Purpose: While progesterone receptor (PR) negativity in luminal-type breast cancer is generally associated with worse oncologic outcomes, its prognostic role in estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-positive breast cancer remains underexplored. This study aimed to evaluate the prognostic significance of PR expression in ER-positive, HER2-positive breast cancer. Methods: A retrospective analysis was conducted on patients diagnosed with ER-positive, HER2-positive breast cancer who underwent primary surgery at Korea University Guro Hospital between January 2009 and December 2019. Patients were grouped by PR expression as negative/low (Allred score, 0–6) or strongly positive (Allred score,7 or 8). Prognostic outcomes, including disease-free survival (DFS), distant recurrence-free survival (DRFS), and breast cancer-specific survival (BCSS) were analyzed. Results: A total of 223 patients were included. Patients in the negative/low PR group were older compared to the strongly positive PR group. The negative/low PR group showed significantly worse DFS (P = 0.005) and DRFS (P = 0.014) but showed no significant difference in BCSS (P = 0.153). On multivariate analysis, negative or low PR expressions were linked to inferior DFS (hazard ratio [HR], 3.10; 95% confidence interval [CI], 1.34–7.16; P = 0.008) and DRFS (HR, 9.55; 95% CI, 1.22– 74.77; P = 0.032). Conclusion In ER-positive, HER2-positive breast cancer, negative or weak PR expression was associated with inferior DFS and DRFS compared to strong PR expression. These findings highlight the potential prognostic value of PR status in this group, underscoring its relevance in guiding treatment and follow-up strategies for more individualized patient care.

Objectives: Drug-induced QT prolongation can lead to life-threatening arrhythmia. In the intensive care unit (ICU), various drugs are administered concurrently, which can increase the risk of QT prolongation. However, no well-validated method to evaluate the risk of QT prolongation in real-world clinical practice has been established. We developed a risk scoring model to continuously evaluate the quantitative risk of QT prolongation in real-world clinical practice in the ICU. Methods: Continuous electrocardiogram (ECG) signals measured by patient monitoring devices and Electronic Medical Records data were collected for ICU patients. QT and RR intervals were measured from raw ECG data, and a corrected QT interval (QTc) was calculated by Bazett’s formula. A case-crossover study design was adopted. A case was defined as an occurrence of QT prolongation ≥12 hours after any previous QT prolongation. The patients served as their own controls. Conditional logistic regression was conducted to analyze prescription, surgical history, and laboratory test data. Based on the regression analysis, a QTc prolongation risk scoring model was established. Results: In total, 811 ICU patients who experienced QT prolongation were included in this study. Prescription information for 13 drugs was included in the risk scoring model. In the validation dataset, the high-risk group showed a higher rate of QT prolongation than the low-and low moderate-risk groups. Conclusions Our proposed model may facilitate risk stratification for QT prolongation during ICU care as well as the selection of appropriate drugs to prevent QT prolongation.

Objectives: Drug-induced QT prolongation can lead to life-threatening arrhythmia. In the intensive care unit (ICU), various drugs are administered concurrently, which can increase the risk of QT prolongation. However, no well-validated method to evaluate the risk of QT prolongation in real-world clinical practice has been established. We developed a risk scoring model to continuously evaluate the quantitative risk of QT prolongation in real-world clinical practice in the ICU. Methods: Continuous electrocardiogram (ECG) signals measured by patient monitoring devices and Electronic Medical Records data were collected for ICU patients. QT and RR intervals were measured from raw ECG data, and a corrected QT interval (QTc) was calculated by Bazett’s formula. A case-crossover study design was adopted. A case was defined as an occurrence of QT prolongation ≥12 hours after any previous QT prolongation. The patients served as their own controls. Conditional logistic regression was conducted to analyze prescription, surgical history, and laboratory test data. Based on the regression analysis, a QTc prolongation risk scoring model was established. Results: In total, 811 ICU patients who experienced QT prolongation were included in this study. Prescription information for 13 drugs was included in the risk scoring model. In the validation dataset, the high-risk group showed a higher rate of QT prolongation than the low-and low moderate-risk groups. Conclusions Our proposed model may facilitate risk stratification for QT prolongation during ICU care as well as the selection of appropriate drugs to prevent QT prolongation.

Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR) and reversible airway obstruction. Methacholine (MCh) is widely used in broncho-provocation test to evaluate airway resistance. For experimental investigation, ovalbumin-induced sensitization is frequently used in rodents (Ova-asthma). However, albeit the inflammatory histology and AHR in vivo, it remains unclear whether the MCh sensitivity of airway smooth muscle isolated from Ova-asthma is persistently changed. In this study, the contractions of airways in precision-cut lung slices (PCLS) from control, Ova-asthma, and IL-13 overexpressed transgenic mice (IL-13TG) were compared by analyzing the airway lumen space (AW). The airway resistance in vivo was measured using plethysmograph. AHR and increased inflammatory cells in BAL fluid were confirmed in Ova-asthma and IL-13TG mice. In the PCLS from all three groups, MCh concentration-dependent narrowing of airway lumen (DeltaAW) was observed. In contrast to the AHR in vivo, the EC50 of MCh for DeltaAW from Ova-asthma and IL-13TG were not different from control, indicating unchanged sensitivity to MCh. Although the AW recovery upon MCh-washout showed sluggish tendency in Ova-asthma, the change was also statistically insignificant. Membrane depolarization-induced DeltaAW by 60 mM K+ (60K-contraction) was larger in IL-13TG than control, whereas 60K-contraction of Ova-asthma was unaffected. Furthermore, serotonin-induced DeltaAW of Ova-asthma was smaller than control and IL-13TG. Taken together, the AHR in Ova-asthma and IL-13TG are not reflected in the contractility of isolated airways from PCLS. The AHR of the model animals seems to require intrinsic agonists or inflammatory microenvironment that is washable during tissue preparation.
Airway Obstruction ; Airway Resistance ; Animals ; Asthma ; Interleukin-13 ; Lung* ; Membranes ; Methacholine Chloride* ; Mice* ; Mice, Transgenic ; Muscle, Smooth* ; Rodentia

Hyperoxic ventilation induces detrimental effects on the respiratory system, and ambient oxygen may be harmful unless compensated by physiological anti-oxidants, such as vitamin C. Here we investigate the changes in electrolyte transport of airway epithelium in mice exposed to normobaric hyperoxia and in gulonolacton oxidase knock-out (gulo[-/-]) mice without vitamin C (Vit-C) supplementation. Short-circuit current (Isc) of tracheal epithelium was measured using Ussing chamber technique. After confirming amiloride-sensitive Na+ absorption (DeltaIsc,amil), cAMP-dependent Cl- secretion (DeltaIsc,forsk) was induced by forskolin. To evaluate Ca2+-dependent Cl- secretion, ATP was applied to the luminal side (DeltaIsc,ATP). In mice exposed to 98% PO2 for 36 hr, DeltaIsc,forsk decreased, DeltaIsc,amil and DeltaIsc,ATP was not affected. In gulo(-/-) mice, both DeltaIsc,forsk and DeltaIsc,ATP decreased from three weeks after Vit-C deprivation, while both were unchanged with Vit-C supplementation. At the fourth week, tissue resistance and all electrolyte transport activities were decreased. An immunofluorescence study showed that the expression of cystic fibrosis conductance regulator (CFTR) was decreased in gulo(-/-) mice, whereas the expression of KCNQ1 K+ channel was preserved. Taken together, the CFTR-mediated Cl- secretion of airway epithelium is susceptible to oxidative stress, which suggests that supplementation of the antioxidant might be beneficial for the maintenance of airway surface liquid.
Animals ; Ascorbic Acid Deficiency/*metabolism ; Biological Transport/drug effects ; Chlorides/*metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator/antagonists & inhibitors/drug ; Forskolin/pharmacology ; Hyperbaric Oxygenation ; Hyperoxia/*physiopathology ; Ion Transport/drug effects ; Mice ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Mice, Knockout/metabolism ; Mice, Transgenic ; Microscopy, Fluorescence ; Oxidative Stress ; Oxygen/adverse effects/pharmacology ; Potassium Channels/metabolism ; Respiratory Mucosa/drug effects/*metabolism/secretion ; Sodium ; Sugar Acids/metabolism