Rapid improvement of severe fatty liver in a case of fulminant type 1 diabetes following insulin treatment.

A 36-year-old woman presented to the emergency room with a consciousness disorder after developing abdominal pain with diarrhea for 2 days. She presented with marked hyperglycemia, ketoacidosis, and increased serum free fatty acid (FFA) levels; however, no elevation in the glycated hemoglobin (HbA1c) levels was observed. Based on the marked depletion of insulin secretion, the patient was diagnosed as diabetic ketoacidosis attributed to fulminant type 1 diabetes (FT1D). Computed tomography on admission revealed severe fatty liver (FL), which improved 17 h following insulin treatment. Insulin treatment also suppressed the serum FFA levels. Some cases of FT1D with FL and liver dysfunction have been reported previously; however, its pathogenesis and clinical course remain unclear. Compared to previous reports, this case reported the shortest time for FL improvement. In this case, rapid and severe insulin deficiency led to a markedly high FFA level and significant accumulation of triglycerides in the hepatocytes, resulting in severe FL. A rapid and large dose of insulin was administered when systemic insulin sensitivity was nearly maximal owing to insulin deficiency, increased insulin efficacy, early reduction of FFA, suppressed triglyceride accumulation in the hepatocytes, and increased triglyceride excretion from the liver. All these factors could have contributed to the rapid improvement in FL.

Primary percutaneous coronary intervention for cardio-cerebral infarction: a case report.

Background: Acute myocardial infarction (AMI) and acute ischemic stroke (AIS) are the leading causes of death globally. Cardio-cerebral infarction (CCI) is the rare occurrence of AMI and AIS, either simultaneously or one after the other. Treatment recommendations are not clear in case of the occurrence of AMI and AIS simultaneously, especially the strategy of primary percutaneous coronary intervention (PCI). Case presentation: We report consecutive seven case series of patients with CCI who underwent primary PCI in our institute. Comorbidities, strategy of primary PCI, and outcomes were investigated. All patients presented with the chief complaints associated with stroke. Atrial fibrillation (AF) was complicated in five of CCI patients, and four of AF patients were not anticoagulated. The major causes of stroke were cardiogenic and/or hemodynamic in this case series. All patients showed total occlusion in the culprit lesion, and six patients had other diseased vessels. Thrombus aspiration was mainly chosen as the reperfusion strategy in PCI. However, only two patients were diagnosed as definitive coronary embolism, and stenting was needed in six patients due to severe atherosclerotic lesion in culprit coronary artery. Final thrombolysis in myocardial infarction (TIMI) 3 flow was achieved only in four patients. Hemorrhagic complications occurred in three patients. Two patients died during in-hospital stay, and most had to be transferred for rehabilitation. Conclusions: CCI was a rare but fatal condition in patients who underwent primary PCI. Although CCI was associated with concomitant atrial fibrillation, organic coronary stenosis requiring stenting for revascularization was present in almost all the cases. Given the complexity of coronary artery lesions and high in-hospital mortality, further investigations are needed to determine the optimal treatment strategy.

Zinc homeostasis governed by Golgi-resident ZnT family members regulates ERp44-mediated proteostasis at the ER-Golgi interface.

Many secretory enzymes acquire essential zinc ions (Zn2+) in the Golgi complex. ERp44, a chaperone operating in the early secretory pathway, also binds Zn2+ to regulate its client binding and release for the control of protein traffic and homeostasis. Notably, three membrane transporter complexes, ZnT4, ZnT5/ZnT6 and ZnT7, import Zn2+ into the Golgi lumen in exchange with protons. To identify their specific roles, we here perform quantitative Zn2+ imaging using super-resolution microscopy and Zn2+-probes targeted in specific Golgi subregions. Systematic ZnT-knockdowns reveal that ZnT4, ZnT5/ZnT6 and ZnT7 regulate labile Zn2+ concentration at the distal, medial, and proximal Golgi, respectively, consistent with their localization. Time-course imaging of cells undergoing synchronized secretory protein traffic and functional assays demonstrates that ZnT-mediated Zn2+ fluxes tune the localization, trafficking, and client-retrieval activity of ERp44. Altogether, this study provides deep mechanistic insights into how ZnTs control Zn2+ homeostasis and ERp44-mediated proteostasis along the early secretory pathway.

