Magnetic resonance imaging features of complete androgen insensitivity syndrome in comparison to Mayer-Rokitansky-Küster-Hauser syndrome.

PURPOSE: Complete androgen insensitivity syndrome (CAIS) and Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) share common clinical features such as female phenotype, vaginal hypoplasia, and primary amenorrhea. Magnetic resonance imaging (MRI) is performed to investigate the cause of primary amenorrhea. However, the MRI features are also similar in both disorders. They are ultimately diagnosed by chromosome testing, but there is a possibility of misdiagnosis if chromosome testing is not performed. This study aimed to identify MRI features that are useful for differentiating CAIS from MRKHS. METHOD: This multicenter retrospective study included 12 patients with CAIS and 19 patients with MRKHS. Three radiologists blindly evaluated the following features: (1) detection of vagina, (2) detection of nodular and cystic structures in the lateral pelvis; undescended testicles and paratesticular cysts in CAIS and rudimentary uteri and ovaries in MRKHS, (3) their location, (4) number of cysts in the cystic structures, and (5) signal intensity on diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) values of the nodular structures. Statistical comparisons were performed using Mann-Whitney U and Fisher's exact tests. RESULTS: Compared with MRKHS, the CAIS group showed significantly detectable vagina, more ventrally located nodular and cystic structures, fewer cysts within the cystic structures, and nodular structures with higher signal intensity on DWI and lower ADC values. CONCLUSIONS: MRI features of detectable vagina, location of nodular and cystic structures, number of cysts within the cystic structures, signal intensity on DWI and ADC values of the nodular structures were useful in differentiating CAIS from MRKHS.

Diagnostic accuracy of Murray law-based quantitative flow ratio in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

BACKGROUND: Murray law-based quantitative flow ratio (µQFR) is a novel computational method that enables accurate estimation of fractional flow reserve (FFR) using a single angiographic projection. However, its diagnostic value in patients with severe aortic stenosis (AS) remains unclear. METHOD: We included 25 consecutive patients who underwent transcatheter aortic valve replacement (TAVR) for severe AS with intermediate or greater (30-90%) coronary artery disease (CAD). Pre- and post-TAVR µQFR, QFR, instantaneous flow reserve (iFR), and post-TAVR invasive FFR values were measured. We evaluated the diagnostic performance of pre-TAVR µQFR, QFR, and iFR using post-TAVR FFR ≤ 0.80 as a reference standard of ischemia. RESULT: Pre-TAVR µQFR was significantly correlated with post-TAVR FFR (r = 0.73, p < 0.0001). The area under the curve of pre-TAVR µQFR on post-TAVR FFR ≤ 0.8 was 0.91 (95% confidence interval [CI] 0.77-0.98), comparable to that of pre-TAVR iFR (0.86 [95% CI 0.71-0.98], p = 0.97). The accuracy, sensitivity, specificity, and positive and negative predictive values of pre-TAVR µQFR on post-TAVR FFR ≤ 0.8 were 84.2% (95% CI 68.7-93.4), 61.6% (95% CI 31.6-86.1), 96.0% (95% CI 79.6-99.9), 88.9% (95% CI 52.9-98.3), and 82.8% (95% CI 70.6-90.6), respectively. For pre-TAVR iFR, these values were 76.5% (95% CI 58.8-89.3), 90.9% (95% CI 58.7-99.8), 69.6% (95% CI 47.1-86.8), 58.8% (95% CI 42.8-73.1), and 94.1% (95% CI 70.8-99.1), respectively. CONCLUSION: µQFR could be useful for the physiological evaluation of patients with severe AS with concomitant CAD.

A novel prediction tool for mortality in patients with acute lower gastrointestinal bleeding requiring emergency hospitalization: a large multicenter study.

