Risk factor analysis of the development of severe radiation pneumonitis in patients with non-small cell lung cancer treated with curative radiotherapy, with focus on underlying pulmonary disease.

BACKGROUND: We aim to identify the multifaceted risk factors that can affect the development of severe radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) treated with curative high-dose radiotherapy with or without concurrent chemotherapy. METHODS: We retrospectively reviewed the medical records of 175 patients with stage-I-III NSCLC treated with curative thoracic X-ray radiotherapy at the Korea University Guro Hospital between June 2019 and June 2022. Treatment-related complications were evaluated using the Common Terminology Criteria for Adverse Events (version 4.03). RESULTS: The median follow-up duration was 15 months (range: 3-47 months). Idiopathic pulmonary fibrosis (IPF) as an underlying lung disease (P < 0.001) and clinical stage, regarded as the concurrent use of chemotherapy (P = 0.009), were associated with a high rate of severe RP. In multivariate analyses adjusting confounding variables, the presence of IPF as an underlying disease was significantly associated with severe RP (odds ratio [95% confidence interval] = 48.4 [9.09-347]; P < 0.001). In a subgroup analysis of stage-I-II NSCLC, the incidence of severe RP in the control, chronic obstructive pulmonary disease (COPD), and IPF groups was 3.2%, 4.3%, and 42.9%, respectively (P < 0.001). The incidence of severe RP was 15.2%, 10.7%, and 75.0% in the control, COPD, and IPF groups, respectively (P < 0.001) in the stage-III NSCLC group. CONCLUSIONS: This study revealed that IPF as an underlying lung disease and the concurrent use of chemotherapy are associated with a high rate of severe RP. In contrast, COPD did not increase the risk of pulmonary toxicity after receiving curative high-dose radiotherapy.

Clinical Outcomes of Stereotactic Ablative Radiotherapy for All Stages of Non-Small Cell Lung Cancer; Definitive versus Consolidative.

Background and Objectives: Stereotactic ablative radiotherapy (SABR) is not confined to early stage non-small cell lung cancer (NSCLC) and has a potential role in stage IV disease. We aimed to evaluate the effect of SABR on local control rates and survival outcomes in patients with all stages of NSCLC according to the treatment aim. Materials and Methods: We retrospectively reviewed the medical records of 88 patients with NSCLC who received SABR at the Korea University Guro Hospital between January 2015 and March 2021. Among these, 64 patients with stage I-II NSCLC ineligible for surgery were treated with a definitive aim. Twenty-four patients with stage IV limited metastatic NSCLC showing a favorable response to prior systemic therapy were treated with a consolidative aim. Results: The median follow-up time was 34 (range: 5-88) months. Thirty-one patients developed recurrence (35.2%), with distant metastasis being the most common (25/31, 80.6%). In-field local recurrence occurred in four patients (4/88 patients, 4.5%). For patients treated with definitive SABR, the 3-year overall survival (OS) and disease-free survival (DFS) rates were 91.8% and 58.6%, respectively. In patients treated with consolidative SABR, the 3-year OS and DFS rates were 86.7% and 53.8%, respectively. With respect to treatment-related pulmonary toxicity, grade 3 radiation pneumonitis incidence requiring hospitalization was 2.3% (2/88). Conclusions: Definitive SABR is appropriate for medically inoperable or high surgical risk patients with early stage NSCLC with acceptable treatment-related toxicities. Consolidative SABR improves local control rates and helps achieve long-term survival in patients with limited metastatic NSCLC.

Survival of Breast-Conserving Surgery Plus Radiotherapy versus Total Mastectomy in Early Breast Cancer.

