Objective: To evaluate the prognostic impact of radiologic and pathologic features in patients with interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF), and to identify the factors associated with the development of progressive pulmonary fibrosis (PPF) and survival. Materials and Methods: This study retrospectively enrolled 75 patients diagnosed with ILD other than IPF who underwent surgical lung biopsy between January 2004 and December 2020. Three chest radiologists independently reviewed the CT features and extent of fibrosis on preoperative and follow-up CT scans. Two pathologists reviewed the histopathological features, including the presence of interstitial pneumonia. The time to PPF and overall survival were estimated using the Kaplan-Meier method. The associations of CT and pathological features with PPF and all-cause mortality were examined using standard Cox regression and time-dependent Cox models, respectively. Results: A total of 75 non-IPF ILD patients (mean age ± standard deviations 56.4 ± 13.2 years; range, 40–88 years) were enrolled. The median follow-up duration was 75.3 months (range, 7.8–189.8 months). Traction bronchiectasis on CT (adjusted hazard ratio [HR], 6.40; P = 0.003) and body mass index (adjusted HR per 1-kg/m2 increase, 0.82; P = 0.002) were found to be significantly associated with PPF in multivariable analysis. Radiological progression (adjusted HR, 18.44;P < 0.001), symptomatic progression (adjusted HR, 4.19; P = 0.011), and age (adjusted HR for 1-year increase, 1.12; P < 0.001) were significantly associated with death. Conclusion Traction bronchiectasis on CT was a significant predictor of PPF, while radiologic and symptomatic progression and older age were associated with poorer survival in patients with ILD other than IPF. These findings indicate that careful radiological evaluation and symptom monitoring may help to predict disease progression and outcomes in patients with nonIPF ILD.

Background: and Purpose Whether perfusion-diffusion mismatch modifies treatment effect of mechanical thrombectomy (MT) for large strokes is poorly known. To address this question, we conducted a post hoc secondary analysis of the Large Stroke Therapy Evaluation (LASTE) randomized controlled trial (RCT). Methods: The LASTE RCT compared MT plus best medical treatment (BMT) to BMT alone in patients with large infarct (Alberta Stroke Program Early CT Score 0–5) in the 0–7-hour timewindow. This secondary analysis was restricted to patients with available baseline MR perfusionweighted imaging. We investigated the potential heterogeneity of MT treatment according to the presence of perfusion-diffusion mismatch, defined as a mismatch ratio ≥1.2, calculated as the time-to-maximum >6 seconds cerebral volume divided by ischemic core volume. The primary outcome was better functional outcome (favorable shift in the distribution of modified Rankin Scale [mRS] at 90 days, analyzed using generalized odds ratio [GenOR]). Results: A total of 102/324 patients were included, among whom 55 (54%) had a perfusiondiffusion mismatch. No significant treatment effect heterogeneity by diffusion-perfusion mismatch was observed for the primary outcome (GenOR for better functional outcome: 1.70 [95% confidence interval, CI, 0.95 to 3.05] and 1.04 [95% CI, 0.57 to 1.87] in patients with and without mismatch, respectively; ratio of GenORs: 1.63 [95% CI, 0.71 to 3.74]; P for heterogeneity=0.24) or for the secondary efficacy and safety outcomes. Conclusions Our study found no evidence of heterogeneity of treatment effect with respect to benefit or safety in patients with unrestricted infarct size at baseline treated with MT by presence of perfusion-diffusion mismatch. An individual participant-data meta-analysis of RCT is needed for definitive conclusions.

This study aimed to investigate changes in candidemia incidence, species distribution, antifungal susceptibility, initial antifungal use, and mortality trends in Korea before and during the COVID-19 pandemic. A retrospective analysis was conducted on candidemia cases from two tertiary care hospitals in Korea between 2017 and 2022. Data were compared between the pre-pandemic (2017-2019) and pandemic (2020-2022) periods. Statistical methods included incidence rate ratios (IRRs) and multivariate Cox regression to assess 30-day mortality risk factors. A total of 470 candidemia cases were identified, with 48.7% occurring pre-pandemic and 51.3% during the pandemic. While the overall incidence of candidemia remained similar across the two periods (IRR 1.15;p=0.13), the incidence in intensive care units (ICUs) significantly increased during the pandemic (IRR 1.50; p<0.01). The distribution of Candida species did not differ significantly between the two periods. Fluconazole non-susceptibility in C. albicans markedly decreased (10.0% vs. 0.9%, p<0.01), whereas C. glabrata exhibited a significant rise in caspofungin non-susceptibility during the pandemic (0% vs. 22.4%, p<0.01).Echinocandin use increased (21.8% vs. 34.4%; p<0.01), while fluconazole use declined (48.0% vs. 32.8%; p<0.01). Although the 30-day mortality rate was higher during the pandemic (60.2% vs. 57.2%), the difference was not statistically significant (p=0.57).The findings highlight the need for region-specific surveillance and tailored management strategies to improve candidemia outcomes, especially during healthcare disruptions like the COVID-19 pandemic.