Successful visible thrombus aspiration in ST-segment elevation myocardial infarction: associated factors and the clinical impact.

BACKGROUND: Thrombus aspiration (TA) has been considered a procedure for controlling distal emboli and improving microvascular perfusion. However, current guidelines classify routine TA as class III recommendation, and it has been reported that the efficacy of TA is limited because of the relatively high incidence of failure in retrieval of thrombotic material. The aim of this study was to explore patient characteristics and procedural factors associated with successful TA in ST-elevation myocardial infarction (STEMI) and to assess the clinical impact of successful TA. METHODS: This single-center retrospective study enrolled 158 STEMI patients who underwent TA as initial recanalization. Factors associated with successful TA, which was defined as retrieving any visible material by aspiration catheter, were explored, and angiographical and short-term outcomes were assessed. RESULTS: In 146 cases (92.4%), the aspiration catheter reached the culprit lesion. Successful TA was achieved in 72 cases (45.6%). The single angiographical characteristic of successful TA was a higher Thrombolysis in Myocardial Infarction grade before TA. Among the procedural characteristics, the rate of successful TA was higher with a 7-French aspiration catheter compared with the rate with a 6-French catheter (57.1% vs. 29.9%, P = 0.01). Thrombolysis in Myocardial Infarction grade 3 flow was more frequent in patients with successful TA immediately after TA (36.1% vs. 16.3%, P = 0.006) and at final angiography (91.7% vs 79.1%, P = 0.04) compared with the grade in patients without successful TA, respectively. CONCLUSIONS: The use of a larger aspiration catheter may be effective in retrieving visible thrombus material, and successful TA led to better angiographical results.

Extracting Multiple Worries From Breast Cancer Patient Blogs Using Multilabel Classification With the Natural Language Processing Model Bidirectional Encoder Representations From Transformers: Infodemiology Study of Blogs.

BACKGROUND: Patients with breast cancer have a variety of worries and need multifaceted information support. Their accumulated posts on social media contain rich descriptions of their daily worries concerning issues such as treatment, family, and finances. It is important to identify these issues to help patients with breast cancer to resolve their worries and obtain reliable information. OBJECTIVE: This study aimed to extract and classify multiple worries from text generated by patients with breast cancer using Bidirectional Encoder Representations From Transformers (BERT), a context-aware natural language processing model. METHODS: A total of 2272 blog posts by patients with breast cancer in Japan were collected. Five worry labels, "treatment," "physical," "psychological," "work/financial," and "family/friends," were defined and assigned to each post. Multiple labels were allowed. To assess the label criteria, 50 blog posts were randomly selected and annotated by two researchers with medical knowledge. After the interannotator agreement had been assessed by means of Cohen kappa, one researcher annotated all the blogs. A multilabel classifier that simultaneously predicts five worries in a text was developed using BERT. This classifier was fine-tuned by using the posts as input and adding a classification layer to the pretrained BERT. The performance was evaluated for precision using the average of 5-fold cross-validation results. RESULTS: Among the blog posts, 477 included "treatment," 1138 included "physical," 673 included "psychological," 312 included "work/financial," and 283 included "family/friends." The interannotator agreement values were 0.67 for "treatment," 0.76 for "physical," 0.56 for "psychological," 0.73 for "work/financial," and 0.73 for "family/friends," indicating a high degree of agreement. Among all blog posts, 544 contained no label, 892 contained one label, and 836 contained multiple labels. It was found that the worries varied from user to user, and the worries posted by the same user changed over time. The model performed well, though prediction performance differed for each label. The values of precision were 0.59 for "treatment," 0.82 for "physical," 0.64 for "psychological," 0.67 for "work/financial," and 0.58 for "family/friends." The higher the interannotator agreement and the greater the number of posts, the higher the precision tended to be. CONCLUSIONS: This study showed that the BERT model can extract multiple worries from text generated from patients with breast cancer. This is the first application of a multilabel classifier using the BERT model to extract multiple worries from patient-generated text. The results will be helpful to identify breast cancer patients' worries and give them timely social support.