BACKGROUND: Breast-conserving surgery (BCS) has been reported to have better survival rates when compared with total mastectomy (TM) in early breast cancer. We evaluated the long-term outcomes of Korean women with early breast cancer who underwent either BCS plus radiotherapy (RT) or TM. METHODS: In this population-based study, we evaluated 45,770 patients from the Korean Breast Cancer Registry (KBCR) who were diagnosed with early breast cancer, and divided them into the BCS + RT and TM groups. To minimize bias caused by factors other than the surgical method, we used exact match pairing of prognostic factors. We compared the 10-year overall survival (OS) and breast cancer-specific survival (BCSS) before and after exact matching. As the KBCR is a multicenter, online-based registry program, we used the Asan Medical Center (AMC) database, a single-center database, to validate the results from the KBCR database. RESULTS: In both the KBCR and AMC cohorts, the BCS + RT group showed better OS and BCSS than the TM group, before and after exact matching. For the KBCR cohort after exact matching, the hazard ratios for OS and BCSS were 1.541 (95% confidence interval [CI] 1.392-1.707, p < 0.001) and 1.405 (95% CI 1.183-1.668, p < 0.001), respectively, favoring the BCS + RT group. For the AMC cohort after exact matching, the hazard ratios for OS and BCSS were 1.854 (95% CI 1.476-2.328, p < 0.001) and 1.807 (95% CI 1.186-2.752, p = 0.006), respectively. CONCLUSIONS: Our results suggest that BCS + RT is at least equivalent to TM in terms of OS and may affect treatment decisions in early breast cancer patients.

Significance of the number of high-risk factors in patients with cervical cancer treated with radical hysterectomy and concurrent chemoradiotherapy.

OBJECTIVE: The purpose of this study was to evaluate the impact of high-risk factors on the survival of patients with cervical cancer treated with surgery followed by adjuvant chemoradiotherapy. METHODS: From 2000 to 2014, medical records of 897 patients with International Federation of Gynecology and Obstetrics stage IB-IIA disease treated with surgery were retrospectively reviewed. Among them, 483 patients with high-risk factors, including pelvic lymph node metastasis, parametrial invasion, or resection margin involvement, were analyzed. RESULTS: The median follow-up time was 57 months (range, 6-205 months). For patients with single and multiple high-risk factors, the 5-year DFS rates were 80.4% and 65.7%, respectively (p < 0.001), and 5-year OS rates were 87.3% and 75.1%, respectively (p = 0.001). Distant metastasis was the most common pattern of recurrence (86.1%). Furthermore, distant metastasis-free survival significantly differed with the number of high-risk factors present (single 82.7% vs. multiple 68.8%, p < 0.001). In the multivariate analysis, while parametrial invasion and resection margin involvement showed no association, the adenocarcinoma histology, pelvic lymph node metastasis, higher metastatic lymph node ratio, and multiple high-risk factors were independent prognosticators associated with poor DFS and OS. CONCLUSIONS: Patients with early-stage cervical cancer having multiple high-risk factors, adenocarcinoma histologic type, and pelvic lymph node metastasis accompanied by a higher lymph node ratio after surgery are more likely to have occult distant metastasis. Further, consolidation with systemic chemotherapy after adjuvant therapy might be considered to improve the survival outcome in this patient population.

Significance of para-aortic lymph node evaluation in patients with FIGO IIIC1 cervical cancer.

OBJECTIVE: This study investigated the effect of para-aortic lymph node sampling or dissection in recently revised International Federation of Gynecology and Obstetrics IIIC1p cervical cancer treated with primary surgery and adjuvant radiation therapy with concurrent chemotherapy. METHODS: We retrospectively reviewed the records of 343 patients with early-stage cervical cancer and pathologically proven pelvic lymph node metastasis following curative surgery from 2001 to 2014. No patient had imaging evidence of para-aortic lymph node involvement, and all patients received adjuvant concurrent chemotherapy with or without concurrent chemotherapy. We investigated the significance of para-aortic lymph node sampling or dissection on disease-free survival and overall survival. RESULTS: After median follow-up of 58.3 months, 5-year disease-free survival and overall survival in all patients were 69.9 and 80.2%, respectively. Disease-free survival and overall survival did not differ between the para-aortic lymph node dissection group and the No para-aortic lymph node dissection group (P = 0.700 and P = 0.605). However, patients with para-aortic lymph node-positive disease had poorer disease-free survival and overall survival compared with those with para-aortic lymph node-negative disease (P < 0.001 and P < 0.001). CONCLUSIONS: This study found no survival benefit of para-aortic lymph node evaluation among patients with International Federation of Gynecology and Obstetrics IIIC1p cervical cancer who were clinically para-aortic lymph node-negative. Although para-aortic lymph node metastasis is a poor prognosticator, the benefit of para-aortic lymph node dissection in terms of survival needs further investigation.

