A case of endobronchial mucosa-associated lymphoid tissue (MALT) lymphoma successfully treated with radiotherapy and a review of the literature.

A 60-year-old man was noted to have an elevated lesion in the right mainstem bronchus on chest computed tomography (CT) during his annual medical checkup 3 years previously. The lesion had gradually increased in size. FDG-PET showed no accumulation. Bronchoscopy revealed 5 nodular smooth surface protrusions on the ventral surface of the right mainstem bronchus, with the largest lesion that measured 5 mm in diameter. Biopsy showed diffuse infiltration of small lymphocytes, positive for CD20 and subsequently diagnosed with mucosa-associated lymphoid tissue (MALT) lymphoma. The lesions disappeared on chest CT after radiotherapy, and no recurrence has been observed after 5 years. We reviewed 48 cases of endobronchial MALT lymphoma in the literature and provided a comprehensive review of the literature to date including our case.

Impact of Antibiotic Time-Outs in Multidisciplinary ICU Rounds for Antimicrobial Stewardship Program on Patient Survival: A Controlled Before-and-After Study.

The antimicrobial stewardship program (ASP) is an important quality improvement initiative that is recommended in the ICU. However, the shortage of infectious disease physicians in Japan has led to the need for simpler methods for implementing ASPs. We investigated whether antibiotic time-outs (ATOs) during multidisciplinary rounds as part of an ASP can improve patient survival and reduce the number of days of therapy (DOT) with antibiotics. DESIGN: Single-center controlled before-and-after study. SETTING: Medical/surgical ICU in a tertiary university medical center in Tokyo, Japan. PATIENTS: All patients 16 years old or older admitted consecutively in the ICU between October 2016 and March 2020. INTERVENTIONS: An intensivist-driven ICU multidisciplinary round was introduced in October 2016, and ATOs with ICU rounds were implemented in June 2018. ATOs were conducted 3, 7, and 14 days after initiation of antibiotics. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the subdistribution hazard ratio (SHR) of survival to hospital discharge compared between multidisciplinary rounds (phase 1) and ATO during multidisciplinary rounds (phase 2) using the multivariable Fine-Gray model. The secondary outcomes were the SHR of survival to ICU discharge and the trends in the DOT with IV antibiotics per 1,000 patient-days between October 2016 and March 2020 by using interrupted time-series analysis. The number of patients in phases 1 and 2 was 777 and 796, respectively. The group that underwent ATO during multidisciplinary rounds showed a significant increase in the survival to hospital discharge in comparison with the multidisciplinary round-only group (SHR, 1.13; 95% CI, 1.02-1.25); however, the SHR of survival to ICU discharge showed no significant intergroup difference. The DOT with total IV antibiotics decreased after ATO implementation (change in intercept, -178.26; 95% CI, -317.74 to -38.78; change in slope, -7.00; 95% CI, -15.77 to 1.78). CONCLUSIONS: ATOs during multidisciplinary rounds are associated with improved patient survival and reduced DOT.

Development, validation, and feature extraction of a deep learning model predicting in-hospital mortality using Japan's largest national ICU database: a validation framework for transparent clinical Artificial Intelligence (cAI) development.

OBJECTIVE: While clinical Artificial Intelligence (cAI) mortality prediction models and relevant studies have increased, limitations including the lack of external validation studies and inadequate model calibration leading to decreased overall accuracy have been observed. To combat this, we developed and evaluated a novel deep neural network (DNN) and a validation framework to promote transparent cAI development. METHODS: Data from Japan's largest ICU database was used to develop the DNN model, predicting in-hospital mortality including ICU and post-ICU mortality by days since ICU discharge. The most important variables to the model were extracted with SHapley Additive exPlanations (SHAP) to examine the DNN's efficacy as well as develop models that were also externally validated. MAIN RESULTS: The area under the receiver operating characteristic curve (AUC) for predicting ICU mortality was 0.94 [0.93-0.95], and 0.91 [0.90-0.92] for in-hospital mortality, ranging between 0.91-0.95 throughout one year since ICU discharge. An external validation using only the top 20 variables resulted with higher AUCs than traditional severity scores. CONCLUSIONS: Our DNN model consistently generated AUCs between 0.91-0.95 regardless of days since ICU discharge. The 20 most important variables to our DNN, also generated higher AUCs than traditional severity scores regardless of days since ICU discharge. To our knowledge, this is the first study that predicts ICU and in-hospital mortality using cAI by post-ICU discharge days up to over a year. This finding could contribute to increased transparency on cAI applications.

