Olive View-UCLA Medical Center

Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.

A Panel of International Experts was convened by the Infectious Diseases Society of America (IDSA) in collaboration with the European Society for Microbiology and Infectious Diseases (ESCMID) to update the 1999 Uncomplicated Urinary Tract Infection Guidelines by the IDSA. Co-sponsoring organizations include the American Congress of Obstetricians and Gynecologists, American Urological Association, Association of Medical Microbiology and Infectious Diseases-Canada, and the Society for Academic Emergency Medicine. The focus of this work is treatment of women with acute uncomplicated cystitis and pyelonephritis, diagnoses limited in these guidelines to premenopausal, non-pregnant women with no known urological abnormalities or co-morbidities. The issues of in vitro resistance prevalence and the ecological adverse effects of antimicrobial therapy (collateral damage) were considered as important factors in making optimal treatment choices and thus are reflected in the rankings of recommendations.

BACKGROUND: Fusions involving one of three tropomyosin receptor kinases (TRK) occur in diverse cancers in children and adults. We evaluated the efficacy and safety of larotrectinib, a highly selective TRK inhibitor, in adults and children who had tumors with these fusions. METHODS: We enrolled patients with consecutively and prospectively identified TRK fusion-positive cancers, detected by molecular profiling as routinely performed at each site, into one of three protocols: a phase 1 study involving adults, a phase 1-2 study involving children, or a phase 2 study involving adolescents and adults. The primary end point for the combined analysis was the overall response rate according to independent review. Secondary end points included duration of response, progression-free survival, and safety. RESULTS: A total of 55 patients, ranging in age from 4 months to 76 years, were enrolled and treated. Patients had 17 unique TRK fusion-positive tumor types. The overall response rate was 75% (95% confidence interval [CI], 61 to 85) according to independent review and 80% (95% CI, 67 to 90) according to investigator assessment. At 1 year, 71% of the responses were ongoing and 55% of the patients remained progression-free. The median duration of response and progression-free survival had not been reached. At a median follow-up of 9.4 months, 86% of the patients with a response (38 of 44 patients) were continuing treatment or had undergone surgery that was intended to be curative. Adverse events were predominantly of grade 1, and no adverse event of grade 3 or 4 that was considered by the investigators to be related to larotrectinib occurred in more than 5% of patients. No patient discontinued larotrectinib owing to drug-related adverse events. CONCLUSIONS: Larotrectinib had marked and durable antitumor activity in patients with TRK fusion-positive cancer, regardless of the age of the patient or of the tumor type. (Funded by Loxo Oncology and others; ClinicalTrials.gov numbers, NCT02122913 , NCT02637687 , and NCT02576431 .).

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is increasingly recognized in infections among persons in the community without established risk factors for MRSA. METHODS: We enrolled adult patients with acute, purulent skin and soft-tissue infections presenting to 11 university-affiliated emergency departments during the month of August 2004. Cultures were obtained, and clinical information was collected. Available S. aureus isolates were characterized by antimicrobial-susceptibility testing, pulsed-field gel electrophoresis, and detection of toxin genes. On MRSA isolates, we performed typing of the staphylococcal cassette chromosome mec (SCCmec), the genetic element that carries the mecA gene encoding methicillin resistance. RESULTS: S. aureus was isolated from 320 of 422 patients with skin and soft-tissue infections (76 percent). The prevalence of MRSA was 59 percent overall and ranged from 15 to 74 percent. Pulsed-field type USA300 isolates accounted for 97 percent of MRSA isolates; 74 percent of these were a single strain (USA300-0114). SCCmec type IV and the Panton-Valentine leukocidin toxin gene were detected in 98 percent of MRSA isolates. Other toxin genes were detected rarely. Among the MRSA isolates, 95 percent were susceptible to clindamycin, 6 percent to erythromycin, 60 percent to fluoroquinolones, 100 percent to rifampin and trimethoprim-sulfamethoxazole, and 92 percent to tetracycline. Antibiotic therapy was not concordant with the results of susceptibility testing in 100 of 175 patients with MRSA infection who received antibiotics (57 percent). Among methicillin-susceptible S. aureus isolates, 31 percent were USA300 and 42 percent contained pvl genes. CONCLUSIONS: MRSA is the most common identifiable cause of skin and soft-tissue infections among patients presenting to emergency departments in 11 U.S. cities. When antimicrobial therapy is indicated for the treatment of skin and soft-tissue infections, clinicians should consider obtaining cultures and modifying empirical therapy to provide MRSA coverage.

