Urological Procedures in Urolithiasis and Their Association with Chronic Kidney Disease.

BACKGROUND AND OBJECTIVES: Epidemiological evidence suggests that patients with urolithiasis are at increased risk for end-stage renal disease (ESRD). It is unclear if urological intervention impacts the progression of chronic kidney disease (CKD). METHODS: We conducted a retrospective observational cohort study of patients in the Marshfield Epidemiologic Study Area database between January 1991 and May 2007, where 1,340 patients diagnosed with urolithiasis were extracted. Of the 1,340 subjects, 446 had urological procedures for management of urolithiasis. Those that underwent these procedures were compared to those that did not. Cox proportional hazards models adjusted for age, gender, and comorbidities were performed to evaluate the risk for CKD, elevated serum creatinine, and any-cause mortality. RESULTS: Baseline comorbidities in patients with and without procedures were not significantly different except for obesity (P<0.0001). Subjects that underwent procedures were at increased risk for elevated serum creatinine (Hazard Ratio (HR) [95% CI] =1.49 [1.19-1.85]) when compared to those that did not undergo a urologic procedure during the study period. The results did not reveal a significant difference in incidence of CKD or any-cause mortality. CONCLUSIONS: Patients who undergo urologic procedures are at increased risk for elevated creatinine. Urological procedures do not appear to impact incidence of CKD or mortality and, in fact, may prevent long-term renal dysfunction.

Tolvaptan for SIADH in Myelodysplastic Syndrome with Blast Crisis.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia in cancer patients. It is most frequently reported in association with small-cell lung cancer, but has been reported in other cancers as well. Here we report the case of a patient with myelodysplastic syndrome and blast crisis who developed concurrent hyponatremia. The patient failed to respond to fluid restriction and administration of hypertonic saline. She was treated with tolvaptan, a vasopressin antagonist licensed for the treatment of adult patients with hyponatremia secondary to syndrome of inappropriate antidiuretic hormone secretion. We conclude that in myelodysplastic syndrome patients with blast crisis, inappropriate antidiuretic hormone secretion should be considered as a cause of hyponatremia and be treated with tolvaptan.

Patient Engagement.

As the health system shifts toward population health approach, there is increasing attention to decreasing costs and improving quality. Measuring and improving patient engagement will become a requisite core competency for health systems and care providers. Approximately 70% of deaths and 40% of costs are attributable to a few chronic diseases, which are largely modifiable by practices such as smoking cessation, healthy eating, and exercise, each of which requires patients to play an active role in owning their health. Caregivers and the health system can support patient engagement, making it more likely that patients will take ownership for their health.

Acute systemic immune activation following vaginal exposure to staphylococcal enterotoxin B--implications for menstrual shock.

Menstrual toxic shock syndrome (mTSS) is an acute systemic inflammatory disease associated with the superantigenic exotoxin, toxic shock syndrome toxin (TSST)-1, produced by Staphylococcus aureus and the use of high absorbency tampons. Even though S. aureus is capable of elaborating several other superantigenic exotoxins, only TSST-1 has been implicated in the pathogenesis of mTSS possibly because most other superantigenic exotoxins are known enterotoxins. Nonetheless, we have shown recently that one of the enterotoxigenic staphylococcal superantigens, staphylococcal enterotoxin B (SEB), can cause robust systemic immune activation following exposure through non-enteric mucosa, including nasal or conjunctival routes. In a similar manner, we show here that vaginal administration of SEB in HLA class II transgenic mice can cause robust systemic immune activation characterized by profound elevation of proinflammatory cytokines in the serum, activation and expansion of SEB-reactive CD4(+) and CD8(+) T cells in peripheral lymphoid organs and SEB-induced deletion of immature thymocytes. Vaginal administration of SEB also caused leukocytic infiltration in major organs, such as liver and lung, reminiscent of human toxic shock syndrome. Systemic immune activation following vaginal superantigen delivery was independent of the stage of the estrus cycle in the mouse. Using HLA class II transgenic mice, we have shown that exposure to SEB through the vaginal canal can cause robust systemic immune activation. SEB could thus play a role in the pathogenesis of mTSS.

Intranasal exposure to staphylococcal enterotoxin B elicits an acute systemic inflammatory response.

