Systematic review of atraumatic splenic rupture

BACKGROUND: Atraumatic splenic rupture (ASR) is an ill defined clinicopathological entity. METHODS: The aim was to characterize aetiological and risk factors for ASR-related mortality in order to aid disease classification and treatment. A systematic literature review (1980-2008) was undertaken and logistic regression analysis employed. RESULTS: Some 632 publications reporting 845 patients were identified. The spleen was normal in 7.0 per cent (atraumatic-idiopathic rupture). One, two or three aetiological factors were found in 84.1, 8.2 and 0.7 per cent respectively (atraumatic-pathological rupture). Six major aetiological groups were defined: neoplastic (30.3 per cent), infectious (27.3 per cent), inflammatory, non-infectious (20.0 per cent), drug- and treatment-related (9.2 per cent) and mechanical (6.8 per cent) disorders, and normal spleen (6.4 per cent). Treatment comprised total splenectomy (84.1 per cent), organ-preserving surgery (1.2 per cent) or conservative measures (14.7 per cent). The ASR-related mortality rate was 12.2 per cent. Splenomegaly (P = 0.040), age above 40 years (P = 0.007) and neoplastic disorders (P = 0.008) were associated with increased ASR-related mortality on multivariable analysis. CONCLUSION: The condition can be classified simply into atraumatic-idiopathic (7.0 per cent) and atraumatic-pathological (93.0 per cent) splenic rupture. Splenomegaly, advanced age and neoplastic disorders are associated with increased ASR-related mortality.

Low bone mineral density, renal dysfunction, and fracture risk in HIV infection: a cross-sectional study

BACKGROUND: Reduced bone mineral density (BMD) is common in adults infected with human immunodeficiency virus (HIV). The role of proximal renal tubular dysfunction (PRTD) and alterations in bone metabolism in HIV-related low BMD are incompletely understood. METHODS: We quantified BMD (dual-energy x-ray absorptiometry), blood and urinary markers of bone metabolism and renal function, and risk factors for low BMD (hip or spine T score, -1 or less) in an ambulatory care setting. We determined factors associated with low BMD and calculated 10-year fracture risks using the World Health Organization FRAX equation. RESULTS: We studied 153 adults (98% men; median age, 48 years; median body mass index, 24.5; 67 [44%] were receiving tenofovir, 81 [53%] were receiving a boosted protease inhibitor [PI]). Sixty-five participants (42%) had low BMD, and 11 (7%) had PRTD. PI therapy was associated with low BMD in multivariable analysis (odds ratio, 2.69; 95% confidence interval, 1.09-6.63). Tenofovir use was associated with increased osteoblast and osteoclast activity (P< or = .002). The mean estimated 10-year risks were 1.2% for hip fracture and 5.4% for any major osteoporotic fracture. CONCLUSIONS: In this mostly male population, low BMD was significantly associated with PI therapy. Tenofovir recipients showed evidence of increased bone turnover. Measurement of BMD and estimation of fracture risk may be warranted in treated HIV-infected adults.

Bacillus Calmette-Guérin Failure in Patients with Non-Muscle-invasive Urothelial Carcinoma of the Bladder May Be Due to the Urologist's Failure to Detect Urothelial Carcinoma of the Upper Urinary Tract and Urethra