PURPOSE: Focal cortical dysplasias (FCD) are localized regions of malformed cerebral cortex and are very frequently associated with epilepsy in both children and adults. A broad spectrum of histopathology has been included in the diagnosis of FCD. An ILAE task force proposes an international consensus classification system to better characterize specific clinicopathological FCD entities. METHODS: Thirty-two Task Force members have reevaluated available data on electroclinical presentation, imaging, neuropathological examination of surgical specimens as well as postsurgical outcome. KEY FINDINGS: The ILAE Task Force proposes a three-tiered classification system. FCD Type I refers to isolated lesions, which present either as radial (FCD Type Ia) or tangential (FCD Type Ib) dyslamination of the neocortex, microscopically identified in one or multiple lobes. FCD Type II is an isolated lesion characterized by cortical dyslamination and dysmorphic neurons without (Type IIa) or with balloon cells (Type IIb). Hence, the major change since a prior classification represents the introduction of FCD Type III, which occurs in combination with hippocampal sclerosis (FCD Type IIIa), or with epilepsy-associated tumors (FCD Type IIIb). FCD Type IIIc is found adjacent to vascular malformations, whereas FCD Type IIId can be diagnosed in association with epileptogenic lesions acquired in early life (i.e., traumatic injury, ischemic injury or encephalitis). SIGNIFICANCE: This three-tiered classification system will be an important basis to evaluate imaging, electroclinical features, and postsurgical seizure control as well as to explore underlying molecular pathomechanisms in FCD.

Evidence-based guidelines for the management of patients with methicillin-resistant Staphylococcus aureus (MRSA) infections were prepared by an Expert Panel of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by health care providers who care for adult and pediatric patients with MRSA infections. The guidelines discuss the management of a variety of clinical syndromes associated with MRSA disease, including skin and soft tissue infections (SSTI), bacteremia and endocarditis, pneumonia, bone and joint infections, and central nervous system (CNS) infections. Recommendations are provided regarding vancomycin dosing and monitoring, management of infections due to MRSA strains with reduced susceptibility to vancomycin, and vancomycin treatment failures.

BACKGROUND AND METHODS: To define better the bacteria responsible for infections of dog and cat bites, we conducted a prospective study at 18 emergency departments. To be eligible for enrollment, patients had to meet one of three major criteria for infection of a bite wound (fever, abscess, and lymphangitis) or four of five minor criteria (wound-associated erythema, tenderness at the wound site, swelling at the site, purulent drainage, and leukocytosis). Wound specimens were cultured for aerobic and anaerobic bacteria at a research microbiology laboratory and, in some cases, at local hospital laboratories. RESULTS: The infected wounds of 50 patients with dog bites and 57 patients with cat bites yielded a median of 5 bacterial isolates per culture (range, 0 to 16) at the reference laboratory. Significantly more isolates grew at the reference laboratory than at the local laboratories (median, 1; range, 0 to 5; P<0.001). Aerobes and anaerobes were isolated from 56 percent of the wounds, aerobes alone from 36 percent, and anaerobes alone from 1 percent; 7 percent of cultures had no growth. Pasteurella species were the most frequent isolates from both dog bites (50 percent) and cat bites (75 percent). Pasteurella canis was the most common isolate of dog bites, and Past. multocida subspecies multocida and septica were the most common isolates of cat bites. Other common aerobes included streptococci, staphylococci, moraxella, and neisseria. Common anaerobes included fusobacterium, bacteroides, porphyromonas, and prevotella. Isolates not previously identified as human pathogens included Reimerella anatipestifer from two cat bites and Bacteroides tectum, Prevotella heparinolytica, and several porphyromonas species from dog and cat bites. Erysipelothrix rhusiopathiae was isolated from two cat bites. Patients were most often treated with a combination of a beta-lactam antibiotic and a beta-lactamase inhibitor, which, on the basis of the microbiologic findings, was appropriate therapy. CONCLUSIONS: Infected dog and cat bites have a complex microbiologic mix that usually includes pasteurella species but may also include many other organisms not routinely identified by clinical microbiology laboratories and not previously recognized as bite-wound pathogens.