Germline BRCA Mutation and Clinical Outcomes in Breast Cancer Patients Focusing on Survival and Failure Patterns: A Long-Term Follow-Up Study of Koreans.

Background and Objectives: This study aimed to evaluate the effect of a BRCA mutation on survival and failure patterns, focusing on the risk of ipsilateral recurrence and contralateral breast cancer in patients. Materials and Methods: We retrospectively reviewed medical records of 300 patients with breast cancer who underwent genetic screening for BRCA1/2 genes and were treated at Samsung Medical Center between 1 January 2000 and 31 December 2010. Ultimately, clinical outcomes of 273 patients were analyzed. Results: The median follow-up duration was 102 months (range, 1 to 220 months). Patients with BRCA1/2-mutated tumors had a shorter 10-year disease-free survival (DFS) rate compared to those with non-mutated tumors (62.8% vs. 80.0%, p = 0.02). Regarding failure patterns, patients with BRCA1/2-mutated tumors showed a higher incidence of contralateral breast cancer than those with non-mutated tumors (BRCA1/2 non-mutated vs. mutated tumors: 4.9% vs. 26.0%, p < 0.001). BRCA mutation status remained a significant prognostic factor for contralateral breast recurrence-free survival (HR: 4.155; 95% CI: 1.789-9.652; p = 0.001). Korean patients with a BRCA mutation showed inferior DFS compared to those without a BRCA mutation. Conclusions: BRCA mutation status is a strong predictor of recurrence in contralateral breast cancer. Strategies such as prophylactic treatment and active surveillance should be discussed with breast cancer patients who have a BRCA mutation.

The association between non-breast and ovary cancers and BRCA mutation in first- and second-degree relatives of high-risk breast cancer patients: a large-scale study of Koreans.

BACKGROUND: As a large-scale study of Koreans, we evaluated the association between BRCA mutation and the prevalence of non-breast and ovary cancers in first- and second-degree relatives of high-risk breast cancer patients. METHODS: We organized familial pedigrees of 2555 patients with breast cancer who underwent genetic screening for BRCA1/2 in Samsung Medical Center between January 2002 and May 2018. Families with a member that had a history of cancer other than of the breast or ovary were regarded positive for other primary cancer. RESULTS: The median age of the population was 40 years (range, 19 to 82 years). BRCA mutation was detected in 377 (14.8%) of the patients. The BRCA-positive group had a higher frequency of family history of breast or ovarian cancer (p <  0.001), bilateral breast cancer (p = 0.021), and the male gender (p = 0.038). There were 103 (27.3%) patients who had multiple risk factors in the BRCA-positive group, while there were 165 (7.6%) patients who had multiple risk factors in the BRCA-negative group (p <  0.001). BRCA mutation was detected in 215 (11.7%) of the 1841 families without history of other primary cancers. Among the 714 families with histories of other primary cancers, 162 (22.7%) had BRCA mutation, and this was significantly more frequent (p < 0.001) than in those without a history. The occurrence of other primary cancers in families of high-risk patients was associated with a younger age at diagnosis (p = 0.044), bilateral breast cancer (p = 0.006), and BRCA mutations (p < 0.001). The most common site for the occurrence of another type of primary cancer was the stomach. In the BRCA-positive group, the proportional incidences of stomach, pancreas, colorectal, lung, and uterine cancer were 13.8, 4.0, 7.7, 8.8, and 5.0%, respectively; these were all relatively higher than those in the BRCA-negative group. CONCLUSIONS: We confirmed that BRCA mutation was associated with having multiple risk factors and an increased prevalence of non-breast and ovary cancers in first- and second-degree relatives of high-risk breast cancer patients. Due to the possibility of inherited cancer risk, genetic counseling with options for risk assessment and management should be provided to both patients and families of BRCA mutation carriers.

Fucoidan-Manganese Dioxide Nanoparticles Potentiate Radiation Therapy by Co-Targeting Tumor Hypoxia and Angiogenesis.

