Publications by authors named "Kei Suzuki"

162 Publications

Lung Cancer Risk in Suspicious Lung Nodules With Negative Positron Emission Tomography Scan.

Ann Thorac Surg 2021 Jul 20. Epub 2021 Jul 20.

Division of Thoracic Surgery, Department of Surgery, Boston University School of Medicine, Boston, MA. Electronic address:

Background: Lung CT Screening Reporting and Data System (LungRADS) Category 4 represents lung nodules with the highest likelihood of cancer. For LungRADS-4 lesions, if positron emission tomography (PET) is negative, there currently exists no uniform guideline on subsequent follow-up, particularly whether the surveillance interval can be extended. We sought to investigate the incidence of cancer, our surveillance practice and any clinical factors associated with cancer in this patient subset.

Methods: We retrospectively stratified LungRADS-4 patients screened at our institution from March 2015 to February 2019 into subgroups: PET-positive, PET-negative, and no PET performed. PET negativity was defined as the absence of a radiologist's suspicion, or a maximum standardized uptake value at or below the mediastinal value.

Results: Of the 191 LungRADS-4 patients identified, 67 (35.1%) met criteria for PET negativity. Cancer was diagnosed in 28.8% (55/191) of the entire cohort, 77.8% (35/45) of the PET-positive subgroup, 22.4% (15/67) of the PET-negative subgroup, and 6.3% (5/79) of the no PET subgroup. The most common follow-up modality after a negative PET scan was a CT scan (47/67, 70.1%), with a median interval of 3.1 months. Clinical variables including nodule location/size, chronic obstructive pulmonary disease, family history of lung cancer, pack-years, and number of years quit in former smokers were not significantly associated with greater cancer risk among PET-negatives.

Conclusion: For LungRADS-4/PET-negative lesions, the cancer risk remained high despite lack of activity on PET. As such, we believe the current surveillance practice of continuing to follow LungRADS-4/PET-negative patients as LungRADS-4 patients is appropriate.
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http://dx.doi.org/10.1016/j.athoracsur.2021.06.041DOI Listing
July 2021

Healthcare disparities in thoracic malignancies.

J Thorac Dis 2021 Jun;13(6):3741-3744

Division of Thoracic Surgery, Department of Surgery, Boston University School of Medicine, Boston, MA, USA.

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http://dx.doi.org/10.21037/jtd-2021-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264713PMC
June 2021

An evaluation of the Japanese Society on Thrombosis and Hemostasis criteria for disseminated intravascular coagulation as a predictor of prognosis in patients with infection.

Int J Lab Hematol 2021 Jul 6. Epub 2021 Jul 6.

Department of General Medicine, Mie Prefectural General Medical Center, Mie, Japan.

Introduction: A criterion for disseminated intravascular coagulation (DIC) that reflects the status of controlled coagulopathy would be useful for determining when to stop treatment. Use of the DIC criteria of the Japanese Society on Thrombosis and Hemostasis (JSTH) for predicting the outcome during recombinant soluble thrombomodulin (thrombomodulin alfa, TM-α) treatment was evaluated.

Methods: A retrospective, multicenter survey was conducted in 798 medical facilities in Japan. Of the 4342 patients who underwent TM-α treatment, 193 with infection-associated DIC were investigated.

Results: The 28-day mortality rate increased with the increase in JSTH DIC scores at the end of TM-α treatment, with a Cramer's coefficient of association of 0.431. A reduced platelet count (odds ratio [OR]: 0.847, P < .001), prolonged prothrombin time ratio (OR: 5.681, P < .001), decreased fibrinogen level (OR: 0.995, P < .001), higher level of fibrinogen and fibrin degradation products (OR: 1.009, P = .026), and lower antithrombin activity (OR: 0.973, P < .001) were correlated with 28-day mortality. On multivariate analysis, the JSTH DIC score at the completion of TM-α therapy was a predictor of mortality (OR: 1.591, 95% CI: 1.219-2.077).

Conclusion: The JSTH DIC score at the end of anticoagulation therapy may be a reliable tool for predicting the outcome in patients with infection-associated DIC.
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http://dx.doi.org/10.1111/ijlh.13643DOI Listing
July 2021

Use and effectiveness of a two-level initiation strategy for fixed-dose prothrombin complex concentrate according to the initial international normalized ratio in an emergency department in Japan.

Acute Med Surg 2021 Jan-Dec;8(1):e669. Epub 2021 Jun 2.

Emergency and Critical Care Center Mie University Hospital Mie Japan.

Aim: Prothrombin complex concentrate (PCC) was recently approved for patients on warfarin therapy with international normalized ratios (INRs) exceeding 2 in Japan. However, rapid normalization of INR is necessary even in patients who do not meet the aforementioned criteria. We previously found that a fixed PCC dose of 500 IU is insufficient in some patients with INR elevation but is effective in patients with INR less than 2.5. On the basis of the results, we revised the protocol to administer a PCC dose of 500 IU to patients with INR less than 2.5 or 1,000 IU to patients with higher INRs. This study aimed to validate this revised protocol at an emergency department (ED) in Japan.

Methods: We retrospectively collected data for all patients who received PCC in accordance with the revised protocol at our ED between October 2014 and December 2017 (period B) and compared the findings with those in the previous period (January 2013 to September 2014, period A).

