Teriparatide-Associated Hypercalcemia Concomitant With Acute Kidney Injury: A Case-Report.

Teriparatide, a recombinant human parathyroid hormone, is an anabolic treatment for osteoporosis with a high risk of fractures. Transient hypercalcemia is an adverse effect of teriparatide and usually resolves within 16h of teriparatide administration owing to its rapid absorption and elimination. Some cases of prolonged hypercalcemia have been reported, but these improved rapidly after teriparatide discontinuation. Here, we describe a rare case of teriparatide-induced hypercalcemia concomitant with acute kidney injury that persisted for four weeks. An 83-year-old woman began taking teriparatide for a vertebral fracture. The patient was immobilized by the fracture. Three weeks later, the patient developed hypercalcemia and acute kidney injury. However, hypercalcemia persisted for four weeks despite the discontinuation of teriparatide and fluid administration. Clinicians should be aware that teriparatide can induce severe hypercalcemia, especially in the setting of immobilization, and that hypercalcemia can persist for more than 3-4 weeks in patients with decreased kidney function.

CD30 expression in an emerging group of mesenchymal spindle cell neoplasms with ALK fusion detected by flow cytometry and immunohistochemistry.

An emerging group of spindle cell neoplasms harboring fusions involving NTRK or non-NTRK kinase genes often share characteristic S100 and/or CD34 expression; however, the diagnostic utility of immunohistochemical stains is not well established in this family owing to their lack of specificity. Recently, CD30 expression in spindle cell neoplasms with kinase gene fusions, such as NTRK, BRAF, RAF1, and RET, has been increasingly identified. We herein report a 10-year-old girl with high-grade spindle cell sarcoma of the neck. Prior to histopathological evaluation, flow cytometry (FCM) analysis and touch smear cytology of the tumor tissue revealed CD34+ and dimCD30+ spindle cell populations. Histopathologically, the case was characterized by monomorphic spindle-shaped cytomorphology with CD30, S100, and CD34 positivity and harbored close similarities with spindle cell neoplasms with NTRK or non-NTRK gene fusions. Subsequently, a comprehensive next-generation sequencing sarcoma panel identified a rare PLEKHH2::ALK fusion, and a diagnosis of ALK-rearranged spindle cell neoplasm was made. The patient showed significant tumor response to single-agent treatment with alectinib, an ALK-tyrosine kinase inhibitor. This case supports that CD30 is expressed in an ALK-rearranged mesenchymal neoplasm. The benefit of the early detection of CD30 expression by FCM for a prompt diagnosis and treatment is highlighted in the context of an aggressive clinical course. This case represents a learning experience regarding the need to the check the status of CD30 expression in these tumors and suggests the potential clinical benefits of CD30-targeted therapy.

Vacuolar Protein-Sorting Proteins Are Reduced Even Before Cognitive Decline in a Mouse Model of Alzheimer's Disease.

Currently, interventions from the preclinical stage are considered necessary for the treatment of Alzheimer's disease (AD). Previous studies have reported that vacuolar protein-sorting protein (VPS), a retromer construct, is involved in the pathogenic mechanisms of AD and Parkinson's disease. This study evaluated VPS26, VPS29, and VPS35 before and after the onset of cognitive decline in an App knock-in mouse model of AD that more closely resembles the human pathology than previous AD models. The results showed that the expression of VPS26 and VPS35 decreased before the onset of cognitive decline, suggesting the possibility of anti-amyloid-ß disease-modifying treatment targeting these proteins.

Isolation of High-Purity Betanin from Red Beet and Elucidation of Its Antioxidant Activity against Peroxynitrite: An in vitro Study.

Reactive oxygen species and reactive nitrogen species (RNS) are damaging for many biomolecules. Peroxynitrite (ONOO-) is the most toxic molecular species among RNS. Betalains are known to possess ONOO- scavenging ability. Betanin, a betalain isolated from red beet, possesses antioxidant, anti-inflammatory, and antitumor activities; however, detailed studies of this isolated pigment have not been conducted, owing to its instability under physiological conditions. This study aimed to isolate highly purified betanin from red beetroots using an improved purification method involving deproteinization and citric acid co-precipitation and evaluated its antioxidant activities. The purified betanin thus obtained had a significantly lower isobetanin content than the commercially available betanin dyes. The antioxidant activity of purified betanin examined in the 2,2-diphenyl-1-picrylhydrazyl assay, the direct ONOO- reaction, ONOO--dependent DNA damage, and lipid peroxidation reactions revealed that betanin possessed higher antioxidant capacity than general antioxidants such as ascorbic acid and quercetin. Furthermore, betanin showed indirect and direct cytoprotective effects against H2O2 and ONOO- cytotoxicity, respectively, in cultured mouse fibroblasts. To the best of our knowledge, this is the first study to demonstrate the cytoprotective effects of betanin against ONOO- toxicity. The highly purified betanin obtained in this study will aid in further exploring its physiological functions.