The study aimed to identify prognostic factors for patients with acute lower gastrointestinal bleeding and to develop a high-accuracy prediction tool. The analysis included 8254 cases of acute hematochezia patients who were admitted urgently based on the judgment of emergency physicians or gastroenterology consultants (from the CODE BLUE J-study). Patients were randomly assigned to a derivation cohort and a validation cohort in a 2:1 ratio using a random number table. Assuming that factors present at the time of admission are involved in mortality within 30 days of admission, and adding management factors during hospitalization to the factors at the time of admission for mortality within 1 year, prognostic factors were established. Multivariate analysis was conducted, and scores were assigned to each factor using regression coefficients, summing these to measure the score. The newly created score (CACHEXIA score) became a tool capable of measuring both mortality within 30 days (ROC-AUC 0.93) and within 1 year (C-index, 0.88). The 1-year mortality rates for patients classified as low, medium, and high risk by the CACHEXIA score were 1.0%, 13.4%, and 54.3% respectively (all P < 0.001). After discharge, patients identified as high risk using our unique predictive score require ongoing observation.

Comparing Three Different Anti-Programmed Death-Ligand 1 Antibodies in Immunohistochemical Evaluation of Combined Chemoimmunotherapy Response in Patients With NSCLC: A Prospective Study.

Introduction: Multiple programmed death-ligand 1 (PD-L1) immunohistochemistry assays performed using different antibodies including DAKO 22C3, DAKO 28-8, and Ventana SP142 PD-L1-predictive markers for response to various immune checkpoint inhibitors in NSCLC-have been approved in several countries. The differences in multiple PD-L1 immunohistochemistry assay results in predicting the therapeutic response to combined chemoimmunotherapy in patients with NSCLC remain unclear. Methods: In this multicenter prospective observational study, we monitored 70 patients with advanced NSCLC treated with combined chemoimmunotherapy at 10 institutions in Japan. The expression of PD-L1 in pretreatment tumors was evaluated using the 22C3, 28-8, and SP142 assays in all patients. Results: The PD-L1 level in tumor cells determined using the 22C3 assay was the highest among the three assays performed with different antibodies. According to the 22C3 assay results, the PD-L1 tumor proportion score greater than or equal to 50% group had a significantly longer progression-free survival period than the PD-L1 tumor proportion score less than 50% group. Nevertheless, the other assays did not reveal remarkable differences in the objective response rate or progression-free survival. Conclusions: In our study, PD-L1 expression determined using the 22C3 assay was more correlated with the therapeutic response of patients with NSCLC treated with combined chemoimmunotherapy than that determined using the 28-8 and SP142 assays. Therefore, the 22C3 assay may be useful for clinical decision-making for patients with NSCLC treated with combined chemoimmunotherapy. Trial registration number: UMIN 000043958.

Choroid plexus and pituitary gland hemochromatosis induced by transfusional iron overload: Two case reports.

Hemochromatosis is a primary or secondary pathological condition characterized by the deposition of excess iron in the body tissues, which can eventually lead to cellular damage and organ dysfunction. Although excess iron deposition in the central nervous system is rare, involvement of the choroid plexus, pituitary gland, cortical surfaces, and basal ganglia has been reported to date. This case report describes 2 cases of transfusion-induced hemochromatosis involving the choroid plexus and pituitary gland, which were diagnosed by magnetic resonance imaging (MRI). In both cases, gradient echo (GRE) sequences, such as T2 star-weighted image and susceptibility-weighted imaging demonstrated markedly low signal intensity in the choroid plexus. Furthermore, the pituitary gland showed low signal intensity on T2-weighted images in Patient 2. Because these low signal intensities were not seen prior to red blood cell transfusion, they were diagnosed with transfusion-induced hemochromatosis. Brain MRI with GRE sequences was useful in detecting iron deposition in the choroid plexus. Considering that iron deposition in the body tissues can lead to irreversible organ damage, MRI with GRE sequences should be considered for patients with suspected iron overload.

Prediction of antenatal bleeding and preterm deliveries using placental magnetic resonance imaging in patients with placenta previa.

