Purpose: To investigate the outcomes of brolucizumab reinjection after intraocular inflammation (IOI) development. Methods: This retrospective study analyzed patients with brolucizumab injections from April 2021 to January 2024. Patients who developed IOI after brolucizumab were included and categorized into subgroups depending on reinjection, discontinuation, and further IOI development. Results: A total of 472 eyes of 432 patients received brolucizumab injections. Thirty-eight cases developed IOI at least once, and 25 continued brolucizumab. Sixteen cases had no more IOI events, and nine experienced a second or more IOI events. Among the nine cases, three maintained brolucizumab injections despite IOI recurrence. The incidence of IOI was 8.1% based on the number of eyes (38 of 472 eyes) and 2.0% based on the number of brolucizumab injections (50 of 2,468 injections). The incidence of occlusive retinal vasculitis was 0.2% (1 of 472 eyes). The recurrence rate was 23.7% (9 of 38 eyes). The average number of injections between the first brolucizumab injection and the injection date on which IOI first developed was 2.15 times in the no-reinjection group, 3.44 times in the no-IOI-recurrence group, and 2.0 times in the second-IOI-episode group. Time to IOI occurrence in cases with first IOI episode was 18.60 ± 16.73 days, with 15 cases developing IOI within 1 week. Conclusions This study elucidates the real-world incidence of brolucizumab associated IOIs, with a description of information related to reinjections after the IOI episodes. A comprehensive understanding of brolucizumab reinjection is essential for its optimal utilization.

Intraflagellar transport (IFT) particles, a multi-protein apparatus composed of complex A and B, are known to be involved in homeostasis of flagella formation. IFT particles have recently become an interesting topic in Giardia lamblia, which has 4 pairs of flagella. In this experiment, we examined the function of giardial IFT components. When 7 components (IFT121, 140, 20, 46, 52, 81, and 88) of IFT were expressed in Giardia trophozoites as a tagged form with mNeonGreen, all of them were found in both flagella pores and cytoplasmic axonemes. In addition, motor proteins for IFT particles (kinesin-13 and kinesin-2b), were localized to a median body and cytoplasmic flagella, respectively. The CRISPRi-mediated knockdown of IFT88 significantly affected the lengths of all 4 flagella compared to the control cells, Giardia expressing dead Cas9 using control guide RNA. Decreased expression of kinesin-2b also resulted in shortening of flagella, excluding the ventral flagella. Live Giardia cells expressing IFT88-mNeonGreen clearly demonstrated fluorescence in flagella pores and cytoplasmic axonemes. These results on IFT88 and kinesin-2b indicate that IFT complex plays a role in maintenance of G. lamblia flagella.

Purpose: To investigate the outcomes of brolucizumab reinjection after intraocular inflammation (IOI) development. Methods: This retrospective study analyzed patients with brolucizumab injections from April 2021 to January 2024. Patients who developed IOI after brolucizumab were included and categorized into subgroups depending on reinjection, discontinuation, and further IOI development. Results: A total of 472 eyes of 432 patients received brolucizumab injections. Thirty-eight cases developed IOI at least once, and 25 continued brolucizumab. Sixteen cases had no more IOI events, and nine experienced a second or more IOI events. Among the nine cases, three maintained brolucizumab injections despite IOI recurrence. The incidence of IOI was 8.1% based on the number of eyes (38 of 472 eyes) and 2.0% based on the number of brolucizumab injections (50 of 2,468 injections). The incidence of occlusive retinal vasculitis was 0.2% (1 of 472 eyes). The recurrence rate was 23.7% (9 of 38 eyes). The average number of injections between the first brolucizumab injection and the injection date on which IOI first developed was 2.15 times in the no-reinjection group, 3.44 times in the no-IOI-recurrence group, and 2.0 times in the second-IOI-episode group. Time to IOI occurrence in cases with first IOI episode was 18.60 ± 16.73 days, with 15 cases developing IOI within 1 week. Conclusions This study elucidates the real-world incidence of brolucizumab associated IOIs, with a description of information related to reinjections after the IOI episodes. A comprehensive understanding of brolucizumab reinjection is essential for its optimal utilization.