Staphylococcus aureus produces a variety of superantigen exotoxins, including staphylococcal enterotoxin B (SEB). Little is known regarding the pathogenesis of SEB entering through the intranasal route. Intranasal exposure to SEB might occur because of nasal packing following surgical procedure, biologic warfare, or even S. aureus colonization. We evaluated the local and systemic effects of intranasally delivered SEB using a series of human leukocyte antigen (HLA) class II transgenic mice as conventional mice expressing endogenous class II molecules mount a poor immune response to SEB. Gene expression profiling using microarrays showed robust up-regulation of genes involved in several proinflammatory pathways as early as 3 h post-intranasal challenge with SEB in HLA class II transgenic mice. This was accompanied by a several hundred-fold increase in serum levels of pro-inflammatory cytokines such as IL-12, IL-6, TNF-alpha, IFN-gamma, as well as MCP-1 in HLA class II transgenic mice but not in C57BL/6 mice; CD4 or CD8 T-cells independently contributed to the systemic cytokine response. Defective IL-12 or IL-4 receptor signaling significantly decreased or increased serum IFN-gamma, respectively. Intranasal exposure to SEB resulted in neutrophil influx into bronchoalveolar lavage fluid and caused expansion of both CD4 and CD8 T-cells expressing TCR V beta 8 in the spleen. This was accompanied by mononuclear cell infiltration in the liver reminiscent of the systemic inflammatory response syndrome. Thus, we have shown, for the first time, that intranasal administration of SEB can cause systemic immune activation.

The association between impact factors and language of general internal medicine journals.

BACKGROUND: We sought to determine the associations between journal country of origin and language and journal impact factor of general medicine journals. METHODS: For each "Medicine, General and Internal" journal listed in the Institute for Scientific Information (ISI) Journal Citation Reports (JCR), the 2003 impact factor, language (ie, English, multiple languages [including English], or non-English), and country of origin (ie, US or non-US) were determined. The mean log impact factors of the journals by language, country of origin, and a combination of country of origin and language were compared. RESULTS: Of the 102 "Medicine, General and Internal" journals listed in the ISI JCR, 41 (40%) were published in the US and 83 (81%) were published in English. English-language journals had a significantly greater 2003 mean log impact factor than non-English journals and journals originating in the US had a significantly greater impact factor than journals originating elsewhere. However, the mean log impact factor of English-language journals originating in the US did not differ significantly from that of English-language journals originating elsewhere. CONCLUSION: Journal impact factor is more associated with journal language (ie, English versus non-English), rather than journal country of origin.

Obstructive sleep apnea and the recurrence of atrial fibrillation.

BACKGROUND: We tested the hypothesis that patients with untreated obstructive sleep apnea (OSA) would be at increased risk for recurrence of atrial fibrillation (AF) after cardioversion. METHODS AND RESULTS: We prospectively obtained data on history, echocardiogram, ECG, body mass index, hypertension, diabetes, NYHA functional class, ejection fraction, left atrial appendage velocity, and medications in patients with AF/atrial flutter referred for DC cardioversion. Forty-three individuals were identified as having OSA on the basis of a previous sleep study. Data regarding the use of continuous positive airway pressure (CPAP) and recurrence of AF were obtained for 39 of these patients. Follow-up data were also obtained in 79 randomly selected postcardioversion patients (controls) who did not have any previous sleep study. Twenty-seven of the 39 OSA patients either were not receiving any CPAP therapy (n=25) or were using CPAP inappropriately (n=2). Recurrence of AF at 12 months in these 27 patients was 82%, higher than the 42% recurrence in the treated OSA group (n=12, P=0.013) and the 53% recurrence (n=79, P=0.009) in the 79 control patients. Of the 25 OSA patients who had not been treated at all, the nocturnal fall in oxygen saturation was greater (P=0.034) in those who had recurrence of AF (n=20) than in those without recurrence (n=5). CONCLUSIONS: Patients with untreated OSA have a higher recurrence of AF after cardioversion than patients without a polysomnographic diagnosis of sleep apnea. Appropriate treatment with CPAP in OSA patients is associated with lower recurrence of AF.

Collecting and Analyzing Patient Experiences of Health Care From Social Media.