Association of SARS-CoV-2 RNA Copy Number with the COVID-19 Mortality Rate and Its Effect on the Predictive Performance of Mortality in Severe Cases.

Factors associated with mortality are important in the treatment of coronavirus disease 2019 (COVID-19). Polymerase chain reaction (PCR) is the gold standard for diagnosing COVID-19, which reflects the viral load in the upper respiratory tract. In total, 523 patients were enrolled in this study; of them, 441 and 75 patients underwent PCR testing of nasopharyngeal swabs and sputum samples, respectively, within 20 days from onset of COVID-19. We investigated the association between RNA copy number and the COVID-19 severity and mortality rate and its effect on the predictive performance for severity and mortality. RNA copy numbers in nasopharyngeal swabs were higher in the non-survivor group than in the survivor group. Multivariate logistic regression analysis identified that the high RNA copy number (≥9 log10 /swab) in nasopharyngeal swabs was a factor associated with mortality (odds ratio, 4.50; 95% confidence interval, 1.510-13.100; P = 0.008). Furthermore, adding RNA copy number (≥9 log10 /swab) in severe cases, adjusted by duration from onset to PCR, improved mortality predictive performance based on known factors. The RNA copy number is a factor associated with the mortality of patients with COVID-19 and can improve the predictive performance of mortality in severe cases.

We Should Pay Attention to "Referred Pain" - A Case of Acute Myocardial Infarction That Masked and Delayed the Diagnosis of Esophageal Perforation.

We herein report a 93-year-old woman diagnosed with acute myocardial infarction (AMI) based on typical laboratory findings of severe chest pain accompanied by throat pain. This condition was initially interpreted as referred pain of cardiac origin. However, the patient had persistent throat pain after successful percutaneous coronary intervention. Upper esophageal perforation with life-threatening acute mediastinitis was unexpectedly identified by a further examination. Clinicians should have a high index of suspicion in cases with persistent symptoms thought to be referred pain among AMI patients, as these symptoms may not be of cardiac origin but rather a sign of another concomitant critical disease.

COVID-19 case of ventilator-induced lung injury on extracorporeal membrane oxygenation: Physicians' clinical struggle and ethical conflict in a novel pandemic.

Resource scarcity was concerned in the initial surge of the COVID-19 pandemic. To open slots for Extracorporeal Membrane Oxygenation (ECMO), we tried ECMO weaning allowing invasive ventilation in a 66-year-old male with severe COVID-19, backfiring as ventilator-induced lung injury. We will discuss ethical conflict in pandemics in this report.

Hydrodynamic Approach for Revealing Venous Anastomotic Stenosis Formation Within a Dialysis Arteriovenous Graft.

A conventional arteriovenous graft in patients on dialysis often leads to anastomotic stenosis, which decreases the blood flow rate and increases the risk of complications. In this study, based on hydrodynamics, the pulsatile pressure at the blood vessel graft-vein junction was investigated experimentally and numerically for revealing the causes of stenosis formation and inward remodeling. In the experiments, the pulsatile pressure and displacement at the anastomotic connection were measured at a branched collapsible tube. It was revealed that the pressure becomes negative between pressure peaks of the pulsatile flow; furthermore, tube diameter changes in accordance with the pressure pulsation. Subsequently, numerical simulations revealed that a relatively large pressure difference occurs at the anastomotic connection because of flow collision and separation as compared with the other part, and the pulsatile pressure. Therefore, it is possible that vein at an anastomotic connection may change its shape under pulsating flow. Furthermore, it was found that the pressure difference slightly increased with the anastomosis angle, but the anastomosis angle did not affect the flow rate. Clinical trials in the next step are required to reveal the causal relationship between stenosis and the pulsatile pressure, but the pulsatile flow and its pressure are likely to be one factor in stenosis and inward remodeling.

Factors associated with the appropriate use of ultra-broad spectrum antibiotics, meropenem, for suspected healthcare-associated pneumonia.