This study aimed to investigate changes in candidemia incidence, species distribution, antifungal susceptibility, initial antifungal use, and mortality trends in Korea before and during the COVID-19 pandemic. A retrospective analysis was conducted on candidemia cases from two tertiary care hospitals in Korea between 2017 and 2022. Data were compared between the pre-pandemic (2017-2019) and pandemic (2020-2022) periods. Statistical methods included incidence rate ratios (IRRs) and multivariate Cox regression to assess 30-day mortality risk factors. A total of 470 candidemia cases were identified, with 48.7% occurring pre-pandemic and 51.3% during the pandemic. While the overall incidence of candidemia remained similar across the two periods (IRR 1.15;p=0.13), the incidence in intensive care units (ICUs) significantly increased during the pandemic (IRR 1.50; p<0.01). The distribution of Candida species did not differ significantly between the two periods. Fluconazole non-susceptibility in C. albicans markedly decreased (10.0% vs. 0.9%, p<0.01), whereas C. glabrata exhibited a significant rise in caspofungin non-susceptibility during the pandemic (0% vs. 22.4%, p<0.01).Echinocandin use increased (21.8% vs. 34.4%; p<0.01), while fluconazole use declined (48.0% vs. 32.8%; p<0.01). Although the 30-day mortality rate was higher during the pandemic (60.2% vs. 57.2%), the difference was not statistically significant (p=0.57).The findings highlight the need for region-specific surveillance and tailored management strategies to improve candidemia outcomes, especially during healthcare disruptions like the COVID-19 pandemic.

This study aimed to investigate changes in candidemia incidence, species distribution, antifungal susceptibility, initial antifungal use, and mortality trends in Korea before and during the COVID-19 pandemic. A retrospective analysis was conducted on candidemia cases from two tertiary care hospitals in Korea between 2017 and 2022. Data were compared between the pre-pandemic (2017-2019) and pandemic (2020-2022) periods. Statistical methods included incidence rate ratios (IRRs) and multivariate Cox regression to assess 30-day mortality risk factors. A total of 470 candidemia cases were identified, with 48.7% occurring pre-pandemic and 51.3% during the pandemic. While the overall incidence of candidemia remained similar across the two periods (IRR 1.15;p=0.13), the incidence in intensive care units (ICUs) significantly increased during the pandemic (IRR 1.50; p<0.01). The distribution of Candida species did not differ significantly between the two periods. Fluconazole non-susceptibility in C. albicans markedly decreased (10.0% vs. 0.9%, p<0.01), whereas C. glabrata exhibited a significant rise in caspofungin non-susceptibility during the pandemic (0% vs. 22.4%, p<0.01).Echinocandin use increased (21.8% vs. 34.4%; p<0.01), while fluconazole use declined (48.0% vs. 32.8%; p<0.01). Although the 30-day mortality rate was higher during the pandemic (60.2% vs. 57.2%), the difference was not statistically significant (p=0.57).The findings highlight the need for region-specific surveillance and tailored management strategies to improve candidemia outcomes, especially during healthcare disruptions like the COVID-19 pandemic.