BACKGROUND: Various reasons exist for so-called bacillus Calmette-Guérin (BCG) failure in patients with non-muscle-invasive urothelial bladder carcinoma (NMIBC). OBJECTIVE: To explore whether urothelial carcinoma of the upper urinary tract (UUT) and/or prostatic urethra may be a cause for BCG failure. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of 110 patients with high-risk NMIBC repeatedly treated with intravesical BCG, diagnosed with disease recurrence, and followed for a median time of 9.1 yr. INTERVENTION: Two or more intravesical BCG induction courses without maintenance. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome was pattern of disease recurrence (BCG failure) within the urinary tract categorised into UUT and/or urethral carcinoma (with or without intravesical recurrence), and intravesical recurrence alone. Secondary outcome was survival. Predictors of UUT and/or urethral carcinoma and the effect of pattern of disease recurrence on cancer-specific survival were assessed with multivariable Cox regression analysis adjusting for multiple clinical and tumour characteristics. RESULTS AND LIMITATIONS: Of the 110 patients, 57 (52%) had UUT and/or urethral carcinoma (with or without intravesical recurrence), and 53 (48%) had intravesical recurrence alone. In patients with UUT and/or urethral carcinoma, bladder carcinoma in situ (Tis) before the first and second BCG course was present in 42 of 57 (74%) and 47 of 57 (82%) patients, respectively. On multivariable analysis, bladder Tis before the first and/or second BCG course was the only independent predictor of UUT and/or urethral carcinoma. Of the 110 patients, 69 (63%) were alive at last follow-up visit, 18 (16%) had died due to metastatic urothelial carcinoma, and 23 (21%) had died of other causes. Pattern of disease recurrence within the urinary tract was not an independent predictor of cancer-specific survival. Main study limitations were retrospective design and limited power for survival analysis. CONCLUSIONS: In our patients with high-risk NMIBC failing after two or more courses of intravesical BCG, UUT and/or urethral carcinoma was detected in >50% of the cases during follow-up. The vast majority of these patients had bladder Tis before the first and/or second BCG course. In patients experiencing the so-called BCG failure, a diagnostic work-up of UUT and prostatic urethra should always be performed to exclude urothelial carcinoma before additional intravesical therapy or even a radical cystectomy is considered.

Chlamydia prevalence in young attenders of rural and regional primary care services in Australia: a cross-sectional survey.

OBJECTIVE To estimate chlamydia prevalence among 16-29-year-olds attending general practice clinics in Australia. DESIGN, PARTICIPANTS AND SETTING A cross-sectional survey was conducted from May 2010 to December 2012. Sexually experienced 16-29-year-olds were recruited from 134 general practice clinics in 54 rural and regional towns in four states and in nine metropolitan clinics (consecutive patients were invited to participate). Participants completed a questionnaire and were tested for chlamydia. MAIN OUTCOME MEASURE Chlamydia prevalence. RESULTS Of 4284 participants, 197 tested positive for chlamydia (4.6%; 95% CI, 3.9%-5.3%). Prevalence was similar in men (5.2% [65/1257]; 95% CI, 3.9%-6.4%) and women (4.4% [132/3027]; 95% CI, 3.5%-5.2%) (P = 0.25) and high in those reporting genital symptoms or a partner with a sexually transmissible infection (STI) - 17.0% in men (8/47; 95% CI, 2.8%-31.2%); 9.5% in women (16/169; 95% CI, 5.1%-13.8%). Nearly three-quarters of cases (73.4% [130/177]) were diagnosed in asymptomatic patients attending for non-sexual health reasons, and 83.8% of all participants (3258/3890) had attended for non-sexual health reasons. Prevalence was slightly higher in participants from rural and regional areas (4.8% [179/3724]; 95% CI, 4.0%-5.6%) than those from metropolitan areas (3.1% [17/548]; 95% CI, 1.5%-4.7%) (P = 0.08). In multivariable analysis, increasing partner numbers in previous 12 months (adjusted odds ratio [AOR] for three or more partners, 5.11 [95% CI, 2.35-11.08]), chlamydia diagnosis in previous 12 months (AOR, 4.35 [95% CI, 1.52-12.41]) and inconsistent condom use with most recent partner (AOR, 2.90 [95% CI, 1.31-6.40]) were significantly associated with chlamydia in men. In women, increasing partner numbers in previous 12 months (AOR for two partners, 2.59 [95% CI, 1.59-4.23]; AOR for three or more partners, 3.58 [95% CI, 2.26-5.68]), chlamydia diagnosis in previous 12 months (AOR, 3.13 [95% CI, 1.62-6.06]) and age (AOR for 25-29-year-olds, 0.23 [95% CI, 0.12-0.44]) were associated with chlamydia. CONCLUSIONS Chlamydia prevalence is similar in young men and women attending general practice. Testing only those with genital symptoms or a partner with an STI would have missed three-quarters of cases. Most men and women are amenable to being tested in general practice, even in rural and regional areas.