Tumor hypoxia is a major mechanism of resistance to radiation therapy (RT), which is associated with poor prognosis in affected cancer patients. Various approaches to treat hypoxic and radioresistant cancers, including pancreatic cancer, have shown limited success. Fucoidan, a polysaccharide from brown seaweed, has antitumor and antiangiogenesis activities. Here, we discuss the development of fucoidan-coated manganese dioxide nanoparticles (Fuco-MnO2-NPs) and testing of the therapeutic potential with RT using pancreatic cancer models. In vitro data showed that Fuco-MnO2-NPs generated oxygen efficiently in the presence of H2O2 and substantially suppressed HIF-1 expression under a hypoxic condition in human pancreatic cancer cells. Fuco-MnO2-NPs reversed hypoxia-induced radioresistance by decreasing clonogenic survival and increasing DNA damage and apoptotic cell death in response to RT. In a BxPC3 xenograft mouse model, the combination treatment with Fuco-MnO2-NPs and RT resulted in a greater tumor growth delay than RT alone. Fucoidan-coated NPs, but not naked ones, further suppressed tumor angiogenesis, as judged by immunohistochemistry data with diminished expression of phosphorylated vascular endothelial growth factor receptor 2 (VEGFR2) and CD31. These data suggest that Fuco-MnO2-NPs may potentiate the effects of RT via dual targeting of tumor hypoxia and angiogenesis, and they are of great clinical potential in the treatment of hypoxic, radioresistant pancreatic cancer.

Foveal microvasculature features of surgically closed macular hole using optical coherence tomography angiography.

BACKGROUND: To describe the features of foveal microvasculature using optical coherence tomography angiography (OCTA) and to determine the related clinical factors in eyes with surgically closed macular hole (MH). METHODS: A retrospective case series of 18 patients with unilateral MH was reviewed. The patients maintained complete hole closure after vitrectomy with inner limiting membrane (ILM) peeling for at least 12 months. The healthy fellow eyes were studied as controls. The foveal microvasculature of both eyes was examined by OCTA. The area of the foveal avascular zone (FAZ) and the vascular density (VD) ratio in the superficial and deep capillary plexuses (SCP and DCP) were determined after surgery. Several clinical factors including age, stage and dimensions of MH, papillofoveal distance, the extent of nasal displacement of the fovea after surgery, postoperative central foveal thickness, and outer-retina integrity were evaluated to determine any relationships with the OCTA parameters. RESULTS: The mean FAZ area in both the SCP and DCP (0.29 ± 0.11 mm2 and 0.39 ± 0.14 mm2) was significantly smaller than those of the controls (0.45 ± 0.14 mm2 and 0.62 ± 0.22 mm2) (p = 0.001 and <0.001, respectively). The mean VD ratio in the SCP (0.270 ± 0.349) was similar to that of the controls (0.321 ± 0.189) (p = 0.231); however, that in the DCP (0.321 ± 0.189) was significantly lower than that of the controls (0.331 ± 0.119) (p = 0.025). Only the extent of nasal displacement of the fovea was correlated with the DCP FAZ-area difference values between the study group and the controls (correlation coefficient = 0.577; p = 0.012). CONCLUSIONS: After successful MH surgery, the FAZ area in both the SCP and DCP was smaller and the VD ratio of the DCP was lower, suggesting a possible DCP vulnerability to tractional stress. As the FAZ area of the DCP in closed-MH eyes became smaller than that in the controls, the fovea was less displaced toward the optic disc, possibly reflecting a lack of retinal redundancy caused by horizontal stretching accompanied by foveal displacement.

Clinical parameters related to metamorphopsia outcome in patients with resolved central serous chorioretinopathy using M-CHARTS: retrospective cohort study.

