Seven-day and In-hospital Mortality According to Left and Right Ventricular Dysfunction in Patients With Septic Shock.

BACKGROUND AND OBJECTIVES: The prognostic implications of septic cardiomyopathy have not been clearly demonstrated. We evaluated serial changes in left ventricular (LV) and right ventricular (RV) function in patients with septic shock and their prognostic value on 7-day and in-hospital mortality. METHODS: Transthoracic echocardiography was performed within 48 hours of the diagnosis of septic shock and 7 days after the initial evaluation. In addition to traditional echocardiographic parameters, LV and RV function was evaluated using global longitudinal strain (GLS), and tricuspid annular plane systolic excursion (TAPSE). RESULTS: A total of 162 patients (men, 83, 51.5%; 70.7±13.4 years; Acute Physiology and Chronic Health Evaluation [APACHE] II, 30.6±9.2) were enrolled. Initial GLS and TAPSE were -14.9±5.2% and 16.9±5.5 mm, and improved in the follow-up evaluation (GLS, -17.6±4.9%; TAPSE, 19.2±5.4 mm). Seven-day and in-hospital mortality were 24 (14.9%) and 64 (39.8%). Seven-day mortality was significantly associated with initial GLS >-16% (odds ratio [OR], 14.066, 95% confidence interval [CI], 1.178-167.969, p=0.037) and APACHE II score (OR, 1.196, 95% CI, 1.047-1.365, p=0.008). The in-hospital mortality of 7-day survivors was associated with follow-up TAPSE <16 mm (OR, 10.109, 95% CI, 1.640-62.322, p=0.013) and Sequential Organ Failure Assessment score (OR, 1.340, 95% CI, 1.078-1.667, p=0.008). GLS was not associated with in-hospital mortality of 7-day survivors. CONCLUSIONS: Fluctuation of both ventricular function was common in septic shock. Seven-day mortality of patients with septic shock was related to GLS, whereas in-hospital mortality of 7-day survivors was related to TAPSE, not to GLS.

COVID-19 versus Other Disease Etiologies as the Cause of ARDS in Patients Necessitating Venovenous Extracorporeal Membrane Oxygenation-A Comparison of Patients' Data during the Three Years of the COVID-19 Pandemic.

Considering the characteristics of coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS), we compared the clinical course and outcomes of patients with ARDS who received venovenous extracorporeal membrane oxygenation (VV ECMO) based on the etiology of ARDS. This retrospective single-center study included adult patients with severe ARDS necessitating VV ECMO during the COVID-19 pandemic. Among 45 patients who received VV ECMO, 21 presented with COVID-19. COVID-19 patients exhibited lower sequential organ failure assessment scores (9 [8-12.75] versus 8 [4-11.5], p = 0.033) but longer duration of VV ECMO support (10.5 days [3.25-29.25] versus 28 days [10.5-70.5] p = 0.018), which was accompanied by an weaning off rate from VV ECMO in 12/24 (50%) versus 12/21 (57.1%) and 28-day mortality in 9/24 [37.5%] versus 2/21 [9.5%] in non-COVID-19 and COVID-19 patients (p = 0.767, p = 0.040), respectively. Finally, in the adjusted Cox regression model for hospital mortality, the hazard ratio of COVID-19 was not significant (hazard ratio 0.350, 95% confidence interval 0.110-1.115, p = 0.076). Although the VV ECMO period was longer, COVID-19 did not significantly impact ECMO weaning off and mortality rates. Nonetheless, judicious patient selections based on risk factors should be followed.

Effects of sitagliptin on peritoneal membrane: The potential role of mesothelial cell tight junction proteins.