Time to renal disease and end-stage renal disease in PROFILE: a multiethnic lupus cohort.

BACKGROUND: Renal involvement is a serious manifestation of systemic lupus erythematosus (SLE); it may portend a poor prognosis as it may lead to end-stage renal disease (ESRD). The purpose of this study was to determine the factors predicting the development of renal involvement and its progression to ESRD in a multi-ethnic SLE cohort (PROFILE). METHODS AND FINDINGS: PROFILE includes SLE patients from five different United States institutions. We examined at baseline the socioeconomic-demographic, clinical, and genetic variables associated with the development of renal involvement and its progression to ESRD by univariable and multivariable Cox proportional hazards regression analyses. Analyses of onset of renal involvement included only patients with renal involvement after SLE diagnosis (n = 229). Analyses of ESRD included all patients, regardless of whether renal involvement occurred before, at, or after SLE diagnosis (34 of 438 patients). In addition, we performed a multivariable logistic regression analysis of the variables associated with the development of renal involvement at any time during the course of SLE.In the time-dependent multivariable analysis, patients developing renal involvement were more likely to have more American College of Rheumatology criteria for SLE, and to be younger, hypertensive, and of African-American or Hispanic (from Texas) ethnicity. Alternative regression models were consistent with these results. In addition to greater accrued disease damage (renal damage excluded), younger age, and Hispanic ethnicity (from Texas), homozygosity for the valine allele of FcgammaRIIIa (FCGR3A*GG) was a significant predictor of ESRD. Results from the multivariable logistic regression model that included all cases of renal involvement were consistent with those from the Cox model. CONCLUSIONS: Fcgamma receptor genotype is a risk factor for progression of renal disease to ESRD. Since the frequency distribution of FCGR3A alleles does not vary significantly among the ethnic groups studied, the additional factors underlying the ethnic disparities in renal disease progression remain to be elucidated.

Impact of Age and Baseline NIHSS Scores on Clinical Outcomes in the Mechanical Thrombectomy Using Solitaire FR in Acute Ischemic Stroke Study

BACKGROUND AND PURPOSE Age and stroke severity are inversely correlated with the odds of favorable outcome after ischemic stroke. A previously proposed score for Stroke Prognostication Using Age and NIHSS Stroke Scale (SPAN) indicated that SPAN-100-positive patients (ie, age + NIHSS score = 100 or more) do not benefit from IV-tPA. If this finding holds true for endovascular therapy, this score can impact patient selection for such interventions. This study investigated whether a score combining age and NIHSS score can improve patients' selection for endovascular stroke therapy. MATERIALS AND METHODS The SPAN index was calculated for patients in the prospective Solitaire FR Thrombectomy for Acute Revascularization study: an international single-arm multicenter cohort for anterior circulation stroke treatment by using the Solitaire FR. The proportion with favorable outcome (90-day mRS score ≤2) was compared between SPAN-100-positive versus-negative patients. RESULTS Of the 202 patients enrolled, 196 had baseline NIHSS scores. Fifteen (7.7%) patients were SPAN-100-positive. There was no difference in the rate of successful reperfusion (Thrombolysis In Cerebral Infarction 2b or 3) between SPAN-100-positive versus -negative groups (93.3% versus 82.8%, respectively; P = .3). Stroke SPAN-100-positive patients had a significantly lower proportion of favorable clinical outcomes (26.7% versus 60.8% in SPAN-100-negative, P = .01). In a multivariable analysis, SPAN-100-positive status was associated with lower odds of favorable outcome (OR, 0.3; 95% CI, 0.1-0.9; P = .04). A higher baseline Alberta Stroke Program Early CT Score and a short onset to revascularization time also predicted favorable outcome in the multivariable analysis. CONCLUSIONS A significantly lower proportion of patients with a positive SPAN-100 achieved favorable outcome in this cohort. SPAN-100 was an independent predictor of favorable outcome after adjusting for time to treatment and the extent of preintervention tissue damage according to the Alberta Stroke Program Early CT Score.