BACKGROUND: The purpose of this study was to determine the clinical parameters related to metamorphopsia outcome in patients with resolved central serous chorioretinopathy (CSCR). METHODS: The charts of 36 eyes with resolved CSCR were retrospectively reviewed. We measured metamorphopsia using M-CHARTS after resolution of serous retinal detachment. We analyzed the relationship between metamorphopsia outcome and clinical parameters including age, visual acuity, chronicity of CSCR, symptom duration and several spectral-domain optical coherence tomography findings using univariate and multivariate forward logistic regression analyses. RESULTS: The M-CHARTS detected metamorphopsia in 19 eyes (52.8 %). In the univariate analysis, the eyes with metamorphopsia were, relative to those without metamorphopsia, significantly associated with a greater proportion of chronic-recurrent CSCR, initial and final irregularities of retinal pigment epithelium, longer symptom duration, thinner final thickness of central fovea and outer nuclear layer, and final disruption of external limiting membrane (ELM), photoreceptor inner and outer segment junction and cone outer segment tip line (P = 0.003, 0.037, 0.019, 0.003, 0.013, 0.015, <0.001, 0. 012 and 0.002, respectively). However, in the multivariate analysis, chronic-recurrent CSCR (OR 22.5, P = 0.019) and final disrupted ELM (OR 82.6, P = 0.004) were the independent clinical parameters related to poor metamorphopsia outcome. CONCLUSIONS: Residual metamorphopsia was detected using M-CHARTS in about half of patients (52.8 %) with resolved CSCR. Chronic-recurrent CSCR and final disrupted ELM were the independent clinical parameters related to poor metamorphopsia outcome in patients with resolved CSCR.

Klebsiella Endophthalmitis as Retinal Vasculitis with Prostatic Abscess.

PURPOSE: To describe an unusual case of endogenous Klebsiella endophthalmitis associated with prostatic abscess in an immunocompetent patient. CASE REPORT: A 59-year-old previously healthy man presented with rapidly progressive retinal vasculitis in the left eye. He received an empirical antibiotic and antiviral agent intravenously followed by oral prednisolone until the etiology was identified; however, intraocular inflammation in the left eye continued to worsen, followed by the development of subretinal abscess in the contralateral eye. Finally, a diagnosis of endogenous Klebsiella endophthalmitis associated with prostatic abscess was made through a culture of the vitreous acquired by diagnostic vitrectomy. However, we could not save the vision of the left eye despite the intensive treatment with intravenous and intravitreal injections of antibiotics. CONCLUSIONS: Rapidly progressive retinal vasculitis could be an initial sign of endogenous Klebsiella endophthalmitis even in an immunocompetent patient.

Experimental evaluation of sodium silicate-based nanosilica against chloride effects in offshore concrete.

This study investigates the effect of a new pore filling material, named sodium silicate-based nanosilica (SS), on resisting the diffusion of the chloride ions. The proposed SS is chosen, mainly due to its smaller particle size, compared to the conventional ethyl silicate-based nanosilica. Each particle of SS is chemically treated to have the negative (-) charge on its surface. Four types of mixes with different amounts of partial replacement with fly ash and slag are prepared. Effect of water to binder ratios (0.35, 0.40, and 0.45) is also examined. Test results showed that the inclusion of SS was significantly beneficial for protecting the concrete from chloride attack. At a given strength, the SS inclusion in concrete was up to three times more effective than the control concrete without SS. It is believed that these excellent results are attributed to the small particle size and the chemical surface treatment of SS. In this study, experiments of compressive strength, hydration heat, accelerated neutralization, and sulfate erosion tests were also conducted to find the general effect of SS inclusion on the fundamental properties and durability of concrete.

Clinical experience of consolidative radiotherapy for localized metastatic non-small cell lung cancer who showed favorable tumor response after systemic treatment.

BACKGROUND: Our study has aimed to assess the effects of consolidative high-dose radiotherapy on clinical outcomes in patients with localized metastatic non-small cell lung cancer (NSCLC) who showed favorable tumor response after systemic treatment. METHODS: We retrospectively reviewed the medical records of 83 patients with localized metastatic NSCLC, who received systemic therapy followed by consolidative local radiotherapy at the Korea University Guro Hospital between March 2017 and June 2022. In the current study, we defined localized metastatic disease as the presence of one to three metastatic sites at the time of diagnosis. And patients who showed favorable tumor response after systemic treatment, including oligo-progressive disease at the thoracic site which was amenable to curative high-dose local radiotherapy, were included. The planned total dose and fraction size mainly depended on the location of lesions. RESULTS: The median follow-up time after consolidative radiotherapy was 16 months (range: 5-52 months). The overall 2-year progression-free survival rates were 81.4%. Of 83 patients, only four (4.3%), treated with intensity-modulated radiation therapy, showed an in-field local recurrence. Interestingly, only one patient experienced a local failure among the 20 patients who showed an oligo-progressive disease at the thoracic site on the tumor response evaluation after systemic treatment. Regarding treatment-related pulmonary toxicity, three patients with grade-3 and one patient with grade-4 radiation pneumonitis were presented. CONCLUSIONS: If the disease is sufficiently controlled and localized by systemic therapy, local consolidative radiotherapy is thought to improves local control rates with acceptable treatment-related toxicities in patients with localized metastatic NSCLC, especially those with oligo-progressive disease.