BACKGROUND: The roles of tight junction (TJ) proteins in peritoneal membrane transport and peritoneal dialysis (PD) require further characterisation. Dipeptidyl peptidase-4 is expressed in mesothelial cells, and its activity may affect peritoneal membrane function and morphology. METHODS: Human peritoneal mesothelial cells (HPMCs) were isolated and cultured from omentum obtained during abdominal surgery, and paracellular transport functions were evaluated by measuring transmesothelial electrical resistance (TMER) and dextran flux. Sprague-Dawley rats were infused daily with 4.25% peritoneal dialysate with and without sitagliptin administration for 8 weeks. At the end of this period, rat peritoneal mesothelial cells (RPMCs) were isolated to evaluate TJ protein expression. RESULTS: In HPMCs, the protein expression of claudin-1, claudin-15, occludin and E-cadherin was decreased by TGF-ß treatment but reversed by sitagliptin co-treatment. TMER was decreased by TGF-ß treatment but improved by sitagliptin co-treatment. Consistent with this, dextran flux was increased by TGF-ß treatment and reversed by sitagliptin co-treatment. In the animal experiment, sitagliptin-treated rats had a lower D2/D0 glucose ratio and a higher D2/P2 creatinine ratio than PD controls during the peritoneal equilibration test. Protein expression of claudin-1, claudin-15 and E-cadherin decreased in RPMCs from PD controls but was not affected in those from sitagliptin-treated rats. Peritoneal fibrosis was induced in PD controls but ameliorated in sitagliptin-treated rats. CONCLUSION: The expression of TJ proteins including claudin-1 and claudin-15 was associated with transport function both in HPMCs and in a rat model of PD. Sitagliptin prevents peritoneal fibrosis in PD and can potentially restore peritoneal mesothelial cell TJ proteins.

Sodium bicarbonate buffer for weaning from venovenous extracorporeal membrane oxygenation in patients with hypercapnic respiratory failure and acute renal failure.

Although the routine use of alkali buffer is not recommended in patients with respiratory acidosis, some patients may benefit from its administration. A 42-year-old man was treated with venovenous extracorporeal membrane oxygenation (VV-ECMO) and continuous venovenous hemodiafiltration (CVVHDF) due to necrotizing pneumonia and emphysematous cystitis with Klebsiella pneumoniae. Although the sweep gas flow rate of the VV-ECMO was gradually reduced, he failed to wean off VV-ECMO due to respiratory acidosis, followed by tachycardia and tachypnea on the 63rd day of VV-ECMO. Therefore, we mixed sodium bicarbonate in the replacement fluid of CVVHDF for 5 days to avoid an intolerable decrease in blood pH after discontinuing the VV-ECMO sweep gas. When the serum bicarbonate concentration was >30 mmol/L and pH was maintained at >7.30 with a PCO2 of >60 mmHg, VV-ECMO was finally decannulated. Sodium bicarbonate buffer through the replacement of CVVHDF fluid facilitated VV-ECMO weaning in a patient with hypercapnic respiratory failure.

Comparison of clinical characteristics and hospital mortality in critically ill patients without COVID-19 before and during the COVID-19 pandemic: a multicenter, retrospective, propensity score-matched study.

BACKGROUND: The high transmission and fatality rates of coronavirus disease 2019 (COVID-19) strain intensive care resources and affect the treatment and prognosis of critically ill patients without COVID-19. Therefore, this study evaluated the differences in characteristics, clinical course, and prognosis of critically ill medical patients without COVID-19 before and during the COVID-19 pandemic. METHODS: This retrospective cohort study included patients from three university-affiliated tertiary hospitals. Demographic data and data on the severity, clinical course, and prognosis of medical patients without COVID-19 admitted to the intensive care unit (ICU) via the emergency room (ER) before (from January 1 to May 31, 2019) and during (from January 1 to May 31, 2021) the COVID-19 pandemic were obtained from electronic medical records. Propensity score matching was performed to compare hospital mortality between patients before and during the pandemic. RESULTS: This study enrolled 1161 patients (619 before and 542 during the pandemic). During the COVID-19 pandemic, the Simplified Acute Physiology Score (SAPS) 3 and Sequential Organ Failure Assessment (SOFA) scores, assessed upon ER and ICU admission, were significantly higher than those before the pandemic (p < 0.05). The lengths of stay in the ER, ICU, and hospital were also longer (p < 0.05). Finally, the hospital mortality rates were higher during the pandemic than before (215 [39.7%] vs. 176 [28.4%], p < 0.001). However, in the propensity score-matched patients, hospital mortality did not differ between the groups (p = 0.138). The COVID-19 pandemic did not increase the risk of hospital mortality (odds ratio [OR] 1.405, 95% confidence interval [CI], 0.937-2.107, p = 0.100). SAPS 3, SOFA score, and do-not-resuscitate orders increased the risk of in-hospital mortality in the multivariate logistic regression model. CONCLUSIONS: In propensity score-matched patients with similarly severe conditions, hospital mortality before and during the COVID-19 pandemic did not differ significantly. However, hospital mortality was higher during the COVID-19 pandemic in unmatched patients in more severe conditions. These findings imply collateral damage to non-COVID-19 patients due to shortages in medical resources during the COVID-19 pandemic. Thus, strategic management of medical resources is required to avoid these consequences.

