Trajectory pattern of serially measured acute kidney injury biomarkers in critically ill patients: a prospective observational study.

BACKGROUND: The clinical value of the trajectory of temporal changes in acute kidney injury (AKI) biomarkers has not been well established among intensive care unit (ICU) patients. METHODS: This is a single-center, prospective observational study, performed at a mixed ICU in a teaching medical institute in Tokyo, Japan. Adult ICU patients with an arterial line and urethral catheter were enrolled from September 2014 to March 2015. Patients who stayed in the ICU for less than 48 h and patients with known end-stage renal disease were excluded from the study. Blood and urine samples were collected for measurement of AKI biomarkers at 0, 12, 24, and 48 h after ICU admission. The primary outcome was major adverse kidney events (MAKE) at discharge, defined as a composite of death, dialysis dependency, and persistent loss of kidney function (≥ 25% decline in eGFR). RESULTS: The study included 156 patients. Serum creatinine-based estimated glomerular filtration rate (eGFR), plasma neutrophil gelatinase-associated lipocalin (NGAL), and urinary liver-type fatty acid-binding protein (uL-FABP) were serially measured and each variable was classified into three groups based on group-based trajectory modeling analysis. While the trajectory curves moved parallel to each other (i.e., "low," "middle," and "high") for eGFR and plasma NGAL, the uL-FABP curves showed distinct trajectory patterns and moved in different directions ("low and constant," "high and exponential decrease," and "high and exponential increase"). These trajectory patterns were significantly associated with MAKE. MAKE occurred in 16 (18%), 16 (40%), and 9 (100%) patients in the "low and constant," "high and exponential decrease," and "high and exponential increase" groups, respectively, based on uL-FABP levels (p-value < 0.001). The initial value and the 12-h change in uL-FABP were both significantly associated with MAKE, even after adjusting for eGFR [Odds ratio (95% confidence interval): 1.45 (1.17-1.83) and 1.43 (1.12-1.88) for increase of initial value and 12-h change of log-transformed uL-FABP by 1 point, respectively]. CONCLUSIONS: Trajectory pattern of serially measured urinary L-FABP was significantly associated with MAKE in ICU patients.

Impact of renal dysfunction on the diagnosis of acute pancreatitis using urinary trypsinogen-2: A retrospective study.

AIM: Early diagnosis of acute pancreatitis is crucial, and urinary trypsinogen has been recently reported as a useful biomarker for diagnosing acute pancreatitis. We aimed to evaluate the impact of renal dysfunction on the diagnostic performance of urinary trypsinogen-2 for acute pancreatitis. METHODS: We conducted a retrospective study using the clinical data of patients who visited the Department of Emergency and Critical Care at the University of Tokyo Hospital between 1 October, 2021, and 30 June, 2022. Patients with available data on qualitative urinary trypsinogen-2 levels were identified. We compared the urinary trypsinogen-2 levels among patients who were clinically diagnosed with acute pancreatitis. We further stratified the patients according to renal function parameters, such as serum creatinine level, blood urea nitrogen level, and estimated glomerular filtration rate, and evaluated the performance of urinary trypsinogen-2 as a biomarker for acute pancreatitis. RESULTS: Within 9 months, 35 patients were identified. Of them, 22 patients showed positive results and 13 showed negative results on the urinary trypsinogen-2 test. The sensitivity, specificity, positive predictive value, and negative predictive value were 0.80, 0.40, 0.18, and 0.92, respectively. Based on the blood urea nitrogen level and estimated glomerular filtration rate, the prevalence of false-positive results was significantly higher in patients with reduced renal function than in those with normal renal function. CONCLUSION: In patients with reduced renal function, the urinary trypsinogen-2 qualitative test results might be interpreted with caution when used for diagnosing acute pancreatitis.

A prospective randomized study to compare standard versus intensive training strategies on long-term improvement in critical care ultrasonography proficiency.

BACKGROUND: Critical care ultrasonography (CCUS) has become a daily diagnostic tool for intensivists. While the effective training measures for ultrasound novices are discussed widely, the best curriculum for the novices to retain a long-term proficiency is yet to be determined. METHODS: Critical care medicine fellows who underwent an introductory CCUS workshop were randomly allocated into the standard training (ST) or the intensive training (IT) group. The IT group received an 8-h training besides the standardized fellowship education that the ST group received. Participant improvement in CCUS proficiency tests (maximum score, 200) after a 6-month training intervention was compared between the groups. CCUS examinations performed in patient care were observed over 2 years. RESULTS: Twenty-one fellows were allocated into the ST (n = 10) or the IT (n = 11) group. No statistically significant difference was observed in the median (interquartile range [IQR]) improvement in CCUS proficiency tests between the ST group and the IT group: 18 (3.8-38) versus 31 (21-46) (P = .09). Median (IQR) test scores were significantly higher in postintervention than preintervention for both groups: ST, 103 (87-116) versus 124 (111-143) (P = .02), and IT, 100 (87-113) versus 143 (121-149) (P < .01). Participating fellows performed 226 examinations over the 2 years of observation. CONCLUSIONS: Fellows improved their CCUS proficiency significantly after 6-month training intervention. However, an additional 8-h training did not provide further benefits.