All AASLD Practice Guidelines are updated annually. If you are viewing a Practice Guideline that is more than 12 months old, please visit www.aasld.org for an update in the material. Ascites is the most common of the three major complications of cirrhosis, the other complications being hepatic encephalopathy and variceal hemorrhage.1 Cirrhosis is the most common cause of ascites in the United States.2 Development of ascites may be the first evidence of the presence of cirrhosis. Obesity makes the physical examination less helpful in detecting ascites.3 Imaging may provide the first evidence of the presence of ascites. Patients with ascites are frequently admitted to hospitals. Effective care of these patients can reduce the frequency of these readmissions. This version of the American Association for the Study of Liver Diseases Practice Guideline is the fourth iteration of this guideline and represents a thorough update of the 2009 version. ALB, albumin; CI, confidence interval; HRS, hepatorenal syndrome; MAP, mean arterial pressure; NASH, nonalcoholic steatohepatitis; RR, relative risk; SBP, spontaneous bacterial peritonitis; TID, three times daily. In this revision, the treatment options are now divided into first-line, second-line, third-line, and experimental options. There is a new section on drugs to be avoided or used with caution. Blood pressure in patients with cirrhosis and ascites is supported by elevated levels of vasoconstrictors; these vasoconstrictors are compensating for the vasodilatory effect of nitric oxide.4 Arterial pressure independently predicts survival in patients with cirrhosis; those with a mean arterial pressure (MAP) >82 mmHg have a 1-year survival of 70%, compared to 40% for those ≤82 mmHg.5 Drugs that inhibit the effects of these vasoconstrictors would be expected to lower blood pressure; they have been documented to do so.6 Lowering blood pressure might worsen survival. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers should be avoided or used with caution in patients with cirrhosis and ascites. The European Association for the Study of the Liver practice guideline on ascites recommends that “…they should generally not be used in patients with ascites.”7 This revised guideline reinforces this admonition. “Cirrhosis cures hypertension.” In the current era, many patients, especially those with obesity and a component of nonalcoholic steatohepatitis (NASH), have hypertension before they decompensate. Normalization of systemic blood pressure is perhaps the only perquisite of cirrhosis. In the situation where angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are used, blood pressure and renal function must be monitored carefully to avoid rapid development of renal failure. Monitoring of blood pressure at home provides useful information for the provider to factor into the decision when to taper or stop antihypertensives. Propranolol has been shown to shorten survival in patients with refractory ascites in a prospective study.8 This could be the result of its negative effect on blood pressure and the increase in the rate of paracentesis-induced circulatory dysfunction that is noted in patients who are taking propranolol in the setting of refractory ascites.9 Blood pressure and renal function should be monitored closely in patients who have refractory ascites. The risks versus benefits of beta blockers must be weighed carefully in each patient. Consideration should be given to discontinuing beta blockers or not initiating beta blockers in those patients with refractory ascites and those who develop worsening hypotension or worsening azotemia. In the current version of this guideline, there are also new sections on umbilical hernias, hepatic hydrothorax, and cellulitis. Chest-tube insertion in hepatic hydrothorax is advised against, based on older and newer studies.10, 11 Percutaneous endoscopic gastrostomy is advised against in patients with cirrhosis and ascites.12 Many patients with cirrhosis and ascites in the current era have multiple insults to the liver, including alcohol. Cessation of alcohol intake can dramatically improve their degree of liver failure, despite the continued presence of hepatitis C and/or NASH. Refractory ascites can revert to diuretic sensitive and can even disappear such that diuretics can be tapered and even stopped over time. Baclofen has been shown, in a randomized trial that included only patients with alcoholic liver disease, to reduce alcohol craving and alcohol consumption; it can be given at a dose of 5 mg orally three times daily (TID) for 3 days and then 10 mg TID.13 The dose can be tailored upward, with the patient carrying “a pill in the pocket” and taking an extra pill as needed to reduce alcohol craving.14 An outpatient appointment within 7 days of discharge from the hospital has been shown to correlate with lower readmissions rates of patients with heart failure.15 Rapid return to clinic may also reduce the readmission rates of patients with cirrhosis and ascites by frequent adjustment of doses of diuretics and prevention of dehydration versus tense ascites. The utility of monitoring urine sodium/potassium ratios is reiterated based on new data.16 Vaptans are discussed in this revision. Earlier studies of vaptans had focused on heart failure and included a relatively small number of patients with cirrhosis. These drugs are very expensive and may cause thirst. The largest randomized trial that specifically included only patients with cirrhosis demonstrated no clinical benefit in long-term management of ascites and provided a signal that mortality could be increased in patients taking drugs in this class.17 Oral midodrine at a dose of 7.5 mg TID has been shown, in a randomized trial in patients with refractory or recurrent ascites, to increase urine volume, urine sodium excretion, MAP, and survival.18 Nurses and care givers may be reluctant to give diuretics to profoundly hypotensive patients. Midodrine can be added to diuretics to increase blood pressure and convert refractory ascites back to diuretic sensitive. Albumin (ALB) infusion after large-volume paracentesis has been controversial. A meta-analysis of 17 trials involving 1,225 patients has been published, demonstrating a reduction in mortality with an odds ratio of death of 0.64 (95% confidence interval [CI]: 0.41-0.98) in the ALB group.19 ALB infusion (6-8 g per liter of fluid removed) is recommended when more than 5 L of ascitic fluid are removed. Information on the use of transjugular intrahepatic stent-shunt to treat ascites has also been updated. Widespread use of quinolones to prevent spontaneous bacterial peritonitis (SBP) in high-risk subgroups of patients, as well as frequent hospitalizations and exposure to broad-spectrum antibiotics, have led to a change in flora of infections in patients with cirrhosis; there are more Gram-positives and extended-spectrum B-lactamase-producing Enterobacteriaceae in recent years.20-22 Risk factors for multiresistant infections include nosocomial origin of infection, long-term norfloxacin prophylaxis, recent infection with multiresistant bacteria, and recent use of B-lactam antibiotics.20 Infections with these resistant organisms are associated with a higher mortality20 and can affect and complicate post-transplant care. We may encounter bacteria for which we have no effective treatment.22 To minimize bacterial resistance, it is prudent to limit prophylactic antibiotics to patients with well-defined criteria for SBP prophylaxis, limit duration of antibiotic treatment of infections, and narrow the spectrum of coverage, once susceptibility testing results are available. A new biomarker may assist with the diagnosis of hepatorenal syndrome (HRS) and may make it less of a diagnosis of exclusion.23 Urinary neutrophil gelatinase-associated lipocalin is 20 ng/mL in healthy controls, 20 ng/mL in prerenal azotemia, 50 ng/mL in chronic kidney disease, 105 ng/mL in HRS, and 325 ng/mL in acute kidney injury.23 This test has been shown to be superior to three other urine biomarkers, but is not presently available in the United States.24 A meta-analysis of vasoconstrictor treatment (including terlipressin, octreotide/midodrine, and norepinephrine) of type I and II HRS reports that vasoconstrictor drugs with or without ALB reduced mortality, compared with no intervention or ALB alone (relative risk [RR]: 0.82; 95% CI: 0.70-0.96).25 Terlipressin plus ALB reduced mortality, compared to albumin alone (RR, 0.81; 95% CI: 0.68-0.97) with a reduction in mortality in type I, but not type II, HRS.25 Enthusiasm is high for these new treatments.26 There are ongoing randomized, controlled trials that should help place these options in the treatment algorithm. Terlipressin is not yet available in the United States. Until further data are available, ALB, octreotide, and midodrine should be considered in the treatment of type I HRS. ALB and norepinephrine or vasopressin can be considered in the intensive care unit. Information on the use of transjugular intrahepatic stent-shunt to treat HRS has also been updated.

