 1.59) for scleritis, 0.98 (0.76 to 1.27) for retinal vein occlusion, 0.89 (0.42 to 1.87) for retinal artery occlusion, and 0.87 (0.44 to 1.70) for optic neuritis. CONCLUSIONS: This self-controlled case series showed no apparent increase in the risk of adverse ocular events after influenza vaccination among older adults. These results mitigate the concerns of older adults who may hesitate to receive influenza vaccination for fear of adverse ocular events. ABBREVIATION: HR = hazard ratio; CI = confidence interval; RVO = retinal vein occlusion; SCCS = self-controlled case series.

Japan Trevo Registry: Real-world Registry of Stent Retriever Alone or in Combined Therapy with Aspiration Catheter for Acute Ischemic Stroke in Japan.

Endovascular therapy (EVT) for real-world patients after extended time frames is associated with concerns about its efficacy and safety. We conducted a prospective registry at 77 centers between November 2019 and October 2020. The registry criteria included patients treated with Trevo Retriever alone or in combined therapy with an aspiration catheter. The primary outcome was effective reperfusion (thrombolysis in cerebral infarction grade ≥ 2b), the secondary outcome was a modified Rankin scale 0-2 at 90 days, and the safety outcomes were worsening of neurologic symptoms within 24 h postoperatively, intracranial hemorrhage (ICH) within 24 h after EVT and mortality. We also exlpored the difference between patients whose last known well time (LKWT) to a puncture was less than 6 h (0-6 h) and those whose LKWT was 6 h or more but less than 24 h (6-24 h). Among the 1041 patients registered, 1025 patients were analyzed. The mean age was 76.9 years, and 53.6% of the participants were males. The 6-24 h group was 206/998 (20.6%), the median National Institute of Health Stroke Scale (NIHSS) score at admission was 18, and the median Alberta Stroke Program Early CT score was 8. Combined technique as the first pass was used on 817 (79.7%) patients. The primary outcome was 934 (91.1%). The secondary outcome was 433/1021 (42.4%). Symptomatic ICH, any ICH, and mortality were 10/1019 (1.0%), 311/1019 (30.5%), and 75 (7.3%). In the subanalysis, the 6-24 h group was lower in NIHSS (median;18 vs 16), and the secondary outcome was not significantly different in the <6 h group. Even after treatment time expansion, this result was comparable to other Trevo-based trials and nationwide registries.

Effectiveness of cefmetazole versus meropenem for invasive urinary tract infections caused by extended-spectrum ß-lactamase-producing Escherichia coli.

Cefmetazole is active against extended-spectrum ß-lactamase-producing Escherichia coli (ESBLEC) and is a potential candidate for carbapenem-sparing therapy. This multicenter, observational study included patients hospitalized for invasive urinary tract infection due to ESBLEC between March 2020 and November 2021 at 10 facilities in Japan, for whom either cefmetazole or meropenem was initiated as a definitive therapy within 96 h of culture collection and continued for at least 3 d. Outcomes included clinical and microbiological effectiveness, recurrence within 28 d, and all-cause mortality (14 d, 30 d, in-hospital). Outcomes were adjusted for the inverse probability of propensity scores for receiving cefmetazole or meropenem. Eighty-one and forty-six patients were included in the cefmetazole and meropenem groups, respectively. Bacteremia accounted for 43% of the cefmetazole group, and 59% of the meropenem group. The crude clinical effectiveness, 14 d, 30 d, and in-hospital mortality for patients in the cefmetazole and meropenem groups were 96.1% vs 90.9%, 0% vs 2.3%, 0% vs 12.5%, and 2.6% vs 13.3%, respectively. After propensity score adjustment, clinical effectiveness, the risk of in-hospital mortality, and the risk of recurrence were similar between the two groups (P = 0.54, P = 0.10, and P = 0.79, respectively). In all cases with available data (cefmetazole : n = 61, meropenem : n = 22), both drugs were microbiologically effective. In all isolates, bla CTX-M was detected as the extended-spectrum ß-lactamase gene. The predominant CTX-M subtype was CTX-M-27 (47.6%). Cefmetazole showed clinical and bacteriological effectiveness comparable to meropenem against invasive urinary tract infection due to ESBLECs.