Intraflagellar transport (IFT) particles, a multi-protein apparatus composed of complex A and B, are known to be involved in homeostasis of flagella formation. IFT particles have recently become an interesting topic in Giardia lamblia, which has 4 pairs of flagella. In this experiment, we examined the function of giardial IFT components. When 7 components (IFT121, 140, 20, 46, 52, 81, and 88) of IFT were expressed in Giardia trophozoites as a tagged form with mNeonGreen, all of them were found in both flagella pores and cytoplasmic axonemes. In addition, motor proteins for IFT particles (kinesin-13 and kinesin-2b), were localized to a median body and cytoplasmic flagella, respectively. The CRISPRi-mediated knockdown of IFT88 significantly affected the lengths of all 4 flagella compared to the control cells, Giardia expressing dead Cas9 using control guide RNA. Decreased expression of kinesin-2b also resulted in shortening of flagella, excluding the ventral flagella. Live Giardia cells expressing IFT88-mNeonGreen clearly demonstrated fluorescence in flagella pores and cytoplasmic axonemes. These results on IFT88 and kinesin-2b indicate that IFT complex plays a role in maintenance of G. lamblia flagella.

Background: In Korea, the patterns of prevalence of gynecological cancers have shifted due to rising obesity-related cancer cases. We evaluated the associations of body mass index (BMI) and waist circumference (WC) with the risk of gynecological malignancy in Korean women. Methods: Using National Health Insurance Service cohort data, we analyzed 365,581 participants among the 1,999,980 women aged ≥ 19 years who underwent health check-ups at the baseline year 2009–2010, excluding those who died, those with prior cancer diagnoses, underwent hysterectomy and/or salpingo-oophorectomy before the index date (January 1st, 2011), or missing/outliers BMI and WC values. Follow-up extended to December 31st, 2021, evaluating the incidences of endometrial, ovarian, and cervical cancer. The hazard ratios (HRs) and 95% confidence intervals (CIs) for each gynecological malignancy according to BMI and WC were calculated using Cox proportional hazard regression. Results: Among the 365,581 participants, 898, 1,268, and 873 cases of endometrial, ovarian, and cervical cancer occurred, respectively. HRs (95% CIs) for endometrial cancer were 1.37 (1.15–1.63), 1.63 (1.38–1.94), and 3.64 (2.81–4.70) for BMIs of 23.0–24.9, 25.0–29.9, and ≥ 30 kg/m2 compared to BMI of 18.5–22.9 kg/m2 (P for trend < 0.001). HRs (95% CIs) for ovarian cancer were 1.16 (1.00–1.33), 1.19 (1.03–1.37), and 1.49 (1.12–1.98) for BMIs of 23.0–24.9, 25.0–29.9, and ≥ 30 kg/m2 compared to BMI of 18.5–22.9 kg/m2 (P for trend = 0.002). No significant association was found between BMI and the risk for cervical cancer (P for trend = 0.266). HRs (95% CIs) for endometrial cancer were 1.35 (1.09–1.66), 1.41 (1.14–1.74), and 1.90 (1.55–2.34) for the 2nd, 3rd, and 4th quartiles of WCs compared to the 1st quartile (P for trend <0.001). Ovarian cancer tended to increase and cervical cancer tended to decrease as WC increased (P for trend = 0.035 for ovarian cancer, P for trend = 0.034 for cervical cancer). Conclusion In Korean women, the risks of endometrial and ovarian cancers increased significantly from the pre-obese level as BMI and WC increased, while cervical cancer risk tended to increase as WC decreased. Management of obesity should be reinforced for the prevention of obesity-related gynecological cancers, considering the increasing incidence of these cancers among Korean women.