BACKGROUND: Plasma uric acid has been associated with hypertension in a variety of disorders, and has been shown to be predictive of hypertension. The mechanistic role of uric acid in the development of hypertension is not known however. METHOD: We tested the hypothesis that uric acid stimulates vascular smooth muscle cell (VSMC) proliferation and oxidative stress by stimulating the vascular renin-angiotensin system (RAS). Rat VSMC were exposed to 0-300 micromol uric acid for 48 h. RESULTS: Uric acid (200 and 300 micromol) stimulated the proliferation of VSMC as measured by thymidine uptake. This effect was prevented by 10(-6) mol losartan or by 10(-6) mol captopril. Incubation of VSMC with uric acid for 48 h also increased angiotensinogen messenger RNA expression and intracellular concentrations of angiotensin II. These responses were also inhibited by losartan and captopril. Increased expression of angiotensinogen mRNA was also inhibited by co-incubation with PD 98059, a mitogen-activated protein (MAP) kinase inhibitor. Uric acid stimulated the production of hydrogen peroxide and 8-isoprostane in VSMC. These increases in oxidative stress indicators were significantly reduced by co-incubating the cells with captopril or losartan. Uric acid also decreased nitrite and nitrate concentrations in the culture medium, an effect that was prevented by losartan and captopril. CONCLUSION: These results demonstrate that uric acid stimulates proliferation, angiotensin II production, and oxidative stress in VSMC through tissue RAS. This suggests that uric acid causes cardiovascular disorders by stimulating the vascular RAS, and this stimulation may be mediated by the MAP kinase pathway.