Protocol of the RACB study: a multicenter, single-arm, prospective study to evaluate the efficacy of resection of initially unresectable hepatocellular carcinoma with atezolizumab combined with bevacizumab.

BACKGROUND: Although the standard therapy for advanced-stage hepatocellular carcinoma (HCC) is systemic chemotherapy, the combination of atezolizumab and bevacizumab (atezo + bev) with a high objective response rate may lead to conversion to resection in patients with initially unresectable HCC. This study aims to evaluate the efficacy of atezo + bev in achieving conversion surgery and prolonged progression-free survival (PFS) for initially unresectable HCC. METHODS: The RACB study is a prospective, single-arm, multicenter, phase II trial evaluating the efficacy of combination therapy with atezo + bev for conversion surgery in patients with technically and/or oncologically unresectable HCC. The main eligibility criteria are as follows: (1) unresectable HCC without a history of systemic chemotherapy, (2) at least one target lesion based on RECIST ver. 1.1, and (3) a Child‒Pugh score of 5-6. The definition of unresectable tumors in this study includes macroscopic vascular invasion and/or extrahepatic metastasis and massive distribution of intrahepatic tumors. Patients will be treated with atezolizumab (1200 mg/body weight) and bevacizumab (15 mg/kg) every 3 weeks. If the patient is considered resectable on radiological assessment 12 weeks after initial chemotherapy, the patient will be treated with atezolizumab monotherapy 3 weeks after combination chemotherapy followed by surgery 3 weeks after atezolizumab monotherapy. If the patient is considered unresectable, the patient will continue with atezo + bev and undergo a radiological assessment every 9 weeks until resectable or until disease progression. The primary endpoint is PFS, and the secondary endpoints are the overall response rate, overall survival, resection rate, curative resection rate, on-protocol resection rate, and ICG retention rate at 15 min after atezo + bev therapy. The assessments of safety and quality of life during the treatment course will also be evaluated. The number of patients has been set at 50 based on the threshold and the expected PFS rate at 6 months after enrollment of 40% and 60%, respectively, with a one-sided alpha error of 0.05 and power of 0.80. The enrollment and follow-up periods will be 2 and 1.5 years, respectively. DISCUSSION: This study will elucidate the efficacy of conversion surgery with atezo + bev for initially unresectable HCC. In addition, the conversion rate, safety and quality of life during the treatment course will also be demonstrated. TRIAL REGISTRATION: This study is registered in the Japan Registry of Clinical Trials (jRCTs051210148, January 7, 2022).

Plasma ANGPTL8 Levels and Risk for Secondary Cardiovascular Events in Japanese Patients With Stable Coronary Artery Disease Receiving Statin Therapy.

BACKGROUND: The ability to predict secondary cardiovascular events could improve health of patients undergoing statin treatment. Circulating ANGPTL8 (angiopoietin-like protein 8) levels, which positively correlate with proatherosclerotic lipid profiles, activate the pivotal proatherosclerotic factor ANGPTL3. Here, we assessed potential association between circulating ANGPTL8 levels and risk of secondary cardiovascular events in statin-treated patients. METHODS: We conducted a biomarker study with a case-cohort design, using samples from a 2018 randomized control trial known as randomized evaluation of high-dose (4 mg/day) or low-dose (1 mg/day) lipid-lowering therapy with pitavastatin in coronary artery disease (REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease])." From that study's full analysis set (n=12 413), we selected 2250 patients with stable coronary artery disease (582 with the primary outcome, 1745 randomly chosen, and 77 overlapping subjects). A composite end point including cardiovascular-related death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergent admission was set as a primary end point. Circulating ANGPTL8 levels were measured at baseline and 6 months after randomization. RESULTS: Over a 6-month period, ANGPTL8 level changes significantly decreased in the high-dose pitavastatin group, which showed 19% risk reduction of secondary cardiovascular events compared with the low-dose group in the REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease] study. In the highest quartiles, relative increases in ANGPTL8 levels were significantly associated with increased risk for secondary cardiovascular events, after adjustment for several cardiovascular disease risk factors and pitavastatin treatment (hazard ratio in Q4, 1.67 [95% CI, 1.17-2.39). Subgroup analyses showed relatively strong relationships between relative ANGPTL8 increases and secondary cardiovascular events in the high-dose pitavastatin group (hazard ratio in Q4, 2.07 [95% CI, 1.21-3.55]) and in the low ANGPTL8 group at baseline (166

