Purpose: Programmed death-1/programmed death-ligand 1 (PD-L1) inhibitors have shown efficacy in metastatic esophageal squamous cell carcinoma (ESCC) therapy. However, data is still limited regarding neoadjuvant immunotherapy for operable ESCC. Materials and Methods: Patients with clinical stage T2 or T3 and N0 ESCC received three cycles of nivolumab therapy every two weeks before surgical resection. The primary endpoint is major pathologic responses (MPR) rate (≤ 10% of residual viable tumor [RVT]). Results: Total 20 patients completed the planned nivolumab therapy. Among them, 17 patients underwent surgery as protocol, showing MPR in two patients (MPR rate, 11.8%), including one pathologic complete response, on conventional pathologic response evaluation. Pathologic response was re-evaluated using the immune-related pathologic response criteria based on immune-related RVT (irRVT). Three patients were classified as immunologic major pathologic response (iMPR; ≤ 10% irRVT, iMPR rate: 17.6%), five as pathologic partial response (> 10% and < 90% irRVT), and nine as pathologic nonresponse (≥ 90% irRVT). The combined positive score (CPS) for PD-L1 in the baseline samples was predictable for iMPR, with the probability as 37.5% in CPS ≥ 10 (3/8) and 0% in CPS < 10 (0/9). Conclusion Although the efficacy of neoadjuvant nivolumab therapy was modest in unselected ESCC patients, further researches on neoadjuvant immunotherapy are necessary in patients with PD-L1 expressed ESCC.

Positional headache refers to a headache that worsens or improves with changes in posture. It is often secondary in nature, associated with various pathologies that may have serious consequences if left undiagnosed or untreated. The authors report a patient who complained of severe positional headache and was diagnosed with concurrent reversible cerebral vasoconstriction syndrome and vertebral artery dissection, thus highlighting the importance of considering such conditions in a patient with postural headaches.

Identifying risk factors and improving prognostication for mortality among patients with sepsis-associated acute kidney injury (AKI) undergoing continuous kidney replacement therapy (CKRT) is important in improving the adverse prognosis of this patient population. This study aimed to compare the prognostic value of existing systemic inflammation biomarkers and determine the optimal systemic inflammation biomarker in patients with sepsis-associated AKI receiving CKRT. Methods: This multi-center, retrospective, observational cohort study included 1,500 patients with sepsis-associated AKI treated with intensive care and CKRT. The main predictor was a panel of 13 different systemic inflammation biomarkers. The primary outcome was 28-day mortality after CKRT initiation. Secondary outcomes included 90-day mortality after CKRT initiation, CKRT duration, kidney replacement therapy dependence at discharge, and lengths of intensive care unit (ICU) and hospital stays. Results: When added to the widely accepted Acute Physiology and Chronic Health Evaluation II score, platelet-to-albumin ratio (PAR) and neutrophil-platelet score (NPS) had the highest improvements in prognostication of 28-day mortality, where the corresponding increases in C-statistic were 0.01 (95% confidence interval [CI], 0.00–0.02) and 0.02 (95% CI, 0.01–0.03). Similar findings were observed for 90-day mortality. The 28- and 90-day mortality rates were significantly lower for the higher PAR and NPS quartiles. These associations remained significant even after adjustment for potential confounding variables in multivariable Cox proportional hazards models. Conclusion: Of the available systemic inflammation biomarkers, the addition of PAR or NPS to conventional ICU prediction models improved the prognostication of patients with sepsis-associated AKI receiving intensive care and CKRT.

This study investigated the association between serum phosphate level and mortality in acute kidney injury (AKI) patients undergoing continuous kidney replacement therapy (CKRT) and evaluated whether this association differed according to disease severity. Methods: Data from eight tertiary hospitals in Korea were retrospectively analyzed. The patients were classified into four groups (low, normal, high, and very high) based on their serum phosphate level at baseline. The association between serum phosphate level and mortality was then analyzed, with further subgroup analysis being conducted according to disease severity. Results: Among the 3,290 patients identified, 166, 955, 1,307, and 862 were in the low, normal, high, and very high phosphate groups, respectively. The 90-day mortality rate was 63.9% and was highest in the very high group (76.3%). Both the high and very high groups showed a significantly higher 90-day mortality rate than did the normal phosphate group (high: hazard ratio [HR], 1.35, 95% confidence interval [CI], 1.21–1.51, p < 0.001; very high: HR, 2.01, 95% CI, 1.78–2.27, p < 0.001). The low group also exhibited a higher 90-day mortality rate than did the normal group among those with high disease severity (HR, 1.47; 95% CI, 1.09–1.99; p = 0.01) but not among those with low disease severity. Conclusion: High serum phosphate level predicted increased mortality in AKI patients undergoing CKRT, and low phosphate level was associated with increased mortality in patients with high disease severity. Therefore, serum phosphate levels should be carefully considered in critically ill patients with AKI.