Results: In total, 15 and 11 patients received PCC without complications during periods A and B, respectively. All but one patient obeyed the protocol during period B. The average INRs at baseline and within 120 min after PCC infusion were 2.58 and 1.39, respectively, in period A ( = 9), versus 2.54 and 1.28, respectively, in period B ( = 8). Significantly more patients exhibited optimal responses (INR < 1.35) during period B (7/8) than during period A (3/9,  = 0.049).

Conclusion: Our revised protocol effectively normalized INR.
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http://dx.doi.org/10.1002/ams2.669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172621PMC
June 2021

The Impact of Residential Racial Segregation on Non-Small Cell Lung Cancer Treatment and Outcomes.

Ann Thorac Surg 2021 May 22. Epub 2021 May 22.

Boston University School of Medicine; Boston University Medical Center, Division of Thoracic Surgery, Department of Surgery. Electronic address:

Background: Despite decreases in lung cancer incidence, racial disparities in diagnosis and treatment persist. Residential segregation and structural racism have effects on socioeconomic status for black people, affecting healthcare access. This study aims to determine the impact of residential segregation on racial disparities in non-small cell lung cancer (NSCLC) treatment and mortality.

Methods: Patient data were obtained from Surveillance, Epidemiology, and End Results Program (SEER) database for black and white patients diagnosed with NSCLC from 2004-2016 in the 100 most populous counties. Regression models were built to assess outcomes of interest - stage at diagnosis and surgical resection of disease. Predicted margins assessed impact of index of dissimilarity (IoD) on these disparities. Competing risk regressions for black and white patients in highest and lowest quartiles of IoD were used to assess cancer-specific mortality.

Results: Our cohort had 193,369 white and 35,649 black patients. Black patients were more likely to be diagnosed at advanced stage than white patients with increasing IoD. With increasing IoD, black patients were less likely to undergo surgical resection than white. Disparities were eliminated at low IoD. Black patients at high IoD had lower cancer-specific survival.

Conclusions: Black patients were more likely to present at advanced disease, were less likely to receive surgery for early stage, and had higher cancer-specific mortality at higher IoD. Our findings highlight the impact of structural racism and residential segregation on NSCLC outcomes. Solutions to these disparities must come from policy reforms to reverse residential segregation and deleterious socioeconomic effects of discriminatory policies.
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http://dx.doi.org/10.1016/j.athoracsur.2021.04.096DOI Listing
May 2021

Constructing an Emotion Estimation Model Based on EEG/HRV Indexes Using Feature Extraction and Feature Selection Algorithms.

Sensors (Basel) 2021 Apr 21;21(9). Epub 2021 Apr 21.

Shibaura Institute of Technology, Tokyo 135-8548, Japan.

In human emotion estimation using an electroencephalogram (EEG) and heart rate variability (HRV), there are two main issues as far as we know. The first is that measurement devices for physiological signals are expensive and not easy to wear. The second is that unnecessary physiological indexes have not been removed, which is likely to decrease the accuracy of machine learning models. In this study, we used single-channel EEG sensor and photoplethysmography (PPG) sensor, which are inexpensive and easy to wear. We collected data from 25 participants (18 males and 7 females) and used a deep learning algorithm to construct an emotion classification model based on Arousal-Valence space using several feature combinations obtained from physiological indexes selected based on our criteria including our proposed feature selection methods. We then performed accuracy verification, applying a stratified 10-fold cross-validation method to the constructed models. The results showed that model accuracies are as high as 90% to 99% by applying the features selection methods we proposed, which suggests that a small number of physiological indexes, even from inexpensive sensors, can be used to construct an accurate emotion classification model if an appropriate feature selection method is applied. Our research results contribute to the improvement of an emotion classification model with a higher accuracy, less cost, and that is less time consuming, which has the potential to be further applied to various areas of applications.
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http://dx.doi.org/10.3390/s21092910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122245PMC
April 2021

Lung adenocarcinoma and pulmonary actinomycosis: a cautionary tale.

Tumori 2021 Apr 20:3008916211010225. Epub 2021 Apr 20.

Department of Surgery, Division of Thoracic Surgery, Boston University School of Medicine, Boston, MA, USA.

Background: Pulmonary actinomycosis is a rare and slowly progressive bacterial infection that is often mistaken for lung cancer. Multiple case reports caution against premature diagnosis of malignancy without proper consideration of potential infection. However, no cases in the English literature have been reported that demonstrate the possible coexistence of and lung cancer.

Case Description: We present two cases of patients with culture-positive who were later found to have concomitant biopsy-proven lung adenocarcinoma.

Conclusions: In the workup of a newly identified lung mass, positive culture for does not rule out an underlying malignancy.
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http://dx.doi.org/10.1177/03008916211010225DOI Listing
April 2021

[Successful treatment with cyclosporine in a patient with rituximab-refractory thrombocytopenic purpura].

Rinsho Ketsueki 2021 ;62(3):176-179

Department of Hematology and Oncology, Mie University Hospital.