Associations between Phosphate Concentrations and Hospital Mortality in Critically Ill Patients Receiving Mechanical Ventilation.

Phosphate concentrations change continuously throughout hospitalization; however, it is unclear which available phosphate measures are most clinically important for predicting hospital mortality. Therefore, we investigated phosphate concentrations in association with hospital mortality following admission to the intensive care unit. We retrospectively enrolled all adult patients receiving mechanical ventilation. Phosphate concentrations were divided into three categories: initially measured phosphate (iP); maximum−minimum phosphate values (ΔP); and phosphate arithmetic average (Pmean). In total, 175 patients were enrolled. The hospital mortality rate was 32.6%, and the most common primary diagnosis was respiratory failure. In multivariable logistic regression analyses, the odds ratios for hospital mortality in association with ΔP and Pmean values were 1.56 and 2.13, respectively (p < 0.0001). According to the obtained receiver operating characteristic curve, ΔP (0.75) and Pmean (0.72) each showed a fair predictive power for hospital mortality. In evaluating relative risks, we found that higher concentrations of Pmean and ΔP were each associated with a higher hospital mortality. ΔP and Pmean values were significantly associated with hospital mortality in critically ill patients, compared to iP. These findings showed that throughout hospitalization, it is important to reduce phosphate level fluctuations and maintain appropriate phosphate concentrations through consistent monitoring and corrections.

Claudins in kidney health and disease.

Claudins are strategically located to exert their physiologic actions along with the nephron segments from the glomerulus. Claudin-1 is normally located in the Bowman's capsule, but its overexpression can reach the podocytes and lead to albuminuria. In the proximal tubule (PT), claudin-2 forms paracellular channels selective for water, Na+, K+, and Ca2+. Claudin-2 gene mutations are associated with hypercalciuria and kidney stones. Claudin-10 has two splice variants, -10a and -10b; Claudin-10a acts as an anion-selective channel in the PT, and claudin-10b functions as a cation-selective pore in the thick ascending limb (TAL). Claudin-16 and claudin-19 mediate paracellular transport of Na+, Ca2+, and Mg2+ in the TAL, where the expression of claudin-3/16/19 and claudin-10b are mutually exclusive. The claudin-16 or -19 mutation causes familial hypomagnesemia with hypercalciuria and nephrocalcinosis. Claudin- 14 polymorphisms have been linked to increased risk of hypercalciuria. Claudin-10b mutations produce HELIX syndrome, which encompasses hypohidrosis, electrolyte imbalance, lacrimal gland dysfunction, ichthyosis, and xerostomia. Hypercalciuria and magnesuria in metabolic acidosis are related to downregulation of PT and TAL claudins. In the TAL, stimulation of calcium-sensing receptors upregulates claudin-14 and negatively acts on the claudin-16/19 complex. Claudin-3 acts as a general barrier to ions in the collecting duct. If this barrier is disturbed, urine acidification might be impaired. Claudin-7 forms a nonselective paracellular channel facilitating Cl- and Na+ reabsorption in the collecting ducts. Claudin-4 and -8 serve as anion channels and mediate paracellular Cl- transport; their upregulation may contribute to pseudohypoaldosteronism II and salt-sensitive hypertension.

Lipid Polysaccharides have a Detrimental Effect on the Function of the Ovaries and Uterus in Mice through Increased Pro-Inflammatory Cytokines.