Background: In Korea, the patterns of prevalence of gynecological cancers have shifted due to rising obesity-related cancer cases. We evaluated the associations of body mass index (BMI) and waist circumference (WC) with the risk of gynecological malignancy in Korean women. Methods: Using National Health Insurance Service cohort data, we analyzed 365,581 participants among the 1,999,980 women aged ≥ 19 years who underwent health check-ups at the baseline year 2009–2010, excluding those who died, those with prior cancer diagnoses, underwent hysterectomy and/or salpingo-oophorectomy before the index date (January 1st, 2011), or missing/outliers BMI and WC values. Follow-up extended to December 31st, 2021, evaluating the incidences of endometrial, ovarian, and cervical cancer. The hazard ratios (HRs) and 95% confidence intervals (CIs) for each gynecological malignancy according to BMI and WC were calculated using Cox proportional hazard regression. Results: Among the 365,581 participants, 898, 1,268, and 873 cases of endometrial, ovarian, and cervical cancer occurred, respectively. HRs (95% CIs) for endometrial cancer were 1.37 (1.15–1.63), 1.63 (1.38–1.94), and 3.64 (2.81–4.70) for BMIs of 23.0–24.9, 25.0–29.9, and ≥ 30 kg/m2 compared to BMI of 18.5–22.9 kg/m2 (P for trend < 0.001). HRs (95% CIs) for ovarian cancer were 1.16 (1.00–1.33), 1.19 (1.03–1.37), and 1.49 (1.12–1.98) for BMIs of 23.0–24.9, 25.0–29.9, and ≥ 30 kg/m2 compared to BMI of 18.5–22.9 kg/m2 (P for trend = 0.002). No significant association was found between BMI and the risk for cervical cancer (P for trend = 0.266). HRs (95% CIs) for endometrial cancer were 1.35 (1.09–1.66), 1.41 (1.14–1.74), and 1.90 (1.55–2.34) for the 2nd, 3rd, and 4th quartiles of WCs compared to the 1st quartile (P for trend <0.001). Ovarian cancer tended to increase and cervical cancer tended to decrease as WC increased (P for trend = 0.035 for ovarian cancer, P for trend = 0.034 for cervical cancer). Conclusion In Korean women, the risks of endometrial and ovarian cancers increased significantly from the pre-obese level as BMI and WC increased, while cervical cancer risk tended to increase as WC decreased. Management of obesity should be reinforced for the prevention of obesity-related gynecological cancers, considering the increasing incidence of these cancers among Korean women.

Background/Aims: Early colorectal cancer (ECC) is commonly resected endoscopically. Perforation is a devastating complication of endoscopic resection. We aimed to identify the characteristics and predictive risk factors for perforation related to endoscopic resection of ECC. Methods: This nationwide retrospective multicenter study included patients with ECC who underwent endoscopic resection. We investigated the demographics, endoscopic findings at the time of treatment, and histopathological characteristics of the resected specimens. Logistic regression analysis was used to investigate the clinical factors associated with procedure-related perforations. Survival analysis was conducted to assess the impact of perforation on the overall survival of patients with ECC. Results: This study included 965 participants with a mean age of 63.4 years. The most common endoscopic treatment was conventional endoscopic mucosal resection (n=573, 59.4%), followed by conventional endoscopic submucosal dissection (n=259, 26.8%). Thirty-three patients (3.4%) experienced perforations, most of which were managed endoscopically (n=23/33, 69.7%). Patients who undergo endoscopic submucosal dissection-hybrid and precut endoscopic mucosal resection have a higher risk of perforation than those who undergo conventional endoscopic mucosal resection (odds ratio, 78.65 and 39.72, p<0.05). Procedure-related perforations were not associated with patient survival. Conclusions Perforation after endoscopic resection had no significant impact on the prognosis of ECC. The type of endoscopic resection was a crucial predictor of perforation. Large-scale prospective studies are needed to further investigate endoscopic resection of ECC.

Background/Aims: This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score. Methods: We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score. Results: A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites. Conclusions The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.

Purpose: Methacholine bronchial provocation tests (MBPTs) are commonly used to assess airway hyperresponsiveness, but some patients show no significant response. This study aimed to compare the clinical characteristics of asthmatic patients based on their sensitivity to MBPTs. Methods: We conducted a retrospective cross-sectional study involving adult asthmatic patients from 6 university hospitals in South Korea. Patients were categorized into 2 groups: those with MBPT sensitivity (the provocative concentration of methacholine that leads to a 20% reduction in forced expiratory volume in 1 second [PC20]≤ 16 mg/mL) and those with lower sensitivity (PC 20 > 16 mg/mL). Clinical characteristics were compared between the 2 groups. Results: Among 346 patients, 213 had PC 20 ≤ 16 mg/mL and 133 had PC 20 > 16 mg/mL. The PC20> 16 mg/mL group had a higher prevalence of late-onset asthma (P= 0.024) and obesity (P= 0.045). While no significant differences in immunoglobulin E (≥ 200 IU/mL) were found, the PC 20 ≤ 16 mg/mL group had greater T2-high inflammation, such as elevated eosinophil counts and fractional exhaled nitric oxide (P< 0.001 and P= 0.004, respectively). Asthma exacerbations requiring emergency visits or hospitalizations were more frequent in the PC 20 > 16 mg/mL group, despite a lower proportion of patients on higher-step treatments according to Global Initiative for Asthma guidelines. Conclusion Asthmatic patients with PC 20 > 16 mg/mL tend to present with late-onset asthma, less T2-high inflammation, and higher rates of asthma exacerbations. Further studies are needed to clarify the clinical features of asthma patients with PC 20 > 16 mg/mL and assess the long-term significance of these findings.