Correlation between the hysteresis of the pressure-volume curve and the recruitment-to-inflation ratio in patients with coronavirus disease 2019.

BACKGROUND: Since the response to lung recruitment varies greatly among patients receiving mechanical ventilation, lung recruitability should be assessed before recruitment maneuvers. The pressure-volume curve (PV curve) and recruitment-to-inflation ratio (R/I ratio) can be used bedside for evaluating lung recruitability and individualing positive end-expiratory pressure (PEEP). Lung tissue recruitment on computed tomography has been correlated with normalized maximal distance (NMD) of the quasi-static PV curve. NMD is the maximal distance between the inspiratory and expiratory limb of the PV curve normalized to the maximal volume. However, the relationship between the different parameters of hysteresis of the quasi-static PV curve and R/I ratio for recruitability is unknown. METHODS: We analyzed the data of 33 patients with severe coronavirus disease 2019 (COVID-19) who received invasive mechanical ventilation. Respiratory waveform data were collected from the ventilator using proprietary acquisition software. We examined the relationship of the R/I ratio, quasi-static PV curve items such as NMD, and respiratory system compliance (Crs). RESULTS: The median R/I ratio was 0.90 [interquartile range (IQR), 0.70-1.15] and median NMD was 41.0 [IQR, 37.1-44.1]. The NMD correlated significantly with the R/I ratio (rho = 0.74, P < 0.001). Sub-analysis showed that the NMD and R/I ratio did not correlate with Crs at lower PEEP (- 0.057, P = 0.75; and rho = 0.15, P = 0.41, respectively). On the contrary, the ratio of Crs at higher PEEP to Crs at lower PEEP (Crs ratio (higher/lower)) moderately correlated with NMD and R/I ratio (rho = 0.64, P < 0.001; and rho = 0.67, P < 0.001, respectively). CONCLUSIONS: NMD of the quasi-static PV curve and R/I ratio for recruitability assessment are highly correlated. In addition, NMD and R/I ratio correlated with the Crs ratio (higher/lower). Therefore, NMD and R/I ratio could be potential indicators of recruitability that can be performed at the bedside.

Comparison of the National Early Warning Scores and Rapid Emergency Medicine Scores with the APACHE II Scores as a Prediction of Mortality in Patients with Medical Emergency Team Activation: a Single-centre Retrospective Cohort Study.

INTRODUCTION: The medical emergency team enables the limitation of patients' progression to critical illness in the general ward. The early warning scoring system (EWS) is one of the criteria for medical emergency team activation; however, it is not a valid criterion to predict the prognosis of patients with MET activation. AIM: In this study, the National Early Warning Score (NEWS) and Rapid Emergency Medicine Score (REMS) was compared with that of the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in predicting the prognosis of patients who had been treated a medical emergency team. MATERIAL AND METHODS: In this single-centre retrospective cohort study, patients treated by a medical emergency team between April 2013 and March 2019 and the 28-day prognosis of MET-activated patients were assessed using APACHE II, NEWS, and REMS. RESULTS: Of the 196 patients enrolled, 152 (77.5%) were men, and 44 (22.5%) were women. Their median age was 68 years (interquartile range: 57-76 years). The most common cause of medical emergency team activation was respiratory failure (43.4%). Univariate analysis showed that APACHE II score, NEWS, and REMS were associated with 28-day prognostic mortality. There was no significant difference in the area under the receiver operating characteristic curve of APACHE II (0.76), NEWS (0.67), and REMS (0.70); however, the sensitivity of NEWS (0.70) was superior to that of REMS (0.47). CONCLUSION: NEWS is a more sensitive screening tool like APACHE II than REMS for predicting the prognosis of patients with medical emergency team activation. However, because the accuracy of NEWS was not sufficient compared with that of APACHE II score, it is necessary to develop a screening tool with higher sensitivity and accuracy that can be easily calculated at the bedside in the general ward.