Acquired thrombotic thrombocytopenic purpura (aTTP) is a life-threatening systemic thrombotic microangiopathy characterized by the presence of anti-ADAMTS13 antibodies (inhibitor). Here we report the case of a patient with refractory aTTP successfully treated with cyclosporine. A 69-year-old man presenting with hematuria and petechiae was referred to our hospital; he was disoriented and febrile. Laboratory results revealed Coombs-negative hemolytic anemia, thrombocytopenia, and renal failure. Undetectable ADAMTS13 activity and presence of anti-ADAMTS13 antibodies (inhibitor) confirmed the diagnosis of aTTP. Despite performing plasma exchange and administering prednisolone and rituximab (375 mg/m), we were unable to restore his platelet counts to the normal level. Therefore, he was treated with cyclophosphamide (500 mg/bodyweight), vincristine (1.4 mg/m), bortezomib (1.3 mg/m), and cyclosporine (2.5 mg/kg). After the cyclosporine therapy, his platelet counts gradually normalized. Continuous cyclosporine maintenance therapy led to complete disappearance of the inhibitor. Therapeutic strategies for refractory aTTP have not yet been established. Further investigations are warranted to establish a therapeutic strategy for refractory aTTP.
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http://dx.doi.org/10.11406/rinketsu.62.176DOI Listing
April 2021

Veno-arterial extracorporeal membrane oxygenation and targeted temperature management in tricyclic antidepressant-induced cardiac arrest: A case report and literature review.

Medicine (Baltimore) 2021 Mar;100(9):e24980

Emergency and Critical Care Center, Mie University Hospital, 2-174 Edobashi, Tsu city, Mie 514-8507, Japan.

Rationale: Cardiotoxicity is a common cause of death in tricyclic antidepressant (TCA) intoxication. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is effective in critically ill poisoned patients who do not respond to conventional therapies, and targeted temperature management (TTM) is associated with improved neurological outcomes and mortality in comatose out-of-hospital cardiac arrest survivors. However, few reports have documented cases of TCA intoxication that required intensive care, including VA-ECMO or TTM.

Patient Concerns: A 19-year-old Japanese man with a history of depression was brought to our hospital because he was in a comatose state with a generalized seizure. Before admission, he had taken an unknown amount of amitriptyline.

Diagnosis: After intubation, the electrocardiogram (ECG) displayed a wide QRS complex tachycardia, and the patient suffered from cardiovascular instability despite intravenous bolus of sodium bicarbonate. At 200 minutes after ingestion, he experienced a TCA-induced cardiac arrest.

Interventions: We initiated VA-ECMO 240 minutes after ingestion. The hemodynamic status stabilized, and the ECG abnormality improved gradually. In addition, we initiated targeted temperature management (TTM) with a target temperature of 34°C.

Outcomes: Twenty seven hours after starting the pump, the patient was weaned off the VA-ECMO. After completing the TTM, his mental status improved, and he was extubated on day 5. He was discharged on day 15 without neurological impairment, and the post-discharge course was uneventful.

Lessons: First, VA-ECMO is effective in patients with TCA-induced cardiac arrest. Second, routine ECG screening during VA-ECMO support is useful for assessing the timing to wean off the VA-ECMO, as well as the degree of cardiotoxicity. Third, TTM is safe in comatose survivors of cardiac arrest caused by severe TCA intoxication.
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http://dx.doi.org/10.1097/MD.0000000000024980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939188PMC
March 2021

Hypofibrinogenemia is associated with a high degree of risk in infectious diseases: a post-hoc analysis of post-marketing surveillance of patients with disseminated intravascular coagulation treated with thrombomodulin alfa.

Thromb J 2021 Feb 25;19(1):12. Epub 2021 Feb 25.

Department of Surgery, Center for Gastroenterology and Liver Disease, Kitakyushu City Yahata Hospital, Fukuoka, Japan.

Background: In patients with infectious diseases, disseminated intravascular coagulation (DIC) is often diagnosed without the fibrinogen value. The relationship between hypofibrinogenemia and outcomes of DIC in infectious diseases has thus remained unclear.

Methods: We analyzed 3204 patients who received with thrombomodulin alfa (TM-α) for DIC and suspected DIC. Hypofibrinogenemia was defined by a fibrinogen level < 1.5 g/L.

Results: Hypofibrinogenemia was observed in 10.3% of patients with infectious diseases. The frequencies of both bleeding and organ failure symptoms, and the scores for organ failure or the DIC diagnostic criteria were significantly higher in infectious disease patients with hypofibrinogenemia, suggesting that in patients with infectious diseases, hypofibrinogenemia is associated with more progressive and severe DIC. Although the 28-day survival rate and the DIC resolution rate were both significantly lower for infectious disease patients with DIC with hypofibrinogenemia than for those without hypofibrinogenemia, this difference was not observed in DIC patients with hematological diseases.

Conclusions: Hypofibrinogenemia among infectious disease patients with DIC may reflect increased consumption of fibrinogen due to accelerated coagulation reactions, while hypofibrinogenemia among hematological disease patients with DIC may be caused by fibrinogenolysis due to hyperfibrinolysis, and frequently results in bleeding and multiple-organ failure.
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http://dx.doi.org/10.1186/s12959-021-00264-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7908729PMC
February 2021

SQAP, an acyl sulfoquinovosyl derivative, suppresses expression of histone deacetylase and induces cell death of cancer cells under hypoxic conditions.

Biosci Biotechnol Biochem 2021 Jan;85(1):85-91

Department of Applied Biological Science, Tokyo University of Science, Chiba, Japan.