Duration of influenza vaccine effectiveness in the elderly in Japan: A retrospective cohort study using large-scale population-based registry data.

BACKGROUND: The immune response to influenza vaccination in the elderly is likely to be lower than that in young adults. Clinical protection may not persist year-round in the elderly. However, the effectiveness of influenza vaccine in the elderly has not been adequately studied, especially in terms of the duration of effectiveness. METHODS: We used a linked database of healthcare administrative claims data and vaccination records maintained by the municipality of a city in Kanto region of Japan. We studied individuals who were aged 65 years or older at baseline and were followed up between April 1, 2014 to March 31, 2020. The duration of influenza vaccine effectiveness by age category was analyzed using a time-dependent piecewise Cox proportional hazard model with time-dependent vaccine status, prior season vaccination and covariates confirmed in the baseline period (age, sex, cancer, diabetes, chronic obstructive pulmonary diseases, asthma, chronic kidney diseases, and cardiovascular diseases). RESULTS: We identified an analysis population of 83,146 individuals, of which 7,401 (8.9%) had experienced influenza and 270 (0.32%) underwent influenza-related hospitalization. Individuals who were vaccinated during the first season (n = 47,338) were older than non-vaccinated individuals (n = 35,808) (average age, 75.8 vs. 74.1 years, respectively). The multivariable analysis showed a lower incidence of influenza in vaccinated individuals (hazard ratio [HR], 0.47; 95% confidence interval [CI], 0.43-0.51; P < 0.001), while the incidence of hospitalization for influenza did not differ significantly by vaccination status (HR, 0.79; 95% CI, 0.53-1.18; P = 0.249). Protective effectiveness against incidence was maintained for 4 or 5 months after vaccination in those aged 65-69 and 80-years, 5 months in 70-79 years. CONCLUSIONS: Our study identified moderate vaccine effectiveness in preventing the incidence of influenza in the Japanese elderly. Vaccine effectiveness showed a trend of gradual attenuation. Clinicians should suspect influenza infection even in those vaccinated, especially in elderly individuals who had received vaccination more than 4 or 5 months previously.

Effect of the 23-valent pneumococcal polysaccharide vaccine on the incidence of hospitalization with pneumonia in adults aged ≥65 years: retrospective cohort study using a population-based database in Japan.

OBJECTIVES: The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPV23) in preventing pneumonia in older adults remains controversial. Some studies have suggested differences in their effectiveness according to age or sex. METHODS: We conducted an observational study using a database of vaccine subsidization data and health insurance claims for a city in Japan. Participants were residents from 2014 to 2018 turning 65, 70, 75, 80, 85, 90, or 95 years during a given fiscal year, and PPV23 during the first year of observation were identified. We matched vaccinated and non-vaccinated individuals of the same age using propensity scores for vaccination. The incidence of hospitalization with pneumonia was compared using the Fine-Gray regression model. We summarized the results for each age using random-effects meta-analysis and conducted a subgroup analysis by sex. RESULTS: A total of 102 136 participants were included, of whom 35% received PPV23. Propensity score matching selected 32 510 pairs of vaccinated and non-vaccinated individuals. Overall, PPV23 administration was associated with a decreased incidence of hospitalization with pneumonia (17.2 vs. 20.4 per 1000 person-years, sub-distribution hazard ratio: 0.84, 95% CI: 0.77 to 0.91). Vaccine effectiveness was the highest among those aged 70 years and decreased with increasing age. No statistically significant effect was observed in those aged 90 or 95 years. Vaccine effectiveness was observed in both males and females. CONCLUSIONS: PPV23 was associated with an overall decrease in hospitalization with pneumonia in older adults. However, vaccine effectiveness was significant in those aged 65 to 85 years but not in the older population.