Using an ICU Diary to Communicate With Family Members of COVID-19 Patients in ICU: A Case Report.

Visitation restrictions for family members are problematic in intensive care management due to the COVID-19 pandemic. We analyzed the usefulness of an intensive care unit (ICU) diary about the experiences of family members of critical COVID-19 patients. Four family members of 2 COVID-19 patients participated in this report. Both patients were transferred to our ICU after 2 weeks of treatment at another ICU. An ICU diary was given to their family members post-transfer. The family members were interviewed before and after the patients' discharge; the recorded interviews were analyzed and categorized into several clusters using a text mining method. Five categories regarding their anxious feelings were classified before the use of the ICU diary, and 3 categories were based on their positive feelings after the use of the ICU diary. Intensive care unit diaries may be beneficial for disclosing patients' information when visitation restrictions are exercised due to the COVID-19 pandemic.

[A case of chronic postural tachycardia syndrome with positive anti-ganglionic acetylcholine receptor (gAChR) antibody].

Postural orthostatic tachycardia syndrome (POTS) is a form of orthostatic intolerance characterized by symptoms such as lightheadedness, fainting, and brain fog that occur with a rapid elevation in heart rate when standing up from a reclining position. The etiology of POTS has yet to be established. However, a growing body of evidence suggests that POTS may be an autoimmune disorder such as autoimmune autonomic ganglionopathy, an acquired, immune-mediated form of diffuse autonomic failure. Many patients have serum antibodies that bind to the ganglionic acetylcholine receptors (gAChRs) in the autonomic ganglia. Herein, we describe a 39-year-old female patient with an eight-year history of orthostatic intolerance. POTS was diagnosed based on the findings of a head-up tilt test, in which a rapid increase in the patient's heart rate from 58 bpm in the lying position to 117 bpm in the upright position without orthostatic hypotension was observed. The POTS symptoms were refractory to various medications except for pyridostigmine bromide, which resulted in a partial resolution of her symptoms. Her serum was found to be strongly positive for anti-gAChR (ß4 subunit) autoantibody (2.162 A.I., normal range: below 1.0). Based on these findings, a limited form of autoimmune POTS was diagnosed. After obtaining written informed consent, she was treated with intravenous immunoglobulin (IVIg) 400 mg/kg/day for five days, which led to clinical improvement by reducing her heart rate increase in the upright position. She was able to return to work with IVIg treatment at regular intervals. Our case provides further evidence of a potential autoimmune pathogenesis for POTS. Aggressive immunotherapy may be effective for POTS even in chronic cases.

Bilateral phrenic nerve block as an effective means of controlling inspiratory efforts in a COVID-19 patient.

Bilateral continuous phrenic nerve block effectively regulates refractory persistent, strong inspiratory effort in a patient with coronavirus disease (COVID-19). A 73-year-old man with acute respiratory distress syndrome (ARDS) due to COVID-19 was admitted to the intensive care unit (ICU). Use of neuromuscular blocking agents (NMBAs) was stopped due to uncontrollable strong inspiratory efforts and worsened lung injury. We performed bilateral continuous phrenic nerve block, which suppressed inspiratory efforts, resulting in lung injury improvement. A bilateral continuous phrenic nerve block is a viable alternative to control refractory strong inspiratory effort leading to lung injury in cases with prolonged NMBA use.

Cardiac Failure Requiring Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) Management in a Refeeding Syndrome Patient with Diabetic Ketoacidosis: A Case Report.

BACKGROUND Refeeding syndrome is a complex metabolic disorder that develops following rapid nutritional administration after a long period of undernutrition. The onset mechanism involves intracellular transport of phosphorus, potassium, and water, in association with rapid glucose administration. The resulting hypophosphatemia is extremely dangerous and can cause severe heart failure and fatal arrhythmia. We successfully used extracorporeal cardiopulmonary support to manage a case of refeeding syndrome that occurred during the course of treatment of diabetic ketoacidosis. There are only a few reports of the use of cardiopulmonary support for the treatment of refeeding syndrome. CASE REPORT A 72-year-old man was admitted to the hospital for treatment of diabetic ketoacidosis. Despite receiving insulin and nutrition therapy, QT prolongation and ventricular fibrillation appeared on the electrocardiogram. Although coronary angiography was performed in consideration of the possibility of ischemic heart disease, no significant stenosis of the coronary arteries was identified. Due to persistent hypotension and recurrence of ventricular fibrillation, extracorporeal cardiopulmonary support was commenced in the ICU. His serum phosphorus level showed a marked decrease on his first day in the ICU, for which daily replacement therapy was administered during his ICU stay. No fatal arrhythmia developed thereafter. He was weaned off extracorporeal cardiopulmonary support on the fourth day of his ICU stay and was subsequently discharged from the hospital. CONCLUSIONS We suggest vigilant monitoring of electrolytes, including phosphate levels, in diabetic ketoacidosis patients, and active circulatory support, as required, in patients with refeeding syndrome.

