A decrease in serum creatinine after ICU admission is associated with increased mortality.

BACKGROUND: The elevation of serum creatinine (SCr), acute kidney injury (AKI), is associated with an increase of mortality in critically ill patients. However, it is uncertain whether a decrease in SCr in the intensive care unit (ICU) has an effect on outcomes. METHODS: In a retrospective study, we enrolled 486 patients who had been admitted to an urban tertiary center ICU between Jan 2014 and Dec 2014. The effect of changes in SCr after ICU admission on 90 day mortality was analyzed. Patients were classified into 3 groups based on change in SCr after ICU admission: a stable SCr group (Δ SCr < 0.3mg/dL during ICU stay), a decreased SCr group (Δ SCr ≥ -0.3 mg/dL during ICU stay) and an increased SCr group with criteria based on the KDIGO AKI criteria. RESULTS: In total, 486 patients were identified. SCr decreased in 123 (25.3%) patients after ICU admission. AKI developed in 125 (24.4%) patients. The overall 90-day mortality rate was 29.0%. In a Kaplan-Meyer analysis, the mortality of the AKI group was higher than that of other groups (p<0.0001). Patients with a decrease in SCr had a higher mortality rate than those with stable SCr (p<0.0001). A Cox analysis showed that both a decrease in SCR (HR, 3.56; 95% CI, 1.59-7.97; p = 0.002) and an increase in SCr (AKI stage 1, HR, 9.35; 95% CI, 4.18-20.9; p<0.0001; AKI stage 2, HR, 11.82; 95% CI, 3.85-36.28; p<0.0001; AKI stage 3, HR, 17.41; 95% CI, 5.50-55.04; p<0.0001) were independent risk factors for death compared to stable SCr. CONCLUSION: Not only an increase in SCr, but also a decrease in SCr was associated with mortality in critically ill patients.

Severity of community acquired hypernatremia is an independent predictor of mortality.

Hypernatremia develops commonly in critically ill patients during hospitalization, and is associated with adverse outcomes. However, community acquired hypernatremia (CAH) has been rarely studied. We conducted a study in patients who presented to an urban referral hospital, and were admitted with CAH. We retrospectively analyzed patients admitted to an urban tertiary care hospital from January 1, 2012 to December 31, 2014. CAH is defined as more than 147 mEq/L at admission in patients not transferred from other hospitals. Severity of hypernatremia is categorized as mild (148-150 mEq/L), moderate (151-154 mEq/L) or severe (≥155 mEq/L). All data were extracted from electronic medical records and the major outcome is hospital mortality. During the study period, 79,998 patients were admitted to the hospital. Of them, 178 patients (0.2%) had hypernatremia at the time of admission. 121 (68.0%) had mild hypernatremia, 33 (18.5%) had moderate hypernatremia, and 24 (13.5%) had severe hypernatremia at admission. During the hospital stay, 91 (51.1%) developed mild hypernatremia, 31 (17.4%) developed moderate hypernatremia and 56 (31.5%) developed severe hypernatremia. Mean duration of hypernatremia was 2.3 ± 2.0 days. The length of hospital stay was 7 (interquartile range 3-23) days and hospital mortality was 24.3%. Multivariate analysis shows that a peak sodium level that qualified as moderate [OR = 11.50, 95% CI (2.67-49.42)] or severe hypernatremia [OR = 5.18, 95% CI (1.43-18.79)] is an independent risk factor for hospital mortality compared to mild hypernatremia. Admission from the emergency department (ED), oral intake restriction, mean arterial pressure (MAP) and respiratory rate (RR) at admission time are also independently associated with hospital mortality. Maximum sodium level in CAH is independently associated with hospital mortality.

A Case of Post-radiotherapy Urethral Stricture with Spontaneous Bladder Rupture, Mimicking Obstructive Uropathy due to Cancer Metastasis.