Background: We investigated osteoporosis management strategies and clinical outcomes following the occurrence of medicationrelated osteonecrosis of the jaw (MRONJ). Methods: We retrospectively studied individuals diagnosed with MRONJ during osteoporosis treatment who were managed in the Osteoporosis Center or the Oral Maxillofacial Surgery & Dental Unit at Queen Mary Hospital in Hong Kong between 2010 and 2022. We examined subsequent osteoporosis management plans, fracture events, and bone mineral density (BMD). Results: Thirty-six individuals were included (mean age, 78.5 years; 94.4% women). The estimated prevalence of MRONJ was 0.26%. All patients had been exposed to bisphosphonates, and seven had also received denosumab before MRONJ. Following MRONJ, only 14 individuals continued anti-osteoporosis treatment, a decision influenced by a higher fracture probability at MRONJ onset. The most common regimen was a teriparatide-raloxifene sequence (n=8): three patients achieved stable BMD, four achieved improving BMD, and one exhibited a mixed response. The patient with a mixed BMD response had also been treated with denosumab. Six patients sustained incident fractures after MRONJ, and these patients had lower BMD T-scores than their counterparts. Two patients experienced MRONJ recurrence, which was associated with the resumption of bisphosphonate or denosumab therapy after MRONJ. These patients had higher BMD T-scores than those who did not experience MRONJ recurrence. Conclusion MRONJ is challenging because high fracture risk necessitates discontinuation of antiresorptive agents. Teriparatide followed by raloxifene may be a reasonable regimen. Individualised decisions in osteoporosis management after MRONJ are required to balance fracture risk reduction with minimising MRONJ recurrence.

Prior research suggests metformin has anti-cancer effects, yet data are limited. We examined the association between diabetes treatment (metformin versus sulfonylurea) and risk of incident diabetes-related and non- diabetes-related cancers in US veterans.This retrospective cohort study included US veterans, without cancer, aged ≥ 55 years, who were new users of metformin or sulfo-nylureas for diabetes between 2001 to 2012. Cox proportional hazards models, with propensity score-matched inverse probability of treatment weighting (IPTW) were constructed. A total of 88,713 veterans (mean age 68.6 ± 7.8 years; 97.7% male; 84.1% White, 12.6% Black, 3.3% other race) were followed for 4.2 ± 3.0 years. Among metformin users (n = 60,476), there were 858 incident diabetes-related cancers (crude incidence rate [IR; per 1,000 person-years] = 3.4) and 3,533 non-diabetes-related cancers (IR = 14.1). Among sulfonylurea users (n = 28,237), there were 675 incident diabetes-related cancers (IR = 5.5) and 2,316 non-diabetes-related cancers (IR = 18.9). After IPTW adjustment, metformin use was associated with a lower risk of incident diabetes-related cancer (hazard ratio [HR] = 0.66, 95% CI 0.58-0.75) compared to sulfonylurea use. There was no association between treatment group (metformin versus sulfonylurea) and non-diabetes-related cancer (HR = 0.96, 95% CI 0.89-1.02). Of diabetes-related cancers, metformin users had lower incidence of liver (HR = 0.39, 95% CI 0.28-0.53), colorectal (HR = 0.75, 95% CI 0.62-0.92), and esophageal cancers (HR = 0.54, 95% CI 0.36-0.81). Among US veterans, metformin users had lower incidence of diabetes-related cancer, particularly liver, colorectal, and esophageal cancers, as compared to sulfonylurea users. Use of metformin was not associated with non-diabetes-related cancer. Further studies are needed to understand how metformin use impacts cancer incidence in different patient populations.

Prior research suggests metformin has anti-cancer effects, yet data are limited. We examined the association between diabetes treatment (metformin versus sulfonylurea) and risk of incident diabetes-related and non- diabetes-related cancers in US veterans.This retrospective cohort study included US veterans, without cancer, aged ≥ 55 years, who were new users of metformin or sulfo-nylureas for diabetes between 2001 to 2012. Cox proportional hazards models, with propensity score-matched inverse probability of treatment weighting (IPTW) were constructed. A total of 88,713 veterans (mean age 68.6 ± 7.8 years; 97.7% male; 84.1% White, 12.6% Black, 3.3% other race) were followed for 4.2 ± 3.0 years. Among metformin users (n = 60,476), there were 858 incident diabetes-related cancers (crude incidence rate [IR; per 1,000 person-years] = 3.4) and 3,533 non-diabetes-related cancers (IR = 14.1). Among sulfonylurea users (n = 28,237), there were 675 incident diabetes-related cancers (IR = 5.5) and 2,316 non-diabetes-related cancers (IR = 18.9). After IPTW adjustment, metformin use was associated with a lower risk of incident diabetes-related cancer (hazard ratio [HR] = 0.66, 95% CI 0.58-0.75) compared to sulfonylurea use. There was no association between treatment group (metformin versus sulfonylurea) and non-diabetes-related cancer (HR = 0.96, 95% CI 0.89-1.02). Of diabetes-related cancers, metformin users had lower incidence of liver (HR = 0.39, 95% CI 0.28-0.53), colorectal (HR = 0.75, 95% CI 0.62-0.92), and esophageal cancers (HR = 0.54, 95% CI 0.36-0.81). Among US veterans, metformin users had lower incidence of diabetes-related cancer, particularly liver, colorectal, and esophageal cancers, as compared to sulfonylurea users. Use of metformin was not associated with non-diabetes-related cancer. Further studies are needed to understand how metformin use impacts cancer incidence in different patient populations.