Sulfoglycolipid, SQAP, is a radiosensitizing agent that makes tumor cells more sensitive to radiation therapy. A previous study revealed that SQAP induced the degradation of hypoxia-inducible factor-1α (HIF-1α) and inhibited angiogenesis in a hepatoma model mouse. Herein, we examined the biological activities of SQAP against hepatocarcinoma cells under low oxygen conditions. Cell growth inhibition of SQAP under hypoxic conditions was significantly higher than that under normoxic conditions. In addition, SQAP was found to impair the expression of histone deacetylase (HDAC) under low oxygen conditions. Our present data suggested that SQAP induced the degradation of HIF-1α and then decreased the expression of HDAC1. Unlike known HDAC inhibitors, SQAP increased the acetylation level of histone in cells without inhibition of enzymatic activity of HDACs. Our data demonstrated hypoxia-specific unique properties of SQAP.
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http://dx.doi.org/10.1093/bbb/zbaa015DOI Listing
January 2021

Venous thromboembolism in benign esophageal surgery patients: potential cost effectiveness of Caprini risk stratification.

Surg Endosc 2021 Jan 25. Epub 2021 Jan 25.

Division of Thoracic Surgery, Department of Surgery, Boston University School of Medicine, 72 East Concord St, Boston, MA, 02118, USA.

Background: The Caprini risk assessment model (RAM) stratifies surgical patients for prescription of post-discharge extended heparin prophylaxis to reduce post-operative venous thromboembolism (VTE) events. The average cost for treatment of a VTE event is $15,123. The 30-day post-operative VTE rate after benign esophageal procedures is < 0.8% per the Society of Thoracic Surgeons database. We hypothesized that the financial cost of selective extended prophylaxis in patients undergoing surgery for benign esophageal disease would exceed the cost of treating these rare events and therefore use of risk stratification for extended prophylaxis would not be beneficial.

Methods: All patients undergoing operations for benign esophageal pathology from July 2014 to May 2019 were reviewed. Patients designated as moderate or high risk for VTE were prescribed a 10- or 30-day post-operative course of extended prophylaxis with low-molecular weight heparin (LMWH). VTE and adverse bleeding events were recorded for the 60-day post-operative period. The cost of LMWH was provided by the institution pharmacy.

Results: Records from 154 patients were eligible for review. Caprini RAM was used for all patients with the following distribution of risk categories: low = 64.9% (100/154); moderate = 31.8% (49/154); and high = 3.2% (5/154). The average cost of extended prophylaxis at discharge for the moderate-risk group was $121.23, while the high-risk group was $446.46. There were no 60-day VTE or adverse bleeding events recorded.

Conclusions: The majority of patients undergoing surgical therapy were at low risk of post-operative VTE event, with only 35% requiring extended VTE prophylaxis at time of discharge. When compared with the average cost of treatment for a VTE event, the cost of extended prophylaxis per patient in moderate or high-risk groups is substantially lower. In the era of cost-containment, risk stratification and extended prophylaxis may reduce healthcare costs and warrant future investigations.
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http://dx.doi.org/10.1007/s00464-020-08269-xDOI Listing
January 2021

Structural studies of reelin N-terminal region provides insights into a unique structural arrangement and functional multimerization.

J Biochem 2021 Jul;169(5):555-564

Institute for Protein Research, Osaka University, 3-2 Yamada-Oka, Suita, Osaka 565-0871, Japan.

The large, secreted glycoprotein reelin regulates embryonic brain development as well as adult brain functions. Although reelin binds to its receptors via its central part, the N-terminal region directs multimer formation and is critical for efficient signal transduction. In fact, the inhibitory antibody CR-50 interacts with the N-terminal region and prevents higher-order multimerization and signalling. Reelin is a multidomain protein in which the central part is composed of eight characteristic repeats, named reelin repeats, each of which is further divided by insertion of a epidermal growth factor (EGF) module into two subrepeats. In contrast, the N-terminal region shows unique 'irregular' domain architecture since it comprises three consecutive subrepeats without the intervening EGF module. Here, we determined the crystal structure of the murine reelin fragment named RX-R1 including the irregular region and the first reelin repeat at 2.0-Å resolution. The overall structure of RX-R1 has a branched Y-shaped form. Interestingly, two incomplete subrepeats cooperatively form one entire subrepeat structure, though an additional subrepeat is inserted between them. We further reveal that Arg335 of RX-R1 is crucial for binding CR-50. A possible self-association mechanism via the N-terminal region is proposed based on our results.
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http://dx.doi.org/10.1093/jb/mvaa144DOI Listing
July 2021

Type 2 diabetes is associated with failure of non-operative treatment for sternoclavicular joint infection.

J Thorac Dis 2020 Oct;12(10):5468-5474

Boston University School of Medicine, Boston, MA, USA.

Background: A standardized treatment algorithm for sternoclavicular joint infection management is lacking in the literature. While major risk factors for sternoclavicular joint infection, including immunosuppression, rheumatoid arthritis, type 2 diabetes, indwelling catheters, and intravenous drug use have been identified, clear association with treatment outcome has not been established. As our safety net hospital treats a patient population with high incidence of intravenous drug use, we sought to identify risk factors associated with failure of non-operative management of sternoclavicular joint infection.

Methods: We conducted a retrospective cohort study, reviewing charts of patients diagnosed with sternoclavicular joint infection between January 2001 and December 2017 to collect demographic information as well as clinical risk factors and treatment patterns. A chi-square test was performed to determine any association between clinical variables and management, as well as relation to treatment outcome.