Effectiveness of vaccination on influenza-related critical illnesses in the elderly population.

OBJECTIVES: The prevention of serious influenza-related severe conditions due to influenza is important, particularly in elderly patients, age is a risk factor for death resulting from influenza-related respiratory diseases. The aim of the present study was to investigate the association of influenza vaccination with severe condition requiring critical care and death in elderly people, using vaccine records and healthcare administrative claims data in a Japanese city. RESULTS: Among 5608 patients aged ≥65 years diagnosed with influenza, we identified 96 patients who had received invasive mechanical ventilation or died. Thereafter, we matched 384 controls with the cases. The cases were less vaccinated than the controls (37.5% vs. 56.0%, P < 0.01). In the multivariate analysis, influenza vaccination was associated with a lower proportion of the composite outcome (odds ratio, 0.35; 95% confidence interval, 0.21-0.60). In patients aged ≥80 years old and those with cardiovascular disease, influenza vaccination was associated with low composite outcomes. CONCLUSIONS: Influenza vaccination was associated with reduced proportions of receiving invasive mechanical ventilation or influenza-related mortality, particularly in those aged ≥80 years old.

Late complication after gastrectomy for clinical stage I cancer: supplementary analysis of JCOG0912.

BACKGROUND: Late complications following gastric cancer surgery, including postgastrectomy syndromes, are complex problems requiring a solution. Reported risk factors for developing late complications include surgery-related factors, such as the surgical approach and the extent of resection and reconstruction. However, this has not been assessed in a prospective study with a large sample size. Therefore, this study aimed to evaluate associations between surgery-related factors and the development of late complications. Data from the JCOG0912 trial were used. It compared laparoscopy-assisted distal gastrectomy (LADG) to open distal gastrectomy (ODG) in clinical stage I gastric cancer patients. METHODS: This study included 881/921 patients enrolled in the JCOG0912 trial. The incidence of late complications was compared between the ODG and the LADG arms. In addition, associations between surgery-related factors and the development of late complications were assessed by multivariable analyses using the proportional odds model to identify relevant risk factors. RESULTS: There was no difference in the type or number of patients with late complications between the LADG and the ODG arms. The multivariable analysis for each late complication revealed that the Billroth-I reconstruction (vs. R-en-Y or Billroth-II) had a lower risk of cholecystitis [odds ratio (OR) 0.187, 95% confidence interval (CI) 0.039-0.905, P = 0.037] or ileus (OR 0.116, 95%CI 0.033-0.406, P < 0.001), and pylorus-preserving gastrectomy (vs. R-en-Y or Billroth-II) had a higher risk of reflux esophagitis (OR 3.348, 95% CI 1.371-8.176, P = 0.008). The surgical approach was not a risk factor for any late complications. CONCLUSION: Differences in surgical approaches did not constitute a risk for developing late complications after gastrectomy. Billroth-I reconstruction reduced the risk of ileus and cholecystitis, but pylorus-preserving gastrectomy carried a risk for reflux esophagitis.

Ocular Adverse Events after Coronavirus Disease 2019 mRNA Vaccination: Matched Cohort and Self-Controlled Case Series Studies Using a Large Database.