Estimated glomerular filtration rate may be an independent predictor for clinical outcomes regardless of acute kidney injury complication in the emergency department.

STUDY OBJECTIVE: Acute kidney injury (AKI), chronic kidney disease (CKD), and decreased estimated glomerular filtration rate (eGFR) are all associated with poor clinical outcomes among emergency department (ED) patients. This study aimed to evaluate the effect of different types of renal dysfunction and the degree of eGFR reduction on the clinical outcomes in a real-world ED setting. METHODS: Adult patients with an eGFR lower than 60 mL/min/1.73m2 in our ED, from October 1, 2016, to December 31, 2016, were enrolled in this retrospective observational study. Besides AKI and CKD, patients with unknown baseline renal function before an ED visit were categorized in the undetermined renal dysfunction (URD) category. RESULTS: Among 1495 patients who had eGFR evaluation at ED, this study finally enrolled 441 patients; 22 patients (5.0%) had AKI only, 32 (7.3%) had AKI on CKD, 196 (44.4%) had CKD only, 27 (6.1%) had subclinical kidney injury (those who met neither criteria for AKI nor CKD), and 164 (37.2%) had URD. There was a significant association between eGFR and critical illness defined as the composite outcome of death or intensive care unit (ICU) need, hospitalization, ICU need, death, and renal replacement therapy need (odds ratio [95% confidence interval]: 1.72 [1.45-2.05], 1.36 [1.16-1.59], 1.66 [1.39-2.00], 1.73 [1.32-2.28], and 2.71 [1.73-4.24] for every 10 mL/min/1.73m2 of reduction, respectively). Multivariate logistic regression analysis showed eGFR was an independent predictor of critical illness composite outcome (death or ICU need), hospitalization, and ICU need even after adjustment with AKI or URD. CONCLUSIONS: Estimated GFR may be a sufficient predictor of clinical outcomes of ED patients regardless of AKI complication. Considerable ED patients were determined as URD, which might have a significant impact on the ED statistics regarding renal dysfunction.

IgG4-Related Disease: Retrospective Analysis of One Hundred Sixty-Six Patients.

OBJECTIVE: To investigate clinical and pathologic aspects of IgG4-related disease (IgG4-RD) in non-Asian populations. METHODS: We conducted a retrospective review of the medical records of patients with IgG4-RD who presented to an academic medical center from January 1994 to September 2012. RESULTS: Among 166 patients identified, the median age at diagnosis was 61 years (interquartile range [IQR] 49-70 years), 75% were male, and 80% were white. The median number of organs involved was 2 (IQR 2-3). When organs were grouped according to anatomic system, the hepatopancreaticobiliary system was most commonly involved (77%). The median highest serum IgG4 level during the clinical course was 215 mg/dl (IQR 122-466). Forty-three patients (26%) had a normal serum IgG4 level. Seventy-nine pathology specimens were available for immunostaining. The median number of IgG4+ cells was 37 (IQR 25-82) per high-power field, with an IgG4+:IgG+ ratio of 0.50 (IQR 0.32-0.68). Among 151 patients who received medical therapy, 72 (48%) received steroid-sparing agents because of relapse, recurrence, or corticosteroid intolerance. Of the 66 patients who were newly diagnosed, started on corticosteroid monotherapy as the initial treatment, and followed up at our institution, 30 (45%) experienced relapse or recurrence despite an initial favorable response. The number of organs involved had a significant impact on time to relapse or recurrence, with a hazard ratio of 1.48 (95% confidence interval [95% CI] 1.12-1.93) (P < 0.01) in multivariate analysis. The standardized incidence ratio of malignancy was 4.5 (95% CI 1.5-7.5). CONCLUSION: IgG4-RD is a multisystem disorder that commonly affects older men and has a propensity for relapse, recurrence, and malignancy.

Critical care ultrasonography differentiates ARDS, pulmonary edema, and other causes in the early course of acute hypoxemic respiratory failure.