Results: The study cohort consisted of 35 patients with diagnosis of sternoclavicular joint infection and complete follow-up. Intravenous drug use was prevalent, seen in 45.6% (16/35) of subjects, though there was no association with failure of non-operative management (P=0.50). Operative management was the initial treatment for 25.7% (9/35) of subjects and was associated with abscess on presentation (P=0.03). Failure of non-operative management was seen in 26.9% (7/26). Type 2 diabetes was associated with failed initial non-operative management, present in 42.9% (3/7) of patients (P=0.03) experiencing failure.

Conclusions: This study constitutes the largest series of sternoclavicular joint infection with intravenous drug use. While intravenous drug use was not associated with failure of non-operative management, we observed that type 2 diabetes is associated with failure of non-operative management and could be considered in determining management of sternoclavicular joint infection patients.
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http://dx.doi.org/10.21037/jtd-20-1897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656360PMC
October 2020

Pulmonary Adenocarcinomas of Low Malignant Potential: Proposed Criteria to Expand the Spectrum Beyond Adenocarcinoma In Situ and Minimally Invasive Adenocarcinoma.

Am J Surg Pathol 2021 04;45(4):567-576

Departments of Pathology & Laboratory Medicine.

Lung cancer screening has improved mortality among high-risk smokers but has coincidentally detected a fraction of nonprogressive adenocarcinoma historically classified as bronchoalveolar carcinoma (BAC). In the National Lung Screening Trial (NLST) the majority of BAC-comprising 29% of computed tomography-detected stage I lung adenocarcinoma-were considered overdiagnosis after extended follow-up comparison with the control arm. In the current classification, adenocarcinoma in situ and minimally invasive adenocarcinoma have replaced BAC but together comprise only ∼5% of stage I lung adenocarcinoma. Lepidic and subsets of papillary and acinar adenocarcinoma also infrequently recur. We, therefore, propose criteria for low malignant potential (LMP) adenocarcinoma among nonmucinous adenocarcinoma measuring ≤3 cm in total, exhibiting ≥15% lepidic growth, and lacking nonpredominant high-grade patterns (≥10% cribriform, ≥5% micropapillary, ≥5% solid), >1 mitosis per 2 mm2, angiolymphatic or visceral pleural invasion, spread through air spaces or necrosis. We tested these criteria in a multi-institutional cohort of 328 invasive stage I (eighth edition) and in situ adenocarcinomas and observed 16% LMP and 7% adenocarcinoma in situ/minimally invasive adenocarcinoma which together (23%) approximated the frequency of overdiagnosed stage I BAC in the NLST. The LMP group had 100% disease-specific survival. The proposed LMP criteria, incorporating multiple histologic parameters, may be a clinically useful "low-grade" prognostic group. Validation of these criteria in additional retrospective cohorts and prospective screen-detected cohorts should be considered.
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http://dx.doi.org/10.1097/PAS.0000000000001618DOI Listing
April 2021

Don't Anger the Host: New Etiquette in Standard Cancer Assessment?

Ann Surg Oncol 2021 Feb 27;28(2):598-599. Epub 2020 Oct 27.

Division of Thoracic Surgery, Department of Surgery, Boston University School of Medicine, Boston, MA, USA.

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http://dx.doi.org/10.1245/s10434-020-09285-wDOI Listing
February 2021

Lymphadenectomy and Survival After Neoadjuvant Chemoradiation for Esophageal Adenocarcinoma: Is More Better?

J Gastrointest Surg 2020 11 1;24(11):2447-2455. Epub 2020 Sep 1.

Department of Surgery, Boston Medical Center, Boston University School of Medicine, 88 East Newton Street, Collamore C500, Boston, MA, 02118, USA.

Purpose: The purpose of this study was to assess the impact of number of lymph nodes examined on survival in patients with esophageal adenocarcinoma who underwent neoadjuvant chemoradiation.

Methods: The National Cancer Database was queried for patients who underwent neoadjuvant chemoradiation followed by surgery for esophageal adenocarcinoma. Propensity scores were created predicting the odds of undergoing resection of ≥ 25 nodes. Patients were matched on propensity score. Overall survival analyses were performed using the Kaplan-Meier method. Sensitivity analyses were performed using various nodal cutoffs.

Results: In total, 3953 patients who underwent neoadjuvant chemoradiation were identified. The median number of resected nodes was 14 nodes (IQR, 8-20 nodes). Resection of ≥ 15 (vs. < 15 nodes: 32 vs. 26 months; p < 0.001), ≥ 20 (vs. < 20 nodes: 36 vs. 28 months; p = 0.001), and ≥ 25 (vs. < 25 nodes: 37 vs. 29 months; p = 0.015) nodes was associated with higher median survival, but resection of ≥ 30 nodes was not (vs. < 30 nodes: 41 vs. 33 months; p = 0.367). Resection of ≥ 25 lymph nodes remained predictive for improved survival on subset analysis in patients with negative nodes and who underwent treatment at high-volume centers.

Conclusions: After neoadjuvant chemoradiation, resection of 25 or more lymph nodes was associated with longer median survival. Prospective trials are warranted to determine the optimal nodal yield after neoadjuvant chemoradiation.
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http://dx.doi.org/10.1007/s11605-020-04750-zDOI Listing
November 2020

Severe Antithrombin Deficiency May be Associated With a High Risk of Pathological Progression of DIC With Suppressed Fibrinolysis.

Clin Appl Thromb Hemost 2020 Jan-Dec;26:1076029620941112

Department of Surgery, Center for Gastroenterology and Liver Disease, 13780Kitakyushu City Yahata Hospital, Fukuoka, Japan.