As the number of coronavirus disease 2019 (COVID-19) vaccinations increases, various side effects are being reported, and menstrual abnormalities have been reported as a side effect in women. However, it is still unclear whether the COVID-19 vaccine has detrimental effects on the female reproductive system. Therefore, we investigated the effect of excessive immune response on reproductive function by administering Lipopolysaccharides (LPS) instead of the COVID-19 vaccine. The immune response in mice was induced by injection of LPS. Mice injected with saline 5 times were used as a control group, and mice injected with LPS 5 times were used as an experimental group. Repeated administration of LPS significantly reduced the number of corpus luteum (CL). On the other hand, the injection of LPS did not affect the development of follicles leading before the CL. The expression of the apoptosis-related genes Fas and Fas-L increased in the experimental group. In addition, the expression of the inflammation-related genes increased in the experimental group. In this study, we confirmed that LPS had detrimental effects on the uterus and ovaries in mice. These results suggest that injection of LPS can cause immune reactions within the uterus and ovaries and cause hormonal changes, which can have adverse effects such as abnormal operation or bleeding of the menstrual cycle. These results are expected to help determine the cause of decreased reproductive function, infertility, or physiological disorders caused by the COVID-19 vaccine.

The Role of Vasopressin V2 Receptor in Drug-Induced Hyponatremia.

Hyponatremia is frequently encountered in clinical practice and usually induced by renal water retention. Many medications are considered to be among the various causes of hyponatremia, because they either stimulate the release of arginine vasopressin (AVP) or potentiate its action in the kidney. Antidepressants, anticonvulsants, antipsychotics, diuretics, and cytotoxic agents are the major causes of drug-induced hyponatremia. However, studies addressing the potential of these drugs to increase AVP release from the posterior pituitary gland or enhance urine concentration through intrarenal mechanisms are lacking. We previously showed that in the absence of AVP, sertraline, carbamazepine, haloperidol, and cyclophosphamide each increased vasopressin V2 receptor (V2R) mRNA and aquaporin-2 (AQP2) protein and mRNA expression in primary cultured inner medullary collecting duct cells. The upregulation of AQP2 was blocked by the V2R antagonist tolvaptan or protein kinase A (PKA) inhibitors. These findings led us to conclude that the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is the main mechanism of drug-induced hyponatremia. Previous studies have also shown that the V2R has a role in chlorpropamide-induced hyponatremia. Several other agents, including metformin and statins, have been found to induce antidiuresis and AQP2 upregulation through various V2R-independent pathways in animal experiments but are not associated with hyponatremia despite being frequently used clinically. In brief, drug-induced hyponatremia can be largely explained by AQP2 upregulation from V2R-cAMP-PKA signaling in the absence of AVP stimulation. This paper reviews the central and nephrogenic mechanisms of drug-induced hyponatremia and discusses the importance of the canonical pathway of AQP2 upregulation in drug-induced NSIAD.

An Integrated Model including the ROX Index to Predict the Success of High-Flow Nasal Cannula Use after Planned Extubation: A Retrospective Observational Cohort Study.

High-flow nasal cannula (HFNC) therapy is commonly used to prevent reintubation after planned extubation. In clinical practice, there are no appropriate tools to evaluate whether HFNC therapy was successful or failed after planned extubation. In this retrospective observational study, we investigated whether the use of the ROX index was appropriate to differentiate between HFNC success and failure within 72 h after extubation and to develop an integrated model including the ROX index to improve the prediction of HFNC success in patients receiving HFNC therapy after planned extubation. Of 276 patients, 50 patients (18.1%) were reintubated within 72 h of extubation. ROX index values of >8.7 at 2 h, >8.7 at 6 h, and >10.4 at 12 h after HFNC therapy were all meaningful predictors of HFNC success in extubated patients. In addition, the integrated model including the ROX index had a better predictive capability for HFNC success than the ROX index alone. In conclusion, the ROX index at 2, 6, and 12 h could be applied to extubated patients to predict HFNC success after planned extubation. To improve its predictive power, we should also consider an integrated model consisting of the ROX index, sex, body mass index, and the total duration of ventilator care.

Anti-Leukemic Properties of Aplysinopsin Derivative EE-84 Alone and Combined to BH3 Mimetic A-1210477.