Purpose: This study compared the malignancy risk of intermediate suspicion thyroid nodules according to the presence of suspicious ultrasonographic (US) findings. Methods: From January 2014 to December 2014, 299 consecutive intermediate suspicion thyroid nodules in 281 patients (mean age, 50.6±12.5 years) with final diagnoses were included in this study. Two radiologists retrospectively reviewed the US findings and subcategorized the intermediate suspicion category into nodules without suspicious findings and nodules with suspicious findings, including punctate echogenic foci, nonparallel orientation, or irregular margins. The malignancy rates were compared between the two subcategory groups. Results: Of the 299 intermediate suspicion thyroid nodules, 230 (76.9%) were subcategorized as nodules without suspicious findings and 69 (23.1%) as nodules with suspicious findings. The total malignancy rate was 33.4% (100/299) and the malignancy rate of nodules with suspicious findings was significantly higher than that of nodules without suspicious findings (47.8% vs. 29.1%, P=0.004). In nodules with suspicious findings, the most common suspicious finding was punctate echogenic foci (48/82, 58.5%) followed by nonparallel orientation (22/82, 26.8%) and irregular margins (12/82, 14.6%). Thirteen nodules had two suspicious findings simultaneously. A linearly increasing trend in the malignancy rate was observed according to the number of suspicious US findings (P for trend=0.001). Conclusion Intermediate suspicion thyroid nodules with suspicious findings showed a higher malignancy rate than those without suspicious findings. Further management guidelines for nodules with suspicious findings should differ from guidelines for nodules without suspicious findings, even in the same US category.

Comorbid conditions impact the survival of patients with severe acute kidney injury (AKI) who require continuous renal replacement therapy (CRRT). The weights assigned to comorbidities in predicting survival vary based on type of index, disease, and advances in management of comorbidities. We developed a modified Charlson Comorbidity Index (CCI) for use in patients with AKI requiring CRRT (mCCI-CRRT) and improved the accuracy of risk stratification for mortality. Methods: A total of 828 patients who received CRRT between 2008 and 2013, from three university hospital cohorts was included to develop the comorbidity score. The weights of the comorbidities were recalibrated using a Cox proportional hazards model adjusted for demographic and clinical information. The modified index was validated in a university hospital cohort (n = 919) using the data of patients treated from 2009 to 2015. Results: Weights for dementia, peptic ulcer disease, any tumor, and metastatic solid tumor were used to recalibrate the mCCI-CRRT. Use of these calibrated weights achieved a 35.4% (95% confidence interval [CI], 22.1%–48.1%) higher performance than unadjusted CCI in reclassification based on continuous net reclassification improvement in logistic regression adjusted for age and sex. After additionally adjusting for hemoglobin and albumin, consistent results were found in risk reclassification, which improved by 35.9% (95% CI, 23.3%–48.5%). Conclusion: The mCCI-CRRT stratifies risk of mortality in AKI patients who require CRRT more accurately than does the original CCI, suggesting that it could serve as a preferred index for use in clinical practice.

Purpose: YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC. Results In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.