Non-traumatic, spontaneous urinary bladder rupture is a rare complication of urethral stricture. Furthermore, its symptoms are often nonspecific, and misdiagnosis is common. The authors experienced a case of urethral stricture with spontaneous bladder rupture and bilateral hydronephrosis, mimicking obstructive uropathy attributed to cancer metastasis. A 55-year-old woman was admitted with abdominal pain and distension, oliguria, and an elevated serum creatinine level. She had undergone radical hysterectomy for uterine cervical cancer and received post-operative concurrent chemoradiation therapy 13 years previously. Non-contrast enhanced computed tomography showed massive ascites and bilateral hydronephrosis. The initial diagnosis was acute kidney injury due to obstructive uropathy caused by malignant disease. After improvement of her renal function by bilateral percutaneous nephrostomy catheterization, contrast-enhanced computed tomography and a cytologic examination of ascites showed no evidence of malignancy. However, during retrograde pyelography, a severe urethral stricture was found, and subsequent cystography showed leakage of contrast into the peritoneal cavity and cystoscopy revealed a defect of the posterior bladder wall. After urethral dilatation and primary closure of the bladder wall, acute kidney injury and ascites were resolved.

Pancreaticothoracic fistula presenting with hemoptysis and pneumothorax in a chronic alcoholic patient.

Pancreaticothoracic fistula is a rare complication of acute or chronic alcoholic pancreatitis. It may present with various symptoms, like dyspnea, abdominal pain, cough, chest pain, fever, back pain, hemoptysis, fatigue, or orthopnea. Pancreaticothoracic fistula can be detected by magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), or computed tomography. MRCP has high sensitivity and fewer side effects, and thus it has recently been recommended as the first choice for the detection of pancreaticothoracic fistula. On the other hand, ERCP enables the detection and treatment of pancreaticothoracic fistula and allows for stent insertion; for this reason it is a commonly used modality in pancreaticothoracic fistula cases. Herein, the authors describe a case of pancreaticothoracic fistula detected by ERCP and MRCP that manifested only respiratory symptoms, namely hemoptysis and pneumothorax without abdominal pain, which commonly accompanies pancreatitis.

Prognostic impact of minimal pleural effusion in non-small-cell lung cancer.

PURPOSE: Minimal (< 10 mm thick) pleural effusion (PE) may represent an early phase of malignant PE, but its clinical relevance has rarely been studied. Therefore, we examined the proportion of minimal PE in patients with non-small-cell lung cancer (NSCLC) and its impact on survival. We also considered possible accumulation mechanisms in our data set. PATIENTS AND METHODS: On the basis of PE status from chest computed tomography scans at diagnosis, 2,061 patients were classified into three groups: no PE, minimal PE, and malignant PE. Twenty-one variables associated with four factors-patient, stage migration, tumor, and treatment-were investigated for correlation with survival. RESULTS: Minimal PE presented in 272 patients (13.2%). Of 2,061 patients, the proportion of each stage was the following: 5.2% stage I, 10.9% stage II, 13.2% stage IIIA, 23.8% stage IIIB, and 13.9% stage IV. Minimal PE correlated significantly with shorter survival time than did no PE (median survival time, 7.7 v 17.7 months; log-rank P < .001), even after full adjustment with all variables (adjusted hazard ratio, 1.40; 95% CI, 1.21 to 1.62). Prognostic impact of minimal PE was higher in early versus advanced stages (Pinteraction = .001). In 237 patients (87.8%) with minimal PE, pleural invasion or attachment as a direct mechanism was observed, and it was an independent factor predicting worse survival (P = .03). CONCLUSION: Minimal PE is a commonly encountered clinical concern in staging NSCLCs. Its presence is an important prognostic factor of worse survival, especially in early-stage disease.

Effect of dialysate sodium concentration on sodium gradient and hemodialysis parameters.

This retrospective study was performed to determine the ranges of the sodium gradient (SG) between the dialysate sodium concentration (DNa) and serum sodium concentration (SNa) in hemodialysis (HD) patients and to examine the relationships between HD parameters over a 1 year period. Fifty-five clinically stable HD patients, who had been on HD >2 years were enrolled. Monthly HD [ultrafiltration (UF) amount, systolic blood pressure (SBP), frequency of intradialytic hypotension (IDH)] and laboratory data were collected and 12-month means were subjected to analysis. The SG was calculated by subtracting SNa from prescribed DNa. Mean SG values were 1.5±3.3 (range -5.6~9.1). SG was positively related to DNa and the frequency of IDH. A higher SG was associated with larger UF amounts and SBP reduction during HD. The percentages of patients with a SG ≥3mEq/L increased as DNa increased. On the other hand, SG was not found to be associated with SNa or pre-HD SBP. DNa appears to cause a significant increase in SG, and this seems to be related to HD parameters, such as, UF amount and IDH.