The frequency of severe antithrombin deficiency (SAD) was examined in the hematopoietic disorder-, infectious-, and basic-types of the disseminated intravascular coagulation (DIC). A posthoc analysis of 3008 DIC patients (infectious-type, 1794; hematological disorder-type, 813; and basic-type, 401) from post-marketing surveillance data of thrombomodulin alfa was performed. The clinical features of patients and outcomes were compared between patients with and without SAD, using an antithrombin cutoff value of 50%. Patients with SAD accounted for 40.4% of infectious-type DIC, 8.0% of hematopoietic disorder-type DIC, and 26.7% of basic-type DIC. There was no significant difference in thrombin-antithrombin complex levels between patients with and without SAD. The decreased fibrinogen level and differences in clinical features were significantly greater but the increases in fibrinolytic markers were significantly lower in patients with SAD than in those without. The 28-day survival rate was significantly lower in patients with SAD than in those without. Severe antithrombin deficiency was observed in all types of DIC, including hematopoietic disorders. Both hypofibrinolysis and hypercoagulability in patients with SAD may cause multiple organ failure and poor outcomes.
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http://dx.doi.org/10.1177/1076029620941112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7448134PMC
June 2021

Impact of Intestinal Microbiota on Reconstitution of Circulating Monocyte, Dendritic Cell, and Natural Killer Cell Subsets in Adults Undergoing Single-Unit Cord Blood Transplantation.

Biol Blood Marrow Transplant 2020 11 14;26(11):e292-e297. Epub 2020 Aug 14.

Department of Hematology/Oncology, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.

The intestinal microbiota plays a fundamental role in the development of host innate immune cells, such as monocytes, dendritic cells (DCs), and natural killer (NK) cells. We examined the association between intestinal microbiota and subsequent immune reconstitution of circulating monocyte, DC, and NK cell subsets in 38 adult patients undergoing single-unit cord blood transplantation (CBT). A higher diversity of intestinal microbiota at 1 month was significantly associated with higher counts of plasmacytoid DCs at 7 months after CBT, as measured by the Chao1 index. Principal coordinate analysis of unweighted UniFrac distances showed significant differences between higher and lower classical monocyte reconstitution at 7 months post-CBT. The families Neisseriaceae, Burkholderiaceae, Propionibacteriaceae, and Coriobacteriaceae were increased in higher classical monocyte reconstitution at 7 months post-CBT, whereas the family Bacteroidaceae was increased in lower classical monocyte reconstitution at 7 months post-CBT. These data show that intestinal microbiota composition affects immune reconstitution of classical monocyte and plasmacytoid DCs following single-unit CBT.
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http://dx.doi.org/10.1016/j.bbmt.2020.08.009DOI Listing
November 2020

Challenges in Diagnosing Comatose Patients with Ethylene Glycol Poisoning.

Am J Med 2021 02 29;134(2):e127-e128. Epub 2020 Jul 29.

Emergency and Critical Care Center, Mie University Hospital, Japan.

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http://dx.doi.org/10.1016/j.amjmed.2020.06.039DOI Listing
February 2021

Esophageal pressure and potential confounders for evaluating patient-ventilator asynchrony.

J Crit Care 2020 12 9;60:344. Epub 2020 Jul 9.

Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan. Electronic address:

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http://dx.doi.org/10.1016/j.jcrc.2020.07.007DOI Listing
December 2020

Prevention of Postoperative Prolonged Air Leak After Pulmonary Resection.

Thorac Surg Clin 2020 Aug 22;30(3):305-314. Epub 2020 May 22.

Division of Thoracic Surgery, Department of Surgery, Boston Medical Center, Boston University School of Medicine, Boston University, 88 East Newton Street, Collamore Building, Suite 7380, Boston, MA 02118, USA. Electronic address:

Postoperative prolonged air leaks (PALs) occur after thoracic surgery in which lung parenchyma is resected, divided, or manipulated. These air leaks can place patients at risk for intensive care unit readmissions, longer hospital length of stay, and infectious complications. Studies have been conducted to identify patients who are at risk for air leak and several methods have been examined for the prevention and treatment of PALs. A standard method of air leak prevention or treatment has not been established. This article discusses the prophylactic measures that have been studied for the prevention of PALs following lung surgery.
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http://dx.doi.org/10.1016/j.thorsurg.2020.04.007DOI Listing
August 2020

Endopharyngeal Ultrasound: description of a novel technique to overcome a common diagnostic dilemma in a patient with a deep neck space mass.

Clin Otolaryngol 2020 Nov 14;45(6):923-925. Epub 2020 Jul 14.

Department of Otolaryngology-Head and Neck Surgery, Boston University Medical Center, Boston, MA, USA.

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http://dx.doi.org/10.1111/coa.13598DOI Listing
November 2020

Endovascular Cooling Catheter-Related Thrombosis After Targeted Temperature Management for Out-of-Hospital Cardiac Arrest: A Case Report.

Ther Hypothermia Temp Manag 2020 Dec 20;10(4):244-247. Epub 2020 Mar 20.

Emergency and Critical Care Center, Mie University Hospital, Tsu, Japan.