PURPOSE: This study aimed to clarify associations between subacute hematoma on placental magnetic resonance imaging (MRI), antenatal bleeding, and preterm deliveries in patients with placenta previa (PP) without placenta accreta spectrum (PAS). MATERIALS AND METHODS: This retrospective study investigated 78 consecutive patients with PP (median age, 34.5 years; interquartile range [IQR], 31-37 years) who underwent placental MRI in the third trimester. Patients with PAS detected intraoperatively or pathologically were excluded. Two radiologists evaluated the presence of subacute hematomas and their locations on placental MRI. We examined associations between presence of subacute hematoma and antenatal bleeding, emergency cesarean section (CS), hysterectomy, gestational age (GA) at delivery, birth weight, and amount of blood loss at CS. We also examined the association between perinatal outcome and subacute hematoma location: marginal, retro-placental, or intra-placental. Inter-observer agreement for the detection of subacute hematoma was calculated using kappa analysis. RESULTS: Subacute hematomas were identified on MRI in 39 of the 78 patients (50.0%). Antenatal bleeding and emergency CS were more prevalent in patients with subacute hematoma on MRI (20 patients [51.3%] and 18 patients [46.2%], respectively) than in patients without (7 patients [17.9%], Fisher's exact test, p = 0.004 and 7 patients [17.9%], p = 0.014, respectively). GA at delivery was significantly lower in patients with subacute hematoma (median 36w3d, IQR 35w4d-37w1d) than in patients without (median 37w1d, IQR 36w4d-37w2d; Mann-Whitney test: p = 0.048). Marginal hematoma was significantly associated with antenatal bleeding and emergency CS. Inter-observer agreement for the presence of subacute hematoma was moderate (κ = 0.573). CONCLUSION: Subacute hematoma on placental MRI was associated with antenatal bleeding, emergency CS and shorter GA at delivery in patients with PP. Marginal hematoma was also associated with antenatal bleeding and emergency CS. Placental MRI appears useful for predicting antenatal bleeding and preterm delivery in patients with PP.

Impact of Pericoronary Adipose Tissue Attenuation on Periprocedural Myocardial Injury in Patients With Chronic Coronary Syndrome.

BACKGROUND: Perivascular inflammation contributes to the development of atherosclerosis and microcirculatory dysfunction. Pericoronary adipose tissue (PCAT) attenuation, measured by coronary computed tomography angiography, is a potential indicator of coronary inflammation. However, the relationship between PCAT attenuation, microcirculatory dysfunction, and periprocedural myocardial injury (PMI) remains unclear. METHODS AND RESULTS: Patients with chronic coronary syndrome who underwent coronary computed tomography angiography before percutaneous coronary intervention were retrospectively identified. PCAT attenuation and adverse plaque characteristics were assessed using coronary computed tomography angiography. The extent of microcirculatory dysfunction was evaluated using the angio-based index of microcirculatory resistance before and after percutaneous coronary intervention. Overall, 125 consecutive patients were included, with 50 experiencing PMI (PMI group) and 75 without PMI (non-PMI group). Multivariable analysis showed that older age, higher angio-based index of microcirculatory resistance, presence of adverse plaque characteristics, and higher lesion-based PCAT attenuation were independently associated with PMI occurrence (odds ratio [OR], 1.07 [95% CI, 1.01-1.13]; P=0.02; OR, 1.06 [95% CI, 1.00-1.12]; P=0.04; OR, 6.62 [95% CI, 2.13-20.6]; P=0.001; and OR, 2.89 [95% CI, 1.63-5.11]; P<0.001, respectively). High PCAT attenuation was correlated with microcirculatory dysfunction before and after percutaneous coronary intervention and its exacerbation during percutaneous coronary intervention. Adding lesion-based PCAT attenuation to the presence of adverse plaque characteristics improved the discriminatory and reclassification ability in predicting PMI. CONCLUSIONS: Adding PCAT attenuation at the culprit lesion level to coronary computed tomography angiography-derived adverse plaque characteristics may provide incremental benefit in identifying patients at risk of PMI. Our results highlight the importance of microcirculatory dysfunction in PMI development, particularly in the presence of lesions with high PCAT attenuation. REGISTRATION: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000057722; Unique identifier: UMIN000050662.

Significance of Persistent Systemic Support in the Clinical Course of Delayed Post-hypoxic Leukoencephalopathy Following Severe Coronavirus Disease 2019.