BACKGROUND: Pathogenic causes of acute hypoxemic respiratory failure (AHRF) can be difficult to identify at early clinical presentation. We evaluated the diagnostic utility of combined cardiac and thoracic critical care ultrasonography (CCUS). METHODS: Adult patients in the ICU were prospectively enrolled from January through September 2010 with a Pao2/Fio2 ratio < 300 on arterial blood gas (ABG) analysis within 6 h of a new hypoxemic event or the ICU admission. Focused cardiac and thoracic CCUS was conducted within 6 h of ABG testing. Causes of AHRF were categorized into cardiogenic pulmonary edema (CPE), ARDS, and miscellaneous causes after reviewing the hospitalization course in electronic medical records. RESULTS: One hundred thirty-four patients were enrolled (median Pao2/Fio2 ratio, 191; interquartile range, 122-253). Fifty-nine patients (44%) received a diagnosis of CPE; 42 (31%), ARDS; and 33 (25%), miscellaneous cause. Analysis of CCUS findings showed that a low B-line ratio (proportion of chest zones with positive B-lines relative to all zones examined) was predictive of miscellaneous cause vs CPE or ARDS (receiver operating characteristic area under the curve [AUC], 0.82; 95% CI, 0.75-0.88). For further differentiation of CPE from ARDS, left-sided pleural effusion (> 20 mm), moderately or severely decreased left ventricular function, and a large inferior vena cava minimal diameter (> 23 mm) were predictive of CPE (AUC, 0.79; 95% CI, 0.70-0.87). CONCLUSIONS: Combined cardiac and thoracic CCUS assists in early bedside differential diagnosis of ARDS, CPE, and other causes of AHRF.

Immunoglobulin G4-related disease mimicking asthma.

Immunoglobulin (Ig) G4-related disease (also known as 'IgG4-related sclerosing disease', 'IgG4-related systemic disease' or 'hyper-IgG4-disease') is a recently recognized systemic fibroinflammatory disease associated with IgG4-positive plasma cells in tissue lesions. IgG4-related disease was initially described as autoimmune pancreatitis, but it is now known to affect virtually any organ. The authors describe a patient presenting with multi-organ manifestations, including airway inflammation mimicking asthma, pulmonary parenchymal infiltrates, intrathoracic lymphadenopathy, submandibular gland swelling and a kidney mass.

Sudden cardiac arrest caused by tuberculous pericarditis with hemorrhagic pericardial effusion.

As tuberculosis still exists in Japan, tuberculous pericarditis is a major health issue. Tuberculous pericarditis is difficult to diagnose and leads to poor outcomes when left untreated. We herein report the case of a patient who was admitted to the hospital after undergoing resuscitation for cardiopulmonary arrest. Mycobacterium tuberculosis was detected in his hemorrhagic pericardial fluid and tuberculous pericarditis was diagnosed. The administration of antituberculous medication resulted in marked improvements. A diagnosis of tuberculous pericarditis, in addition to other causes such as malignant tumors, should therefore be considered in the differential diagnosis for cases presenting with hemorrhagic pericardial effusion, even in those involving sudden cardiac arrest.

IgG4-related systemic disease presenting with lung entrapment and constrictive pericarditis.

We describe a 29-year-old woman who presented with chronic pleuropericarditis complicated by lung entrapment and constrictive pericarditis. Pleural biopsy performed during the decortication procedure revealed fibrinous pleuritis with lymphoplasmacytic inflammation including IgG4-positive plasma cells. The patient responded favorably to corticosteroid therapy with resolution of pleural effusion and constrictive physiology. To our knowledge, this is the first reported case of IgG4-related systemic disease manifesting as lung entrapment and constrictive pericarditis.

Spectrum of Disorders Associated with Elevated Serum IgG4 Levels Encountered in Clinical Practice.

IgG4-related disease (IgG4-RD) is a recently described systemic fibroinflammatory disease associated with elevated circulating levels of IgG4 and manifests a wide spectrum of clinical presentations. Although serum IgG4 level has been described to be the most sensitive and specific laboratory test for the diagnosis of IgG4-RD, it is recognized that an elevated serum IgG4 level can be encountered in other diseases. In this study, we sought to identify the frequency of IgG4-RD and other disease associations in patients with elevated serum IgG4 levels seen in clinical practice. Among 3,300 patients who underwent IgG subclass testing over a 2-year period from January 2009 to December 2010, 158 (4.8%) had an elevated serum IgG4 level (>140 mg/dL). IgG4 subclass testing was performed for evaluation of suspected IgG4-RD or immunodeficiency. Twenty-nine patients (18.4%) had definite or possible IgG4-RD. Among those patients without IgG4-RD, a broad spectrum of biliary tract, pancreatic, liver, and lung diseases, as well as systemic vasculitis, was diagnosed. We conclude that patients with elevated serum IgG4 levels encountered in clinical practice manifest a wide array of disorders, and only a small minority of them has IgG4-RD.