Endovascular cooling catheter-related thrombosis is an under-recognized clinical complication of targeted temperature management (TTM), which is widely used in the treatment of comatose out-of-hospital cardiac arrest survivors. A 16-year-old boy, who survived an out-of-hospital cardiac arrest, underwent TTM with an endovascular cooling system. A target temperature of 34°C was maintained for 24 hours, followed by rewarming at a rate of 0.5°C/12 hours. On day 5, his body temperature rose sharply after the removal of the endovascular cooling catheter. He was diagnosed with pneumonia and methicillin-resistant bacteremia. Tomography investigations also revealed a marked abnormality in the liver function. On day 7, a large thrombus extending through the right iliac vein and into the inferior vena cava (IVC) was detected. Owing to bacteremia, the IVC filter placement was not indicated, and the thrombus disappeared after intravenous administration of heparin and antithrombin. In addition to the potential risk of catheter-related thrombosis and hypercoagulability in the postcardiac arrest state, acute liver injury and an infective state may contribute to thrombosis.
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http://dx.doi.org/10.1089/ther.2019.0044DOI Listing
December 2020

Evaluation of the Role of P-glycoprotein (P-gp)-Mediated Efflux in the Intestinal Absorption of Common Substrates with Elacridar, a P-gp Inhibitor, in Rats.

Eur J Drug Metab Pharmacokinet 2020 Jun;45(3):385-392

Exploratory Research Section III, Exploratory Research Laboratories, Drug Research Department, TOA EIYO LTD., 1, Yuno-tanaka, Iizaka-machi, Fukushima-shi, Fukushima, 960-0280, Japan.

Background And Objectives: P-glycoprotein (P-gp) has been shown previously to contribute to the intestinal absorption of verapamil, diltiazem, tacrolimus, colchicine and indinavir in situ; however, its contribution in vivo is unknown. The present study aimed to evaluate the in vivo involvement of P-gp using elacridar as its inhibitor to distinguish the contribution of P-gp from cytochrome P450 (CYP) 3A.

Methods: Fexofenadine (5 mg/kg) and buspirone (1 mg/kg) were used as probe substrates of P-gp and CYP3A, respectively. Each dual substrate (1 or 2 mg/kg) was orally administered to rats after elacridar pre-treatment (3 mg/kg). Additionally, verapamil, diltiazem or tacrolimus was orally co-administered with fexofenadine.

Results: Elacridar drastically increased the area under the plasma concentration-time curve (AUC) of oral fexofenadine by 8.6-fold; however, it did not affect the AUC of oral buspirone. Therefore, elacridar inhibited P-gp without affecting CYP3A. The absorption of oral verapamil, diltiazem and tacrolimus was not influenced by elacridar pre-treatment, and the increase in the AUC of fexofenadine was approximately 3-fold when co-administered with each substrate; the minimal effect of elacridar was attributable to the limited contribution of P-gp but not to their self-inhibition against the transporter. Conversely, elacridar significantly increased the AUC of colchicine (5.3-fold) and indinavir (2.0-fold), indicating that P-gp contributes to their absorption.

Conclusions: Elacridar is useful for distinguishing the contribution of P-gp from CYP3A to the absorption of drugs in rats. The in vivo contribution of P-gp is minimal for high permeable compounds owing to their fraction absorbed of nearly 1.0.
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http://dx.doi.org/10.1007/s13318-019-00602-7DOI Listing
June 2020

Case of toxic epidermal necrolysis in immunocompromised patient possibly due to Streptococcus pneumoniae serotype uncovered by vaccine.

J Dermatol 2020 Apr 13;47(4):e106-e107. Epub 2020 Feb 13.

Department of Dermatology, Mie University Graduate School of Medicine, Tsu, Japan.

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http://dx.doi.org/10.1111/1346-8138.15268DOI Listing
April 2020

Analysis of the association between resolution of disseminated intravascular coagulation (DIC) and treatment outcomes in post-marketing surveillance of thrombomodulin alpha for DIC with infectious disease and with hematological malignancy by organ failure.

Thromb J 2020 7;18. Epub 2020 Feb 7.

Department of Surgery, Center for Gastroenterology and Liver Disease, Kitakyushu City Yahata Hospital, Fukuoka, Japan.

Background: Although disseminated intravascular coagulation (DIC) is life-threatening, any organ failure associated with DIC resolution and outcomes have been unclear.

Patients And Methods: A total of 2795 DIC patients (infection: 1990, hematological malignancy: 805) were analyzed in the post-marketing surveillance of thrombomodulin alpha (TM-α). The background factors of sequential organ failure assessment (SOFA) and antithrombin (AT) were investigated in DIC with infectious disease for their association with DIC resolution and outcome using κ statistics, indicating DIC resolution and survival or DIC non-resolution and non-survival. The same analyses were performed for total bilirubin, creatinine, lactate dehydrogenase, and underlying disease in DIC with hematological malignancy.

Results: In DIC with infectious disease, higher SOFA score severity was closely correlated with lower overall survival in both the DIC resolution and non-resolution groups, but AT activity was not. κ coefficients were 0.234, 0.295, and 0.311 for the SOFA score 0-6, 7-12, and 13-24 groups, respectively. In DIC with hematological malignancy, κ coefficients of total bilirubin were 0.251 and 0.434, and those of creatinine were 0.283 and 0.437 in the normal and abnormal groups, respectively, showing better concordance in the abnormal group than in the normal. Other factors had poor concordance.