A 45-year-old woman was hospitalized with severe coronavirus disease 2019 pneumonia. Following cytokine storm-induced multiorgan failure and lethal arrhythmia, the patient developed a sustained coma with flaccid quadriplegia. A cerebrospinal fluid examination excluded infectious and immunogenic encephalopathies, and diffusion-weighted magnetic resonance imaging demonstrated high-intensity areas in the white matter with a cortex-sparing distribution, suggesting delayed post-hypoxic leukoencephalopathy. As a result of intensive cardiopulmonary support for a month, the neurological function gradually recovered. Based on the reversible clinical course noted in this patient, accurate diagnosis and persistent medical approaches are important for the management of coronavirus disease 2019-related delayed post-hypoxic leukoencephalopathy.

Diagnostic Accuracy of Pre-Transcatheter Aortic Valve Replacement Nitroglycerin-Free Fractional Flow Reserve-Computed Tomography-Based Physiological Assessment in Patients With Severe Aortic Stenosis for Predicting Post-Transcatheter Aortic Valve Replacement Ischemia.

BACKGROUND: Fractional flow reserve-computed tomography (FFRCT) has not been validated in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) for coronary artery disease due to theoretical difficulties in using nitroglycerin for such patients.Methods and Results: In this single-center study, we prospectively enrolled 21 patients (34 vessels) and performed pre-TAVR FFRCTwithout nitroglycerin, pre-TAVR invasive instantaneous wave-free ratio (iFR) measurements, and post-TAVR FFR measurements using a pressure wire. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of pre-TAVR FFRCT≤0.80 to predict post-TAVR invasive FFR ≤0.80 were 82%, 83%, 82%, 71%, and 90%, respectively. A receiver operating characteristic analysis demonstrated an optimal cutoff of 0.78 for pre-TAVR FFRCTto indicate post-TAVR FFR ≤0.80, with an area under the curve (AUC) of 0.84, and the counterpart cutoff of pre-TAVR iFR was 0.89 with an AUC of 0.86. CONCLUSIONS: FFRCTwithout nitroglycerin could be a useful non-invasive imaging modality for assessing the severity of coronary artery lesions in patients with severe AS.

Characteristics, outcomes, and risk factors of surgery for acute lower gastrointestinal bleeding: nationwide cohort study of 10,342 hematochezia cases.

BACKGROUND: Current evidence on the surgical rate, indication, procedure, risk factors, mortality, and postoperative rebleeding for acute lower gastrointestinal bleeding (ALGIB) is limited. METHODS: We constructed a retrospective cohort of 10,342 patients admitted for acute hematochezia at 49 hospitals (CODE BLUE J-Study) and evaluated clinical data on the surgeries performed. RESULTS: Surgery was performed in 1.3% (136/10342) of the cohort with high rates of colonoscopy (87.7%) and endoscopic hemostasis (26.7%). Indications for surgery included colonic diverticular bleeding (24%), colorectal cancer (22%), and small bowel bleeding (16%). Sixty-four percent of surgeries were for hemostasis for severe refractory bleeding. Postoperative rebleeding rates were 22% in patients with presumptive or obscure preoperative identification of the bleeding source and 12% in those with definitive identification. Thirty-day mortality rates were 1.5% and 0.8% in patients with and without surgery, respectively. Multivariate analysis showed that surgery-related risk factors were transfusion need ≥ 6 units (P < 0.001), in-hospital rebleeding (P < 0.001), small bowel bleeding (P < 0.001), colorectal cancer (P < 0.001), and hemorrhoids (P < 0.001). Endoscopic hemostasis was negatively associated with surgery (P = 0.003). For small bowel bleeding, the surgery rate was significantly lower in patients with endoscopic hemostasis as 2% compared to 12% without endoscopic hemostasis. CONCLUSIONS: Our cohort study elucidated the outcomes and risks of the surgery. Extensive exploration including the small bowel to identify the source of bleeding and endoscopic hemostasis may reduce unnecessary surgery and improve the management of ALGIB.