ABSTRACT: Pneumonia is a common disease-causing hospitalization. When a healthcare-associated infection is suspected, antibiotics that provide coverage for multi-drug resistant (MDR) or extended-spectrum beta-lactamase (ESBL) bacteria are frequently prescribed. Limited data is available for guidance on using meropenem as a first-line empiric antimicrobial in hospitalized patients with risk factors for MDR/ESBL bacterial infections.This was a single-center, retrospective study designed and conducted to identify factors associated with positive cultures for MDR/ESBL pathogens in hospitalized patients with suspected healthcare-associated pneumonia.Of the 246 patients, 103 patients (41%) received meropenem. Among patients prescribed meropenem, MDR/ESBL pathogens were detected in only 20 patients (13%). Patients admitted from a skilled nursing facility/long-term acute care (SNF/LTAC) or with a history of a positive culture for MDR/ESBL pathogens were significantly associated with positive cultures of MDR/ESBL pathogens during the hospitalization (odds ratio [95% confidence intervals], 31.40 [5.20-189.6] in SNF/LTAC and 18.50 [2.98-115.1] in history of culture-positive MDR/ESBL pathogen). There was no significant difference in mortality between the 3 antibiotic groups.Admission from a SNF/LTAC or having a history of cultures positive for MDR/ESBL pathogens were significantly associated with a positive culture for MDR/ESBL pathogens during the subsequent admission. We did not detect significant association between meropenem use as a first-line drug and morbidity and mortality for patients admitted to the hospital with suspected healthcare-associated pneumonia, and further prospective studies with larger sample size are needed to confirm our findings.

Conventional risk prediction models fail to accurately predict mortality risk among patients with coronavirus disease 2019 in intensive care units: a difficult time to assess clinical severity and quality of care.

Since the start of the coronavirus disease 2019 (COVID-19) pandemic, it has remained unknown whether conventional risk prediction tools used in intensive care units are applicable to patients with COVID-19. Therefore, we assessed the performance of established risk prediction models using the Japanese Intensive Care database. Discrimination and calibration of the models were poor. Revised risk prediction models are needed to assess the clinical severity of COVID-19 patients and monitor healthcare quality in ICUs overwhelmed by patients with COVID-19.

Predictors associated with clinical improvement of SARS-CoV-2 pneumonia.

BACKGROUND: There are few agents that have been proven effective for COVID-19. Predicting clinical improvement as well as mortality or severity is very important. OBJECTIVES: This study aimed to investigate the factors associated with the clinical improvement of COVID-19. METHODS: Overall, 74 patients receiving treatment for COVID-19 at Tokyo Medical and Dental University Hospital from April 6th to May 15th, 2020 were included in this study. Clinical improvement was evaluated, which defined as the decline of two levels on a six-point ordinal scale of clinical status or discharge alive from the hospital within 28 days after admission. The clinical courses were particularly investigated and the factors related to time to clinical improvement were analyzed with the log-rank test and the Cox proportional hazard model. RESULTS: Forty-nine patients required oxygen support during hospitalization, 22 patients required invasive mechanical ventilation, and 5 patients required extracorporeal membrane oxygenation. A total of 83% of cases reached clinical improvement. Longer period of time from onset to admission (≥10 days) (HR, 1.057; 95% CI, 1.002-1.114), no hypertension (HR, 2.077; 95% CI, 1.006-4.287), and low D-dimer levels (<1 µg/ml) (HR, 2.372; 95% CI, 1.229-4.576) were confirmed to be significant predictive factors for time to clinical improvement. Furthermore, a lower SARS-CoV-2 RNA copy number was also a predictive factor for clinical improvement. CONCLUSIONS: Several predictors for the clinical improvement of COVID-19 pneumonia were identified. These results may be important for the management of COVID-19 pneumonia.

A laceration of a wired silastic tracheostomy tube: A case report and review of the literature.

Fractured tracheostomy tube is a rare, late complication. It typically occurs at the junction of metallic tube. We report an atypical case with laceration of the main trunk of a silastic tube after short period of use (10 days).