Morphological Differences between Liquid-Based Cytology and Conventional Preparation in Endometrial Endometrioid Carcinoma Grade 1 and Grade 3, and the Differentiation of Grades in Each Method.

INTRODUCTION: Direct smearing preparation (conventional preparation [CP]) has been widely used for endometrial cytology in Japan. In CP, sampling and screening errors are problematic. In liquid-based cytology preparation (LBC), the problems of CP can be solved. But there is a problem that cytological findings of LBC are different from those of CP. The purpose of this study was to evaluate the differences of morphological findings of endometrial cytology between LBC and CP, and the usefulness of the endometrial LBC to differentiate endometrioid carcinoma grade 1 (G1) from grade 3 (G3). METHODS: Thirteen cases of endometrioid carcinoma G1, and 5 cases of G3 collected by the Softcyte device and prepared by LBC and CP (split specimen) were used. We focused on the following items: (1) the number of clusters per cm2, (2) the number of layers of clusters, (3) area of clusters, (4) perimeter of clusters, (5) roundness of clusters, (6) complexity of clusters, (7) area of nucleus, (8) perimeter of nucleus, (9) roundness of nucleus, (10) complexity of nucleus, (11) area of nucleolus, and (12) nucleolus-nucleus ratio (N/N). RESULTS: Compared with CP, the number of clusters and layers of the clusters in LBC were significantly larger in G1. The area and perimeters of the clusters and the nucleus were significant smaller, and the N/N ratio was greater in LBC than that in CP in both G1 and G3. Regarding morphological differences between G1 and G3 in LBC and CP, the number of layers was significantly larger in G1 than in G3 in LBC and CP. The area of the clusters in LBC was significantly larger in G1 than in G3. The area and perimeters of the nucleus in CP and the area of the nucleolus and N/N ratio in LBC and CP were significantly smaller in G1 than in G3. CONCLUSION: In the endometrial cytology, it became clear that the cell image was different between LBC and CP and between G1 and G3. By microscopic examination understanding the characteristics of the cell image in LBC, endometrial LBC could be useful to diagnose endometrial carcinoma.

Exogenous Cell Surface Modification with Cell Penetrating Peptide-Conjugated Lipids Causes Spontaneous Cell Adhesion.

The technique of cell patterning on a substrate is of great importance for platforms in cell-based assays. Chemical treatment of the substrate is commonly performed for cell patterning using cationic polymers, extracellular matrices, and antibodies. However, cell patterning could be easier if there is an approach to immobilize cells without treating the substrate surface. We previously reported that cell adhesion could be induced by the modification of the cellular surface with a cell-penetrating peptide (CPP)-conjugated poly(ethylene glycol)-phospholipid (CPP-PEG-lipid). This approach does not require chemical modification of the substrate surface, such as polystyrene or glass, and can be used for the cell patterning of floating cells. Here, we aimed to study the mechanism of induced cell adhesion using a representative CPP, Tat peptide (Tat-PEG-lipid). We found that cell adhesion was induced via electrostatic interactions between the Tat peptide and the substrate surface, which could be induced more efficiently by increasing the molecular weight of PEG together with CPPs but not with cationic peptides. The excluded volume effect between neighboring PEG chains could stretch the cell shape better than PEG with lower molecular weight, allowing the cell to spread firmly. In addition, Tat-PEG-lipid did not activate actin filament formation and did not influence the expression of focal adhesion kinase. Thus, the induced cell adhesion by CPP-PEG-lipid did not affect internal cell signaling.

Endoscopic Insertion of Nasojejunal Feeding Tube at Bedside for Critically Ill Patients: Relationship between Tube Position and Intragastric Countercurrent of Contrast Medium.