Aplysinopsins are a class of marine indole alkaloids that exhibit a wide range of biological activities. Although both the indole and N-benzyl moieties of aplysinopsins are known to possess antiproliferative activity against cancer cells, their mechanism of action remains unclear. Through in vitro and in vivo proliferation and viability screening of newly synthesized aplysinopsin analogs on myelogenous leukemia cell lines and zebrafish toxicity tests, as well as analysis of differential toxicity in noncancerous RPMI 1788 cells and PBMCs, we identified EE-84 as a promising novel drug candidate against chronic myeloid leukemia. This indole derivative demonstrated drug-likeness in agreement with Lipinski's rule of five. Furthermore, EE-84 induced a senescent-like phenotype in K562 cells in line with its cytostatic effect. EE-84-treated K562 cells underwent morphological changes in line with mitochondrial dysfunction concomitant with autophagy and ER stress induction. Finally, we demonstrated the synergistic cytotoxic effect of EE-84 with a BH3 mimetic, the Mcl-1 inhibitor A-1210477, against imatinib-sensitive and resistant K562 cells, highlighting the inhibition of antiapoptotic Bcl-2 proteins as a promising novel senolytic approach against chronic myeloid leukemia.

Psychotropic drugs upregulate aquaporin-2 via vasopressin-2 receptor/cAMP/protein kinase A signaling in inner medullary collecting duct cells.

Psychotropic drugs may be associated with hyponatremia, but an understanding of how they induce water retention in the kidney remains elusive. Previous studies have postulated that they may increase vasopressin production in the hypothalamus without supporting evidence. In this study, we investigated the possibility of drug-induced nephrogenic syndrome of inappropriate antidiuresis using haloperidol, sertraline, and carbamazepine. Haloperidol, sertraline, or carbamazepine were treated in inner medullary collecting duct (IMCD) suspensions and primary cultured IMCD cells prepared from male Sprague-Dawley rats. The responses of intracellular cAMP production, aquaporin-2 (AQP2) protein expression and localization, vasopressin-2 receptor (V2R) and AQP2 mRNA, and cAMP-responsive element-binding protein (CREB) were tested with and without tolvaptan and the protein kinase A (PKA) inhibitors H89 and Rp-cAMPS. In IMCD suspensions, cAMP production was increased by haloperidol, sertraline, or carbamazepine and was relieved by tolvaptan cotreatment. In primary cultured IMCD cells, haloperidol, sertraline, or carbamazepine treatment increased total AQP2 and decreased phosphorylated Ser261-AQP2 protein expression. Notably, these responses were reversed by cotreatment with tolvaptan or a PKA inhibitor. AQP2 membrane trafficking was induced by haloperidol, sertraline, or carbamazepine and was also blocked by cotreatment with tolvaptan or a PKA inhibitor. Furthermore, upregulation of V2R and AQP2 mRNA and phosphorylated CREB was induced by haloperidol, sertraline, or carbamazepine and was blocked by tolvaptan cotreatment. We conclude that, in the rat IMCD, psychotropic drugs upregulate AQP2 via V2R-cAMP-PKA signaling in the absence of vasopressin stimulation. The vasopressin-like action on the kidney appears to accelerate AQP2 transcription and dephosphorylate AQP2 at Ser261.NEW & NOTEWORTHY It is unclear whether antipsychotic drugs can retain water in the kidney in the absence of vasopressin. This study demonstrates that haloperidol, sertraline, and carbamazepine can produce nephrogenic syndrome of inappropriate antidiuresis because they directly upregulate vasopressin-2 receptor and aquaporin-2 (AQP2) via cAMP/PKA signaling. We showed that, in addition to AQP2 trafficking, AQP2 protein abundance was rapidly increased by treatment with antipsychotic drugs in association with dephosphorylation of AQP2 at Ser261 and accelerated AQP2 transcription.

Early enteral nutrition and factors related to in-hospital mortality in people on extracorporeal membrane oxygenation.