Full genomic characterization of a group C rotavirus isolated from a child in South Korea.

During an epidemiological survey of human rotavirus infection in Seoul, Korea, from 2010 to 2011, one isolate of group C rotavirus (GCRV), named CAU10-312, was detected in a 5-year-old child admitted to the hospital with acute gastroenteritis, and its complete genomic sequence was determined. The 11 gene segments of the strain possessed G4-P[2]-I2-R2-C2-M2-A2-N2-T2-E2-H2 genotypes. The genotype of strain CAU10-312 appears to be closely related to strains from Bangladesh (DhakaC13 and BS347), India (v508), and England (Bristol), but distinct from Far East Asian strains, Chinese (Wu82 and YNR001) and Japanese (OH567 and BK0830). These findings may clarify the relationship of the genetics, evolutionary biology, and epidemiology of GCRVs and suggest that two very distinct genotype strains are in circulation in the world.

Polypoidal choroidal vasculopathy: evidence-based guidelines for clinical diagnosis and treatment.

BACKGROUND: Polypoidal choroidal vasculopathy (PCV) is an exudative maculopathy affecting vision, with clinical features distinct from neovascular age-related macular degeneration. Currently, no evidence-based guidelines exist for its diagnosis and treatment. METHODS: A panel of experts analyzed a systematic literature search on PCV together with results of the EVEREST trial, the only published randomized controlled clinical trial in PCV. At a subsequent Roundtable meeting, recommendations for the management of PCV were agreed based on this analysis and their own expert opinion. RESULTS: Diagnosis of PCV should be based on early-phase nodular hyperfluorescence from choroidal vasculature visualized using indocyanine green angiography. Recommended initial treatment of juxtafoveal and subfoveal PCV is either indocyanine green angiography-guided verteporfin photodynamic therapy or verteporfin photodynamic therapy plus 3 × 0.5 mg ranibizumab intravitreal injections 1 month apart. If there is incomplete regression of polyps by indocyanine green angiography, eyes should be retreated with verteporfin photodynamic therapy monotherapy or verteporfin photodynamic therapy plus ranibizumab. If there is complete regression of polyps by indocyanine green angiography, but there is leakage on fluorescein angiography and other clinical or anatomical signs of disease activity, eyes should be retreated with ranibizumab. CONCLUSION: Practical guidance on the clinical management of PCV is proposed based on expert evaluation of current evidence.

Consolidative high-dose thoracic radiotherapy for limited metastatic nonsmall cell lung cancer: Focusing on oligo-progressive disease.

AIM: Prior clinical data have shown a significant survival benefit of consolidative local radiotherapy for patients with limited metastatic non-small cell lung cancer (NSCLC). Therefore, this study aimed to evaluate the impact of consolidative high-dose thoracic radiotherapy on local control rates and survivals in patients with limited metastatic NSCLC, especially focusing on oligo-progressive disease. METHODS: We retrospectively reviewed the medical records of 45 patients with limited metastatic NSCLC who received consolidative high-dose thoracic radiotherapy at the Korea University Guro Hospital between March 2015 and December 2020. In the current study, we included patients who showed partial response, stable disease, or oligo-progressive disease on tumor response evaluation after systemic treatment. All patients underwent stereotactic body radiation therapy (23 patients) or intensity-modulated radiation therapy (IMRT, 22 patients). RESULTS: The median follow-up time was 42 months (range: 5-88 months). The overall 2-year disease-free survival (DFS) and overall survival (OS) rates were 80.7% and 88.4%, respectively. Among the 45 patients, only two patients treated with IMRT showed in-field local recurrence. There was no local failure among the patients who showed oligo-progressive disease after systemic treatment. In addition, the response to systemic treatment was not a significant factor for either DFS or OS rates (p = .471 and p = .414, respectively) in univariate analysis. CONCLUSIONS: Consolidative high-dose thoracic radiotherapy improves local control rates and helps achieve long-term survival in patients with limited metastatic NSCLC. It is also effective and should be considered in patients with oligo-progressive disease after systemic treatment.