Background and Oblectives: We evaluated the success rate of endoscopically positioned nasojejunal feeding tubes and the intragastric countercurrent of contrast medium thereafter. METHOD: This retrospective observational study investigated patients who were admitted to a single intensive care unit and required endoscopic placement of a post-pyloric feeding tube between January 2010 and June 2016. The feeding tube was grasped with forceps via a transoral endoscope and inserted into the duodenum or jejunum. Thereafter, we assessed the position of the tube and the intragastric countercurrent using abdominal radiography with contrast medium. RESULTS: The tube tip was inserted at the jejunum and the duodenal fourth portion in 55.8 and 33.6% of patients, respectively. The tip of the inserted tube had moved into the jejunum of 71.7% of patients by the following day. The countercurrent rate was significantly lower among patients with a tube inserted into the duodenal fourth portion or more distal than among those with tubes inserted more proximally (8.4 vs. 45.4%, p = 0.0022). CONCLUSIONS: The endoscopic insertion and positioning of a nasojejunal feeding tube seemed effective because the rate of tube insertion into the duodenal fourth portion or more distal was about 90%. The findings of intragastric countercurrents indicated that feeding tubes should be inserted into the duodenal fourth portion or beyond to prevent vomiting and the aspiration of enteral nutrients.

Influence of contrast media on renal function and outcomes in patients with sepsis-associated acute kidney injury: a propensity-matched cohort study.

BACKGROUND: Recent studies have suggested a low potential risk for contrast medium-induced kidney injury in patients with relatively normal renal function. However, whether contrast media cause additional deterioration of renal function in patients with acute kidney injury (AKI), including those with sepsis-associated AKI, remains unclear. This study aimed to evaluate the effect of contrast media on renal function and mortality in patients with sepsis who already had AKI. METHODS: We performed a propensity score-matched historical cohort study in the medico-surgical intensive care unit of Jichi Medical University Hospital. Adult patients who were diagnosed with sepsis and AKI were enrolled. Records from our sepsis database from 2011 to 2017 were examined. Septic patients with AKI who received contrast media within 24 h of admission (C group) were matched 1:1 with septic patients who did not receive contrast media (NC group). The primary outcome was deterioration of kidney function (DRF), which was defined as an elevation of serum creatinine levels (> 0.3 mg/dL or 1.5-fold from baseline) or induction of renal replacement therapy. RESULTS: A total of 339 septic patients with AKI were included. After propensity score adjustment, the DRF rate was similar between the C and NC groups (34.0% versus 35.0%; P = 1.00). The 7-day mortality (3.0% versus 6.0%; P = 0.50), 28-day mortality (9.2% versus 15.0%; P = 0.25), and 90-day mortality (25.8% versus 32.1%; P = 0.45) rates were comparable between the two groups. In propensity-adjusted subsets of a high-risk subset (AKI stages 2 and 3 on admission), the rate of DRF was also similar between the two groups. CONCLUSIONS: A single administration of contrast media was not associated with exacerbation of AKI or increased short/long-term mortality in patients with sepsis.

Thrombomodulin, Plasminogen Activator Inhibitor-1 and Protein C Levels, and Organ Dysfunction in Sepsis.

Since endothelial function is closely related to organ dysfunction in sepsis and the relationship among endothelial injury, organ dysfunction, and other biomarkers remains unclear, we aimed to evaluate the correlation among endothelial injury, organ dysfunction, and several biomarkers in patients with sepsis. DESIGN: This was a retrospective observational study. SETTING: The study was conducted in a university hospital with 14 mixed ICU beds. PATIENTS: ICU patients with sepsis from June 2011 to December 2017 were enrolled in this study. INTERVENTIONS: Endothelial biomarkers (soluble thrombomodulin, plasminogen activator inhibitor-1, and protein C) and markers of inflammation and coagulation were evaluated during the ICU stay. Sequential Organ Failure Assessment scores were assessed for 7 days after ICU admission to determine organ dysfunction. Variables were compared among five stratified groups according to the Sequential Organ Failure Assessment score (0-2, 3-5, 6-8, 9-12, and 13-24). Regression analysis and 95% CIs were used to evaluate trends in biomarkers. MEASUREMENTS AND MAIN RESULTS: The patients were divided into five stratified groups (Sequential Organ Failure Assessment 0-2, n = 159 [20.5%]; Sequential Organ Failure Assessment 3-5, n = 296 [38.2%]; Sequential Organ Failure Assessment 6-8, n = 182 [23.5%]; Sequential Organ Failure Assessment 9-12, n = 75 [9.7%]; Sequential Organ Failure Assessment 13-24, n = 31 [4.0%]). Protein C activity was significantly correlated with the severity of organ dysfunction. It was lower on day 1, increased upon successful treatment, and was significantly higher in groups with lower Sequential Organ Failure Assessment scores. CONCLUSIONS: Trends and activity of protein C were superior in predicting organ dysfunction compared with other endothelial biomarkers. Monitoring the level of protein C activity is an ideal tool to monitor organ dysfunctions in patients with sepsis.