OBJECTIVES: There are concerns about adverse events related to early enteral nutrition (EN) in people receiving extracorporeal membrane oxygenation (ECMO). This was a retrospective study evaluating. This nutritional support of people receiving ECMO, factors that may confer benefits in outcomes. METHODS: 60 adults on ECMO who survived for more than 48 h were enrolled in the study. We evaluated energy and protein intake and the associations of the timing, adequacy, and route of nutrition with in-hospital mortality. RESULTS: Thirty-three participants (55%) were successfully weaned off ECMO, and 30 (50%) survived. EN was initiated on day 2 of ECMO (interquartile range, 1-3), and the mean energy intake on day 7 of ECMO was 94.1% ± 41.8% of the energy requirement. Although early EN significantly decreased in-hospital mortality (hazard ratio, 0.413; 95% confidence interval, 0.174-0.984; P = 0.046), neither adequate energy intake (hazard ratio, 0.982; 95% confidence interval, 0.292-3.301; P = 0.977) nor EN-dominant nutritional support (hazard ratio, 0.394; 95% confidence interval, 0.138-1.128; P = 0.083) in the first week influenced survival. CONCLUSIONS: Although adequate nutritional support and EN-dominant nutritional support were not associated with changes in outcome, early EN was associated with reduced in-hospital mortality. Therefore, even when EN is not the dominant route of nutritional support, early EN may be recommended for better outcomes in people on ECMO.

Predictive Role of Lung Injury Prediction Score in the Development of Acute Respiratory Distress Syndrome in Korea.

PURPOSE: Early recognition and therapeutic intervention are important in patients at high risk of acute respiratory distress syndrome (ARDS). The lung injury prediction score (LIPS) has been used to predict ARDS development; however, it was developed based on the previous definition of ARDS. We investigated the predictive role of LIPS in ARDS development according to its Berlin definition in the Korean population. MATERIALS AND METHODS: This was a retrospective study that enrolled adult patients admitted to the intensive care unit (ICU) at a single university-affiliated hospital in Korea from September 1, 2018, to August 31, 2019. LIPS at the time of ICU admission and the development of ARDS were evaluated. RESULTS: Of the 548 enrolled patients, 33 (6.0%) fulfilled the Berlin ARDS definition. The LIPS for non-ARDS and ARDS groups were 4.96±3.05 and 8.53±2.45, respectively (p<0.001); it was significantly associated with ARDS development (odds ratio 1.48, 95% confidence interval, 1.29-1.69; p<0.001). LIPS >6 predicted the development of ARDS with a sensitivity of 84.8% and a specificity of 67.2% [area under the curve (AUC)=0.82]. A modified LIPS model adjusted for age and severity at ICU admission predicted ICU mortality in patients with ARDS (AUC=0.80), but not in those without ARDS (AUC=0.54). CONCLUSION: LIPS predicted the development of ARDS as diagnosed by the Berlin definition in the Korean population. LIPS provides useful information for managing patients with ARDS.

Thick ascending limb claudins are altered to increase calciuria and magnesiuria in metabolic acidosis.

Urinary calcium and magnesium wasting is a characteristic feature of metabolic acidosis, and this study focused on the role of the thick ascending limb of Henle's loop in metabolic acidosis-induced hypercalciuria and hypermagnesiuria because thick ascending limb is an important site of paracellular calcium and magnesium reabsorption. Male Sprague-Dawley rats were used to determine the effects of acid loading (by adding NH4Cl, 7.2 mmol/220 g body wt/day to food slurry for 7 days) on renal expression of claudins and then to evaluate whether the results were reversed by antagonizing calcium-sensing receptor (using NPS-2143). At the end of each animal experiment, the kidneys were harvested for immunoblotting, immunofluorescence microscopy, and quantitative PCR (qPCR) analysis of claudins and the calcium-sensing receptor. As expected, NH4Cl loading lowered urinary pH and increased excretion of urinary calcium and magnesium. In NH4Cl-loaded rats, renal protein and mRNA expression of claudin-16, and claudin-19, were decreased compared with controls. However, claudin-14 protein and mRNA increased in NH4Cl-loaded rats. Consistently, the calcium-sensing receptor protein and mRNA were up-regulated in NH4Cl-loaded rats. All these changes were reversed by NPS-2143 coadministration and were confirmed using immunofluorescence microscopy. Hypercalciuria and hypermagnesiuria in NH4Cl-loaded rats were significantly ameliorated by NPS-2143 coadministration as well. We conclude that in metabolic acidosis, claudin-16 and claudin-19 in the thick ascending limb are down-regulated to produce hypercalciuria and hypermagnesiuria via the calcium-sensing receptor.NEW & NOTEWORTHY This study found that the thick ascending limb of Henle's loop is involved in the mechanisms of hypercalciuria and hypermagnesiuria in metabolic acidosis. Specifically, expression of claudin-16/19 and claudin-14 was altered via up-regulation of calcium-sensing receptor in NH4Cl-induced metabolic acidosis. Our novel findings contribute to understanding the regulatory role of paracellular tight junction proteins in the thick ascending limb.