Background: As industrialization and urbanization are accelerating, the distribution of green areas is decreasing, particularly in developing countries. Since the 2000s, the effects of surrounding greenness on self-perceived health, including physical and mental health, longevity, and obesity have been reported. However, the effects of surrounding green space on chronic kidney disease are not well understood. Therefore, we investigated the impact of residential greenness on the mortality of chronic kidney disease patients and progression from chronic kidney disease to end-stage renal disease (ESRD). Methods: Using a large-scale observational study, we recruited chronic kidney disease patients (n = 64,565; mean age, 54.0 years; 49.0% of male) who visited three Korean medical centers between January 2001 and December 2016. We investigated the hazard ratios of clinical outcomes per 0.1-point increment of exposure to greenness using various models. Results: During the mean follow-up of 6.8 ± 4.6 years, 5,512 chronic kidney disease patients developed ESRD (8.5%) and 8,543 died (13.2%). In addition, a 0.1-point increase in greenness reduced all-cause mortality risk in chronic kidney disease and ESRD patients and progression of chronic kidney disease to ESRD in a fully adjusted model. The association between mortality in ESRD patients and the normalized difference vegetation index was negatively correlated in people aged >65 years, who had normal weight, were nonsmokers, and lived in a nonmetropolitan area. Conclusion Chronic kidney disease patients who live in areas with higher levels of greenness are at reduced risk of all-cause mortality and progression to ESRD.

Purpose: YoungPEARL (KCSG-BR15-10) trial demonstrated a significant progression-free survival (PFS) benefit for premenopausal patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HR+/HER2–) metastatic breast cancer (MBC) for palbociclib plus exemestane with ovarian function suppression compared to capecitabine. However, the number of tamoxifen-sensitive premenopausal patients was small because most recurrences occurred early during adjuvant endocrine therapy (ET), with tamoxifen being the only drug used; hence, the data for these patients were limited. Here we present a subgroup analysis according to tamoxifen sensitivity from the YoungPEARL study. Materials and Methods Patients were randomized 1:1 to receive palbociclib+ET (oral exemestane 25 mg/day for 28 days, palbociclib 125 mg/day for 21 days, plus leuprolide 3.75 mg subcutaneously every 4 weeks) or chemotherapy (oral capecitabine 1,250 mg/m2 twice daily for 14 days every 3 weeks). Tamoxifen resistance was defined as: relapse while on adjuvant tamoxifen, relapse within 12 months of completing adjuvant tamoxifen, or progression while on first-line tamoxifen within 6 months for MBC. Results In total, 184 patients were randomized and 178 were included in the modified intention-to-treat population. PFS improvement in the palbociclib+ET group was observed in tamoxifen-sensitive patients (hazard ratio, 0.38; 95% confidence interval, 0.12 to 1.19). Furthermore, palbociclib+ET prolonged median PFS compared with capecitabine in tamoxifen-sensitive (20.5 months vs. 12.6 months) and tamoxifen-resistant (20.1 months vs. 14.5 months) patients. Palbociclib+ET demonstrated a higher rate of objective response, disease control, and clinical benefit in tamoxifen-sensitive patients. Conclusion This post hoc exploratory analysis suggests that palbociclib+ET is a promising therapeutic option for premenopausal HR+/HER2– MBC patients irrespective of tamoxifen sensitivity.

Background: As industrialization and urbanization are accelerating, the distribution of green areas is decreasing, particularly in developing countries. Since the 2000s, the effects of surrounding greenness on self-perceived health, including physical and mental health, longevity, and obesity have been reported. However, the effects of surrounding green space on chronic kidney disease are not well understood. Therefore, we investigated the impact of residential greenness on the mortality of chronic kidney disease patients and progression from chronic kidney disease to end-stage renal disease (ESRD). Methods: Using a large-scale observational study, we recruited chronic kidney disease patients (n = 64,565; mean age, 54.0 years; 49.0% of male) who visited three Korean medical centers between January 2001 and December 2016. We investigated the hazard ratios of clinical outcomes per 0.1-point increment of exposure to greenness using various models. Results: During the mean follow-up of 6.8 ± 4.6 years, 5,512 chronic kidney disease patients developed ESRD (8.5%) and 8,543 died (13.2%). In addition, a 0.1-point increase in greenness reduced all-cause mortality risk in chronic kidney disease and ESRD patients and progression of chronic kidney disease to ESRD in a fully adjusted model. The association between mortality in ESRD patients and the normalized difference vegetation index was negatively correlated in people aged >65 years, who had normal weight, were nonsmokers, and lived in a nonmetropolitan area. Conclusion Chronic kidney disease patients who live in areas with higher levels of greenness are at reduced risk of all-cause mortality and progression to ESRD.