PURPOSE: To investigate the risk of ocular adverse events after Coronavirus Disease 2019 (COVID-19) mRNA vaccination. DESIGN: Matched cohort and self-controlled case series (SCCS) studies. PARTICIPANTS: We used a population-based database of medical claims and vaccination records in a large Japanese city. In the matched cohort study, we identified individuals who received COVID-19 vaccination (BNT162b2) from February 2021 to September 2021. One control was selected from nonvaccinated individuals by matching time, date of birth, sex, Charlson comorbidity index, and the enrollment period for health insurance. In the SCCS study, we analyzed individuals who developed ocular adverse events. METHODS: In the matched cohort study, we applied the Kaplan-Meier estimator to estimate the cumulative incidence of ocular adverse events over 21 days after the first dose and 84 days after the second dose. In the SCCS method, we used conditional Poisson regression to estimate the incidence rate ratio (IRR) of ocular adverse events during the risk periods (0-21 days after the first dose and 0-84 days after the second dose) compared with the remaining periods. MAIN OUTCOME MEASURES: Composite outcome of uveitis, scleritis, retinal vein occlusion (RVO), and optic neuritis. RESULTS: There were 99 718 pairs eligible for the matched cohort study after the first dose (mean age, 69.3 years; male, 44%). The vaccinated and control groups developed 29 and 21 events, respectively, over 21 days after the first dose, and 79 and 28 events, respectively, over 84 days after the second dose. The differences in cumulative incidence (reference, the control group) were 2.9 (95% confidence interval, -14.5 to 19.1) events/100 000 persons and 51.3 (16.2-84.3) events/100 000 persons, respectively, for the first and second doses. The SCCS study showed the IRRs of 0.89 (0.62-1.28) and 0.89 (0.71-1.11) for the first and second doses, respectively. CONCLUSIONS: The matched cohort analysis found an increased risk for the composite outcome after the second dose; however, the SCCS analysis showed no increased risk. Considering that the SCCS can cancel out time-invariant confounders, the current results suggest that COVID-19 vaccination is unlikely to causally increase the risk of ocular adverse events. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Surgical aortic valve replacement provides better left ventricular mass regression than transcatheter aortic valve replacement in patients with small aortic annulus.

OBJECTIVES: This study aimed to evaluate the incidence of patient-prosthesis mismatch (PPM) and degree of left ventricular (LV) mass regression after surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) in patients with small aortic annulus (defined as annular diameter of ≤ 21 mm). METHODS: We retrospectively analyzed echocardiographic findings in total of 277 patients with aortic stenosis and small aortic annulus (63 underwent SAVR and 214 underwent TAVR) between October 2013 and March 2019. PPM was defined as an effective orifice area index (EOAI) ≤ 0.85 cm2/m2. LV mass regression was evaluated as percentage change in LV mass index (LVMI) from baseline to the 1-year follow-up. RESULTS: The median EOAI before discharge was slightly larger in the TAVR group than in the SAVR group (1.09 vs. 1.07 cm2/m2; P = 0.030). However, the incidence of PPM before discharge (9.4 vs. 12.7%; P = 0.438) and at the 1-year follow-up (11.7 vs. 11.1%; P = 0.901) was similar between groups. Mild or greater paravalvular leakage (PVL) after the procedure was more frequent in the TAVR group (11.7 vs. 0%; P = 0.002). Reduction in LVMI was significantly higher in the SAVR group (19.3 vs. 6.4%; P < 0.001). Multivariate analysis demonstrated that reduction in LVMI was positively associated with higher baseline transaortic pressure gradient (P < 0.001) and higher baseline LVMI (P < 0.001) and negatively associated with older age (P < 0.001) and mild or greater PVL (P < 0.001). CONCLUSIONS: SAVR provides better LV mass regression than TAVR with a comparable rate of PPM in patients with small aortic annulus.

Usefulness of LacdiNAc-glycosylated Prostate-specific Antigen Density for Predicting Pathological Findings of Magnetic Resonance Imaging-transrectal Ultrasound Fusion Image-guided Prostate Biopsy for the Patients With Highest Prostate Imaging Reporting and Data System Category ≥3.