Organizing an in-class hackathon to correct PDF-to-text conversion errors of Genomics & Informatics 1.0.

This paper describes a community effort to improve earlier versions of the full-text corpus of Genomics & Informatics by semi-automatically detecting and correcting PDF-to-text conversion errors and optical character recognition errors during the first hackathon of Genomics & Informatics Annotation Hackathon (GIAH) event. Extracting text from multi-column biomedical documents such as Genomics & Informatics is known to be notoriously difficult. The hackathon was piloted as part of a coding competition of the ELTEC College of Engineering at Ewha Womans University in order to enable researchers and students to create or annotate their own versions of the Genomics & Informatics corpus, to gain and create knowledge about corpus linguistics, and simultaneously to acquire tangible and transferable skills. The proposed projects during the hackathon harness an internal database containing different versions of the corpus and annotations.

Transmural difference in myocardial damage assessed by layer-specific strain analysis in patients with ST elevation myocardial infarction.

We performed layer-specific strain analysis with speckle-tracking echocardiography to investigate the transmural difference of myocardial damage as the predicting factor for the viability of damaged myocardium in patients with ST segment elevation myocardial infarction (STEMI). We analysed patients with acute STEMI who had undergone primary percutaneous coronary intervention and echocardiography within 24 h from the intervention and 2 months after the event. Segmental strains of the left ventricular (LV) endocardium, myocardium, epicardium, and strain gradient (SG) between the endocardium and epicardium were evaluated. In 34 patients, 112 akinetic/dyskinetic and 94 hypokinetic segments were observed among 612 segments of the LV at baseline, and 65 akinetic/dyskinetic segments had viability. In our study, layer-specific strains were gradually deteriorated by their wall motion. SG was augmented in the hypokinetic segments where inhomogeneous wall motion impairment was progressed. SG in the akinetic/dyskinetic segments was different between the viable and non-viable myocardium and was maintained in viable segments. We therefore believe that significantly reduced SG is indicative of irreversible transmural damage in the acute stage of STEMI and can be suitably used as a parameter for predicting myocardial viability.

Factors Associated With Failure of High-Flow Nasal Cannula.

BACKGROUND: The use of high-flow nasal cannula (HFNC) is rapidly increasing without clear indications, creating the potential for overuse or misuse and the accompanying risk of adverse events. The purpose of this study was to determine the factors associated with HFNC failure by examining the current clinical practice of HFNC. METHODS: From July 1, 2017, to June 30, 2018, in 5 university-affiliated hospitals in the Republic of Korea, a total of 1,161 admitted adult subjects who had HFNC administered were retrospectively enrolled and their medical records were reviewed. RESULTS: Pulmonary diseases including pneumonia (n = 757, 65.2%) were the most common reason for use of HFNC. Subjects with do-not-resuscitate (DNR) or do-not-intubate (DNI) orders comprised 33.8% of the study population (n = 392); 563 subjects (48.5%) were escalated directly to HFNC from low-flow devices without applying reservoir or other high-flow devices. In the non-DNR/DNI subjects, arterial blood gas was not monitored in 15.2% and 14.8% of subjects before and after HFNC application, respectively, and it was not monitored in 28.0% just before HFNC weaning. The HFNC failure rate was 27.0% in non-DNR/DNI subjects, and the HFNC failure was significantly associated with the decision by residents to apply HFNC (odds ratio [OR] 2.03, 95% CI 1.29-3.18, P = .002), high breathing frequency (OR 1.07, 95% CI 1.04-1.10, P < .001) ≤ 6 h before HFNC application, low [Formula: see text] (OR 0.92, 95% CI 0.89-0.95, P < .001) ≤ 6 h before HFNC application, low [Formula: see text] (OR 0.95, 95% CI 0.93-0.98, P < .001) ≤ 6 h before HFNC application, and the ratio of [Formula: see text]/[Formula: see text] to breathing frequency (ROX index) ≤ 6 h after HFNC application (OR 0.88, 95% CI 0.84-0.92, P < .001). CONCLUSIONS: HFNC was practiced without applying reservoir or other high-flow devices before application and without appropriate arterial blood gas monitoring during HFNC therapy. HFNC failure was significantly associated with the decision by the resident to use HFNC, breathing frequency, [Formula: see text], and [Formula: see text] ≤ 6 h before HFNC application, and with the ROX index ≤ 6 h after HFNC application.