Antibiotic resistance and the collapse of the antibiotic research-and-development pipeline continue to worsen despite our ongoing efforts. If we're to develop countermeasures that have lasting effects, new ideas that complement traditional approaches are needed.

Brain trauma is accompanied by regional alterations of brain metabolism, reduction in metabolic rates and possible energy crisis. We hypothesize that microdialysis markers of energy crisis are present during the critical period of intensive care despite the absence of brain ischemia. In all, 19 brain injury patients (mean GCS 6) underwent combined positron emission tomography (PET) for metabolism of glucose (CMRglu) and oxygen (CMRO(2)) and cerebral microdialysis (MD) at a mean time of 36 h after injury. Microdialysis values were compared with the regional mean PET values adjacent to the probe. Longitudinal MD data revealed a 25% incidence rate of metabolic crisis (elevated lactate/pyruvate ratio (LPR) > 40) but only a 2.4% incidence rate of ischemia. Positron emission tomography imaging revealed a 1% incidence of ischemia across all voxels as measured by oxygen extraction fraction (OEF) and cerebral venous oxygen content (CvO(2)). In the region of the MD probe, PET imaging revealed ischemia in a single patient despite increased LPR in other patients. Lactate/pyruvate ratio correlated negatively with CMRO(2) (P < 0.001), but not with OEF or CvO(2). Traumatic brain injury leads to a state of persistent metabolic crisis as reflected by abnormal cerebral microdialysis LPR that is not related to ischemia.

Prostate-specific membrane antigen (PSMA)-ligand PET imaging provides unprecedented accuracy for whole-body staging of prostate cancer. As PSMA-ligand PET/CT is increasingly adopted in clinical trials and routine practice worldwide, a unified language for image reporting is urgently needed. We propose a molecular imaging TNM system (miTNM, version 1.0) as a standardized reporting framework for PSMA-ligand PET/CT or PET/MRI. miTNM is designed to organize findings in comprehensible categories to promote the exchange of information among physicians and institutions. Additionally, flowcharts integrating findings of PSMA-ligand PET and morphologic imaging have been designed to guide image interpretation. Specific applications, such as assessment of prognosis or impact on management, should be evaluated in future trials. miTNM is a living framework that evolves with clinical experience and scientific data.