BACKGROUND: Social Media, such as Yelp, provides rich information of consumer experience. Previous studies suggest that Yelp can serve as a new source to study patient experience. However, the lack of a corpus of patient reviews causes a major bottleneck for applying computational techniques. OBJECTIVE: The objective of this study is to create a corpus of patient experience (COPE) and report descriptive statistics to characterize COPE. METHODS: Yelp reviews about health care-related businesses were extracted from the Yelp Academic Dataset. Natural language processing (NLP) tools were used to split reviews into sentences, extract noun phrases and adjectives from each sentence, and generate parse trees and dependency trees for each sentence. Sentiment analysis techniques and Hadoop were used to calculate a sentiment score of each sentence and for parallel processing, respectively. RESULTS: COPE contains 79,173 sentences from 6914 patient reviews of 985 health care facilities near 30 universities in the United States. We found that patients wrote longer reviews when they rated the facility poorly (1 or 2 stars). We demonstrated that the computed sentiment scores correlated well with consumer-generated ratings. A consumer vocabulary to describe their health care experience was constructed by a statistical analysis of word counts and co-occurrences in COPE. CONCLUSIONS: A corpus called COPE was built as an initial step to utilize social media to understand patient experiences at health care facilities. The corpus is available to download and COPE can be used in future studies to extract knowledge of patients' experiences from their perspectives. Such information can subsequently inform and provide opportunity to improve the quality of health care.

Cardiovascular physiology and sleep.

Sleep is a natural periodic suspension of consciousness during which processes of rest and restoration occur. The cognitive, reparative and regenerative accompaniments of sleep appear to be essential for maintenance of health and homeostasis. This brief overview will examine the cardiovascular responses to normal and disordered sleep, and their physiologic and pathologic implications. In the past, sleep was believed to be a passive state. The tableau of sleep as it unfolds is anything but a passive process. The brain's activity is as complex as wakefulness, never "resting" during sleep. Following the demise of the 'passive theory of sleep' (the reticular activating system is fatigued during the waking day and hence becomes inactive), there arose the 'active theory of sleep' (sleep is due to an active general inhibition of the brain) (1). Hess demonstrated the active nature of sleep in cats, inducing "physiological sleep" with electrical stimulation of the diencephalon (2). Classical experiments of transection of the cat brainstem (3) at midpontine level inhibited sleep completely, implying that centers below this level were involved in the induction of sleep (1, 4). For the first time, measurement of sleep depth without awakening the sleeper using the electroencephalogram (EEG) was demonstrated in animals by Caton and in humans, by Berger (1). This was soon followed by discovery of the rapid eye movement sleep periods (REM) by Aserinski and Kleitman (5), demonstration of periodical sleep cycles and their association with REM sleep (6, 7). Multiple studies and steady discoveries (4) made polysomnography, with its ability to perform simultaneous whole night recordings of EEG, electromyogram (EMG), and electrooculogram (EOC), a major diagnostic tool in study of sleep disorders. This facility has been of further critical importance in allowing evaluation of the interaction between sleep and changes in hemodynamics and autonomic cardiovascular control. Consequently the effects of sleep could be objectively differentiated from the effects of rest and recumbency. Furthermore, the specific effects of sleep onset and termination, and the effects of different sleep stages, could be assessed. Technological advances, with consequently enhanced and relatively non-invasive approaches to cardiovascular regulation, have greatly broadened our understanding of the effects of sleep stage on cardiovascular function. Continuous monitoring of simultaneous measures of polysomnographic and cardiovascular variables enables characterization of the effects of dynamic changes and rapid transitions in sleep stage, such as arousals. The capacity for measuring acute and immediate changes in autonomic, EEG and hemodynamic responses to sleep and arousal on a continuous basis has played an important role in enabling us to understand the interplay between changes in EEG and changes in the more peripheral measurements of neural and circulatory variables, such as sympathetic nerve traffic, heart rate (HR) and blood pressure (BP). Measurements of heart rate variability (HRV) (8-10), baroreflex sensitivity (BRS) (11-16), and intraneural measurement of sympathetic nerve traffic to muscle (MSNA) (17-22) and skin (SSNA) (23-24) have further advanced our understanding of mechanisms linking sleep and cardiovascular physiology.