Identification of hand-foot syndrome from cancer patients' blog posts: BERT-based deep-learning approach to detect potential adverse drug reaction symptoms.

Early detection and management of adverse drug reactions (ADRs) is crucial for improving patients' quality of life. Hand-foot syndrome (HFS) is one of the most problematic ADRs for cancer patients. Recently, an increasing number of patients post their daily experiences to internet community, for example in blogs, where potential ADR signals not captured through routine clinic visits can be described. Therefore, this study aimed to identify patients with potential ADRs, focusing on HFS, from internet blogs by using natural language processing (NLP) deep-learning methods. From 10,646 blog posts, written in Japanese by cancer patients, 149 HFS-positive sentences were extracted after pre-processing, annotation and scrutiny by a certified oncology pharmacist. The HFS-positive sentences described not only HFS typical expressions like "pain" or "spoon nail", but also patient-derived unique expressions like onomatopoeic ones. The dataset was divided at a 4 to 1 ratio and used to train and evaluate three NLP deep-learning models: long short-term memory (LSTM), bidirectional LSTM and bidirectional encoder representations from transformers (BERT). The BERT model gave the best performance with precision 0.63, recall 0.82 and f1 score 0.71 in the HFS user identification task. Our results demonstrate that this NLP deep-learning model can successfully identify patients with potential HFS from blog posts, where patients' real wordings on symptoms or impacts on their daily lives are described. Thus, it should be feasible to utilize patient-generated text data to improve ADR management for individual patients.

A case of juvenile-onset pheochromocytoma with KIF1B p.V1529M germline mutation.

In 2008, a familial noradrenergic pheochromocytoma (PCC) with a KIF1B germline mutation in exon 41 was reported in a 24-year-old female proband and her family. However, in 2020, the same research group reported that the cause of PCC in this family was a MAX germline mutation and was not due to the KIF1B mutation. In this study, we investigated the pathogenicity of a KIF1B germline mutation detected in a 26-year-old woman with juvenile-onset noradrenergic PCC. She was surgically treated and did not have a family history of PCC. We performed whole-exome sequencing, Sanger sequencing, and immunohistochemical and gene expression analyses of catecholamine-synthesizing enzymes. Three tumors with associated somatic mutations were used as the control group. Whole-exome sequencing revealed a p.V1529M KIF1B germline mutation in exon 41 in our patient, and no other associated germline and somatic mutations, including MAX, were detected. Sanger sequencing confirmed the presence of both mutant and wild-type alleles in the tumor. Among the catecholamine-synthesizing enzymes, the expression of phenylethanolamine-N-methyl transferase was suppressed. An in silico analysis of the p.V1529M mutation showed a score suggestive of pathogenicity. After evaluation with the international guideline for sequence variants, p.V1529M mutation was still classified as a variant with uncertain significance; however, our data, including the in silico analysis data, provided certain evidences that met the criteria supporting its pathogenicity. Therefore, this study can support future studies in proving the pathogenicity of the KIF1B p.V1529M mutation.

Protocol for synthesis and use of a turn-on fluorescent probe for quantifying labile Zn2+ in the Golgi apparatus in live cells.

Quantitative analysis using a turn-on fluorescent probe is inherently difficult due to the dependency of the fluorescence intensity on the probe concentration. To overcome this limitation, we developed an in situ quantification method using a turn-on fluorescent probe and a standard fluorophore, which are colocalized by protein tag technology. This protocol describes the synthesis of a Zn2+ probe, named ZnDA-1H, and the procedure to quantify the labile Zn2+ concentration in the Golgi of live HeLa cells by confocal fluorescence microscopy. For complete details on the use and execution of this protocol, please refer to Kowada et al. (2020).

Cost analysis of transcatheter versus surgical aortic valve replacement in octogenarians: analysis from a single Japanese center.