Machine Learning for Multi-Vessel Coronary Artery Disease Prediction on Electrocardiogram Gated Single-Photon Emission Computed Tomography.

Background: Single-photon emission computed tomography (SPECT) encounters difficulties in diagnosing severe multi-vessel coronary artery disease (svMVD) because of balanced ischemia. We estimated the predictive value of electrocardiogram-gated SPECT for svMVD and improved it using machine learning (ML). Methods and results: We enrolled consecutive 335 patients (median age, 74 years; 255 men) who underwent adenosine stress-gated SPECT (99mTechnesium) and coronary angiography. svMVD was defined as three-vessel disease or left main tract stenosis. Predictive models were constructed using statistical and ML methods. Eighteen cases (5%) showed svMVD, and diabetes, summed stress score (SSS), and the max difference among segmental time of stroke volume per cardiac cycle (MDSV: a parameter of left ventricular [LV] end-systolic dyssynchrony) on adenosine stress were independent significant predictors. The area under the receiver operating characteristic curve (AUC) of SSS and MDSV on stress were 0.759 and 0.763, respectively. Conversely, the extra trees classifier and light gradient boosting machine had improved AUC values of 0.826 and 0.870, respectively, and the MDSV on stress and diabetes showed high feature values in the ML models. Conclusion: ML on SPECT helped to improve the diagnostic performance of svMVD and diabetes, and the parameters of LV dyssynchrony played essential roles in the ML predictive models.

Risk prediction of inappropriate implantable cardioverter-defibrillator therapy using machine learning.

We aimed to develop machine learning-based predictive models for identifying inappropriate implantable cardioverter-defibrillator (ICD) therapy. Our study included 182 consecutive cases (average age 62.2 ± 4.5 years, 169 men) and employed 14 non-deep learning models for prediction (hold-out method). These models utilized selected electrocardiogram parameters and clinical features collected after ICD implantation. From the feature importance analysis of the best ML model, we established easily calculable scores. Among the patients, 25 (13.7%) experienced inappropriate therapy, and we identified 16 significant predictors. Using recursive feature elimination with cross-validation, we reduced the features to six with high feature importance: history of atrial arrhythmia (Atr-arrhythm), ischemic cardiomyopathy (ICM), absence of diabetes mellitus (DM), lack of cardiac resynchronization therapy (CRT), V3 ST level at J point (V3 STJ), and V5 R-wave amplitudes (V5R amp). The extra-trees classifier yielded the highest area under receiver operating characteristics curve (AUROC; 0.869 on test data). Thus, the Cardi35 score was defined as [+ 5.5*Atr-arrhythm - 1.5*CRT + 1.0*V3STJ + 1.0*V5R - 1.0*ICM - 0.5*DM], which demonstrated a hazard ratio of 1.62 (P < 0.001). A cut-off value of the score + 5.5 showed high AUROC (0.826). The ML approach can yield a robust prediction model, and the Cardi35 score was a convenient predictor for inappropriate therapy.

Pulmonary Vein Stenosis after Catheter Ablation for Atrial Fibrillation: An Early Diagnosis Using Unenhanced Computed Tomography.

Pulmonary vein stenosis (PVS) is a serious complication of catheter ablation (CA) for atrial fibrillation (AF). PVS generally occurs several months after CA and presents with non-specific symptoms and imaging findings. There have been reports of delayed diagnoses due to a misdiagnosis as infection, interstitial pneumonia, or organizing pneumonia. We introduced six cases of PVS after CA, all of which showed narrowing of the unilateral pulmonary vessels with or without lobar volume loss in the left lung on unenhanced computed tomography. We report these findings as important results indicating the possibility of PVS after CA for AF and contributing to the early diagnosis and management of PVS.

Early feeding reduces length of hospital stay in patients with acute lower gastrointestinal bleeding: A large multicentre cohort study.