Blinded by PRISMA: are systematic reviewers focusing on PRISMA and ignoring other guidelines?

BACKGROUND PRISMA guidelines have been developed to improve the reporting of systematic reviews (SRs). Other reporting guidelines and techniques to assess methodological quality of SRs have been developed. We aimed to assess the frequency of the use of reporting and other guidelines in SRs to assess whether PRISMA is being used inappropriately as a substitute for other relevant guidelines. METHODS Web of Knowledge was searched to identify articles citing the PRISMA guidelines over a 12-month period. The use of reporting guidelines (including PRISMA and MOOSE) and tools for assessing methodological quality (including QUADAS) was assessed. Factors associated with appropriate use of guidelines including review type, field of publication and involvement of a methodologist were investigated. RESULTS Over the 12-month period, 701 SRs were identified. MOOSE guidelines were cited in just 17% of epidemiologic reviews; QUADAS or QUADAS-2 was referred to in just 40% of diagnostic SRs. In the multivariable analysis, medical field of publication and methodologist involvement (OR = 1.97, 95% CI: 1.37, 2.83) were significant predictors of appropriate use of guidelines. Inclusion of a meta-analysis resulted in 73% higher odds of appropriate usage of systematic review guidelines (OR = 1.73, 95% CI: 1.22, 2.35). CONCLUSIONS Usage of SR reporting guidelines and tools for assessment of methodological quality other than PRISMA may be under-utilized with negative implications both for the reporting and methodological quality of systematic reviews.

Comparative therapeutic value of post-remission approaches in patients with acute myeloid leukemia aged 40-60 years.

The preferred type of post-remission therapy (PRT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1) is a subject of continued debate, especially in patients at higher risk of nonrelapse mortality (NRM), including patients >40 years of age. We report results of a time-dependent multivariable analysis of allogenic hematopoietic stem cell transplantation (alloHSCT) (n=337) versus chemotherapy (n=271) or autologous HSCT (autoHSCT) (n=152) in 760 patients aged 40-60 years with AML in CR1. Patients receiving alloHSCT showed improved overall survival (OS) as compared with chemotherapy (respectively, 57±3% vs 40±3% at 5 years, P<0.001). Comparable OS was observed following alloHSCT and autoHSCT in patients with intermediate-risk AML (60±4 vs 54±5%). However, alloHSCT was associated with less relapse (hazard ratio (HR) 0.51, P<0.001) and better relapse-free survival (RFS) (HR 0.74, P=0.029) as compared with autoHSCT in intermediate-risk AMLs. AlloHSCT was applied following myeloablative conditioning (n=157) or reduced intensity conditioning (n=180), resulting in less NRM, but comparable outcome with respect to OS, RFS and relapse. Collectively, these results show that alloHSCT is to be preferred over chemotherapy as PRT in patients with intermediate- and poor-risk AML aged 40-60 years, whereas autoHSCT remains a treatment option to be considered in patients with intermediate-risk AML.Leukemia advance online publication, 23 December 2014; doi:10.1038/leu.2014.332.

Optimization of extracorporeal shock wave lithotripsy delivery rates achieves excellent outcomes in ureteral stones. Results of a prospective, randomized trial