Transcatheter aortic valve replacement (TAVR) has revolutionized the prognosis of intermediate- or high-risk patients with severe aortic stenosis, particularly among older adults. However, in possible candidates for surgical aortic valve replacement (SAVR), the implantation of expensive prostheses may be questionable in an era when healthcare costs are becoming a major concern. In this retrospective analysis of a single Japanese center, we focused on patients aged over 80 years; the objectives of this study were: (1) to compare TAVR and SAVR in terms of total hospitalization costs and (2) to describe the itemized cost of TAVR and SAVR to identify patients aged over 80 years in whom TAVR or SAVR would be cost-effective. A total of 146 patients aged over 80 years who underwent TAVR or SAVR for severe aortic stenosis were included. These patients were divided into a high-risk group (Society of Thoracic Surgeons [STS] mortality score > 8%; 36: TAVR and 12: SAVR) with 48 patients and a non-high-risk group (STS mortality score < 8%; 45: TAVR and 53 SAVR) with 98 patients. No 30-day mortality was observed in either group. In both groups, postoperative intensive care unit stay and hospital stay were longer with SAVR than with TAVR. In the non-high-risk group, the total cost was comparable for TAVR and SAVR; however, in the high-risk group, the total cost was significantly higher with SAVR than that with TAVR. A breakdown analysis of the total cost in the high-risk group showed both pre- and postoperative costs to be significantly higher with SAVR than with TAVR; however, operative costs were higher with TAVR. Up to 3 years, the overall survival in both groups did not significantly differ between TAVR and SAVR. Our findings suggest that from the perspective of total medical costs, TAVR is more suitable than SAVR for high-risk older adults.

Impact of Number of Drugs on Rehabilitation Outcomes in Patients after Traumatic Brain Injury: A Retrospective Cohort Study.

OBJECTIVE: To investigate the impact of the number of drugs on rehabilitation outcomes for patients with acute traumatic brain injury. DESIGN: Retrospective cohort study. SETTING: Hospital-based database created by the Japan Medical Data Center. PARTICIPANTS: Patients with acute traumatic brain injury admitted between April 2014 and November 2017. METHODS: Analysis of relationships among 1-5 and ≥ 6 drugs as well as clinical outcomes in 2603 patients. MAIN OUTCOME MEASUREMENTS: The primary outcome was defined as the Barthel index efficiency, and the secondary outcome was Barthel index gain and length of hospital stay. RESULTS: Median Barthel index score on admission was 40. Barthel index efficiency and Barthel index gain were significantly higher in the group that had taken 1-5 drugs than in the group that had taken ≥6 drugs on admission (median: 1.19 vs 0.50, 20.0 vs 10.0). Also, the group that had taken 1-5 drugs had a significantly shorter length of hospital stay than in the group that had taken ≥6 drugs on admission (median 11.0 vs 14.0). Moreover, multiple linear regression analysis showed that having taken ≥6 drugs on admission was independently associated with Barthel index efficiency, Barthel index gain, and length of stay. CONCLUSIONS: Taking≥6 drugs for acute traumatic brain injury was associated with lower Barthel index efficiency, lower Barthel index gain, and longer length of stay than taking 1-5 drugs.

Quantitative Imaging of Labile Zn2+ in the Golgi Apparatus Using a Localizable Small-Molecule Fluorescent Probe.

Fluorescent Zn2+ probes used for the quantitative analysis of labile Zn2+ concentration ([Zn2+]) in target organelles are crucial for understanding the role of Zn2+ in biological processes. Although several fluorescent Zn2+ probes have been developed to date, there is still a lack of consensus concerning the [Zn2+] in intracellular organelles. In this study, we describe the development of ZnDA-1H, a small-molecule fluorescent probe for Zn2+, which exhibits less pH sensitivity, high Zn2+ selectivity, and large fluorescence enhancement upon binding to Zn2+. Through protein labeling technology, ZnDA-1H was precisely targeted in various intracellular organelles, such as the nucleus, mitochondria, endoplasmic reticulum, and Golgi apparatus. ZnDA-1H exhibited a reversible fluorescence response toward labile Zn2+ in these organelles in live cells. Using this probe, the [Zn2+] in the Golgi apparatus was estimated to be 25 ± 1 nM, suggesting that labile Zn2+ plays a physiological role in the secretory pathway.

Cell wall Glycine-rich Protein2 is involved in tapetal differentiation and pollen maturation.