PURPOSE: This study aimed to evaluate the usefulness of the LDN-PSA (LacdiNAc-glycosylated-prostate specific antigen) in detecting clinically significant prostate cancer in patients suspected of having clinically significant prostate cancer on multiparametric magnetic resonance imaging. MATERIALS AND METHODS: Patients with prostate specific antigen levels ranging between 3.0 ng/mL and 20 ng/mL and suspicious lesions with PI-RADS (Prostate Imaging-Reporting and Data System) category ≥3 were included prospectively. The LDN-PSA was measured using an automated 2-step Wisteria floribunda agglutinin lectin-anti-prostate specific antigen antibody sandwich immunoassay. RESULTS: Two hundred four patients were included. Clinically significant prostate cancer was detected in 105 patients. On multivariable logistic regression analysis, prostate specific antigen density (OR 1.61, P = .010), LDN-PSAD (OR 1.04, P = .012), highest PI-RADS category (3 vs 4, 5; OR 14.5, P < .0001), and location of the lesion with highest PI-RADS category (transition zone vs peripheral zone) (OR 0.34, P = .009) were significant risk factors for detecting clinically significant prostate cancer. Among the patients with the highest PI-RADS category 3 (n=113), clinically significant prostate cancer was detected in 28 patients. On multivariable logistic regression analysis to predict the detection of clinically significant prostate cancer in patients with the highest PI-RADS category 3, age (OR 1.10, P = .026) and LDN-PSAD (OR 1.07, P < .0001) were risk factors for detecting clinically significant prostate cancer. CONCLUSIONS: LDN-PSAD would be a biomarker for detecting clinically significant prostate cancer in patients with prostate specific antigen levels ≤20 ng/mL and suspicious lesions with PI-RADS category ≥3. The use of LDN-PSAD as an adjunct to the use of prostate specific antigen levels would avoid unnecessary biopsies in patients with the highest PI-RADS category 3. Multi-institutional studies with large population are recommended.

Comparative Effectiveness of BNT162b2 and mRNA-1273 Booster Dose After BNT162b2 Primary Vaccination Against the Omicron Variants: A Retrospective Cohort Study Using Large-Scale Population-Based Registries in Japan.

BACKGROUND: Direct comparative effectiveness of booster doses of BNT162b2 and mRNA-1273 after BNT162b2 primary vaccination is unknown. METHODS: We investigated comparative effectiveness of BNT162b2 and mRNA-1273 booster dose using data from registry systems for vaccination and coronavirus disease 2019 (COVID-19) infection in a local city in Japan. We followed participants aged ≥16 years who completed the BNT162b2 primary vaccination between 22 November 2021, and 15 April 2022. We collected information on age, sex, vaccination status, vaccine type, and infection status. Age was categorized as 16-44, 45-64, 65-84, and ≥85 years. Vaccine effectiveness for mRNA-1273 and no booster vaccination against BNT162b2 was estimated using age-stratified Cox regression adjusted for age, sex, and days since the second vaccination. The estimated hazard ratios for mRNA-1273 and no booster vaccinations were integrated separately using random effects meta-analyses. RESULTS: During the study period, we identified 62 586 (40.4%), 51 490 (33.2%), and 40 849 (26.4%) participants who received BNT162b2, mRNA-1273, and no booster dose, respectively. The median age was 69, 71, and 47 years for BNT162b2, mRNA-1273, and no booster dose, respectively. The integrated hazard ratio with reference to BNT162b2 was 1.72 for no booster vaccination and 0.62 for mRNA-1273. The comparative effectiveness of mRNA-1273 was similar across age categories. CONCLUSIONS: Both homologous and heterologous vaccinations are effective against Omicron variants. In the head-to-head comparison, the effect was stronger in people who received heterologous vaccination than in those who received homologous vaccination. These findings may help improve logistics and decision making in future vaccination programs.

The disease severity of COVID-19 caused by Omicron variants: A brief review.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in November 2021 and spread worldwide. This review summarizes the reported mortality and morbidity rates of coronavirus disease (COVID-19) caused by Omicron variants. In 21 previous studies, the mortality of patients infected with Omicron variants ranged from 0.01 to 13.1%, whereas that of those infected with previous variants was from 0.08% to 29.1%. The proportions of intensive care unit admissions and mechanical ventilation were lower for Omicron variants than for the previous variants. Future studies should clarify the mechanisms of transmissibility and severity of COVID-19 caused by the Omicron variants.