Impact of FUTON and NAA bias on visibility of research.

OBJECTIVE: To determine whether availability of journals on MEDLINE as FUTON (full text on the Net) affects their impact factor. MATERIAL AND METHODS: A comprehensive search identified 324 cardiology, nephrology, and rheumatology/immunology journals on-line until May 2003. The status of these journals was ascertained in MEDLINE as having FUTON, abstracts only, and NAA (no abstract available). Impact factors for all available journals from the Institute for Scientific Information (ISI) were abstracted. RESULTS: Of the 324 Journals, 124 (38.3%) were FUTON, 138 (42.6%) had abstracts only, and 62 (19.1%) had NAA. The mean (+/-SEM) impact factor was 3.24 (+/-0.32), 1.64 (+/-0.30), and 0.14 (+/-0.45), respectively. Of the 324 current journals, 159 existed in both the pre- and the post-Internet era. An analysis of the change (ie, delta) in impact factor from the pre- to post-Internet era revealed a trend between journals with FUTON and abstracts only (P=.17, Wilcoxon rank sum test). Similar analyses of the delta of cardiology journals revealed a statistically significant difference between Journals with FUTON and abstracts only (P=.04, Wilcoxon rank sum test). CONCLUSION: FUTON bias is the tendency to peruse what is more readily available. This is the first study to show that on-line availability of medical literature may increase the impact factor and that such increase tends to be greater in FUTON journals. Failure to consider this bias may affect a journal's impact factor. Also, it could limit consideration of medical literature by ignoring relevant NAA articles and thereby influence medical education akin to publication or language bias.

Pilot Study of the Effect of Lanthanum Carbonate (Fosrenol®) In Patients with Calciphylaxis: A Wisconsin Network for Health Research (WiNHR) Study.

BACKGROUND: Currently there is a lack of effective treatment options for patients with calciphylaxis. There is anecdotal evidence that non-calcium based phosphorus binders may offer some benefit. The aim of this pilot study is to determine if lanthanum carbonate is effective in inducing remission of calciphylaxis lesions and demonstrate an improved DLQI (Dermatology Life Quality Index). METHODS: This is a multi-site exploratory pilot study conducted through the Wisconsin Network for Health Research (WiNHR), a collaboration of health services researchers across the state of Wisconsin. Dialysis patients were recruited from in-center dialysis units, clinics and hospital admissions over a period of 24-months. RESULTS: Due to the low inclusion rate, the trial was terminated after which 4 patients were prospectively analyzed. Dose of lanthanum carbonate was escalated to 3750 mg divided into 3 meals and titrated according to level of serum phosphorus. Gastrointestinal symptoms were the most common adverse effect. All 4 patients achieved complete remission by definition of skin re-epithelialization. Secondary outcome measurements showed a significant improvement in serum albumin (B coeff 0.17, 95% CI 0.002-0.031; p=0.023) and a significant improvement in overall DLQI score (B coeff -0.46, 95% CI -0.85- -0.08; p=0.019). CONCLUSIONS: Lanthanum carbonate appears to be efficacious as an adjunctive therapy to improve calciphylaxis lesions and symptom burden. More prospective clinical trials are warranted to determine the feasibility of this novel treatment strategy.

A fuzzy-match search engine for physician directories.

BACKGROUND: A search engine to find physicians' information is a basic but crucial function of a health care provider's website. Inefficient search engines, which return no results or incorrect results, can lead to patient frustration and potential customer loss. A search engine that can handle misspellings and spelling variations of names is needed, as the United States (US) has culturally, racially, and ethnically diverse names. OBJECTIVE: The Marshfield Clinic website provides a search engine for users to search for physicians' names. The current search engine provides an auto-completion function, but it requires an exact match. We observed that 26% of all searches yielded no results. The goal was to design a fuzzy-match algorithm to aid users in finding physicians easier and faster. METHODS: Instead of an exact match search, we used a fuzzy algorithm to find similar matches for searched terms. In the algorithm, we solved three types of search engine failures: "Typographic", "Phonetic spelling variation", and "Nickname". To solve these mismatches, we used a customized Levenshtein distance calculation that incorporated Soundex coding and a lookup table of nicknames derived from US census data. RESULTS: Using the "Challenge Data Set of Marshfield Physician Names," we evaluated the accuracy of fuzzy-match engine-top ten (90%) and compared it with exact match (0%), Soundex (24%), Levenshtein distance (59%), and fuzzy-match engine-top one (71%). CONCLUSIONS: We designed, created a reference implementation, and evaluated a fuzzy-match search engine for physician directories. The open-source code is available at the codeplex website and a reference implementation is available for demonstration at the datamarsh website.