BACKGROUND: Thromboses of the hepatic artery (HAT) and portal vein (PVT) may complicate orthotopic liver transplantation (OLT) and result in graft loss and mortality. Revision and retransplantation are treatment options, but their longterm outcomes remain undefined. This study was undertaken to evaluate the incidence of major vascular complications after OLT, determine efficacy of therapies, and identify factors influencing longterm outcomes. STUDY DESIGN: All patients undergoing OLT from 1984 to 2007 were evaluated. Kaplan-Meier analysis was performed to define the effects of vascular complications on posttransplant survival. Anastomotic revision and arterial thrombolysis were compared with retransplantation as treatment for HAT. After 2002, porta hepatis dissection was initiated with early occlusion of common hepatic artery (CHA) inflow; its impact on HAT incidence was determined. RESULTS: From 1984 to 2007, 4,234 OLTs were performed. HAT occurred in 203 patients (5%) and PVT in 84 (2%). Graft survival was significantly reduced by HAT or PVT; patient survival was reduced only by PVT. Retransplantation for HAT improved patient survival over revision or thrombolysis in the first year but did not provide longterm survival advantage (56% versus 56% at 5 years; p=0.53). Patients with HAT had only 10% graft salvage with anastomotic revision or thrombolysis. HAT was significantly reduced with early CHA inflow occlusion (1.1% versus 3.7%; p=0.002). Factors increasing risk of HAT included pediatric recipients, liver cancer, and aberrant arterial anatomy requiring complex reconstruction. CONCLUSIONS: Both HAT and PVT significantly reduce graft survival after OLT; PVT more adversely affects patient survival. Revision and thrombolysis rarely salvage grafts after HAT; retransplantation provides superior short-term, but not longterm, survival. Avoidance of vascular complications in OLT is critical, especially with today's scarcity of donor livers. Early atraumatic CHA occlusion significantly reduces the incidence of HAT.

The past 20 years have seen major advances in the diagnosis and management of brain abscess, with a corresponding improvement in the survival rates. The advances in radiographic scanning, the availability of new antimicrobials, and the development of novel surgical techniques have all contributed to the decreases in associated morbidity and mortality. The relative rarity of brain abscess and the frequent delays in making the diagnosis render this condition a significant challenge for the clinician. A high index of suspicion is required so that effective therapy can be instituted as soon as possible. Close coordination of care between neurosurgeons and infectious diseases specialists is increasingly important in the complicated management of brain abscess. Adequate abscess drainage and appropriate antimicrobial therapy remain the cornerstones of proper treatment of this condition.

PURPOSE: To determine the long-term efficacy of vagus nerve stimulation (VNS) for refractory seizures. VNS is a new treatment for refractory epilepsy. Two short-term double-blind trials have demonstrated its safety and efficacy, and one long-term study in 114 patients has demonstrated a cumulative improvement in efficacy at 1 year. We report the largest prospective long-term study of VNS to date. METHODS: Patients with six or more complex partial or generalized tonic-clonic seizures enrolled in the pivotal EO5 study were prospectively evaluated for 12 months. The primary outcome variable was the percentage reduction in total seizure frequency at 3 and 12 months after completion of the acute EO5 trial, compared with the preimplantation baseline. Subjects originally randomized to low stimulation (active-control group) were crossed over to therapeutic stimulation settings for the first time. Subjects initially randomized to high settings were maintained on high settings throughout the 12-month study. RESULTS: The median reduction at 12 months after completion of the initial double-blind study was 45%. At 12 months, 35% of 195 subjects had a >50% reduction in seizures, and 20% of 195 had a >75% reduction in seizures. CONCLUSIONS: The efficacy of VNS improves during 12 months, and many subjects sustain >75% reductions in seizures.