Efficacy of multidisciplinary team approach with extracorporeal membrane oxygenation for COVID-19 in a low volume ECMO center.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) is an effective and proven adjunct support for various severe respiratory failures requiring invasive mechanical ventilation and cardiovascular support. In response to the rapidly increasing number of COVID-19 patients in Japan, we launched an ECMO support team comprised of multidisciplinary experts including physicians, nurses, perfusionists, and bioethicists in preparation for the threat of a pandemic. From April 2 to July 15, 2020, Tokyo Medical and Dental University hospital treated 104 PCR confirmed COVID-19 patients. Among those, 34 patients were admitted to intensive care unit (ICU) and 5 patients required VV ECMO. All management related to ECMO was decided by the ECMO support team in addition to participation of the ECMO support team in daily multidisciplinary rounds in the ICU. Median age was 54 years old. Duration from onset to mechanical ventilation (MV) and MV to ECMO were 8 and 7 days, respectively. Four patients (80%) were successfully weaned off from ECMO. One patient died after 81 days of ECMO run. Four patients were discharged and recovered to their prehospital quality of life without major disability. We achieved a high survival rate using ECMO in our low volume ECMO institution during the COVID-19 pandemic. Multidisciplinary decision-making and a team approach for the unclear pathology with an emerging infectious disease was effective and contributed to the survival rate.

Development and validation of the predictive risk of death model for adult patients admitted to intensive care units in Japan: an approach to improve the accuracy of healthcare quality measures.

BACKGROUND: The Acute Physiology and Chronic Health Evaluation (APACHE) III-j model is widely used to predict mortality in Japanese intensive care units (ICUs). Although the model's discrimination is excellent, its calibration is poor. APACHE III-j overestimates the risk of death, making its evaluation of healthcare quality inaccurate. This study aimed to improve the calibration of the model and develop a Japan Risk of Death (JROD) model for benchmarking purposes. METHODS: A retrospective analysis was conducted using a national clinical registry of ICU patients in Japan. Adult patients admitted to an ICU between April 1, 2018, and March 31, 2019, were included. The APACHE III-j model was recalibrated with the following models: Model 1, predicting mortality with an offset variable for the linear predictor of the APACHE III-j model using a generalized linear model; model 2, predicting mortality with the linear predictor of the APACHE III-j model using a generalized linear model; and model 3, predicting mortality with the linear predictor of the APACHE III-j model using a hierarchical generalized additive model. Model performance was assessed with the area under the receiver operating characteristic curve (AUROC), the Brier score, and the modified Hosmer-Lemeshow test. To confirm model applicability to evaluating quality of care, funnel plots of the standardized mortality ratio and exponentially weighted moving average (EWMA) charts for mortality were drawn. RESULTS: In total, 33,557 patients from 44 ICUs were included in the study population. ICU mortality was 3.8%, and hospital mortality was 8.1%. The AUROC, Brier score, and modified Hosmer-Lemeshow p value of the original model and models 1, 2, and 3 were 0.915, 0.062, and < .001; 0.915, 0.047, and < .001; 0.915, 0.047, and .002; and 0.917, 0.047, and .84, respectively. Except for model 3, the funnel plots showed overdispersion. The validity of the EWMA charts for the recalibrated models was determined by visual inspection. CONCLUSIONS: Model 3 showed good performance and can be adopted as the JROD model for monitoring quality of care in an ICU, although further investigation of the clinical validity of outlier detection is required. This update method may also be useful in other settings.

Sarcoidosis and breast cancer: A retrospective case series.

BACKGROUND: Sarcoidosis and breast cancer co-incidence is reported in the literature in the form of case reports. AIM: To describe our experience from a single large sarcoidosis clinic. METHODS: Retrospective chart review of 1000 sarcoidosis cases seen in our clinic from 2003 to 2008. RESULTS: 429/1000 female sarcoidosis cases were identified. Among them 20/429 had a history of sarcoidosis and breast cancer. In 12/20 breast cancer preceded sarcoidosis by 52 months, in 4/20 sarcoidosis preceded breast cancer by 200 months and in 4/20 they presented concurrently. Mean age of sarcoidosis diagnosis was 53.9 (±12.4) years. Majority were of European decent (16/20), 3 were African-Americans and 1 Asian. Scadding radiography stages distribution was (n) 4/11/3/2/0 for stages 0/I/II/III/IV respectively. They had 3.4 (±1.3) organs involved, mainly with intrathoracic involvement. 10/20 were asymptomatic and 11/20 received chronic treatment. Compared to 409 cases of sarcoidosis sine breast cancer (mean age 46.7 ± 13.1), sarcoidosis-breast cancer cases had sarcoidosis diagnosed at a significantly later age (p = 0.01). Histological diagnosis applied in all co-incidence cases, in 5 via mediastinoscopy. CONCLUSIONS: Older females with breast cancer may develop sarcoidosis, with features indistinguishable from stand-alone sarcoidosis. When sarcoidosis is suspected histological diagnosis is mandatory.