PURPOSE Management of ureteral stones remains controversial. To determine whether optimizing extracorporeal shock wave lithotripsy (ESWL) delivery rates improves treatment of solitary ureteral stones, we compared outcomes of two SW delivery rates in a prospective, randomized trial. MATERIALS AND METHODS From July 2010 to October 2012, 254 consecutive patients were randomized to undergo ESWL at SW delivery rates of either 60 pulses (n=130) or 90 pulses (n=124) per min. The primary endpoint was stone-free rate at 3-month follow-up. Secondary endpoints included stone disintegration, treatment time, complications, and the rate of secondary treatments. Descriptive statistics were used to compare endpoints between the two groups. Adjusted odds ratios and 95% confidence intervals were calculated to assess predictors of success. RESULTS The stone-free rate at 3 months was significantly higher in patients who underwent ESWL at a SW delivery rate of 90 pulses per min than in those receiving 60 pulses (91% vs. 80%, p=0.01). Patients with proximal and mid-ureter stones, but not those with distal ureter stones, accounted for the observed difference (100% vs. 83%; p=0.005; 96% vs. 73%, p=0.03; and 81% vs. 80%, p=0.9, respectively). Treatment time, complications, and the rate of secondary treatments were comparable between the two groups. In multivariable analysis, SW delivery rate of 90 pulses per min, proximal stone location, stone density, stone size and the absence of an indwelling JJ stent were independent predictors of success. CONCLUSIONS Optimization of ESWL delivery rates can achieve excellent results for ureteral stones.

Impact of synchronous metastasis distribution on cancer specific survival in renal cell carcinoma after radical nephrectomy with tumor thrombectomy

PURPOSE Metastatic renal cell carcinoma can be clinically diverse in terms of the pattern of metastatic disease and response to treatment. We studied the impact of metastasis and location on cancer specific survival. MATERIALS AND METHODS The records of 2,017 patients with renal cell cancer and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 centers in the United States and Europe were analyzed. Number and location of synchronous metastases were compared with respect to patient cancer specific survival. Multivariable Cox regression models were used to quantify the impact of covariates. RESULTS Lymph node metastasis (155) or distant metastasis (725) was present in 880 (44%) patients. Of the patients with distant disease 385 (53%) had an isolated metastasis. The 5-year cancer specific survival was 51.3% (95% CI 48.6-53.9) for the entire group. On univariable analysis patients with isolated lymph node metastasis had a significantly worse cancer specific survival than those with a solitary distant metastasis. The location of distant metastasis did not have any significant effect on cancer specific survival. On multivariable analysis the presence of lymph node metastasis, isolated distant metastasis and multiple distant metastases were independently associated with cancer specific survival. Moreover higher tumor thrombus level, papillary histology and the use of postoperative systemic therapy were independently associated with worse cancer specific survival. CONCLUSIONS In our multi-institutional series of patients with renal cell cancer who underwent radical nephrectomy and tumor thrombectomy, almost half of the patients had synchronous lymph node or distant organ metastasis. Survival was superior in patients with solitary distant metastasis compared to isolated lymph node disease.

Impact of histologic subtype on cancer-specific survival in patients with renal cell carcinoma and tumor thrombus

BACKGROUND Although different prognostic factors for patients with renal cell carcinoma (RCC) and vena cava tumor thrombus (TT) have been studied, the prognostic value of histologic subtype in these patients remains unclear. OBJECTIVE We analyzed the impact of histologic subtype on cancer-specific survival (CSS). DESIGN, SETTINGS, AND PARTICIPANTS We retrospectively analyzed the records of 1774 patients with RCC and TT who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 US and European centers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Multivariable ordered logistic and Cox regression models were used to quantify the impact of tumor histology on CSS. RESULTS AND LIMITATIONS Overall 5-yr CSS was 53.4% (confidence interval [CI], 50.5-56.2) in the entire group. TT level (according to the Mayo classification of macroscopic venous invasion in RCC) was I in 38.5% of patients, II in 30.6%, III in 17.3%, and IV in 13.5%. Histologic subtypes were clear cell renal cell carcinoma (cRCC) in 89.9% of patients, papillary renal cell carcinoma (pRCC) in 8.5%, and chromophobe RCC in 1.6%. In univariable analysis, pRCC was associated with a significantly worse CSS (p<0.001) compared with cRCC. In multivariable analysis, the presence of pRCC was independently associated with CSS (hazard ratio: 1.62; CI, 1.01-2.61; p<0.05). Higher TT level, positive lymph node status, distant metastasis, and fat invasion were also independently associated with CSS. CONCLUSIONS In our multi-institutional series, we found that patients with pRCC and vena cava TT who underwent radical nephrectomy and tumor thrombectomy had significantly worse cancer-specific outcomes when compared with patients with other histologic subtypes of RCC. We confirmed that higher TT level and fat invasion were independently associated with reduced CSS.