Sulfur mustard primes human neutrophils for increased degranulation and stimulates cytokine release via TRPM2/p38 MAPK signaling.

Sulfur mustard (2,2'-bis-chloroethyl-sulfide; SM) has been a military threat since the World War I. The emerging threat of bioterrorism makes SM a major threat not only to military but also to civilian world. SM injury elicits an inflammatory response characterized by infiltration of neutrophils. Although SM was reported to prime neutrophils, the mechanism has not been identified yet. In the present study, we investigated the mechanism of SM-induced priming in human neutrophils. SM increased [Ca(2+)](i) in human neutrophils in a concentration-dependent fashion. Transient receptor potential melastatin (TRPM) 2 inhibitors (clotrimazole, econazole and flufenamic acid) and silencing of TRPM2 by shRNA attenuated SM-induced [Ca(2+)](i) increase. SM primed degranulation of azurophil and specific granules in response to activation by fMLP as previously reported. SB203580, an inhibitor of p38 MAPK, inhibited SM-induced priming. Neither PD98057, an ERK inhibitor, nor SP600215, a JNK inhibitor, inhibited SM-induced priming. In addition, SM enhanced phosphorylation of NF-kB p65 and release of TNF-α, interleukin (IL)-6 and IL-8. SB203580 inhibited SM-induced NF-kB phosphorylation and cytokine release. These results suggest the involvement of TRPM2/p38 MAPK pathway in SM-induced priming and cytokines release in neutrophils.

Lysophosphatidylcholine increases neutrophil bactericidal activity by enhancement of azurophil granule-phagosome fusion via glycine.GlyR alpha 2/TRPM2/p38 MAPK signaling.

Neutrophils are the first-line defense against microbes. Enhancing the microbicidal activity of neutrophils could complement direct antimicrobial therapy for controlling intractable microbial infections. Previously, we reported that lysophosphatidylcholine (LPC), an endogenous lipid, enhances neutrophil bactericidal activity (Yan et al. 2004. Nat. Med. 10: 161-167). In this study we show that LPC enhancement of neutrophil bactericidal activity is dependent on glycine, and is mediated by translocation of intracellularly located glycine receptor (GlyR) alpha2 to the plasma membrane, and subsequent increase in azurophil granule-phagosome fusion/elastase release. LPC induced GlyRalpha2-mediated [Cl(-)](i) increase, leading to transient receptor potential melastatin (TRPM)2-mediated Ca(2+) influx. Studies using human embryonic kidney 293 cells heterologously expressing TRPM2 and neutrophils showed that TRPM2 channel activity is sensitive to [Cl(-)](i). Finally, LPC induced p38 MAPK phosphorylation in an extracellular calcium/glycine dependent manner. SB203580, a p38 MAPK inhibitor, blocked LPC-induced enhancement in Lucifer yellow uptake, azurophil granule-phagosome fusion, and bactericidal activity. These results propose that enhancement of azurophil granule-phagosome fusion via GlyRalpha2/TRPM2/p38 MAPK signaling is a novel target for enhancement of neutrophil bactericidal activity.

Transgenic overexpression of translationally controlled tumor protein induces systemic hypertension via repression of Na+,K+-ATPase.

Inhibition of Na(+),K(+)-ATPase has been implicated in the pathogenesis of hypertension via its effect on smooth muscle reactivity and myocardial contractility. We recently demonstrated that translationally controlled tumor protein (TCTP) interacts with the 3rd cytoplasmic domain of Na(+),K(+)-ATPase alpha(1)-subunit and acts as its cytoplasmic repressor. Therefore, we hypothesized that repression of Na(+),K(+)-ATPase by overexpressed TCTP might underlie the development of hypertension. In the present study, we confirmed that transgenic mice overexpressing TCTP developed systemic arterial hypertension at about 6 weeks after birth. Vascular smooth muscle of TCTP-overexpressing transgenic mice also displayed augmented contractile response to vasoconstrictors and attenuated relaxation response to vasodilators. These responses seem to be caused by reduced Na(+),K(+)-ATPase activity and increased intracellular calcium, suggesting that inhibition of Na(+),K(+)-ATPase by overexpression of TCTP is involved in the pathogenesis of hypertension. This study provides a new link between alteration of sodium pump activity and hypertension in vivo, and suggests that TCTP might be a therapeutic target for the treatment of hypertension.