The tapetum plays important roles in anther development by providing materials for pollen-wall formation and nutrients for pollen development. Here, we report the characterization of a male-sterile mutant of glycine-rich protein 2 (OsGRP2), which exhibits irregular cell division and dysfunction of the tapetum. GRP is a cellwall structural protein present in the cell walls of diverse plant species, but its function is unclear in pollen development. We found that few GRP genes are expressed in rice and thus focused on one highly expressed gene, OsGRP2. The tapetal cell walls of an OsGRP2 mutant did not thicken at the pollen mothercell stage, as a result, pollen maturation and fertility rate decreased. High OsGRP2 expression was detected in male-floral organs, and OsGRP2 was distributed in the tapetum. OsGRP2 participated in establishment of the cellwall network during early tapetum development. In conclusion, our results indicate that OsGRP2 plays important roles in the differentiation and function of the tapetum.

Neurological Prognostic Value of Adjusted Ca2+ Concentration in Adult Patients with Out-of-Hospital Cardiac Arrest.

Many patients are transferred to hospital due to out-of-hospital cardiac arrest (OHCA), and, unfortunately, most suffer from cerebral damage. Currently, it is difficult to predict the recovery of neurological function after return of spontaneous circulation (ROSC) in the acute phase. Increased intracellular Ca2+ induces cell death in the acute phase. Accordingly, we predicted that serum adjusted Ca2+ will decrease following Ca2+ influx into cells. Consequently, serum adjusted Ca2+ in the acute phase may be able to predict recovery of neurological function in patients with ROSC from OHCA. This is a retrospective and observational study from 2 centers. A total of 190 consecutive patients with ROSC from OHCA were recruited, with 33 patients meeting the inclusion criteria. The relationship between serum adjusted Ca2+ within 48 hours after ROSC and neurological function at discharge (as evaluated by the Glasgow-Pittsburgh cerebral performance category) was examined. Serum adjusted Ca2+ was measured every 4 hours within a 48-hour period after ROSC. There were no significant differences in hemodynamical state and laboratory data between the 2 groups. However, lowest serum adjusted Ca2+ within 48 hours after ROSC was significantly lower in the poor neurological outcome group (0.96 ± 0.06 versus 1.02 ± 0.06 mmol/L, P = 0.011). Thus, lowest serum adjusted Ca2+ within 48 hours after ROSC may be a predictive factor for recovery of neurological function at discharge in patients with ROSC from OHCA.

Impact of delayed hyperenhancement obtained by non-contrast computed tomography following coronary angiography in patients undergoing extracorporeal cardiopulmonary resuscitation.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) has the potential to improve outcomes in patients with refractory cardiac arrest. However, the outcome is difficult to predict on admission. Recent reports have described early evaluation of myocardial damage in patients with acute myocardial infarction by detecting delayed enhancement in non-contrast computed tomography (CT) following coronary angiography (CAG). We investigated the impact of delayed hyperenhancement obtained by non-contrast CT following CAG in patients with ischaemic and non-ischaemic cardiovascular diseases who underwent ECPR for refractory cardiac arrest. METHODS: Forty-two patients who underwent ECPR, CAG, and postprocedural CT for refractory cardiac arrest in our institute were retrospectively enrolled. Two blinded readers independently and semi-quantitatively judged whether hyperenhancement was present or absent in non-contrast axial CT images following CAG. We evaluated the relationship between in-hospital death and delayed hyperenhancement. RESULTS: The identification of delayed hyperenhancement was highly consistent between the two readers (kappa ​= ​0.71). The survival rate was 21.4% in this cohort. The only significant difference between the survival group and in-hospital death group was the presence of delayed hyperenhancement, which was detected only in the in-hospital death group (p ​= ​0.03). The prevalence of cardiac death was higher in patients with than without delayed hyperenhancement. Delayed hyperenhancement was observed even in areas perfused by non-obstructive coronary arteries. CONCLUSIONS: Delayed hyperenhancement of the left ventricular wall on non-contrast CT imaging following CAG might help to predict in-hospital death in patients undergoing ECPR for refractory cardiac arrest.

Preoperative rehabilitation for patients undergoing colorectal cancer surgery: a retrospective cohort study.