AIM: No studies have compared the clinical outcomes of early and delayed feeding in patients with acute lower gastrointestinal bleeding (ALGIB). This study aimed to evaluate the benefits and risks of early feeding in a nationwide cohort of patients with ALGIB in whom haemostasis was achieved. METHODS: We reviewed data for 5910 patients with ALGIB in whom haemostasis was achieved and feeding was resumed within 3 days after colonoscopy at 49 hospitals across Japan (CODE BLUE-J Study). Patients were divided into an early feeding group (≤1 day, n = 3324) and a delayed feeding group (2-3 days, n = 2586). Clinical outcomes were compared between the groups by propensity matching analysis of 1508 pairs. RESULTS: There was no significant difference between the early and delayed feeding groups in the rebleeding rate within 7 days after colonoscopy (9.4% vs. 8.0%; p = 0.196) or in the rebleeding rate within 30 days (11.4% vs. 11.5%; p = 0.909). There was also no significant between-group difference in the need for interventional radiology or surgery or in mortality. However, the median length of hospital stay after colonoscopy was significantly shorter in the early feeding group (5 vs. 7 days; p < 0.001). These results were unchanged when subgroups of presumptive and definitive colonic diverticular bleeding were compared. CONCLUSION: The findings of this nationwide study suggest that early feeding after haemostasis can shorten the hospital stay in patients with ALGIB without increasing the risk of rebleeding.

Weekend Effect on Clinical Outcomes of Acute Lower Gastrointestinal Bleeding: A Large Multicenter Cohort Study in Japan.

INTRODUCTION: Weekend admissions showed increased mortality in several medical conditions. This study aimed to examine the weekend effect on acute lower gastrointestinal bleeding (ALGIB) and its mortality and other outcomes. METHODS: This retrospective cohort study (CODE BLUE-J Study) was conducted at 49 Japanese hospitals between January 2010 and December 2019. In total, 8,120 outpatients with acute hematochezia were enrolled and divided into weekend admissions and weekday admissions groups. Multiple imputation (MI) was used to handle missing values, followed by propensity score matching (PSM) to compare outcomes. The primary outcome was mortality; the secondary outcomes were rebleeding, length of stay (LOS), blood transfusion, thromboembolism, endoscopic treatment, the need for interventional radiology, and the need for surgery. Colonoscopy and computed tomography (CT) management were also evaluated. RESULTS: Before PSM, there was no significant difference in mortality (1.3% vs. 0.9%, p = 0.133) between weekend and weekday admissions. After PSM with MI, 1,976 cases were matched for each admission. Mortality was not significantly different for weekend admissions compared with weekday admissions (odds ratio [OR] 1.437, 95% confidence interval [CI] 0.785-2.630; p = 0.340). No significant difference was found with other secondary outcomes in weekend admissions except for blood transfusion (OR 1.239, 95% CI 1.084-1.417; p = 0.006). Weekend admission had a negative effect on early colonoscopy (OR 0.536, 95% CI 0.471-0.609; p < 0.001). Meanwhile, urgent CT remained significantly higher in weekend admissions (OR 1.466, 95% CI 1.295-1.660; p < 0.001). CONCLUSION: Weekend admissions decrease early colonoscopy and increase urgent CT but do not affect mortality or other outcomes except transfusion.

Optic pathway involvement in the posterior reversible encephalopathy syndrome: A case report and review of the literature.

Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological condition characterized by reversible vasogenic edema of the white matter and acute neurological symptoms. PRES typically affects the parieto-occipital regions but rarely affects the optic pathway. Herein, we describe a case of central-variant PRES in a 57-year-old man with abnormal signal intensities in the optic pathway on magnetic resonance imaging (MRI). The patient underwent hemodialysis, initiated diuretics and antihypertensive medications, and the abnormal signal intensities of the brainstem and optic pathway on MRI improved. Although rare, PRES can affect the optic pathway, thus suggesting the possibility of fragility of the optic pathway itself to hyperperfusion.

Magnetic resonance imaging findings of sclerosing microcystic adenocarcinoma: A case report and review of the literature.