Association between Left Ventricular Systolic Dysfunction and Mortality in Patients with Septic Shock.

BACKGROUND: The impact of myocardial damage on the prognosis of patients with septic shock is not clearly elucidated because complex hemodynamic changes in sepsis obscure the direct relationship. We evaluated left ventricular (LV) conditions that reflect myocardial damage independently from hemodynamic changes in septic shock and their influence on the prognosis of patients. METHODS: We retrospectively enrolled 208 adult patients who were admitted to the intensive care unit and underwent echocardiography within 7 days from the diagnosis of septic shock. Patients who were previously diagnosed with structural heart disease or coronary artery disease were excluded. Left ventricular ejection fraction (LVEF) was divided into four categories: normal, ≥ 50%; mild, ≥ 40%; moderate, ≥ 30%; and severe dysfunction, < 30%. Wall motion impairment was categorized into the following patterns: normal, diffuse, ballooning, and focal. RESULTS: There were 141 patients with normal LVEF. Among patients with impaired LV wall motion, the diffuse pattern was the most common (34 patients), followed by the ballooning pattern (26 patients). Finally, 102 patients died, and in-hospital mortality was significantly higher in patients with severe LV systolic dysfunction (hazard ratio [HR], 1.97; 95% confidence interval [CI], 1.04-3.75; P = 0.039) and in patients with diffuse pattern of LV wall motion impairment (HR, 2.28; 95% CI, 1.19-4.36; P = 0.013) than in those with a normal LV systolic function. CONCLUSION: Severe LV systolic dysfunction and diffuse pattern of LV wall motion impairment significantly affected in-hospital mortality in patients with septic shock. Conventional echocardiographic evaluation provides adequate information on the development of myocardial damage and accurately predicts the prognosis of patients with septic shock.

Association of Proteinuria with Urinary Concentration Defect in Puromycin Aminonucleoside Nephrosis.

BACKGROUND: Puromycin aminonucleoside (PA) can induce nephrotic syndrome in rats, and proteinuria is an important mediator of tubulointerstitial injury in glomerulopathy. We assumed that glomerular proteinuria may affect tubular function, such as urinary concentration, and investigated whether a urinary concentration defect is associated with proteinuria in puromycin aminonucleoside nephrosis (PAN). We also investigated the defect response to enalapril. METHODS: Glomerular proteinuria was induced by a single intraperitoneal injection of PA (150mg/kg BW) in male Sprague-Dawley rats. In a half of these rats, enalapril (35mg/kg BW) was administered daily in a food mixture for two weeks. After the animal experiment, kidneys were harvested for immunoblot analysis and histopathologic examination. RESULTS: Compared with the control group, PA-treated rats had severe proteinuria, polyuria, and a lower urine osmolality. PA treatment induced remarkable tubulointerstitial injury and significant reductions in protein abundances of aquaporin-1 and Na-K-2Cl co-transporter type 2 (NKCC2). Proteinuria significantly correlated with osteopontin expression in the kidney and inversely correlated with renal expression of aquaporin-1, aquaporin-2, and NKCC2. The degree of tubulointerstitial injury significantly correlated with proteinuria, urine output, and osteopontin expression and inversely correlated with urine osmolality and renal expression of aquaporin-1, aquaporin-2, and NKCC2. No significant differences in parameters were found between PA-treated rats with and without enalapril. CONCLUSION: In PAN, glomerular proteinuria was associated with tubulointerstitial injury and water diuresis. Downregulation of aquaporin-1 and NKCC2 can impair countercurrent multiplication and cause a urinary concentration defect in PAN.