Transient hyperlactatemia during intravenous administration of glycerol: a prospective observational study.

BACKGROUND: Intravenous glycerol treatment, usually administered in the form of a 5% fructose solution, can be used to reduce intracranial pressure. The administered fructose theoretically influences blood lactate levels, although little is known regarding whether intravenous glycerol treatment causes transient hyperlactatemia. This study aimed to evaluate blood lactate levels in patients who received intravenous glycerol or mannitol. METHODS: This single-center prospective observational study was performed at a 14-bed general intensive care unit between August 2016 and January 2018. Patients were excluded if they were < 20 years old or had pre-existing hyperlactatemia (blood lactate > 2.0 mmol/L). The included patients received intravenous glycerol or mannitol to reduce intracranial pressure and provided blood samples for lactate testing before and after the drug infusion (before the infusion and after 15 min, 30 min, 45 min, 60 min, 90 min, 120 min, and 150 min). RESULTS: Among the 33 included patients, 13 patients received 200 mL of glycerol over 30 min, 13 patients received 200 mL of glycerol over 60 min, and 7 patients received 300 mL of mannitol over 60 min. Both groups of patients who received glycerol had significantly higher lactate levels than the mannitol group (2.8 mmol/L vs. 2.2 mmol/L vs. 1.6 mmol/L, P < 0.0001), with the magnitude of the increase in lactate levels corresponding to the glycerol infusion time. There were no significant inter-group differences in cardiac index, stroke volume, or stroke volume variation. In the group that received the 30-min glycerol infusion, blood lactate levels did not return to the normal range until after 120 min. CONCLUSIONS: Intravenous administration of glycerol leads to higher blood lactate levels that persist for up to 120 min. Although hyperlactatemia is an essential indicator of sepsis and/or impaired tissue perfusion, physicians should be aware of this phenomenon when assessing the blood lactate levels.

Body weight definitions for evaluating a urinary diagnosis of acute kidney injury in patients with sepsis.

BACKGROUND: We hypothesized that the use of actual body weight might lead to more frequent misdiagnosis of acute kidney injury (AKI) than when ideal body weight is used in underweight and/or obese patients. We examined which definition of body weight is most effective in establishing a urinary diagnosis of AKI in septic patients. METHODS: Consecutive patients aged ≥ 20 years admitted to the intensive care unit of a university hospital between June 2011 and December 2016 were analyzed. Sepsis was defined in accordance with the Sepsis-3 criteria. AKI was defined as a urinary output of < 0.5 mL/kg/6h during intensive care unit stay. Patients were divided into one of four body mass index-based classes. The severity of illness and 90-day mortality were compared across the body mass index subgroups in patients diagnosed using the actual body weight or ideal body weight. RESULTS: Of 5764 patients, 569 septic patients were analyzed. One hundred and fifty-three (26.9%) and 140 (24.6%) patients were diagnosed as having AKI using actual body weight and ideal body weight, respectively. There were no significant differences in the severity of illness among these groups. Also, 90-day mortality did not differ significantly among these groups. According to body mass index, 90-day mortality significantly differed in patients diagnosed using their actual body weights (underweight vs. normal vs. overweight vs. obese: 76.7% vs. 39.5% vs. 26.0% vs. 35.7%, P = 0.033). CONCLUSION: Generally, using actual body weight to calculate the weight-adjusted hourly urine output for diagnosing AKI increased the sensitivity compared to ideal body weight, irrespective of the severity of illness in septic patients. Delayed diagnosis, however, was more common among underweight patients in this situation, and clinicians should be cautious when diagnosing urinary AKI using actual body weight.

Time course of immature platelet count and its relation to thrombocytopenia and mortality in patients with sepsis.