Risk factors for potentially avoidable readmissions due to end-of-life care issues

BACKGROUND Repeated hospitalizations are frequent toward the end of life, where each admission should be an opportunity to initiate advance-care planning to high-risk patients. OBJECTIVE To identify the risk factors for having a 30-day potentially avoidable readmission due to end-of-life care issues among all medical patients. DESIGN Nested case-control study. SETTING/PATIENTS All 10,275 consecutive discharges from any medical service of an academic tertiary medical center in Boston, Massachusetts between July 1, 2009 and June 30, 2010. MEASUREMENTS A random sample of all the potentially avoidable 30-day readmissions was independently reviewed by 9 trained physicians to identify the ones due to end-of-life issues. RESULTS Among 534, 30-day potentially avoidable readmission cases reviewed, 80 (15%) were due to an end-of-life care issue. In multivariable analysis, the following risk factors were significantly associated with a 30-day potentially avoidable readmission due to end-of-life care issues: number of admissions in the previous 12 months (odds ratio [OR]: 1.10 per admission, 95% confidence interval [CI]: 1.02-1.20), neoplasm (OR: 5.60, 95% CI: 2.85-10.98), opiate medications at discharge (OR: 2.29, 95% CI: 1.29-4.07), Elixhauser comorbidity index (OR: 1.16 per 5-point increase, 95% CI: 1.10-1.22). The discrimination of the model (C statistic) was 0.85. CONCLUSIONS In a medical population, we identified 4 main risk factors that were significantly associated with 30-day potentially avoidable readmission due to end-of-life care issues, producing a model with very good to excellent discrimination. Patients with these risk factors might benefit from palliative care consultation prior to discharge in order to improve end-of-life care and possibly reduce unnecessary rehospitalizations.

Prevalence, characteristics, and publication of discontinued randomized trials.

IMPORTANCE The discontinuation of randomized clinical trials (RCTs) raises ethical concerns and often wastes scarce research resources. The epidemiology of discontinued RCTs, however, remains unclear. OBJECTIVES To determine the prevalence, characteristics, and publication history of discontinued RCTs and to investigate factors associated with RCT discontinuation due to poor recruitment and with nonpublication. DESIGN AND SETTING Retrospective cohort of RCTs based on archived protocols approved by 6 research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We recorded trial characteristics and planned recruitment from included protocols. Last follow-up of RCTs was April 27, 2013. MAIN OUTCOMES AND MEASURES Completion status, reported reasons for discontinuation, and publication status of RCTs as determined by correspondence with the research ethics committees, literature searches, and investigator surveys. RESULTS After a median follow-up of 11.6 years (range, 8.8-12.6 years), 253 of 1017 included RCTs were discontinued (24.9% [95% CI, 22.3%-27.6%]). Only 96 of 253 discontinuations (37.9% [95% CI, 32.0%-44.3%]) were reported to ethics committees. The most frequent reason for discontinuation was poor recruitment (101/1017; 9.9% [95% CI, 8.2%-12.0%]). In multivariable analysis, industry sponsorship vs investigator sponsorship (8.4% vs 26.5%; odds ratio [OR], 0.25 [95% CI, 0.15-0.43]; P < .001) and a larger planned sample size in increments of 100 (-0.7%; OR, 0.96 [95% CI, 0.92-1.00]; P = .04) were associated with lower rates of discontinuation due to poor recruitment. Discontinued trials were more likely to remain unpublished than completed trials (55.1% vs 33.6%; OR, 3.19 [95% CI, 2.29-4.43]; P < .001). CONCLUSIONS AND RELEVANCE In this sample of trials based on RCT protocols from 6 research ethics committees, discontinuation was common, with poor recruitment being the most frequently reported reason. Greater efforts are needed to ensure the reporting of trial discontinuation to research ethics committees and the publication of results of discontinued trials.