Background: We evaluated changes in glycemic status, over 1 year, of coronavirus disease 2019 (COVID-19) survivors with dysglycemia in acute COVID-19. Methods: COVID-19 survivors who had dysglycemia (defined by glycosylated hemoglobin [HbA1c] 5.7% to 6.4% or random glucose ≥10.0 mmol/L) in acute COVID-19 were recruited from a major COVID-19 treatment center from September to October 2020. Matched non-COVID controls were recruited from community. The 75-g oral glucose tolerance test (OGTT) were performed at baseline (6 weeks after acute COVID-19) and 1 year after acute COVID-19, with HbA1c, insulin and C-peptide measurements. Progression in glycemic status was defined by progression from normoglycemia to prediabetes/diabetes, or prediabetes to diabetes. Results: Fifty-two COVID-19 survivors were recruited. Compared with non-COVID controls, they had higher C-peptide (P< 0.001) and trend towards higher homeostasis model assessment of insulin resistance (P=0.065). Forty-three COVID-19 survivors attended 1-year reassessment. HbA1c increased from 5.5%±0.3% to 5.7%±0.2% (P<0.001), with increases in glucose on OGTT at fasting (P=0.089), 30-minute (P=0.126), 1-hour (P=0.014), and 2-hour (P=0.165). At baseline, 19 subjects had normoglycemia, 23 had prediabetes, and one had diabetes. Over 1 year, 10 subjects (23.8%; of 42 non-diabetes subjects at baseline) had progression in glycemic status. C-peptide levels remained unchanged (P=0.835). Matsuda index decreased (P=0.007) and there was a trend of body mass index increase from 24.4±2.7 kg/m2 to 25.6±5.2 (P=0.083). Subjects with progression in glycemic status had more severe COVID-19 illness than non-progressors (P=0.030). Reassessment was not performed in the control group. Conclusion Subjects who had dysglycemia in acute COVID-19 were characterized by insulin resistance. Over 1 year, a quarter had progression in glycemic status, especially those with more severe COVID-19. Importantly, there was no significant deterioration in insulin secretory capacity.

Prior research suggests metformin has anti-cancer effects, yet data are limited. We examined the association between diabetes treatment (metformin versus sulfonylurea) and risk of incident diabetes-related and non- diabetes-related cancers in US veterans.This retrospective cohort study included US veterans, without cancer, aged ≥ 55 years, who were new users of metformin or sulfo-nylureas for diabetes between 2001 to 2012. Cox proportional hazards models, with propensity score-matched inverse probability of treatment weighting (IPTW) were constructed. A total of 88,713 veterans (mean age 68.6 ± 7.8 years; 97.7% male; 84.1% White, 12.6% Black, 3.3% other race) were followed for 4.2 ± 3.0 years. Among metformin users (n = 60,476), there were 858 incident diabetes-related cancers (crude incidence rate [IR; per 1,000 person-years] = 3.4) and 3,533 non-diabetes-related cancers (IR = 14.1). Among sulfonylurea users (n = 28,237), there were 675 incident diabetes-related cancers (IR = 5.5) and 2,316 non-diabetes-related cancers (IR = 18.9). After IPTW adjustment, metformin use was associated with a lower risk of incident diabetes-related cancer (hazard ratio [HR] = 0.66, 95% CI 0.58-0.75) compared to sulfonylurea use. There was no association between treatment group (metformin versus sulfonylurea) and non-diabetes-related cancer (HR = 0.96, 95% CI 0.89-1.02). Of diabetes-related cancers, metformin users had lower incidence of liver (HR = 0.39, 95% CI 0.28-0.53), colorectal (HR = 0.75, 95% CI 0.62-0.92), and esophageal cancers (HR = 0.54, 95% CI 0.36-0.81). Among US veterans, metformin users had lower incidence of diabetes-related cancer, particularly liver, colorectal, and esophageal cancers, as compared to sulfonylurea users. Use of metformin was not associated with non-diabetes-related cancer. Further studies are needed to understand how metformin use impacts cancer incidence in different patient populations.