Renal upregulation of HO-1 reduces albumin-driven MCP-1 production: implications for chronic kidney disease.

Proteinuria contributes to chronic kidney disease by stimulating renal tubular epithelial cells to produce cytokines such as monocyte chemoattractant protein-1 (MCP-1). The present study determined whether cellular overexpression of heme oxygenase-1 (HO-1) can influence albumin-stimulated MCP-1 production. In response to bovine serum albumin, NRK-52E cells constitutively overexpressing HO-1 (HO-1 OE cells) exhibit less induction of MCP-1 mRNA and less production of MCP-1 protein compared with similarly treated, control NRK-52E cells (CON cells). In wild-type NRK-52E cells, and under these conditions, we demonstrate that the induction of MCP-1 is critically dependent on intact NF-kappaB binding sites in the MCP-1 promoter. In response to albumin, CON cells exhibit activation of NF-kappaB, and this is reduced in HO-1 OE cells. Albumin also activates ERK1/2 and increases ERK activity, both of which are exaggerated in HO-1 OE cells. Studies with an inhibitor of MAPK/ERK kinase (U0126) demonstrate that the inhibitory effects of U0126 on MCP-1 production are attenuated in HO-1 OE cells. We conclude that HO-1 overexpression in the proximal tubule reduces MCP-1 production in response to albumin, and this occurs, at least in part, by inhibiting an ERK-dependent, NF-kappaB-dependent pathway at a site that is distal to the activation of ERK. These findings suggest that the induction of HO-1 in the proximal tubule, as occurs in chronic kidney disease, may be a countervailing response that reduces albumin-stimulated production of cytokines such as MCP-1.

Proteinuria as a determinant of renal expression of heme oxygenase-1: studies in models of glomerular and tubular proteinuria in the rat.

Heme oxygenase-1 (HO-1), a cytoprotective gene, is commonly induced in renal tubules in the diseased kidney. Because proteinuria is a hallmark for kidney disease, we examined the relationship between proteinuria and tubular induction of HO-1, specifically questioning whether increased trafficking of protein across the renal tubular epithelium, as a consequence of proteinuria, induces tubular expression of HO-1. We examined a model of glomerular proteinuria induced by daily injections of BSA, which is associated with increased tubular uptake of filtered protein, and a model of tubular proteinuria induced by maleate, the latter exhibiting decreased tubular uptake and trafficking of protein. The BSA model of glomerular proteinuria failed to exhibit induction of HO-1; HO-1 was not induced in proximal tubular epithelial cells exposed to BSA. In contrast, in maleate nephropathy wherein tubular uptake of protein is decreased because of generalized proximal tubular injury induced by maleate, HO-1 was strongly induced in proximal tubules; inhibition of HO activity in maleate nephropathy worsened proteinuria, renal histological injury, and apoptosis. In renal proximal tubular epithelial cells, maleate induced HO-1 and caused apoptosis, the latter increased when HO activity was inhibited. From these studies, we conclude that expression of HO-1 in the diseased kidney cannot be ascribed to the tubular uptake and metabolism of protein such as albumin, and that the expression of HO-1 in a model of tubular proteinuria reflects a functionally significant stress response to toxin-induced proximal tubular injury.

IL-10-deficiency unmasks unique immune system defects and reveals differential regulation of organ-specific autoimmunity in non-obese diabetic mice.