A comprehensive assessment of the applicability of RoboColumn as a chromatography scale-down model for use in biopharmaceutical process validation.

High-throughput process development has become a standard practice in the biopharmaceutical industry to enable time, cost, and material savings. In downstream biopharmaceutical process development, miniaturized, parallelized chromatography columns, known as RoboColumn, have become the standard for process development, as RoboColumn have shown generally comparable performance to bench and manufacturing scale columns. However, RoboColumn have yet to be widely implemented in process validation and characterization, where many multifactor experiments are typically executed, and there is a strong value proposition for performing high-throughput experiments. The hesitancy to utilize RoboColumn in process validation arises from scale differences that result in exacerbated peak broadening at RoboColumn scale relative to traditional bench or manufacturing scales. Thus, to support reliable application of RoboColumn in process validation, the present study provides a comprehensive investigation to understand how scale differences affect chromatographic performance by comparing RoboColumn, bench, and manufacturing scales using seven different production processes covering three different antibody formats, five different resin types, and three chromatographic modes of operation. RoboColumn chromatographic performance was compared at target and off-target conditions to emulate scale-down model qualification and multifactor studies, respectively. RoboColumn demonstrated good comparability at both target and off-target process conditions. To further demonstrate an understanding of comparability, a study was performed to show a rare case in which product quality offsets may occur as a result RoboColumn scale differences. By showing scale comparability and an understanding of potential offsets, this work demonstrates that RoboColumn can be used in any stage of process development, including process validation and characterization.

Viral load dynamics and shedding kinetics of mpox infection: a systematic review and meta-analysis.

BACKGROUND: Viral load dynamics and shedding kinetics are critical factors for studying infectious diseases. However, evidence on the viral dynamics of mpox remains limited and inconclusive. Thus, we aimed to provide a comprehensive understanding of the viral load and viability of the re-emerged mpox virus since 2022. METHODS: For this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase and Google Scholar for published articles that are related to mpox viral dynamics up to April 2023. RESULTS: From 19 studies, 880 samples and 1477 specimens were collected. The pooled median Ct values appeared in the following order: skin lesion [Ct value 21.7 (IQR 17.8-25.5)], anorectal [22.3 (16.9-27.6)], saliva [25.9 (22.5-31.1)], oral [29.0 (24.5-32.8)], semen [29.6 (25.9-33.4)], urine [30.5 (24.6-36.4)], pharyngeal [31.9 (26.5-37.3)], urethra [33.0 (28.0-35.0)] and blood [33.2 (30.4-36.1)]. People living with human immunodeficiency virus (HIV) have a lower Ct value in the skin [skin HIV+, 19.2 (18.3-20.0) vs skin HIV-, 25.4 (21.2-29.0)]. From the Ct values and test day since symptom onset, we identified temporal trends of viral load for each specimen type. Changes in the trend were observed at 4 days in saliva, 5 days in blood, 6 days in skin, 7 days in anorectal, urine, semen and pharyngeal and 8 days in the urethra. We determined optimal Ct cutoff values for anorectal (34.0), saliva (27.7) and urethra (33.0) specimens, where a Ct value above each cutoff suggests minimal viral viability. Using these cutoff values, we derived the duration of viable viral isolation in each specific specimen type (anorectal 19 days, saliva 14 days and urethra 14 days). CONCLUSION: Skin lesion, anorectal and saliva samples contained the highest viral load. The peak viral load manifests within 4-8 days after symptom onset, and viable virus detection was presumed to cease within 14-19 days from symptom onset in anorectal, saliva and urethral samples.

Survival After Development of Contralateral Breast Cancer in Korean Patients With Breast Cancer.