The Safety and Effect of Early Mobilization in the Intensive Care Unit According to Cancellation Criteria.

OBJECTIVE: The aim of this study was to investigate the effect and risk management of early mobilization in the intensive care unit (ICU) with multidisciplinary collaboration and daily goal planning. METHODS: Rehabilitation of ICU patients in our hospital between April 1, 2019, and September 30, 2019, was investigated retrospectively. The following factors were evaluated: age and sex of the subjects; diseases; the total number of early mobilization therapy sessions done at a lowered goal level; the clinical course of the step-down sessions; reasons for lowering goal levels that corresponded to the cancellation criteria from the officially issued guidelines of the Japanese Association of Rehabilitation Medicine, the expert consensus on ICU, or other reasons for step down; and the rate of planned goals that were achieved. RESULTS: Of the 1908 overall rehabilitation sessions carried out during the period of investigation, 9.6% had the planned level lowered; changes in vital signs accounted for 54.6% of the reasons for lowering the level. Of the step-down sessions, 92.3% corresponded with the cancellation criteria of rehabilitation. Early mobilization in the ICU in accordance with daily goal planning via collaboration within the multidisciplinary team during rounds was accomplished in 90.4% of sessions. No serious mobilization-related adverse events were noted during the study period. CONCLUSION: Early mobilization should be performed with daily goal planning by a multidisciplinary team during rounds and should be governed by the cancellation criteria of rehabilitation.

Immune status in sarcoidosis: one size does not fit all.

B-cell immunity and immunoglobulins are less commonly affected in sarcoidosis. We aimed to evaluate immune status in sarcoidosis patients. Retrospective chart review of sarcoidosis patients attending a out-patient clinic over 3 months period. Immunoglobulins levels were recorded (A, M, G, E) along with clinical and serological data. They were divided in group A (normal IgG), group B (increased IgG), group C (decreased IgG) and group D (decreased IgG and IgM and/or IgA). Of 50 subjects, 68% were females and 62% of Caucasian origin. 22 (44%) had normal IgG levels, 16 (32%) had increased IgG levels, 10 (20%) had hypogammaglobulinemia and 2 (4%) had combined hypogammaglobulinemia, diagnosed with combined sarcoidosis and common variable immunodeficiency. Decreased IgA values was found in groups C and D. IgE was high in group B. Globulin was increased in group B and decreased in groups C and D. Decreased neutrophils were found in group D (all statistically significant). Correlation analysis showed significant association of angiotensin converting enzyme with IgA and IgM, inverse correlation of IgG with white blood cells and neutrophils, of IgA with globulin and inverse with albumin and of calcium with albumin. Most sarcoidosis patients have normal or increased immunoglobulin levels, that correlate with serum biomarkers of disease activity. Hypogammaglobulinemia may reflect treatment side effects and accompanied by blood leukocytosis. Combined severe immunodeficiency occurs in sarcoidosis.

The Japanese Intensive care PAtient Database (JIPAD): A national intensive care unit registry in Japan.

PURPOSE: The Japanese Intensive care PAtient Database (JIPAD) was established to construct a high-quality Japanese intensive care unit (ICU) database. MATERIALS AND METHODS: A data collection structure for consecutive ICU admissions in adults (≥16 years) and children (≤15 years) has been established in Japan since 2014. We herein report a current summary of the data in JIPAD for admissions between April 2015 and March 2017. RESULTS: There were 21,617 ICU admissions from 21 ICUs (217 beds) including 8416 (38.9%) for postoperative or procedural monitoring, defined as adult admissions following elective surgery or for procedures and discharged alive within 24 h, 11,755 (54.4%) critically ill adults other than monitoring, and 1446 (6.7%) children. The standardized mortality ratios (SMRs) based on the Acute Physiology and Chronic Health Evaluation (APACHE) III-j, APACHE II, and Simplified Acute Physiology Score II scores in adults ranged from 0.387 to 0.534, whereas the SMR based on the Paediatric Index of Mortality 2 in children was 0.867. CONCLUSION: The data revealed that the SMRs based on general severity scores in adults were low because of high proportions of elective and monitoring admission. The development of a new mortality prediction model for Japanese ICU patients is needed.