Risk of infections during interferon-based treatment in patients with chronic HCV infection and advanced hepatic fibrosis.

BACKGROUND & AIMS Pegylated interferon-based treatment is still the backbone of current hepatitis C therapy and is associated with bone marrow suppression and an increased risk of infections. The aim of this retrospective cohort study was to assess the risk of infections during interferon-based treatment among patients with chronic HCV infection and advanced hepatic fibrosis and its relation to treatment-induced neutropenia. METHODS This cohort study included all consecutive patients with chronic HCV infection and biopsy-proven bridging fibrosis or cirrhosis (Ishak 4-6) who started treatment between 1990 and 2003 in five large hepatology units in Europe and Canada. Neutrophil counts between 500/μL-749/μL and below 500/μL were considered as moderate and severe neutropenia, respectively. RESULTS This study included 723 interferon-based treatments, administered to 490 patients. In total, 113 infections were reported during 88 (12%) treatments, of which 24 (21%) were considered severe. Only one patient was found to have moderate neutropenia and three patients were found to have severe neutropenia at the visit before the infection. Three hundred and twelve (99.7%) visits with moderate neutropenia and 44 (93.6%) visits with severe neutropenia were not followed by an infection. Multivariable analysis showed that cirrhosis (OR 2.85, 95%CI 1.38-5.90, p=0.005) and severe neutropenia at the previous visit (OR 5.42, 95%CI 1.34-22.0, p=0.018) were associated with the occurrence of infection, while moderate neutropenia was not. Among a subgroup of patients treated with PegIFN, severe neutropenia was not significantly associated (OR 1.63, 95%CI 0.19-14.2, p=0.660). CONCLUSIONS In this large cohort of patients with bridging fibrosis and cirrhosis, infections during interferon-based therapy were generally mild. Severe interferon-induced neutropenia rarely occurred, but was associated with on-treatment infection. Moderate neutropenia was not associated with infection, suggesting that current dose reduction guidelines might be too strict.

Clinical impact of gastrointestinal bleeding in patients undergoing percutaneous coronary interventions.

BACKGROUND The risk factors and clinical sequelae of gastrointestinal bleeding (GIB) in the current era of drug-eluting stents, prolonged dual antiplatelet therapy, and potent P2Y12 inhibitors are not well established. We determined the frequency, predictors, and clinical impact of GIB after percutaneous coronary interventions (PCIs) in a contemporary cohort of consecutive patients treated with unrestricted use of drug-eluting stents. METHODS AND RESULTS Between 2009 and 2012, all consecutive patients undergoing PCI were prospectively included in the Bern PCI Registry. Bleeding Academic Research Consortium (BARC) GIB and cardiovascular outcomes were recorded within 1 year of follow-up. Among 6212 patients, 84.1% received new-generation drug-eluting stents and 19.5% received prasugrel. At 1 year, GIB had occurred in 65 patients (1.04%); 70.8% of all events and 84.4% of BARC ≥3B events were recorded >30 days after PCI. The majority of events (64.4%) were related to upper GIB with a more delayed time course compared with lower GIB. Increasing age, previous GIB, history of malignancy, smoking, and triple antithrombotic therapy (ie, oral anticoagulation plus dual antiplatelet therapy) were independent predictors of GIB in multivariable analysis. GIB was associated with increased all-cause mortality (adjusted hazard ratio, 3.40; 95% confidence interval, 1.67-6.92; P=0.001) and the composite of death, myocardial infarction, or stroke (adjusted hazard ratio, 3.75; 95% confidence interval, 1.99-7.07; P<0.001) and was an independent predictor of all-cause mortality during 1 year. CONCLUSIONS Among unselected patients undergoing PCI, GIB has a profound effect on prognosis. Triple antithrombotic therapy emerged as the single drug-related predictor of GIB in addition to patient-related risk factors within 1 year of PCI. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT02241291.