Importance: Contralateral breast cancer (CBC) is the most frequently diagnosed primary cancer in patients with breast cancer. Although many studies have reported survival after the development of CBC, results have been inconsistent. Objective: To investigate whether the development of CBC is associated with survival among patients with breast cancer. Design, Setting, and Participants: This cohort study was conducted at the Asan Medical Center, Korea, among patients who were diagnosed with primary unilateral, nonmetastatic, stage 0 to III breast cancer between 1999 and 2013 and followed up through 2018. The median (IQR) follow-up was 107 (75-143) months. Patients were categorized into CBC and no-CBC groups by whether they developed CBC during the follow-up period. Data were analyzed from November 2021 to March 2023. Exposure: Development of CBC. Main outcomes and measures: Survival rates of CBC and no-CBC groups were compared using a time-dependent Cox proportional hazard model in the entire study population and in subgroup analyses by interval of CBC development and subtype of the primary breast cancer. Results: Among 16 251 patients with breast cancer (all Asian, specifically Korean; mean [SD] age, 48.61 [10.06] years), 418 patients developed CBC. There was no significant difference in overall survival between CBC and no-CBC groups (hazard ratio, 1.166; 95% CI, 0.820-1.657). Patients who developed CBC within 1.5 years after the surgery of the primary breast cancer had a higher risk for overall death during the study period (hazard ratio, 2.014; 95% CI, 1.044-3.886), and those who developed CBC after 1.5 years showed no significant difference in survival compared with the no-CBC group. Patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (ERBB2, formerly HER2)-negative breast cancer had a higher risk for overall death in the CBC group (hazard ratio, 1.882; 95% CI, 1.143-3.098) compared with the no-CBC group. Conclusions and Relevance: This study found that development of CBC in patients with breast cancer was not associated with survival but that early development of CBC after diagnosis of the primary breast cancer or development of CBC in patients with HR-positive/ERBB2-negative breast cancer was associated with survival. These results may provide valuable information for patients seeking advice on opting for contralateral prophylactic mastectomy.

Age-Related Incidence and Peak Occurrence of Contralateral Breast Cancer.

Importance: Young patients with breast cancer have higher risk for developing contralateral breast cancer (CBC) and have epidemiologic characteristics different from those of older patients. Objective: To examine the incidence and peak occurrence of CBC according to age at primary breast cancer (PBC) surgery. Design, Setting, and Participants: This cohort study included patients who were diagnosed with and underwent surgery for unilateral nonmetastatic breast cancer at Asan Medical Center, Korea, between January 1, 1999, and December 31, 2013, with follow-up through December 31, 2018. Data were analyzed from December 1, 2021, through April 30, 2023. Patients were divided into 2 groups according to their age at surgery for PBC: younger (≤35 years) vs older (>35 years). Main Outcomes and Measures: The main outcomes were cumulative incidence and hazard rate of CBC in the entire study population and in subgroups divided by cancer subtype, categorized according to hormone receptor (HR) and ERBB2 status. Results: A total of 16 251 female patients with stage 0 to III breast cancer were analyzed; all patients were Korean. The mean (SD) age was 48.61 (10.06) years; 1318 patients (8.11%) were in the younger group, and 14 933 (91.89%) were in the older group. Median follow-up was 107 months (IQR, 79-145 months). Compared with the older group, the younger group had significantly higher incidence of CBC (10-year cumulative incidence, 7.1% vs 2.9%; P < .001) and higher risk (hazard ratio, 2.10; 95% CI, 1.62-2.74) of developing CBC. The hazard rate, which indicates risk for developing CBC at a certain time frame, differed according to the subtype of primary cancer. In patients with the HR+/ERBB2- subtype, the risk increased continuously in both age groups. In patients with the triple negative subtype, the risk increased until approximately 10 years and then decreased in both age groups. Meanwhile, in the HR-/ERBB2+ subtype, risk peaked earlier, especially in the younger group (1.7 years since first surgery in the younger group and 4.8 years in the older group). Conclusions and Relevance: In this cohort study, patients aged 35 years or younger with breast cancer had a higher risk of developing CBC than older patients. Moreover, young patients with the HR-/ERBB2+ subtype tended to have a shorter interval for developing CBC. These findings might be useful in guiding treatment decisions, such as contralateral prophylactic mastectomy.