A 48-Year-Old Man With Multiple Pulmonary Nodular Opacities and Elevated KL-6 Level.

CASE PRESENTATION: A 48-year-old man was referred for evaluation of an abnormal chest shadow noted on a routine chest radiograph during physical examination. He was asymptomatic and had no significant medical history and occupational exposure. The patient lived in Tokyo and had no significant travel history. He had smoked approximately 20 cigarettes daily for 20 years. He had no illicit drug use and no animal-rearing history.

Safety and efficacy of ustekinumab or golimumab in patients with chronic sarcoidosis.

Sarcoidosis is characterised by non-caseating granulomas that secrete pro-inflammatory cytokines, including interleukin (IL)-12, IL-23, and tumour necrosis factor (TNF)-α. Ustekinumab and golimumab are monoclonal antibodies that specifically inhibit IL-12/IL-23 and TNF-α, respectively. Patients with chronic pulmonary sarcoidosis (lung group) and/or skin sarcoidosis (skin group) received either 180 mg ustekinumab at week 0 followed by 90 mg every 8 weeks, 200 mg golimumab at week 0 followed by 100 mg every 4 weeks, or placebo. Patients underwent corticosteroid tapering between weeks 16 and 28. The primary end-point was week 16 change in percentage predicted forced vital capacity (ΔFVC % pred) in the lung group. Major secondary end-points were: week 28 for ΔFVC % pred, 6-min walking distance, St George's Respiratory Questionnaire (lung group), and Skin Physician Global Assessment response (skin group). At week 16, no significant differences were observed in ΔFVC % pred with ustekinumab (-0.15, p = 0.13) or golimumab (1.15, p = 0.54) compared with placebo (2.02). At week 28, there were no significant improvements in the major secondary end-points, although a nonsignificant numerically greater Skin Physician Global Assessment response was observed following golimumab treatment (53%) when compared with the placebo (30%). Serious adverse events were similar in all treatment groups. Although treatment was well tolerated, neither ustekinumab nor golimumab demonstrated efficacy in pulmonary sarcoidosis. However, trends towards improvement were observed with golimumab in some dermatological end-points.

The WASOG Sarcoidosis Organ Assessment Instrument: An update of a previous clinical tool.

INTRODUCTION: A Case Control Etiology of Sarcoidosis Study (ACCESS) sarcoidosis organ assessment instrument has been used for more than a decade to establish uniform standards for the probability of sarcoidosis organ involvement. The ACCESS instrument has become increasingly outdated as new technologies have been developed. Furthermore, the ACCESS instrument failed to address all possible organs involved with sarcoidosis. For these reasons, the World Association of Sarcoidosis and Other Granulomatous Diseases (WASOG) developed a new sarcoidosis organ assessment instrument. METHODS: Clinical sarcoidosis experts assessed various clinical manifestations for the probability of sarcoidosis organ involvement. Two criteria were required to apply this assessment: 1) histologic evidence of granulomatous inflammation of unknown cause in an organ that was not being assessed; 2) the clinical manifestation being addressed required that alternative causes other than sarcoidosis had been reasonably excluded. Clinical manifestations were assessed as either: a) highly probable: likelihood of sarcoidosis causing this manifestation of at least 90%.; b) probable: likelihood of sarcoidosis causing this manifestation of between 50 and 90%; c) possible: likelihood of sarcoidosis causing this manifestation of less than 50%. The sarcoidosis experts voted on the likelihood of sarcoidosis causing each manifestation using Delphi study methodology where at least 70% agreement of the experts was needed for consensus. RESULTS: Various clinical manifestations were classified as highly probable, at least probable, possible, or indeterminate when no consensus could be reached. CONCLUSION: An instrument was developed by expert opinion that may be useful for the clinician and researcher in establishing criteria for sarcoidosis organ involvement.