Conclusion: In DIC with infectious disease, DIC resolution is an important therapeutic target in patients who have higher SOFA score severity. In DIC with hematological malignancy, DIC resolution is similarly important in patients with abnormality of bilirubin and/or creatinine.

Trial Registration: The clinical characteristics and treatment outcomes of patients with DIC treated with TM-α between May 2008 and April 2010 were retrospectively analyzed by subgroup analysis of the post-marketing surveillance data.
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http://dx.doi.org/10.1186/s12959-020-0216-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7006199PMC
February 2020

Reconstitution of Circulating Mucosal-Associated Invariant T Cells after Allogeneic Hematopoietic Cell Transplantation: Its Association with the Riboflavin Synthetic Pathway of Gut Microbiota in Cord Blood Transplant Recipients.

J Immunol 2020 03 10;204(6):1462-1473. Epub 2020 Feb 10.

Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.

Mucosal-associated invariant T (MAIT) cells are a type of innate lymphocyte and recognize riboflavin (vitamin B2) synthesis products presented by MHC-related protein 1. We investigated long-term reconstitution of MAIT cells and its association with chronic graft-versus-host disease (cGVHD) in a cross-sectional cohort of 173 adult patients after allogeneic hematopoietic cell transplantation. According to donor source, the number of MAIT cells significantly correlated with time after cord blood transplantation (CBT) but not with time after bone marrow transplantation or peripheral blood stem cell transplantation. The number of MAIT cells was significantly lower in patients with cGVHD compared with patients without cGVHD. We also examined the association between MAIT cell reconstitution and gut microbiota as evaluated by 16S ribosomal sequencing of stool samples 1 mo post-CBT in 27 adult patients undergoing CBT. The diversity of gut microbiota was positively correlated with better MAIT cell reconstitution after CBT. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States analysis indicated that amounts of and genes were significantly higher in the microbiomes of patients with subsequent MAIT cell reconstitution after CBT. In conclusion, long-term MAIT cell reconstitution is dependent on the type of donor source. Our data also unveiled an important role for the interaction of circulating MAIT cells with gut microbiota in humans.
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http://dx.doi.org/10.4049/jimmunol.1900681DOI Listing
March 2020

Age, Race, and Income Are Associated With Lower Screening Rates at a Safety Net Hospital.

Ann Thorac Surg 2020 05 22;109(5):1544-1550. Epub 2020 Jan 22.

Division of Thoracic Surgery, Department of Surgery, Boston University School of Medicine, Boston, Massachusetts. Electronic address:

Background: While lung cancer screening improves cancer-specific mortality and is recommended for high-risk patients, barriers to screening still exist. We sought to determine our institution's (an urban safety net hospital) screening rate and to identify socioeconomic barriers to lung cancer screening.

Methods: We identified 8935 smokers 55 to 80 years of age evaluated by a primary care physician between March 2015 and March 2017 at our institution. We randomly selected one-third of these (n = 2978) to review for eligibility using the U.S. Preventive Services Task Force criteria for lung cancer screening. Using our institution's Lung Cancer Screening Program clinical tracking database, we identified patients who were screened from March 2015 to March 2017. We collected demographic information (race, primary language, education status, and median income) and evaluated possible associations with screening.

Results: Among our institution population, 99 patients meeting U.S. Preventive Services Task Force screening criteria underwent screening computed tomography, whereas 516 eligible patients were not screened, making our institution's estimated screening rate 16.1%. Comparing the unscreened population with those who received screening at our institution, the unscreened population was significantly older (median age of screened patients was 63 years, of unscreened patients was 66 years; P < .001). African Americans had a lower screening rate (37.6% of the screened population and 47.5% of the unscreened population; P < .001). Unscreened patients had a lower annual household income.

Conclusions: The lung cancer screening rate at our hospital is 16.1%. Unscreened patients were older, were more likely to be African American, and had a lower median income. These findings highlight possible screening barriers and potential areas for targeted strategies to decrease disparities in lung cancer screening.
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http://dx.doi.org/10.1016/j.athoracsur.2019.11.052DOI Listing
May 2020

Cardiopulmonary resuscitation of a cardiac arrest patient with left ventricular assist device in an out-of-hospital setting: A case report.

Medicine (Baltimore) 2020 Jan;99(2):e18658

Emergency and Critical Care Center, Mie University Hospital.

Rationale: Despite increasing number of left ventricular assist device (LVAD) implantation, standardized cardiopulmonary resuscitation (CPR) protocol for patients with LVAD, especially in out-of-hospital settings are not well known.

Patient Concerns: A 41-year-old LVAD implanted man became cardiac arrest in an out-of-hospital setting. Bystander CPR was started and the patient was brought to our hospital without noticing LVAD. Upon arrival, the medical staff noted the LVAD and that the battery of the LVAD was exhausted.

Diagnosis: Cardiac arrest on LVAD.

Interventions: It took 50 minutes to change the battery, then the patient has become ventricular fibrillation; hence, we introduced extracorporeal membranous oxygenation and defibrillated the patient. After the sinus rhythm was restored, the LVAD started working uneventfully.

Outcomes: The patient became brain dead.

Lessons: There are several difficulties in treating these patients. First, hemodynamic collapse is difficult to diagnose. Second, chest compression for LVAD implanted patients remains controversial. Third, education to first responders who are not familiar with LVAD are not enough. Appropriate education for those issues is needed.
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http://dx.doi.org/10.1097/MD.0000000000018658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6959936PMC
January 2020
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