CONTEXT: The optimal antimicrobial regimen and treatment duration for acute uncomplicated pyelonephritis are unknown. OBJECTIVE: To compare the efficacy and safety of a 7-day ciprofloxacin regimen and a 14-day trimethoprim-sulfamethoxazole regimen for the treatment of acute pyelonephritis in women. DESIGN: Randomized, double-blind comparative trial conducted from October 1994 through January 1997. SETTING: Twenty-five outpatient centers in the United States. PATIENTS: Of 378 enrolled premenopausal women aged at least 18 years with clinical diagnosis of acute uncomplicated pyelonephritis, 255 were included in the analysis. Other individuals were excluded for no baseline causative organism, inadequate receipt of study drug, loss to follow-up, no appropriate cultures, and other reasons. INTERVENTIONS: Patients were randomized to oral ciprofloxacin, 500 mg twice per day for 7 days (with or without an initial 400-mg intravenous dose) followed by placebo for 7 days (n = 128 included in analysis) vs trimethoprim-sulfamethoxazole, 160/800 mg twice per day for 14 days (with or without intravenous ceftriaxone, 1 g) (n = 127 included in the analysis). MAIN OUTCOME MEASURE: Continued bacteriologic and clinical cure, such that alternative antimicrobial drugs were not required, among evaluable patients through the 4- to 11-day posttherapy visit, compared by treatment group. RESULTS: At 4 to 11 days posttherapy, bacteriologic cure rates were 99% (112 of 113) for the ciprofloxacin regimen and 89% (90 of 101) for the trimethoprim-sulfamethoxazole regimen (95% confidence interval [CI] for difference, 0.04-0.16; P = .004). Clinical cure rates were 96% (109 of 113) for the ciprofloxacin regimen and 83% (92 of 111) for the trimethoprim-sulfamethoxazole regimen (95% CI, 0.06-0.22; P = .002). Escherichia coli, which caused more than 90% of infections, was more frequently resistant to trimethoprim-sulfamethoxazole (18%) than to ciprofloxacin (0%; P<.001). Among trimethoprim-sulfamethoxazole-treated patients, drug resistance was associated with greater bacteriologic and clinical failure rates (P<.001 for both). Drug-related adverse events occurred in 24% of 191 ciprofloxacin-treated patients and in 33% of 187 trimethoprim-sulfamethoxazole-treated patients, respectively (95% CI, -0.001 to 0.2). CONCLUSIONS: In our study of outpatient treatment of acute uncomplicated pyelonephritis in women, a 7-day ciprofloxacin regimen was associated with greater bacteriologic and clinical cure rates than a 14-day trimethoprim-sulfamethoxazole regimen, especially in patients infected with trimethoprim-sulfamethoxazole-resistant strains.

BACKGROUND: Domestic violence is the most common cause of nonfatal injury to women in the United States. To identify risk factors for such injuries, we examined the socioeconomic and behavioral characteristics of women who were victims of domestic violence and the men who injured them. METHODS: We conducted a case-control study at eight large, university-affiliated emergency departments. The 256 intentionally injured women had acute injuries resulting from a physical assault by a male partner. The 659 controls were women treated for other conditions in the emergency department. Information was collected with a standardized questionnaire; no information was obtained directly from the male partners. RESULTS: The 256 intentionally injured women had a total of 434 contusions and abrasions, 89 lacerations, and 41 fractures and dislocations. In a multivariate analysis, the characteristics of the partners that were most closely associated with an increased risk of inflicting injury as a result of domestic violence were alcohol abuse (adjusted relative risk, 3.6; 95 percent confidence interval, 2.2 to 5.9); drug use (adjusted relative risk, 3.5; 95 percent confidence interval, 2.0 to 6.4); intermittent employment (adjusted relative risk, 3.1; 95 percent confidence interval, 1.1 to 8.8); recent unemployment (adjusted relative risk, 2.7; 95 percent confidence interval, 1.2 to 6.5); having less than a high-school-graduate's education (adjusted relative risk, 2.5; 95 percent confidence interval, 1.4 to 4.4); and being a former husband, estranged husband, or former boyfriend (adjusted relative risk, 3.5; 95 percent confidence interval, 1.5 to 8.3). CONCLUSIONS: Women at greatest risk for injury from domestic violence include those with male partners who abuse alcohol or use drugs, are unemployed or intermittently employed, have less than a high-school-graduate's education, and are former husbands, estranged husbands, or former boyfriends of the women.