PURPOSE: We investigated the impact of preoperative short-term rehabilitation on activities of daily living among patients with colorectal cancer. METHODS: This retrospective cohort study utilized a hospital-based database containing Diagnosis Procedure Combination survey data from over 100 participating acute-care hospitals. We extracted data on consecutive inpatients hospitalized with stage 1 and 2 colorectal cancer. We compared characteristics and outcomes between patients who underwent short-term rehabilitation before surgery and those who did not. Primary outcomes measured were Barthel Index decline and number of complications during hospitalization. RESULTS: Among of included inpatients (male, 57%; older individuals aged over 65 years, 79%; mean Barthel Index, 93.4), the number of patients who underwent preoperative rehabilitation was 760 (39.3%). Patients in the preoperative rehabilitation group were less likely to have a decline in the Barthel Index compared with the control group (5.9% vs 10.1%, P < 0.001) and after propensity score adjustment using inverse probability weighting (6.3% vs 9.8%, P = 0.024). The preoperative rehabilitation group had fewer complications during hospitalization compared with the control group (P < 0.001) and after inverse probability weighting (P = 0.001). CONCLUSION: Our study showed that preoperative short-term rehabilitation was associated with maintenance and improvement of activities of daily living and fewer complications among patients with stage 1 and 2 colorectal cancer.

Myocardial delayed enhancement on dual-energy computed tomography: The prevalence and related factors in patients with suspicion of coronary artery disease.

BACKGROUND: We aimed to assess the prevalence of myocardial delayed enhancement (MDE) in patients with suspected obstructive coronary artery disease (CAD), and to investigate factors related to the presence or absence of MDE. METHODS: We retrospectively evaluated 191 consecutive patients who underwent coronary computed tomography angiography (CCTA) with MDE imaging for clinical suspicion of CAD from December 2014 to December 2016. The presence of MDE on iodine-density images using dual-energy CT was assessed by two independent readers. Multivariable logistic regression analyses were used to determine factors associated with the presence of MDE. RESULTS: MDE was detected in 58 (30%) patients. Male gender, hypertension, prior heart failure (HF) hospitalization, and CCTA-detected CAD were independent factors related to the presence of MDE. When CCTA-detected CAD was excluded to narrow down the analysis to factors obtainable before CCTA, interventricular septum thickness (IVST) ≥12 mm was added as another independent factor. The combination of the following four factors: female gender, no history of hypertension, no history of prior HF hospitalization, and IVST < 12 mm demonstrated high specificity (98.3%) and positive predictive value (96.2%) for predicting the absence of MDE. CONCLUSIONS: Male gender, hypertension, prior HF hospitalization, and CAD were independently associated with the presence of MDE in patients with suspected CAD. The combination of female gender, no history of hypertension, no history of prior HF hospitalization, and IVST < 12 mm is likely to be a helpful predictor in discriminating patients without MDE before CCTA.

Effectiveness of Early Rehabilitation for Acute Heart Failure: A RETROSPECTIVE COHORT STUDY.

PURPOSE: This study sought to investigate the impact of early rehabilitation on activities of daily living in patients with acute heart failure. METHODS: This retrospective cohort study utilized a hospital-based database created by the Japan Medical Data Center and contained Diagnosis Procedure Combination survey data from more than 100 participating acute care hospitals across Japan. Data were extracted on consecutive inpatients hospitalized because of acute heart failure from 2014 to 2017. The characteristics and outcomes between patients who underwent early rehabilitation (early rehabilitation group) were compared with those who did not undergo rehabilitation (no rehabilitation group). The primary outcome measure was Barthel Index decline. RESULTS: After applying exclusion criteria, a total of 8351 eligible patients with acute heart failure were included in this study. Significantly more Barthel Index decline (18.7% vs 12.4%, P < .001) was seen in patients in the no rehabilitation group than in those in the early rehabilitation group. Multiple linear regression analysis showed that early rehabilitation was negatively associated with Barthel Index decline after adjustment (OR = 0.57; 95% CI, 0.46-0.67). CONCLUSION: This study showed that early rehabilitation could possibly be a feasible alternative for maintenance of the Barthel Index in patients with acute heart failure.