INTRODUCTION: The pathogenesis of thrombocytopenia in patients with sepsis is not fully understood. The aims of this study were to investigate changes in thrombopoietic activity over time by using absolute immature platelet counts (AIPC) and to examine the impact of platelet production on thrombocytopenia and mortality in patients with sepsis. METHODS: This retrospective observational study included adult patients with sepsis admitted to the intensive care unit at a university hospital. Two hundred five consecutive sepsis patients were stratified into four groups according to nadir platelet count: severe (nadir ≤40×103/µL), moderate (41-80×103/µL), or mild thrombocytopenia (81-120×103/µL), or normal-increased platelet count (>120×103/µL). The development of thrombocytopenia was assessed during the first week; mortality was assessed at day 28. RESULT: Of the 205 patients included, 61 (29.8%) developed severe thrombocytopenia. On admission, AIPC did not differ among the four groups. In patients with severe thrombocytopenia, AIPC decreased significantly from days 2 to 7, but remained within or above the normal range in the other three groups (overall group comparison, P<0.0001). Multivariate analysis including coagulation biomarkers revealed that AIPC was independently associated with the development of severe thrombocytopenia (day 3 AIPC, odds ratio 0.49 [95% confidence interval (CI) 0.35-0.66], P<0.0001; day 5 AIPC, 0.59 [95% CI 0.45-0.75], P<0.0001). AIPC was a significant predictor of 28-day mortality in Cox hazard models adjusted for Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores (day 3 AIPC, hazard ratio 0.70 [95% CI 0.52-0.89], P = 0.0029; day 5 AIPC, 0.68 [95% CI 0.49-0.87], P = 0.0012). CONCLUSIONS: Thrombopoietic activity was generally maintained in the acute phase of sepsis. However, a decrease in AIPC after admission was independently associated with the development of severe thrombocytopenia and mortality, suggesting the importance of suppressed thrombopoiesis in the pathophysiology of sepsis-induced thrombocytopenia.

Light-triggered hydrophilic drug release from liposomes through removal of a photolabile protecting group.

The antibiotic penicillin G cannot be completely incorporated into hydrophobic lipid-membranes owing to its hydrophilicity. Through modification with a hydrophobic and photolabile protecting group, penicillin G was effectively incorporated into liposomes and released by photoirradiation at 365 nm.

Markers of acute kidney injury in patients with sepsis: the role of soluble thrombomodulin.

BACKGROUND: Endothelial activation and damage occur early during sepsis, with activated coagulopathy and playing a major role in the pathophysiology of sepsis-induced acute kidney injury (AKI). The aim of this study was to compare the various biomarkers of endothelial injury with the biomarkers of coagulation and inflammation and to determine a significant predictor of AKI in patients with sepsis. METHODS: We conducted a single-center, retrospective, observational study on patients with sepsis fulfilling the Third International Consensus Definitions for Sepsis and Septic Shock criteria admitted to an adult intensive care unit (ICU) at a university hospital from June 2011 to December 2016. Levels of 13 biomarkers were measured on ICU admission, including markers of endothelial injury (soluble thrombomodulin [sTM], E-selectin, protein C, and plasminogen activator inhibitor-1 [PAI-1]) and markers of coagulation derangement (platelet count, fibrin degradation product [FDP], prothrombin time [PT], fibrinogen, α2-plasminogen inhibitor [α2-PI], antithrombin III [AT III], plasminogen, thrombin-antithrombin complex, and plasmin-α2-plasmin inhibitor complex). All patients with sepsis were reviewed, and the development of AKI was evaluated. Multivariate logistic regression analysis was performed to identify significant independent predictive factors for AKI. RESULTS: Of the 514 patients admitted with sepsis, 351 (68.3%) developed AKI. Compared with the non-AKI group, all the endothelial biomarkers were significantly different in the AKI group (sTM [23.6 vs. 15.6 U/ml, P < 0.0001], E-selectin [65.5 vs. 46.2 ng/ml, P = 0.0497], PAI-1 [180.4 vs. 75.3 ng/ml, P = 0.018], and protein C [45.9 vs. 58.7 ng/ml, P < 0.0001]). Biomarkers of coagulopathy and inflammation, platelet counts, FDP, PT, α2-PI, AT III, plasminogen, and C-reactive protein were significantly different between the two groups. Multivariable logistic regression analysis showed that sTM was an independent predictive factor of AKI, with an AUROC of 0.758 (P < 0.0001). CONCLUSIONS: Endothelial biomarkers were significantly changed in the sepsis patients with AKI. Particularly, sTM was an independent predictive biomarker for the development of AKI that outperformed other coagulation and inflammation biomarkers as well as organ function in patients with sepsis.