OBJECTIVE: To assess the efficacy of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) and the impact of current staging criteria on long term survival. SUMMARY BACKGROUND DATA: HCC is becoming an increasingly common indication for OLT. Medicare approves OLT only for HCCs meeting the Milan criteria, thus limiting OLT for an expanding pool of potential liver recipients. We analyzed our experience with OLT for HCC to determine if expansion of criteria for OLT for HCC is warranted. METHODS: : All patients undergoing OLT for HCC from 1984 to 2006 were evaluated. Outcomes were compared for patients who met Milan criteria (single tumor < opr =5 cm, maximum of 3 total tumors with none >3 cm), University of California, San Francisco (UCSF) criteria (single tumor <6.5 cm, maximum of 3 total tumors with none >4.5 cm, and cumulative tumor size <8 cm), or exceeded UCSF criteria. RESULTS: A total of 467 transplants were performed for HCC. At mean follow up of 6.6 +/- 0.9 years, recurrence rate was 21.2%, and overall 1, 3, and 5-year survival was 82%, 65%, and 52%, respectively. Patients meeting Milan criteria had similar 5-year post-transplant survival to patients meeting UCSF criteria by preoperative imaging (79% vs. 64%; P = 0.061) and explant pathology (86% vs. 71%; P = 0.057). Survival for patients with tumors beyond UCSF criteria was significantly lower and was below 50% at 5 years. Multivariate analysis showed that tumor number (P < 0.001), lymphovascular invasion (P < 0.001), and poor differentiation (P = 0.002) independently predicted poor survival. CONCLUSIONS: This largest single institution experience with OLT for HCC demonstrates prolonged survival after liver transplantation for tumors beyond Milan criteria but within UCSF criteria, both when classified by preoperative imaging and by explant pathology. Measured expansion of OLT criteria is justified for tumors not exceeding the UCSF criteria.

Several molecules present in the diet, including flavonoids, can inhibit the growth of cancer cells with an ability to act as "chemopreventers". Their cancer-preventive effects have been attributed to various mechanisms, including the induction of cell-cycle arrest and/or apoptosis as well as the antioxidant functions. The antioxidant activity of chemopreventers has recently received a great interest, essentially because oxidative stress participates in the initiation and progression of different pathological conditions, including cancer. Since antioxidants are capable of preventing oxidative damage, the wide use of natural food-derived antioxidants is receiving greater attention as potential anti-carcinogens. Among flavonoids, quercetin (Qu) is considered an excellent free-radical scavenging antioxidant, even if such an activity strongly depends on the intracellular availability of reduced glutathione. Apart from antioxidant activity, Qu also exerts a direct, pro-apoptotic effect in tumor cells, and can indeed block the growth of several human cancer cell lines at different phases of the cell cycle. Both these effects have been documented in a wide variety of cellular models as well as in animal models. The high toxicity exerted by Qu on cancer cells perfectly matches with the almost total absence of any damages for normal, non-transformed cells. In this review we discuss the molecular mechanisms that are based on the biological effects of Qu, and their relevance for human health.

Hypomagnesemia has been reported to occur at an increased frequency among patients with type 2 diabetes compared with their counterparts without diabetes. Despite numerous reports linking hypomagnesemia to chronic diabetic complications, attention to this issue is poor among clinicians. This article reviews the literature on the metabolism of magnesium, incidence of hypomagnesemia in patients with type 2 diabetes, implicated contributing factors, and associated complications. Hypomagnesemia occurs at an incidence of 13.5 to 47.7% among patients with type 2 diabetes. Poor dietary intake, autonomic dysfunction, altered insulin metabolism, glomerular hyperfiltration, osmotic diuresis, recurrent metabolic acidosis, hypophosphatemia, and hypokalemia may be contributory. Hypomagnesemia has been linked to poor glycemic control, coronary artery diseases, hypertension, diabetic retinopathy, nephropathy, neuropathy, and foot ulcerations. The increased incidence of hypomagnesemia among patients with type 2 diabetes presumably is multifactorial. Because current data suggest adverse outcomes in association with hypomagnesemia, it is prudent to monitor magnesium routinely in this patient population and treat the condition whenever possible.