Interleukin (IL)-10 is a potent anti-inflammatory cytokine and ablation of IL-10 exacerbates Th1-type autoimmune diseases. Even though type 1 diabetes (T1D) in NOD mice is believed to be Th1-mediated, the incidence and severity of T1D is unaltered in IL-10-deficient NOD mice raised under pathogen-free conditions. We describe for the first time, the outcome of IL-10 deficiency on islet and other organ-specific autoimmunity in NOD mice raised in a conventional facility. IL-10-deficient NOD mice under such conditions were protected from spontaneous as well as cyclophosphamide-induced diabetes, but were susceptible to diabetes induced by adoptive transfer of splenocytes from spontaneously diabetic NOD mice. Whereas the incidence of rectal prolapse was very high in this NOD.IL-10(-/-) mouse colony, IL-10-deficient C57Bl/6 mice raised under similar conditions seldom developed rectal prolapse. While injection of complete Freund's adjuvant (CFA) significantly reduced insulitis, it did not ameliorate colitis in IL-10-deficient NOD mice indicating differential regulation of organ-specific autoimmunity by CFA. Phenotypic characterization of IL-10(-/-) mice revealed a significant increase in splenic macrophage numbers in NOD but not on the B6 background. This was accompanied by a heightened systemic inflammatory cytokine response and mortality following in vivo challenge with a toll-like receptor 9 agonist, CpG-containing DNA.

Anomalous renal effects of tin protoporphyrin in a murine model of sickle cell disease.

In human and murine models of sickle cell disease (SCD), heme oxygenase-1 (HO-1) is induced in the kidney, an organ commonly involved in SCD. The present study assessed the role of HO-1 by using a competitive inhibitor of HO activity, tin protoporphyrin (SnPP), in protocols affording a composite, clinically relevant analysis of the kidney in SCD under unstressed and stressed conditions. Whereas short-term administration of SnPP exerted comparable renal hemodynamic effects in wild-type and sickle mice, chronic administration of SnPP exerted divergent effects: SnPP provoked tubulointerstitial inflammation and up-regulation of injury-related genes in wild-type mice, whereas in sickle mice SnPP reduced expression of injury-related genes and vascular congestion without provoking tubulointerstitial inflammation. SnPP also protected against the heightened sensitivity to renal ischemia observed in sickle mice, preventing ischemia-induced worsening of renal injury in sickle mice above that observed in wild-type mice. Effective and comparable inhibition of HO activity by SnPP in wild-type and sickle mice was confirmed. These findings suggest that induction of HO-1, at least as assessed by this approach, may contribute to renal injury in this murine model of SCD and uncover an experimental maneuver that protects the kidney in murine SCD.

Endogenous superantigens shape response to exogenous superantigens.

Endogenous superantigen-mediated thymic negative selection resulted in a paucity of mature T cells bearing T-cell receptor (TCR) Vbeta8 in the periphery. Consequently, the magnitude of immune response to exogenous superantigen staphylococcal enterotoxin B, which activates TCR Vbeta8(+) T cells, was significantly reduced and conferred protection from superantigen-induced mortality.

High sensitivity C-reactive protein: a novel predictor for recurrence of atrial fibrillation after successful cardioversion.

OBJECTIVES: We sought to test the hypothesis that C-reactive protein (CRP) can predict the recurrence of atrial fibrillation (AF) after successful electrical cardioversion (CV). BACKGROUND: In patients with AF, CRP levels are predictive of immediate failure of CV. METHODS: We prospectively measured high-sensitivity CRP in 67 patients with AF or atrial flutter who underwent successful electrical CV. RESULTS: At one-month follow-up, 22 patients (33%) had recurrence of their arrhythmia. Arrhythmia recurrence was associated with significantly higher pre-CV CRP levels (odds ratio [OR] 1.84; 95% confidence interval [CI] 1.14 to 2.98; p = 0.013) even after adjusting for age (OR 2.22; 95% CI 1.25 to 3.93; p = 0.006), for gender (OR 1.89; 95% CI 1.16 to 3.09; p = 0.011), or duration of arrhythmia (OR 1.86; 95% CI 1.13 to 3.07; p = 0.015). On multivariate analysis, CRP was the only independent predictor of arrhythmia recurrence (OR 2.19; 95% CI 1.05 to 4.55; p = 0.036). CONCLUSIONS: Our data suggest that high levels of CRP are associated with an increased risk of recurrence of AF within one month. These data support the hypothesis that anti-inflammatory interventions may help in maintenance of normal sinus rhythm after CV. These data also may have implications for the identification of patients who are most likely to experience substantial benefit from CV therapy for AF.