Sclerosing microcystic adenocarcinoma (SMA) is a rare malignant tumor of the salivary glands that closely resembles cutaneous microcystic adnexal carcinoma (MAC). It was newly listed in the 5th edition of the WHO classification of head and neck tumors. This report describes the case of a 61-year-old woman who presented with masses on the floor of the mouth. The masses showed low signal intensity on T2-weighted images (T2WI) and with low apparent diffusion coefficient (ADC) values. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) revealed a plateau or persistence after rapid initial enhancement. Histopathologically, the tumors comprised small infiltrating strands of cells that formed small ducts and cysts embedded in thick fibrous stroma, consistent with SMA. Low signal intensity on T2WI with a low ADC value and a plateau or persistence after rapid initial enhancement on DCE-MRI reflect the fibrous and cellular components of the tumor and can be considered characteristic MRI findings of SMA.

LONG-HOSP Score: A Novel Predictive Score for Length of Hospital Stay in Acute Lower Gastrointestinal Bleeding - A Multicenter Nationwide Study.

INTRODUCTION: Length of stay (LOS) in hospital affects cost, patient quality of life, and hospital management; however, existing gastrointestinal bleeding models applicable at hospital admission have not focused on LOS. We aimed to construct a predictive model for LOS in acute lower gastrointestinal bleeding (ALGIB). METHODS: We retrospectively analyzed the records of 8,547 patients emergently hospitalized for ALGIB at 49 hospitals (the CODE BLUE-J Study). A predictive model for prolonged hospital stay was developed using the baseline characteristics of 7,107 patients and externally validated in 1,440 patients. Furthermore, a multivariate analysis assessed the impact of additional variables during hospitalization on LOS. RESULTS: Focusing on baseline characteristics, a predictive model for prolonged hospital stay was developed, the LONG-HOSP score, which consisted of low body mass index, laboratory data, old age, nondrinker status, nonsteroidal anti-inflammatory drug use, facility with ≥800 beds, heart rate, oral antithrombotic agent use, symptoms, systolic blood pressure, performance status, and past medical history. The score showed relatively high performance in predicting prolonged hospital stay and high hospitalization costs (area under the curve: 0.70 and 0.73 for derivation, respectively, and 0.66 and 0.71 for external validation, respectively). Next, we focused on in-hospital management. Diagnosis of colitis or colorectal cancer, rebleeding, and the need for blood transfusion, interventional radiology, and surgery prolonged LOS, regardless of the LONG-HOSP score. By contrast, early colonoscopy and endoscopic treatment shortened LOS. CONCLUSIONS: At hospital admission for ALGIB, our novel predictive model stratified patients by their risk of prolonged hospital stay. During hospitalization, early colonoscopy and endoscopic treatment shortened LOS.

Analysis of Tumor Heterogeneity Through AXL Activation in Primary Resistance to EGFR Tyrosine Kinase Inhibitors.

Introduction: EGFR tyrosine kinase inhibitors are standard therapeutic agents for patients with advanced NSCLC harboring EGFR mutations. Nevertheless, some patients exhibit primary resistance to EGFR tyrosine kinase inhibitors in the first-line treatment setting. AXL, a member of the TYRO3, AXL, and MERTK family of receptor tyrosine kinases, is involved in primary resistance to EGFR tyrosine kinase inhibitors in EGFR-mutated NSCLC. Methods: We investigated spatial tumor heterogeneity using autopsy specimens and a patient-derived cell line from a patient with EGFR-mutated NSCLC having primary resistance to erlotinib plus ramucirumab. Results: Quantitative polymerase chain reaction analysis revealed that AXL mRNA expression differed at each metastatic site. In addition, AXL expression levels were likely to be negatively correlated with the effectiveness of erlotinib plus ramucirumab therapy. Analysis of a patient-derived cell line established from the left pleural effusion before initiation of treatment revealed that the combination of EGFR tyrosine kinase inhibitors and an AXL inhibitor remarkably inhibited cell viability and increased cell apoptosis in comparison with EGFR tyrosine kinase inhibitor monotherapy or combination therapy of these inhibitors with ramucirumab. Conclusions: Our observations suggest that AXL expression may play a critical role in the progression of spatial tumor heterogeneity and primary resistance to EGFR tyrosine kinase inhibitors in patients with EGFR-mutated NSCLC.